SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00063232

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Treatment of Nonalcoholic Steatohepatitis With Metformin

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.

NCT00063232 Hepatitis
MeSH: Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO: Hepatic steatosis Hepatitis

1 Interventions

Name: Metformin

Description: After complete medical evaluation and liver biopsy, patients who qualified for therapy were started on metformin in an initial dose of 500 mg once daily. After 2 weeks, the dose was increased to 500 mg twice daily and after 4 weeks to the full dose of 1000 mg twice daily. Subsequent dose reductions were carried out based on tolerance, with particular attention to gastrointestinal upset and abdominal bloating. Patients were seen in the out-patient clinic, had a brief medical history and examination and routine blood tests at 2 and 4 weeks after enrolment and every 4 weeks thereafter. The oral and intravenous glucose tolerance tests were repeated after 40 and 44 weeks respectively and liver biopsy and imaging tests at 48 weeks. Metformin was discontinued after 48 weeks in patients without diabetes on the pre-treatment evaluation.

Type: Drug


Primary Outcomes

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 Weeks

Secondary Outcomes

Description: 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 weeks

Description: 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 weeks

Purpose: Treatment


There are 2 SNPs

SNPs


1 C282Y

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 ---


2 H63D

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 --- --- H63D ---



HPO Nodes


HPO:
Hepatic steatosis
Genes 102
GABRD GPD1 HFE MPV17 LDLRAP1 TRAPPC11 HNF1B PNPLA2 ATP6AP1 ATP7B ZMPSTE24 ACADL ACADM ACADVL EARS2 LYRM4 DNAJC19 CYP7A1 MARS IARS ACAD9 POLD1 FOS ACOX1 RRM2B CYP19A1 POLG MRPL44 VPS33A AGPAT2 ETFA ETFB TMEM199 ETFDH LARS KCNAB2 FARSB COX15 APOB LMNB2 CAV1 MCCC1 APOE PPARG CPT1A XRCC4 TARS2 CPT2 SKI NSMCE2 TYMP HNF4A BCS1L HNRNPA1 CBS TFAM HNRNPA2B1 LDLR SLC40A1 COA8 DDOST PGM1 POLR3A ADK TRMU MRPS7 LRPPRC LIPA LIPE ABHD5 FBP1 NDUFAF1 LMNA ALMS1 CLPB COG6 DGUOK CIDEC SLC25A13 SAR1B SLC22A5 AKT2 CAVIN1 BSCL2 HADHA HADHB RERE HADH RMND1 HSD17B4 PLIN1 CARS2 ALDOB PRDM16 ABCG5 PCK1 ABCG8 PCK2 VCP PCSK9 CEP19 PMM2
Hepatitis
Genes 74
TTC7A MST1 TRAF3IP2 TPP2 TBX19 IL12A MET IL12RB1 RASGRP1 TCF4 HSD3B7 KRT8 SERPINA1 TCF3 VIPAS39 ATP7A IGF2R MMEL1 ATP7B ALMS1 SPIB KRT18 VPS33B CIITA PDGFRL PIK3CA GPR35 CYP7A1 GUSB PIK3R1 AMACR RFXANK SHPK IGHM PIEZO1 SLC25A15 BTK IL21R CD40LG BLNK GLIS3 APC CLEC7A AIRE LRRC8A CASP8 POU2AF1 XIAP CASP10 C1S CYP7B1 PRKCD CD79A CD79B IRF5 C4B IL17RC IL17RA IGLL1 CTNNB1 FAS SKIV2L FASLG SH2D1A RFX5 IL17F RFXAP TNFSF15 TNPO3 PGM1 STAT1 TP53 AXIN1 FOXP3