There are 49 clinical trials
Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred. This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.
Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---
- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---
Exclusion Criteria: 1. Contra-indications to either treatment modality 2. Patients who are not able to co-operate 3. Lack of informed consent Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---
However, the criteria for ferritin levels have been set at 300 micrograms/L for patients who are homozygous for the C282Y mutation, and also heterozygous individuals will be included if ferritin is higher than 500 micrograms/L. --- C282Y ---
Inclusion criteria 1. Diagnosis 1. Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---
2. Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---
Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the hypotheses are that an iron supplementation adapted to values of hemoglobin at the start of the pregnancy will would be more effective in preventing iron deficiency, without increasing the risk of hemoconcentration by the end of pregnancy. This would be helped optimize mother-child health status. The aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. To accomplish this objective a Randomized Clinical Trial (RCT) triple-blinded was designed. The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. This study will be conducted in non-anemic pregnant women at early gestation stage, and their subsequent newborns. The data recollected to mothers will be: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children, the data collected will be: ultrasound fetal biometry, anthropometric measurements, and temperament development Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.
In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). --- C282Y ---
- Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).. C282Y polymorphisms of HFE gene. --- C282Y ---
Presence or absence of polymorphisms: C282Y and H63D. --- C282Y ---
Description: - Anemia is defined as Hb <110 g/L in the 1st and 3rd trimester, Hb <110 in 2nd trimester (Centers for Disease Control and Prevention, 1998).
Measure: Anemia Time: at week 36 of gestation (3rd visit of study)Description: - Ferropenic anemia is defined as: Hb < the normal limit, and serum ferritin (SF) <15 μg/L (WHO, 2007)
Measure: ferropenic anemia Time: at week 36 of gestation (3rd visit of study)Description: - Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).
Measure: Risk of hemoconcentration Time: at week 36 of gestation (3rd visit of study)Description: Presence or absence of polymorphisms: C282Y and H63D
Measure: C282Y polymorphisms of HFE gene Time: Blood analysis at 12 weeks of gestation.Description: weight (g)
Measure: Anthropometric parameters of newborn. Time: At birthDescription: Units on a scale (score).
Measure: Neurorconductual development of newborn (Bayley Scales) Time: 40days post-partumDescription: Presence or absence of polymorphisms: C282Y and H63D
Measure: H63D polymorphisms of HFE gene Time: Blood analysis at 12 weeks of gestation.This study will examine the effectiveness of S-adenosyl methionine (SAMe) in combination with peginterferon and ribavirin for treating hepatitis C virus. One out of three patients with hepatitis C develops cirrhosis of the liver, which can lead to liver failure or liver cancer. SAMe is a nutritional supplement that is made naturally in all cells of the body and acts to improve how the body handles stress. In laboratory experiments with liver cells, SAMe decreases the injury caused by liver toxins and improves the ability of interferon to block hepatitis C virus. Patients 18 years of age and older with hepatitis C infection who did not respond successfully to prior treatment with interferon and ribavirin or peginterferon and ribavirin may be eligible for this study. Participants receive the following treatment: - Peginterferon (given by injection) and ribavirin (taken by mouth) for 2 weeks - Washout period (no medications) for 4 weeks - SAMe (taken by mouth) for 2 weeks - Peginterferon, ribavirin and SAMe for 12-48 weeks, depending on patient response to treatment. Participants have a thorough physical evaluation before beginning treatment and again at the study's end. After starting treatment, patients return for clinic visits and blood tests weekly for the first several weeks, then less frequently (at 2-week, then 4-week and 8-week intervals until up to 72 weeks) to monitor symptoms, drug side effects, hepatitis C virus levels, liver enzyme levels and immune responses to hepatitis C. ...
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---
Description: Improvement of slopes of decline in hepatitis C virus Ribonucleic acid in second course compared with first course in days 7 to 14 of therapy
Measure: Improvement in Viral Kinetics During the First 2 Weeks of Therapy Time: Days 7 to 14 of therapyDescription: 2-log decline in HCV RNA by week 12 (early virological response) and sustained eradication of HCV RNA (sustained virological response).
Measure: 2-log Decline in HCV RNA by Week 12 (Early Virological Response) and Sustained Eradication of HCV RNA (Sustained Virological Response). Time: 12 weeks from start of therapyThis is a phase II study with direct individual benefit. It is a randomized, double blind placebo controlled study whose aim is to evaluate the efficacy and tolerance of ursodesoxycholic acid in patients who have been diagnosed with non-alcoholic steatohepatitis. The hepatoprotective effects of ursodesoxycholic acid may ameliorate the hepatic impairment associated with non-alcoholic steatohepatitis leading to subsequent significant decreases in transaminase elevations and non-invasive markers for hepatic fibrosis A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group. The duration of the study will be 12 months. An end of treatment evaluation (EoT) will take place at the end of the 12th month of treatment.
- Alcohol consumption of >20 g/day for women and > 30 g/day for men - Hepatitis from other causes: chronic viral hepatitis B or C, elevated ferritin levels associated with C282Y homozygosity, primary biliary cirrhosis, primary sclerosing cholangitis, well documented auto-immune hepatitis (specific autoantibodies, hypergammaglobulinemia, consistent histologic changes), alpha1 antitrypsin deficiency, Wilson's disease, HIV infection. --- C282Y ---
Metabolic syndrome (MS) has an increasing prevalence worldwide and there is an urgent need for improvement of medical treatment. In traditional medicine phlebotomy (blood letting) is a recommended treatment for subjects with obesity and vascular disease. Recent studies showed that blood letting with iron depletion may improve insulin sensitivity in patients with diabetes mellitus. The investigators aimed to test if traditional blood letting has beneficial effects in patients with MS. A randomized trial with a sample size of 64 self-referred MS patients was conducted. Patients in the blood letting group were allocated to blood letting intervention and the control group was offered a later treatment (waiting list). In the intervention group 300-400 ml of venous blood were withdrawn at day 1 and after 4 weeks. Primary outcomes were the change of systolic blood pressure and of insulin sensitivity as measured by HOMA-Index.
Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Syndrome Metabolic Syndrome Insulin Resistance null --- Cys282Tyr ---
Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Syndrome Metabolic Syndrome Insulin Resistance null --- Cys282Tyr --- --- Cys282Tyr ---
Description: Glucose and insulin are measured on the basis of overnight fasting blood samples and Insulin sensitivity calculated according to HOMA-Index
Measure: insulin sensitivity Time: change from baseline at 6 weeksDescription: Blood pressure is measured twice after 5 minutes rest in the sitting position by sphygmomanometry
Measure: systolic blood pressure Time: change from baseline at 6 weeksThe purpose of this study is to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with HH at risk of iron-related morbidity. This evaluation will provide information on the two treatment options in terms of the rate of response of proportion of patients reaching the study target SF ≤ 100 μg/L and their associated safety profiles. In addition to exploring the safety and efficacy of deferasirox FCT in hereditary hemochromatosis (HH), this study is being conducted to fulfill an FDA post-marketing requirement [PMC 750-10 (Exjade) /PMR 2888-8 (Jadenu)] to provide additional randomized data to confirm the ocular safety profile of deferasirox through detailed ocular assessments in patients treated with deferasirox FCT for 2 years.
Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y ---
Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y --- --- C282Y ---
Description: Assess the response rate (RR) of deferasirox film coated tablet (FCT) and phlebotomy treatment arms where response is defined by achieving target serum ferritin (SF) ≤ 100 μg/L on or before 24 months. Estimate of the RR and corresponding 95% confidence interval (CI) will be provided for each arm. No formal hypothesis testing is planned in this study.
Measure: Proportion of patients achieving target SF ≤ 100 μg/L for the first time. Time: Response is defined by achieving target SF ≤ 100 μg/L on or before 24 months.Description: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by the incidence of treatment-emergent ocular adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.
Measure: Incidence of ocular adverse events (AEs) overall Time: 24 monthsDescription: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by AE severity (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.
Measure: Incidence of ocular adverse events (AEs) by severity Time: 24 monthsA subset of patients with NAFLD that have not been extensively studied are those infected with human immunodeficiency virus (HIV). Currently, there is no FDA approved treatment for NAFLD or NASH. Additionally, there have been no significant clinical trials for HIV patients with NAFLD and there are no approved treatment options. We plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to examine the efficacy of 600 mg of Aramchol daily (including 200 mg tablet and 400 mg tablet) versus identical placebo given over 12 weeks to improve HIV-associated hepatic steatosis as measured by a validated and accurate magnetic resonance imaging (MRI)-based technique.
Evidence of another form of liver disease: Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg), Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum, Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy, Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with rimary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis, Wilsons disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilsons disease Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D, Drug-induced liver disease as defined on the basis of typical exposure and history,Bile duct obstruction as shown by imaging studies. --- C282Y ---
Description: To examine the efficacy of aramchol at 600 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD
Measure: Efficacy of Aramchol 600 mg vs. placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD Time: 12 weeksDescription: To examine the efficacy of two doses of aramchol: 200 mg/tablet and 400 mg/tablet / day orally daily versus placebo in improving serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with HIV-associated NAFLD
Measure: Efficacy of aramchol 600 mg orally daily versus placebo in improving serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with HIV-associated NAFLD Time: 12 WeeksDescription: To examine the efficacy of aramchol in improving imaging-based biomarkers associated with changes in NAFLD
Measure: Efficacy of aramchol in improving imaging-based biomarkers associated with changes in NAFLD Time: 12 weeksObjective: To evaluate the effect of Iron supplement with two different amounts (one in the higher limit and another in the lower limit of the suggested amount) according to the presence of mutations in the HFE gene in the physical, immune and neurobehavioral development in the 6 to 12 moth toddlers. Methodology: Subjects: 340 toddlers coming from Paediatric Serves of Sant Joan Hospital. Methods: At 6 and 12 months it done clinical history, food registry, biochemist determinations: haemoglobin, iron, transferrin, ferritin, reactive C protein and immune response (IL4, IL10, IL6 IFN, IgA, IgM, IgG, IgE). Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. Mental, psychomotor and behavioual development (Bayley Scales of Infant Development 2on Edition: 1993). We evaluate the level of language and communication (MacArthur), regulation and sensory process (Infant Toddler Symptom Checklist), familiar and environment surroundings (Scale Health General Parental Stress Index).
Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. --- C282Y ---
Background:
- Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure
in the blood vessels of the liver. It seems to start slowly and not have many warning signs.
Many people may not even know that they have a liver disease. There are no specific
treatments for NCPH.
Objectives:
- To learn more about how NCPH develops over time.
Eligibility:
- People age 12 and older who have NCPH or are at risk for getting it. In the past year, they
cannot have had other types of liver disease that typically result in cirrhosis, liver
cancer, or active substance abuse.
Design:
- Participants will have 2 screening visits.
- Visit 1: to see if they have or may develop NCPH.
- Medical history
- Physical exam
- Urine and stool studies
- Abdominal ultrasound
- Fibroscan. Sound waves measure liver stiffness.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy or homozygosity for C282Y. --- C282Y ---
Observational study.
- Inclusion criteria: - homozygous C282Y ; - in the maintenance phase for at least 6 months ; - follow-up at Rennes University Hospital ; - patient who has not expressed his opposition to participate in the study. --- C282Y ---
Hemochromatoses, Genetic Hemochromatosis Asthenia The linked HFE genetic hemochromatosis (C282Y mutation in the homozygous state) is the most common form of genetic iron overload. --- C282Y ---
Our objective is to evaluate, in patients homozygous C282Y in maintenance phase, the association between quality of life and Transferrin Saturation Coefficient . --- C282Y ---
Hypothesis: The reduction of total body iron by phlebotomy will be safe and feasible in the post-HSCT setting Iron overload is common after hematopoietic stem cell transplantation. It is associated with chronic liver disease, with increased rates of infection and decreased survival. Eligible, consenting patients will have once monthly phlebotomy procedures (500ml) for 12 months. SAFETY: At each visit, patients will have a comprehensive assessment prior to starting and after completing the phlebotomy. This assessment will include determination of pain at phlebotomy site, local infection and an assessment of symptoms of anemia including presyncope, fatigue and dyspnea. The patient's pulse, blood pressure, respiratory rate and temperature will also be determined before and following the phlebotomy. EFFICACY: Iron stores will be measured serially in each patient. Measurements will be performed prior to the start of phlebotomy, and at 6 months and 12 months following the start of the series of 12 phlebotomies. These evaluations will be undertaken regardless of the number of phlebotomies which the patient actually undergoes. Iron stores will be estimated by measuring serum ferritin and transferrin saturation levels. Total body iron will be estimated from hepatic and cardiac iron concentration as measured by magnetic resonance imaging (MRI). Gandon et al. (12) described a non-invasive technique using MRI to measure hepatic iron stores. Iron is a paramagnetic substance which causes local magnetic field inhomogeneities leading to dephasing and signal loss in MRI. Gradient echo sequences are most susceptible to their effects because they do not use a 180° refocusing pulse, unlike conventional spin-echo sequences. Gandon et al. used multiple gradient echo sequences, compared the signal in liver to adjacent muscle and used this ratio to correlate with hepatic iron levels measured on tissue biopsy samples using spectrophotometric analysis. Multiple sequences were used because the nomogram comparing the L/M signal ratio is linear over only a small concentration of tissue iron.
Serum samples will also be collected at baseline to screen for the most common mutations of the HFE gene (C282Y mutation and H63D mutation) as hereditary hemochromatosis is common in the general population and may contribute to iron overload in HSCT recipients. --- C282Y ---
The aim of this study is to measure the variations of serum and urinary hepcidin levels following a single intravenous injection of erythropoietin in healthy volunteers. Hepcidin is a major regulator of iron homeostasis. It acts by binding on ferroportin, and limits cellular efflux of iron through enterocytes and macrophages. Anemia and hypoxia are known to modulate hepcidin synthesis. In these situations, erythropoietin synthesis is increased, so it can be postulated that erythropoietin could modulate hepcidin synthesis.
Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y ---
Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y --- --- C282Y ---
The purpose of this study is to evaluate the effect of Protandim on the degree of liver injury after one year of supplementation. Protandim is a nutritional supplement composed of the following 5 botanical extracts: Bacopa Moniera extract, Milk Thistle extract, Ashwagandha powder, Green tea, and Turmeric extract. Protandim is commercially available and can be purchased without a prescription. Our findings could lead to a better understanding of the role of oxidative stress and antioxidant therapy in NASH and may ultimately help improve patient care. Hypothesis #1: Protandim will lead to a significant improvement in NAS compared to placebo. Hypothesis #2: Protandim will lead to a significant decrease in serum markers of oxidative stress and liver chemistry tests. Hypothesis #3: Protandim will lead to decreased levels of TNF- α compared to placebo.
7. Iron overload/hemochromatosis, as defined by the following: elevated transferrin saturation (greater than 45 percent) OR serum ferritin (> 300 microg/L in men or >200 microg/L in women), with one of the following: 1) presence of 3+ or 4+ stainable iron on liver biopsy (if obtained); or 2) Hemochromatosis gene testing showing homozygosity for C282Y or compound heterozygosity for C282Y/H63D (if obtained). --- C282Y ---
Dysmetabolic iron overload syndrome and genetic hemochromatosis are frequent causes of iron overload. Polyphenols are efficient iron-chelators. Investigator hypothesize that polyphenol supplementation can reduce iron absorption in iron overload disease. Iron absorption can be studied by the area-under-the-curve of serum iron after iron oral loading. The primary outcome is the decrease of post-prandial serum iron after rich-iron meal, due to polyphenol supplementation.
- For Genetic Haemochromatosis type 1 Group: homozygosity mutation C282Y in HFE gene ; patients undergoing therapeutic phlebotomies. --- C282Y ---
Description: decrease of intestinal iron absorption after standardized oral loading dose through rich-iron meal, expressed by area-under-the-curve of serum iron, due to concomitant administration of a single dose of dietary polyphenos (nutrient complement) versus placebo administration. This outcome is a quantitative variable, treated and analysed as such.
Measure: Decrease of post-prandial iron absorption after dietary polyphenol supplementation Time: at day 3Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry
Measure: Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols supplementation Time: at day 1 (fasting versus 3 hours after rich-iron meal, versus 3 hours after rich-iron meal with polyphenol supplementation)Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO).
Measure: Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting. Time: at baselineHereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload causing damage of different important organs like heart, liver, pancreas and joints. Complications and symptoms can regress by intensive treatment reducing the iron overload stores.Different genes have been identified playing a role in the pathophysiology of iron overload. A clinically important HFE gene mutation is the C282Y, located on chromosome 6. Phlebotomy is currently the standard therapy which consists of removal of 500 ml whole blood weekly, representing a loss of 250 mg iron. In naive patients between 20 to 100 phlebotomies are required to reduce the serum ferritine levels to 50 μg/L. Thereafter, a lifelong maintenance therapy of 3 to 6 phlebotomies yearly is needed. For absorption, dietary iron ( 70%) is reduced by gastric acid form the ferric (Fe3+) to the ferrous form (Fe2+). Recently, in an observational open study, Hutchinson et al. found that HH patients treated with proton pump inhibitors (PPI) needed fewer phlebotomies, resulting in a drop of 2.5 (SEM 0.25) to 0.5 (SEM 0.25) liter per year. Research question: The primary objective is to determine the effectiveness and cost effectiveness of PPI's compared to standard phlebotomy therapy in the prevention of iron overload in HH patients. Multi-center trial in two hospitals in the South of Limburg (Atrium medical Center, Maastricht university medical center ) and hospital in Belgium (University Hospital Gasthuisberg). The study will be conducted in randomised double blind manner. The follow up will be one year. Patients are randomized either for the group receiving a PPI or a placebo. Every 2 month the ferritin level is measured and decided if the patient need a phlebotomy (Ferritin >100 µg/L).
A clinically important HFE gene mutation is the C282Y, located on chromosome 6. --- C282Y ---
Inclusion Criteria: - Patients with hereditary hemochromatosis (HH), homozygous for C282Y, currently treated with phlebotomy as maintenance therapy for at least 12 months with ≥ 3 phlebotomies per year. --- C282Y ---
HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily reabsorbed iron for a subject whose iron stock is stable and less than 50 µg / L. The IRI is constant over time, reflecting the importance of the underlying functional deficit. Hepcidin / ferritin (H / F) ratio may be an independent and constant over time marker of disease stage.No data are available on the validated values of this ratio. The goal of this project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI.
Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---
- Person with a measure of legal protection (guardianship) Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---
- Person with a measure of legal protection (guardianship) Hereditary Hemochromatosis C282Y Homozygous Hemochromatosis HFE-related hereditary hemochromatosis has a highly variable penetrance : 1% of homozygous women and 30% of homozygous men would develop a clinically expressed disease. --- C282Y ---
The study involve 30 C282Y homozygous men, followed in a reference center with phlebotomy maintenance therapy and stabilized at a low level of ferritin (<50 µg / L) for at least 1 year. --- C282Y ---
Description: values of Hepcidin / ferritin plasma ratio
Measure: distribution of values of Hepcidin / ferritin plasma ratio Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same timeTreatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.
Inclusion Criteria: - Patients with age equal to or over 18 years old, - Patients with proved hereditary hemochromatosis with homozygosity for the C282Y mutation of the HFE gene, - Patients with rheumatism related to hemochromatosis, considered by the rheumatologist refractory to usual treatment defined by a persistent painful symptomatology despite a treatment of at least one month with level 2 analgesics (weak opioids) at maximal dose, NSAID, colchicine, steroid injection or a combination of these treatments, - Patients with pain > 40/100mm measured by VAS (pain of the last 48 hours), - Effective contraception to be used during treatment and until 48h after the last administration for women of reproductive age, - Patients who have given written informed consent. --- C282Y ---
Description: Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)
Measure: Rate of patients with improvement of joint pain Time: Day 15Description: Assessment of the disease activity by Visual analog scale (VAS)
Measure: Assessment of the disease activity Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the number of painful joints by a clinical exam
Measure: Assessment of the number of painful joints Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the number of swollen joints by a clinical exam
Measure: Assessment of the number of swollen joints Time: Day 0, day 15, day 30, day 60, day 90Description: Assessment of the quality of life by the SF36 questionnaire
Measure: Assessment of the quality of life Time: Day 0, day 15, day 30, day 90Description: Assessment of the quality of life by the HAQ questionnaire
Measure: Assessment of the quality of life Time: Day 0, day 15, day 30, day 90Description: Functional evaluation by WOMAC index for hip and knee
Measure: Functional evaluation Time: Day 0, day 15, day 30, day 90Description: Functional evaluation by Dreiser index for hands
Measure: Functional evaluation Time: Day 0, day 15, day 30, day 90Description: Assessment of joint damage by X-rays and Doppler ultrasound
Measure: Assessment of joint damage Time: Day 0, day 90Description: Puncture if acute joint effusion : cells count
Measure: Synovial fluid analysis Time: 3 monthsDescription: Puncture if acute joint effusion : search for crystals presence
Measure: Synovial fluid analysis Time: 3 monthsDescription: Puncture if acute joint effusion : iron parameters markers
Measure: Synovial fluid analysis Time: 3 monthsDescription: Biological/Vaccine : iron and inflammatory markers
Measure: Biological effects on inflammation and iron metabolism Time: Day 0, day 15, day 30, day 60, day 90Description: Pharmacokinetics study
Measure: Time at which Cmax of anakinra was observed (Tmax) Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Maximum observed concentration (Cmax) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Half-life (T1/2) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseDescription: Pharmacokinetics study
Measure: Plasma clearance after administration (CL/F) of anakinra Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-doseNonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Description: Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.
Measure: Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF Time: Baseline and 24 weeksDescription: AST, measured in IU/L at baseline and 24 weeks
Measure: AST, Aspartate Aminotransferase Time: Baseline and 24 weeksDescription: ALT, measured in IU/L at baseline and 24 weeks
Measure: ALT, Alanine Aminotransferase Time: Baseline and 24 weeksDescription: LDL, measured in mg/dL at baseline and 24 weeks
Measure: LDL, Low-density Lipoprotein Time: Baseline and 24 weeksDescription: HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks
Measure: HOMA-IR, Homeostatic Model Assessment of Insulin Resistance Time: Baseline and 24 weeksThis study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus. HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures: - Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV. - Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period. - Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy. - Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.
- Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---
Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---
Description: SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.
Measure: Number of Participants With Sustained Virologic Response (SVR) Time: 72 weeksDescription: normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L
Measure: Number of Participants With Normalization of Liver Enzymes Time: week 24, week 48, week 72Description: Adverse Events - Anemia, Neutropenia and Psychiatric adverse events
Measure: Number of Participants With Adverse Events Time: 48 weeksChronic iron overload is responsible for morbidity and mortality. There are many genetic and acquired causes. One of them is an hepcidin deficiency. Hepcidin is the regulating hormone for iron. The study explores this specific cause, and aim to characterize this iron overload in term of clinical, biological, genetic and functional specificities.
Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y ---
Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y --- --- C282Y ---
Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Inclusion criteria: - Biological profile suggesting hepcidin deficiency: - high serum iron (> 25μmol / l) checked at least 2 times. --- C282Y ---
Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y ---
Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y --- --- C282Y ---
The main objective of this study is the clinical, biological, genetic and functional characterization of rare iron overload phenotypes associated with hepcidin deficiency except C282Y homozygosity. --- C282Y ---
Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective. Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.
Pilot Study.. Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---
Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---
Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y ---
Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y --- --- C282Y ---
The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.
- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Inclusion Criteria - Histological evidence of NAFLD and enrollment in NASH CRN Database Study - Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo. --- C282Y ---
- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Diabetes Mellitus Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. --- C282Y ---
The aim of this study is to evaluate the effect of muscular exercise on iron metabolism in healthy volunteers. Fourteen healthy male subjects will have to pedal on an ergocycle for 45 minutes, and urine and blood samples will be collected regularly to measure hemojuvelin, hepcidin, iron and transferrin levels.
Inclusion Criteria: - Male individuals aged between 18 and 40 years old - Body mass index (BMI) between 18 and 25 - Normal at clinical examination - Normal biological variables - Written informed consent Exclusion Criteria: - Mutation C282Y of the HFE gene - Iron metabolism abnormality - Inflammatory syndrome - Chronic pathology or ongoing treatment - Tobacco smoking, alcohol consuming more than 30g/day - History of transfusion or blood-giving within 3 months - Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV. --- C282Y ---
The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.
Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y ---
Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y --- --- H63D --- --- C282Y ---
Description: IL-6, TNF alpha, CRP
Measure: inflammation markers Time: 6 monthsDescription: adiponectin, PAI1, leptin
Measure: Adipokins markers Time: 6 monthsDescription: transaminase (ALT, AST), gamma GT
Measure: Hepatic iron overload (MRI) Time: 6 monthsDescription: serum iron, ferritin, saturation of transferrin
Measure: iron parameters Time: at 6 monthsDescription: HDL-c, LDL-c, triglycerides
Measure: lipid profile Time: at 6 monthsThis study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury. Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale. Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe. After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.
Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than or equal to 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---
Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.
7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Description: Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies.
Measure: Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category) Time: from baseline to 48 WeeksDescription: Alanine transaminase <42 U/L is considered normal
Measure: Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category) Time: from baseline to 48 weeksDescription: HOMA-IR is calculated from Fasting Glucose and Fasting Insulin
Measure: Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline Time: from baseline to 48 weeksThis study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy. Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray. Participants will undergo the following tests and procedures over 2 to 5 days: - Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test. - Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be injected in an arm vein if needed to enhance the ultrasound images. - Exercise stress echocardiography: The participant exercises on a stationary bike while heart function is measured with an echocardiogram, EKG, and blood pressure cuff. - 24-hour Holter EKG: The participant wears a small machine that records heart rhythm continuously for 24 hours. The recorder is connected by cables to electrodes placed on the chest. - Magnetic resonance imaging: This test uses a magnetic field and radio waves to obtain detailed images of the heart and blood vessels. The participant lies flat on a table that slides inside the scanner, which is a large hollow tube. All tests are performed once in normal volunteers and in patients who have received standard treatment for HH. Untreated patients repeat the tests 6 months after beginning phlebotomy or chelation. Additional time points for these tests might be added if further evaluation is needed.
- INCLUSION CRITERIA: HH Patients Group A patients (untreated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---
Group B patients (treated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---
No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation. --- Cys282Tyr ---
Homozygosity for the Cys282Tyr mutation, which is the most common known mutation with a predisposition to iron overload, occurs with an estimated frequency of 8 per 1000 in the Caucasians. --- Cys282Tyr ---
Although the pathophysiology remains incompletely understood, a homozygote mutation in Cys282Tyr is present in 84 to 100% of clinically confirmed HH cases. --- Cys282Tyr ---
Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...
Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Description: A histological response was defined as a reduction in the NASH activity index by 3 points or more with improvements of at least 1 point each in steatosis, parenchymal inflammation, and hepatocellular injury.
Measure: Number of Patients With Improvement in Liver Histology Time: 48 weeksThe aim of the study is to determine, in patients presenting hepatic iron overload (genetic haemochtomatisis or dysmetabolic iron overload syndrome), the effects of venesection therapy on cytochrome P450 2E1 activity by comparing the rates of metabolization of chlorzoxazone before and after venesection.
Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---
- Inflammatory syndrome (CRP > 3ng/ml) Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---
Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y.
A Phase I/II Open Label, Dose Escalation Trial and a Six Month Extension to Explore the Safety and Efficacy of ICL670 in Patients With Iron Overload Resulting From Hereditary Hemochromatosis.. Safety and Efficacy of Deferasirox (ICL670) in Patients With Iron Overload Resulting From Hereditary Hemochromatosis Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y. --- C282Y ---
The mean trough concentration at each time point was calculated.. Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---
Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---
Description: Mean absolute change in serum ferritin from baseline to the end of the extension study.
Measure: Absolute Change of Serum Ferritin From Baseline to the End of Extension, by Dose Cohort (Extension Per-protocol Population) Time: 0 to 48 weeksDescription: A blood sample was collected just prior to administration of the next dose of Deferasirox (pre-dose trough level) or approximately 24 hours after the previous dose at weeks 4, 8, 12, 16, 20 and 24. The mean trough concentration at each time point was calculated.
Measure: Trough Concentrations of Deferasirox (ICL670), by Dose Cohort (Per-protocol Population) Time: 4, 8, 12, 16, 20, and 24 weeksPeriodontitis is a chronic inflammatory disease that affects tissues surrounding the teeth. It is strongly associated with the major pathogenic "red complex", including Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola1 and thus is considered an infection. Recent advances in the pathogenesis of periodontal disease have suggested that polymicrobial synergy and microbiota dysbiosis together with a dysregulated immune response can induce inflammation-mediated damage in periodontal tissues2-4. Interestingly, currently periodontitis is associated with a growing number of systemic diseases, including cardiovascular diseases, adverse pregnancy outcomes, diabetes5-7 and hereditary haemochromatosis8.
Inclusion Criteria: - Patients aged 35 to 64 years with homozygosity hemochromatosis C282Y - Patients regularly enrolled in a health insurance plan - Patients with at least 10 natural teeth - Patients who have given informed written, dated and signed consent Exclusion Criteria: - Diabetic patients - Simultaneous participation in another study - Pregnant or lactating women - The incapacitated persons and persons deprived of their liberty - Patients who do not speak French, both written and spoken - Patients previously included in this trial - Patients with heart valves or endovascular equipment (risk of infective endocarditis ...) - Patients with a history of maxillofacial surgery - Patients whose oral status is considered incompatible with entry into the study, at the discretion of the investigator - Patients on drugs that can cause gingival hypertrophy, such as Hydantoins (phenytoin), Dihydropyridines, Diltiazem or Ciclosporin - Patients on medication that can cause gingival bleeding (anticoagulants, antiplatelet agents and aspirin). --- C282Y ---
Description: To evaluate the prevalence of periodontal diseases in patients with hemochromatosis at the time of diagnosis and / or their usual therapeutic
Measure: prevalence of periodontal diseases Time: 2 yearsPolyphenolic compounds are very strong Inhibitors of non-heme iron absorption, as they form insoluble complexes with ferrous iron. Patients with hereditary hemochromatosis (HH) have an increased intestinal non-heme iron absorption due to a genetic mutation in the regulatory pathway, leading to excess iron in the body. In this Study we investigate the inhibitory effect of a natural polyphenol Supplement in subjects with HH.
Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Iron Overload Metabolic Diseases Hemochromatosis Iron Metabolism Disorders null --- C282Y ---
Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Iron Overload Metabolic Diseases Hemochromatosis Iron Metabolism Disorders null --- C282Y --- --- C282Y ---
Description: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes
Measure: change from baseline in the isotopic ratio of iron in blood at week 2 Time: baseline, 2 weeksDescription: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes
Measure: change from baseline in the isotopic ratio of iron in blood at week 4 Time: 2 weeks, 4 weeksDescription: commonly measured iron status markers (Serum iron, transferrin saturation, Serum Ferritin, hemoglobin, and erythrocyte volume)
Measure: Iron status markers Time: baseline, weeks 2, and 4Description: fasting Serum hepcidin concentrations
Measure: Hepcidin Time: baseline, and weeks 2The purpose of this study is to determine the impact of curcumin, administrated orally, on iron metabolism in healthy volunteers. Iron metabolism will be describe by hepcidin expression that the investigators observed in vitro and serum hepcidin levels.
In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.. Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---
Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---
Description: Iron, ferritin, transferrin, transferrin saturation
Measure: Plasmatic iron bioavailability Time: 30min, 1H, 2H, 3H, 4H, 6H, 8H, 12H, 24H et 48HDescription: In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.
Measure: Evaluation of the inhibitory activity of volunteers's serum on hepcidin expression by hepatocytes Time: 30min, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24hThis study will evaluate the effectiveness of a test called MCV in guiding phlebotomy (blood drawing) therapy in patients with hemochromatosis an inherited disorder that causes too much iron to be absorbed by the intestine. The excess damages body tissues, most severely in the liver, heart, pancreas and joints. Because iron is carried in the hemoglobin of red blood cells, removing blood can effectively lower the body s iron stores. Patients with hemochromatosis undergo weekly phlebotomy treatments (1 pint per session) to deplete iron stores. This usually requires 10 to 50 treatments, after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron. A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients. This study will compare the usefulness of the ferritin test with that of MCV, which measures red blood cell size, in guiding phlebotomy therapy. In addition, the study will 1) examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients, and 2) design a system for making blood collected from hemochromatosis donors available for transfusion into other patients. Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study. Candidates will have a history, physical evaluation, review of medical records and blood tests, and complete a symptoms questionnaire. Participants will have the following procedures: - Phlebotomy therapy every 1 to 2 weeks, depending on iron levels - Blood sample collection for blood cell counts and iron studies at every phlebotomy session - Blood sample collection (about 2 tablespoons) every 1 to 2 weeks after iron stores have been depleted - Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron With each blood donation that will be made available for transfusion to other patients, participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors. These include screening for the HIV and hepatitis viruses and for syphilis. Patients who meet height and weight requirements may be asked to consider "double red cell" donations using apheresis. In this procedure, whole blood is collected through a needle placed in an arm vein, similar to routine phlebotomy. The blood then circulates through a machine that separates it into its components. The red cells are removed and the rest of the blood is returned to the body, either through the same needle or through a second needle in the other arm. Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service. Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy. If cirrhosis is found, the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved. Patients with arthritis will be offered evaluation by the NIH Arthritis Service and, depending on symptoms, may be advised to have X-ray studies or a joint biopsy. ...
- INCLUSION CRITERIA: Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. --- C282Y ---
Although the molecular pathophysiology remains incompletely understood, a homozygous mutation in the HFE gene (Cys282Tyr) is observed in nearly 100% of clinically confirmed cases. --- Cys282Tyr ---
To determine the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample of 100,000 adults. The study is conducted by the Division of Epidemiology and Clinical Applications of the NHLBI, the Division of Blood Diseases and Resources of the NHLBI, and the Ethical, Legal, and Social Implications (ELSI) Research Program of the NHGRI.
Evidence suggests that early diagnosis and treatment can prevent disease manifestations and enable normal life expectancy The discovery of the HFE C282Y and H63D variants in the HLA gene region on chromosome 6 provides an opportunity for early and rapid genetic identification of individuals at risk for development of hereditary hemochromatosis. --- C282Y ---
In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40 percent of the 101,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. --- C282Y ---
This study will evaluate the effectiveness of pioglitazone, a new diabetes medicine, on decreasing insulin resistance and improving liver disease in patients with nonalcoholic steatohepatitis (NASH). NASH is a chronic liver disease with unknown cause that involves fat accumulation and inflammation in the liver, leading to liver cirrhosis in 10 to 15 percent of patients and significant liver scarring in another 30 percent. Although similar to a condition that affects people who drink excessive amounts of alcohol, NASH occurs in people who drink only minimal or no alcohol. It is most often seen in patients with insulin resistance. Pioglitazone decreases insulin resistance and improves blood lipid (fat) levels, so that it may improve liver disease in NASH. Patients with NASH 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history and physical examination and routine blood tests. They will see a dietitian for counseling on diet and weight reduction, if needed. They will stop taking any medications for liver disease and take a daily multivitamin pill. After 2 months, those eligible for participation will be enrolled in the study. Participants will be admitted to the Clinical Center for 2 to 3 days for a complete medical history, physical examination, blood tests, urinalysis, chest X-ray, electrocardiogram, abdominal ultrasound and a liver biopsy. After the diagnosis of NASH is confirmed, the following procedures will be performed: - Echocardiography - imaging test using sound waves shows the heart structure and function - Resting metabolic rate - measures amount of oxygen (and calories) used to maintain body functions at rest. While lying down, the patient wears a clear plastic hood over the head for 20 minutes while the amount of oxygen used is measured. - Magnetic resonance imaging (MRI) scans - shows the size of the liver and other organs. The patient lies on a table in a metal cylinder that contains a magnetic field (the scanner) for no more than 30 minutes while the organs are imaged. - Dual energy X-ray absorptiometry (DEXA) scan measures whole body composition, including amount of fat. The patient lies under an X-ray scanning machine for about 2 minutes. - Oral glucose tolerance test (OGTT) - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected at various intervals during the 3-hour test. The blood is drawn through a catheter (thin plastic tube) placed in the arm before the test begins. - Intravenous glucose tolerance test (IVGTT) - determines how the tissues respond to insulin and glucose. Glucose is injected into a vein, followed by a short infusion of insulin. Blood samples are collected through a catheter at various intervals during the 3-hour test. When the above procedures are completed, patients start taking pioglitazone by mouth once a day for 48 weeks, keeping track of the medication and any side effects. They will be seen at the clinic every 2 weeks for the first month and then every 4 weeks for the rest of the treatment period. The visits will include an interview and examination by a physician and blood draw for laboratory tests. Female patients will have a pregnancy test at each clinic visit. At the end of the treatment period patients will be admitted to the Clinical Center for a repeat medical evaluation that will include the procedures described above.
Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.
To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.. Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---
Exclusion Criteria: 1. HH due to genotypes other than HFE C282Y homozygosity. --- C282Y ---
Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---
Description: Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.
Measure: Fatigue Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have approximately 6 third weekly treatments however this will vary depending on initial SF.Description: Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).
Measure: Change in markers of liver fibrosis Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).Description: Medical Outcomes Study 36-item short form (SF36). As there are no specific quality of life tools available for HH, we will use this very widely used generic tool that has been used in a number of HH studies. This tool covers eight dimensions of health and wellbeing. One study found that individuals seen in a HH clinic and who had no clinical symptoms had significantly lower scores on a number of dimensions of the SF36 compared to population norms.
Measure: Quality of life Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).Description: The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure designed to screen for anxiety symptoms and depression symptoms in a hospital setting. It is composed of two seven-item subscales, the Anxiety (HADS-A) and Depression (HADS-D) subscales, and a 14-item total scale (HADS-T). Participants use a four-point Likert-type scale to rate how they have felt in the past week. It has been found to be valid and reliable in various populations.
Measure: Depression and Anxiety Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).Description: The presence and impact of arthritis will be measured by the Arthritis Impact Measurement Scales 2 short form. This is a 24 item validated scale that assesses the impact of arthritis on the individual over the past four weeks. We will also ascertain the use of arthritis medication at baseline and end of erythrocytapheresis/sham erythrocytapheresis.
Measure: Arthritis Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).Description: To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.
Measure: Markers of oxidative stress Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. Nonalcoholic steatohepatitis (NASH) represents the more severe end of this spectrum and is characterized by steatosis, ballooning degeneration and lobular inflammation with or without fibrosis. The etiology of NASH is not completely understood, but it is often associated with obesity, type 2 diabetes, hyperlipidemia and insulin resistance. Lipotoxicity, insulin resistance and oxidative stress appear to be central to the pathogenesis of NASH. Currently, there is no FDA approved treatment for NAFLD/NASH. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. Ezetimibe is an LDL lowering agent that works through inhibition of the fat absorption from the small intestine. In this study, we propose to treat 50 patients with NASH with either Ezetimibe or placebo for 24 weeks. After an initial evaluation for insulin sensitivity, MRI liver fat distribution and liver biopsy, patients will receive either 10 mg/day of Ezetimibe or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of Ezetimibe and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and liver biopsy. Pre and post treatment MRI-derived liver fat content, liver histology and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity, liver histology and liver biochemistry.
7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---
Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.
Inclusion Criteria: - Patients with hemochromatosis, aged > 30 years, C282Y- homozygote, with serum-ferritin =/> 1000 µg/L - Patients aged > 18 years with verified low-risk or intermediate-1 risk of myelodysplastic syndrome, with normal cytogenetics and serum-ferritin > 1500 µg/L, or with a transfusion history of =/> red- blood-cell-transfusions. Exclusion Criteria: - Previous or current venesection - MDS patients eligible for hematopoietic stem cell transplantation - Subject complies with one or more of the following standard exclusion criteria for MRI examination; - If the patient has a pacemaker. --- C282Y ---
The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y ---
Homozygosity for C282Y is the strongest risk factor for serious iron overload and disease which develops after a long-lasting, asymptomatic period. --- C282Y ---
The study by Phatak et al (2010) was the first clinical trial to demonstrate the safety and efficacy of deferasirox in patients with C282Y-homzygot hemochromatosis. --- C282Y ---
Description: Marker of oxidative DNA damage
Measure: Change of 8-oxodG in urine Time: 0, 6 and 12 monthsDescription: Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme
Measure: Change of Cu,Zn-SOD activity in erythrocyte hemolysate Time: 0, 6 and 12 monthsDescription: Serum analysis
Measure: Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin. Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatmentDescription: Morning spot urine sample.
Measure: Urine routine test strip for detection of blood, protein, and nitrite Time: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 monthsHereditary hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload. Phlebotomy is currently the standard therapy. More recently Therapeutic Erythrocytapheresis (TE) has become a new therapeutic modality, which potentially offers a more efficient method to remove iron overload with fewer procedures.In the proposed clinical trial the investigators will examine whether TE can keep the ferritin levels in patients requiring maintenance therapy below 50 microg/L, with minimally half the number of treatment procedures when compared to current standard therapy by P.
Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y ---
Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y ---
Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y --- --- C282Y ---
Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria). Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.
Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. --- C282Y ---
*Hemochromatosis, as defined by homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D mutations or Hepatic Iron Index ≥ 1.9. --- C282Y ---
Insulin resistance-associated hepatic iron overload (IR-HIO), also defined as dysmetabolic iron overload syndrome or dysmetabolic liversiderosis, is a common cause or iron overload in France, mainly in middle-age patients with increased serum ferritin levels associated with normal serum transferrin saturation, and normal serum iron concentration in the absence of other known cause of increased serum ferritin levels. Treatment includes a combination of dietary measures and physical activity to correct metabolic disorders. Phlebotomies seem to be beneficial when serum ferritin level is high. This study aims at comparing the effect of iron depletion (by phlebotomy) plus lifestyle and diet advices versus lifestyle and diet advices alone on blood glucose level and insulin sensitivity in subjects with IR-HIO in order to assess the benefits of phlebotomies on the reduction of risk of diabetes and cardiovascular associated complications.
Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y ---
Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y --- --- C282Y ---
Description: Two dimensional (2D) speckle tracking echocardiography (STE)
Measure: myocardial deformation Time: 12 monthsRATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy. PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer.
DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Anemia Plasmacytoma Lymphoproliferative Disorders Precancerous Conditions OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y ---
DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Anemia Plasmacytoma Lymphoproliferative Disorders Precancerous Conditions OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y --- --- H63D --- --- C282Y ---
Description: Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.
Measure: Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response Time: 16 WeeksDescription: Value at 7 weeks minus value at baseline.
Measure: Mean Increment in Hemoglobin Level at Week 7 Time: Baseline and 7 weeksDescription: Value at 16 weeks minus value at baseline.
Measure: Mean Increment in Hemoglobin Level at Week 16 Time: Baseline and 16 weeksDescription: Hematopoietic response was defined as Hb increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.
Measure: Time to Hematopoietic Response Time: 16 weeksDescription: Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.
Measure: Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA) Time: Baseline and 16 weeksDescription: SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.
Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study Time: Baseline and 16 weeksDescription: Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.
Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study Time: Baseline and 16 weeksDescription: FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.
Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study Time: Baseline and 16 weeksDescription: MCV is a measure of the average red blood cell volume.
Measure: Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16 Time: Baseline, 7 weeks and 16 weeksThe study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities.
Hepcicor Cohort : Clinical, Biological, Genetic and Fonctional charactérization of Rare Iron Overlaod phénotypes Associated With Hepcidin Deficiency Excluding C282Y Homozygosity. --- C282Y ---
Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y ---
Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y --- --- C282Y ---
to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).. comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism. --- C282Y ---
Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Inclusion Criteria: - Biological profile suggestive of hepcidin deficiency: - increase of transferrin saturation coefficient (> 50 %) verified on at least 2 times, and calculated from the transferrinemia. --- C282Y ---
Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Rare Iron Overlaods Chronic iron overload are responsible for morbidity and mortality. --- C282Y ---
The main objective of this study is to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic). --- C282Y ---
Description: to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).
Measure: Number of patients presenting with mutation in gene know to be associated with iron metabolism Time: InclusionDescription: To Identificate potential explanatory factors of hepcidino deficiency phenotype
Measure: comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism Time: inclusionDescription: - Identification of potentially explanatory factors visceral consequences of iron overload in hepcidino deficiency phenotype (overweight, high blood pressure, diabetes)
Measure: Number of patients presenting with associated causes of iron overload Time: inclusionDescription: To Research correlations genotype-phenotype
Measure: Genotype-Phenotype correlation Time: InclusionDescription: Validation of the hepatic iron concentration measurements imaging ( nuclear magnetic resonance (NMR)) in the various centers
Measure: Hepatic and splenic iron concentration measurements by NMR Time: InclusionDescription: - Assessment of the clinical value of biomarkers of iron metabolism
Measure: Number of patients with detectable abnormal iron species in blood (non transferrin bound iron, labile pool iron) Time: InclusionThe purpose of this study is to perform laboratory based studies to determine if the growth and development of the malaria parasite is effected by iron status of its host (the person infected with the malaria parasite). Iron deficiency affects over 500 million people including many pregnant women and children from areas of the world that are plagued by malaria. Some population based studies have suggested that iron deficiency protects people from getting malaria and this has raised questions about the wisdom of public health policies that provide universal iron supplementation in countries where malaria is common. We will use red blood cells and sera from patients with iron deficiency anemia, hereditary hemochromatosis and normal individuals who are taking iron supplements to look at this question in a very systematic way. This study should provide information for or against a possible mechanism by which iron deficiency may affect the malaria parasite. The results will contribute to efforts to develop evidence-based public health policies on iron supplementation policies in malaria-endemic areas. There are three different types of individuals involved in this study (1) people with iron deficiency anemia who will be taking iron supplementation (2) people without iron deficiency anemia who will be taking iron supplementation and (3) people with a condition called hereditary hemochromatosis who have an excess of iron in their bodies.
From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. --- C282Y ---
Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease ranging from simple steatosis to cirrhosis of the liver. Nonalcoholic fatty liver (NAFL) without substantial hepatocellular injury is thought to be relatively benign whereas nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, inflammation and varying degrees of fibrosis from none to cirrhosis. NASH is strongly associated with insulin resistance and metabolic syndrome and thus is recognized as a major public health concern as the most prevalent liver disease. Liver biopsy is the gold standard for a diagnosis of NASH. However, given the large population of patients at risk for NASH, liver biopsy is not a practical method for determining which patients may benefit from NASH therapy. Non-invasive methods to estimate inflammation and fibrosis are in clinical use, but there remains a dichotomy between gold standard inclusion criteria and end points that are utilized in clinical trials and real world diagnostic methods that are more common in clinical practice. Thus, the investigators would like to conduct an observational study to head-to-head compare the non-invasive methods and liver biopsy in differential liver steatosis and liver biopsy in a real-world setting. Also, by following up patients for a relatively long time (proposed 10 years), the investigators can present the natural history of disease progression.
Exclusion Criteria: - Unable to provide written informed consent (or assent in pediatric subjects) - Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is half pint of beer [285 mL; 9.64 oz], 1 glass of spirits [25 mL; 0.85 oz] or 1 glass of wine [125 mL; 4.23 oz] - Enrolled in NASH-related clinical trials - Presence of other forms of chronic liver disease: 1. Chronic hepatitis B (HBsAg positive) 2. Chronic hepatitis C (HCV RNA positive) 3. Iron overload disorders (3-4+ iron on liver biopsy or known hemochromatosis gene (HFE) C282Y homozygous with ferritin > 200 ng/ml; note: an elevated ferritin alone is common in NASH and is not exclusionary) 4. Autoimmune liver disease (biopsy evidence or clinical diagnosis of autoimmune hepatitis or Primary biliary cholangitis (PBC) requiring ongoing treatment, imaging evidence of Primary sclerosing cholangitis (PSC)) 5. Wilson's disease 6. Alpha-1 antitrypsin mutations that in the opinion of the principal investigator is contributing to the patient's liver disease; - Prior bariatric surgery unless the surgery was performed more than one year before the biopsy diagnosis of NASH (i.e., NASH is present despite prior bariatric surgery); - Planned bariatric surgery (e.g. --- C282Y ---
Description: The change in NASH Clinical Research Network (CRN) score based on liver biopsy
Measure: Histological endpoint Time: 10 yearsDescription: Number of all-cause death
Measure: Number of all-cause death Time: 10 yearsDescription: Number of liver-related death
Measure: Number of liver-related death Time: 10 yearsDescription: Number of liver transplant
Measure: Number of liver transplant Time: 10 yearsDescription: Number of hepatocellular carcinoma (HCC)
Measure: Number of hepatocellular carcinoma (HCC) Time: 10 yearsThe purpose of this study is to evaluate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir (ASC08) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1.
Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody，positive hepatitis B surface antigen，syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Inclusion Criteria: - Willing and able to provide written informed consent - Chronic HCV infection (≥ 6 months) ; - Positive HCV antibody - Serum HCV RNA of ≥ 1 × 104 IU/mL - Hepatitis C virus GT1 - Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV - The liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. --- C282Y ---
Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody，positive hepatitis B surface antigen，syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Chronic Hepatitis C Hepatitis Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic null --- C282Y ---
Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration
Measure: Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment Time: 24 weeksThe purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.
- History or presence of decompensated liver disease (history of ascites, hepatic encephalopathy, HCC, or bleeding esophageal varices) - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Positive hepatitis B surface antigen or HIV antibody at screening - History or presence of liver cirrhosis - History of severe psychiatric disease, including psychosis and/or depression, who is not able to participate or able to give written informed consent and to comply with the study restrictions - History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin) - History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia's requiring ongoing treatment, unstable angina or other unstable, uncontrolled or significant cardiovascular disease within 6 months). --- C282Y ---
Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration
Measure: Proportion of participants with Sustained Virologic Response 12 weeks after end of treatment (SVR12) Time: 12 weeksDescription: SVR24, defined as undetectable HCV RNA 24 weeks after the last day of study drug administration
Measure: Proportion of participants with Sustained virologic response 24 weeks after end of treatment Time: 24 weeksThis study will determine if Albumin-linked interferon (Albinterferon alfa-2b) every 2 weeks is safe and tolerated by patients infected by both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This is a new medication developed for HCV. It may help the immune system fight infections, especially those caused by viruses. Albinterferon alfa-2b appears quite similar to other interferons, in side effects and action in controlling HCV. Patients ages 18 and older who are infected with HCV genotype 1, are HIV positive, are infected with HCV, and have evidence of HCV-induced liver disease; and who are not pregnant or breast feeding may be eligible for this study. Many visits to NIH over a 76-week period are required. There will be collection of blood and urine, pregnancy test, and tests of HCV in the blood. A liver biopsy is required before start of the study if patients have not had one within 1 year. Another is done at the end of 72 weeks. An eye exam is done before start of the study and repeated later. An optional procedure called automated pheresis is done at the study beginning. Researchers can study patients' immunity to control HCV. Blood is drawn through a needle in an arm vein and spun in a machine to separate the desired blood component. Remaining blood is returned to the patient. Patients will receive Albinterferon alfa-2b at a dose of 900 mcg every 2 weeks for 48 weeks, by injection under the skin. Ribavirin is given at 1,000 mg or 1,200 mg by mouth twice daily, depending on a patient's weight. Side effects of Albinterferon alfa-2b are fatigue, headache, joint and muscle pain, and sleeplessness. The major side effect of ribavirin is anemia. Visits ranging from week 3 to 44 will determine the safety of Albinterferon alfa-2b and ribavirin and to see effects on reducing the HCV viral load. For weeks 48, 52, 56, 64, 72, and 76, patients will return for a clinic visit and blood tests. At week 72, an abdominal ultrasound and liver biopsy are done. Week 76 includes discussion of biopsy results.
Those subjects with, or a history of previous phlebotomy for iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---
Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---