SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03816449

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Influence of Specifically Designed Exercise Program on Serum Matrix Metalloproteinases and Functional Status in Women With Postmenopausal Osteoporosis

Osteoporosis is a chronic, systemic and the most frequently metabolic bone disease, characterized by low bone mass and microarchitectural remodeling of bone, which results in a greater fragility of the bone and risk of fracture. With the purpose of explaining the patophysiological mechanisms responsible for osteoporosis, it is necessary to determine the factors that influence on the activity and differentiation of osteoblasts and osteoclasts, as well as their dynamic change depending on the use of an appropriate treatment. According to the recommendations of the International Association for osteoporosis (the National Osteoporosis Fondation- NOF) the treatment of osteoporosis includes pharmacological and non-pharmacological treatment of. Pharmacological includes a range of different drug, where the bisphosphonates, non-hormonal antiresorptive drugs, present gold standard in the treatment of postmenopausal osteoporosis . Non-pharmacological treatment implies the daily physical activity and the specific exercise program, for the purpose of slowing or stopping the loss of bone mass, improve balance, and reduce the risk of falling and fractures. It is known that the mechanical loading of the bone has to be strong enough to achieve the effect of osteogenesis. The load due to the long bones of gravity and the tension force produced by the muscular activity, are the natural stimulus for maintenance of bone mass and muscle strength. This can be achieved by practice involving the activities in which the net mass of the body constitutes an additional load (so-called. "Weight-bearing exercises"), as well as exercise resistance from. Exercise with one's own mass include actions to counter gravity in an upright standing position, and then may be a stronger (high-impact) collides with the substrate (e.g., jumping) and the lower (low-impact) collides with the substrate (e.g., walking). Aerobic exercise, especially walking, is the most common type of intervention because of the ease administration and safety. Resistance training is another effective type of exercises that can affect the maintenance or improvement of bone mineral density, with the most frequently applied with the combination of the dynamic resistance exercises that engage multiple joints, large groups of muscles, and the burden on the hips and the spine. In order to strength training, with the aim of maintaining and stimulating bone mineral density had the best effect, it is necessary to include the basic principles of specificity, load and progression. Training should be directed to the adaptation of a specific part of the body, should be sufficiently intense to and beyond the common load, and a variety of progressive enough. Progression loads should be slow and gradual to avoid injury. We assumed that this type of exercise can be achieved by changing the activity of serum matrix metalloproteinases. It has been proven that in the process of remodeling of the extracellular matrix of the bone, matrix-metalloproteinases play an important role, both, the occurrence of bone as well as in pathological processes of bone resorption . Also, it is known that metalloproteinases, particularly the MMP-2 and MMP-9 play a significant role in the development of skeletal muscle recovery from injury or remodeling of the same after exercise.Taking into account the results of the latest studies on the role of metalloproteinases in the development and remodeling of bone, also and muscle, we assumed that the value of metalloproteinases could serve as markers for early assessment of treatment response of patients with osteoporosis. In our study, we will follow the changes of serum levels of metalloproteinases as well as tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in the serum of patients with postmenopausal osteoporosis, which have prescribed bisphosphonates, before and after application to the specifically designed exercise program . A functional genetic polymorphisms (PM), by modulating the expression of the MMP can be associated with a differential response to the application of our patients of the same exercise program. Specifically designed exercise program in patients with osteoporosis, which affects the increase in BMD and muscle strength, can be associated with a specific MMP genotyp . In our research we will follow the influence of polymorphisms of the mentioned metalloproteinases on the efficacy of the treatment (the specifically designed exercise program ) in patients with postmenopausal osteoporosis.

NCT03816449 Influence of Specifically Designed Exercise Program on Serum Matrix Metalloproteinases and Functional Status in Women With Postmenopausal Osteoporosis
MeSH: Osteoporosis Osteoporosis, Postmenopausal
HPO: Generalized osteoporosis Osteoporosis

1 Interventions

Name: exercises

Description: Aerobic exercise will be conducted as a dose walk, 3-5 km / h, lasting 50 minutes per day, least five days per week, for 12 weeks. The intensity of the training will be around 70% of the maximal heart rate. Resistance training and balance exercises will be conducted as a group program and will involve exercises to strengthen the muscles of the upper and lower extremities and balance exercises. The intensity of the training will be increased on weekly, starting from 3-5 repeating load and its own weight, up to 8-12 repetitions and load straps. Progression and maintenance load tapes will be carried out depending on the capacity of individualized persons. Frequency of training will be 3 times a week,will last 70 minutes per day for 12 weeks.

Type: Other

experimental group control group


Primary Outcomes

Description: For the following biochemical parameters, patients will be taken peripheral blood (on an empty stomach), centrifuged at 3000 rpm / min, split up into aliquots (serum and plasma) and kept in the freezer (at -20 ° C) for determination the following parameters.

Measure: Changes in enzyme activity of matrix metalloproteinase-2 , matrix metalloproteinase- 9 and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) in serum

Time: Change measures ( "baseline , 4 weeks and 12 weeks")

Description: "Timed-Up and Go Test" is an effective method for estimating the motion and function of the musculoskeletal system, in patients with osteoporosis. Performed by being the person required to get up from the chair usual height with backrest (seat height about 46 cm, height of armrest 65 cm) to walk 3 m normal walking speed, turned back to the chair and then sit on the same. Typically this activity is carried out in less than 12 seconds, over this is considered to be an increased risk for the drop and reduced muscle function.

Measure: Functional assessment of the musculoskeletal system using Timed-Up and Go Test" (TUG test)

Time: Change measures ( "baseline , 4 weeks and 12 weeks")

Description: "Chair Rising Test "is a simple test that is used to assess the strength of the lower extremities and is often used for assessing the risk of falls in patients with osteoporosis. It is performed by the request from the person to get up from the chair height and common to sit on the same 5 times as fast as possible, without using hands. His hands were clasped in front of her chest. Inability to 5 times stand up or sit down, or over the test duration of 10 seconds is interpreted as a decrease in muscular strength and increased risk of falling.

Measure: Functional assessment of the musculoskeletal system using "Chair Rising Test ".

Time: Change measures ( "baseline , 4 weeks and 12 weeks")

Description: One-Leg Stance Test" (OLST) is a clinical tool that is used for a quantitative assessment of static balance, and consequently the risk assessment for the pad and the functional dependence. Is performed so that the respondent is required to stand on one foot (dominant) to a stable platform without the support and aids, with eyes open, and the hands to the body, wherein a stop watch measuring time for which the respondent can perform a task in seconds. It will be made of two measurements, wherein the best value is adopted in the assay and assessment of the risk is determined according to the set values for a given age.

Measure: Functional assessment of the musculoskeletal system using "One-Leg Stance Test".

Time: Change measures ( "baseline , 4 weeks and 12 weeks")

Secondary Outcomes

Description: Detection of genotypes for the polymorphisms: rs243866 in the gene for MMP-2 will be effected Real time PCR method with the use of standardized TaqMan®SNP Genotyping assay.

Measure: Detection of genotypes for the polymorphisms: rs243866 in the gene for MMP-2

Time: Change measures ( "baseline and 12 weeks")

Description: The genotypes of rs3918242 polymorphism in the MMP-9 gene will be determined by reaction of the polymerization chain (PCR) and restriction products of the reaction the restriction enzyme. Analysis of the genotypes will be performed after electrophoretic separation in 8% polyacrylamide gels nondenaturated, coloring Sybr®safe DNA stain and illumination under UV transillumination.

Measure: Detection of genotypes of rs3918242 polymorphism in the MMP-9

Time: Change measures ( "baseline and 12 weeks")

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 rs243866

It will be made of two measurements, wherein the best value is adopted in the assay and assessment of the risk is determined according to the set values for a given age.. Detection of genotypes for the polymorphisms: rs243866 in the gene for MMP-2.

Detection of genotypes for the polymorphisms: rs243866 in the gene for MMP-2 will be effected Real time PCR method with the use of standardized TaqMan®SNP Genotyping assay.. Detection of genotypes of rs3918242 polymorphism in the MMP-9.


2 rs3918242

Detection of genotypes for the polymorphisms: rs243866 in the gene for MMP-2 will be effected Real time PCR method with the use of standardized TaqMan®SNP Genotyping assay.. Detection of genotypes of rs3918242 polymorphism in the MMP-9.

The genotypes of rs3918242 polymorphism in the MMP-9 gene will be determined by reaction of the polymerization chain (PCR) and restriction products of the reaction the restriction enzyme.



HPO Nodes


HPO:
Generalized osteoporosis
Genes 15
COL2A1 LMNA MMP14 CBS TENT5A STAT1 B3GAT3 CDC73 ZBTB20 CHST3 COL1A1 MEN1 SP7 COL1A2 GCM2
Osteoporosis
Genes 242
MKRN3 SOX3 ADCY10 SNORD115-1 HFE SOX9 IL12A IL12RB1 SPARC ZBTB20 ATP7A ERCC6 ATP7B GALNS GPAA1 ZMPSTE24 WWOX GCM2 GALT SPIB RTEL1 CYP11A1 CYP11B1 CYP17A1 TMEM165 ESR1 CYP19A1 CYP27A1 SRC AKR1D1 GATA4 IPW PWRN1 CDH23 PEX12 IRF5 SRY NDN TNFRSF11A TRIP11 POF1B BANF1 IFT43 MRPS22 PHGDH SNORD116-1 HESX1 STAT1 B3GAT3 FGF17 MAP3K1 RNU4ATAC MEN1 XYLT2 CCN6 IFIH1 BMP1 MALT1 ZNF469 ANOS1 GK SLC9A3R1 KISS1R DMRT3 ANTXR2 GLB1 PROKR2 AEBP1 TINF2 SC5D CANT1 GLI2 HPGD HS6ST1 KCNJ8 RIN2 WNT3A RECQL4 GORAB VAMP7 NR0B1 NPAP1 WDR35 PSMC3IP PYCR1 DKC1 FGF8 NOP10 TAC3 FGFR1 HSD3B2 ALB TACR3 FLRT3 MMP1 CDC73 MMP2 GNAS PWAR1 HERC2 HSD17B4 MMP14 KISS1 PLOD1 PLOD2 EIF2AK3 GNRH1 TNFSF15 GNRHR PLS3 NOTCH2 PDE11A CHST3 COL1A1 PMM2 VDR COL1A2 COL2A1 HJV PROK2 FKBP10 HSPG2 TCF4 COL7A1 PSAT1 FAT4 FBLN5 MAGEL2 LHX4 NUP107 SLC25A4 USB1 ADAMTS2 CLIP2 CTC1 GPR35 NSD2 NELFA WNT1 POLD1 FOS TENT5A RRM2B POLG DUSP6 EFEMP2 AGPAT2 WRN WT1 LAMA3 BAZ1B POR B3GALT6 POU1F1 LAMB3 POU2AF1 ABCC9 TWNK LAMC2 CHD7 AIP CAV1 RUNX2 PPARG RFC2 WRAP53 SLC7A7 GTF2IRD1 PRDM5 NHP2 TERC TERT CBS AR LETM1 TNFRSF11B ZFPM2 MKRN3-AS1 WDR19 MST1 TGFBR2 LIFR USP8 MLXIPL HSD3B7 LIMK1 TRMT10A RAB3GAP1 SH3PXD2B PIGT IGF1 OTX2 GTF2I IFT52 MMEL1 NSMF NDUFAF1 DKK1 LMNA WDR11 SLC34A1 ASAH1 PDE8B SLCO2A1 ARMC5 SPRY4 FSHR CTDP1 PRKACA PRKAR1A LRP5 PARN SMPD1 CAVIN1 SMS BSCL2 NR5A1 ASXL2 IFT122 ELN NGLY1 HAMP SPIDR POLG2 SLC25A19 HBB IL17RD PCCA PCCB G6PC VPS53 SLC37A4 SNRPN TNPO3 TBL2 PRLR RPL11 CYB5A SMAD3 BMP15 PROP1 SP7