SNPMiner Trials (Home Page)
Report for SNP rs1128503
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 Influence of ABCB1 Polymorphisms on Plasma Concentrations of New Oral Anticoagulants in Case of Serious Adverse Events
Vitamin K antagonists were hampered by several disadvantages, such as the need for frequent monitoring. In this context, new oral anticoagulants (NOACs) have been developed and are now available on the market. These NOACs, like all anticoagulant drugs, continue to be associated with an increased risk of bleeding. In addition, the lack of antidote and the absence of valid data regarding biological monitoring can pose problems in case of overdose or when emergency surgery is required. Studies investigating the pharmacokinetic properties of rivaroxaban and dabigatran, two NOACs now approved for the market, have shown high variability between individuals, with coefficients of variation of up to 60% for some pharmacokinetic parameters in patients treated after orthopaedic surgery. The relation between plasma concentrations of NOAC and bleeding risk has been clearly established in clinical trials. Dabigtran, rivaroxaban and apixaban are known substrates of P-glycoprotein (Pgp). Pgp activity can be affected by pharmacological inducing or inhibiting agents. This can lead to a significant change in the pharmacokinetics of NOACs, with a decrease or increase (respectively) in the level of intestinal absorption, leading to respectively reduced or increased plasma concentrations of the drug. Furthermore, there exist genetic mutations of Pgp, presenting in particular a lower level of activity than the non-mutated protein. We hypothesized that the polymorphisms (mutations) of the ABCB1 gene that codes for Pgp could influence plasma concentrations of dabigatran, rivaroxaban and apixaban, and consequently, impact on the concentration of NOACs and as a corollary, on the bleeding and thromboembolic risk of patients treated with these molecules. The main objective of this study is to study the relation between polymorphisms of the ABCB1 gene that codes for Pgp and plasma concentrations of NOACs in patients treated for a hemorrhagic or thromboembolic complication occurring under NOAC therapy. Secondary objectives are to evaluate the distribution of ABCB1 polymorphisms among the various hemorrhagic risk factors, and to compare the frequency of the polymorphism in patients from the study population vs the general population.
NCT02103101 Anticoagulants Thromboembolism Hemorrhage Other: Measurement of Plasma Concentrations of NOACs Genetic: Identification of ABCB1 polymorphisms coding for P-gp MeSH:Thromboembolism Hemorrhage
HPO:Thromboembolism
To investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167).. Inclusion Criteria: - Patients aged >18 and <80 years of age - Patients admitted to the University Hospital of Besancon for a serious adverse event (major bleeding complication or thrombo-embolic event) occurring under treatment with any one of the three commercially available new oral anticoagulant agents (rivaroxaban, apixaban or dabigatran).
Primary Outcomes
Description: Plasma concentrations of dabigatran, rivaroxaban or apixaban will be measured using High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry (MS/MS). Blood samples will be taken in an EDTA tube and rapidly centrifugated. Plasma will be aliquoted and frozen at minus 80 degrees Celsius for later analysis.
Measure: Measurement of plasma concentrations of new oral anticoagulant agents Time: 0 days (at inclusion)Description: To investigate the existence of a relation between polymorphisms of ABCB1 and plasma concentrations of new oral anticoagulants, the SNaPshot® Multiplex System will be used enabling multiplexing of SNPs (single nucleotide polymorphisms) of the ABCB1 gene (namely rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167).
Measure: Identification of polymorphisms of the gene ABCB1 coding for P-gp Time: 0 days (at inclusion)2 TrAstuzumab Cardiomyopathy Therapeutic Intervention With Carvedilol (TACTIC) Trial
Breast cancer patients undergoing trastuzumab-based HER2-directed therapy are at risk of heart function decline or heart failure symptoms, but it is unknown if, when, and for how long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study randomly assigns those taking curative-intent trastuzumab-based HER2-directed therapy to the beta-blocker carvedilol—either when significant heart function decline or subtle early signs of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or preventatively before beginning trastuzumab-based HER2-directed therapy. This study will further randomly assign those patients on carvedilol to either discontinuation at the end of trastuzumab-based HER2-directed therapy or continuation for another year, providing much needed clinical trial data on what the best strategy ("tactic") for those at risk of cardiotoxicity with trastuzumab-based HER2-directed therapy is.
NCT03879629 Breast Cancer Drug: Carvedilol MeSH:Cardiomyopathies
HPO:Cardiomyopathy
Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip.
Primary Outcomes
Description: Incidence of heart failure or asymptomatic decline in left-ventricular ejection fraction (LVEF) by >10% in patients whose LVEF is ≥50% or LVEF drop ≥5% in those with a decrease to <50% (primary outcome measure)
Measure: Rate of asymptomatic and symptomatic cardiac dysfunction Time: 1 yearDescription: Reversible LVEF decline to within 5% of baseline (secondary primary outcome measure)
Measure: Rate of reversible cardiac function decline Time: 1 yearSecondary Outcomes
Description: Delta change in LVEF from completion to one year after completion of trastuzumab-based HER2-directed therapy
Measure: Cardiac function changes after completion of HER2-directed therapy Time: 1 yearDescription: Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip
Measure: Gene variants and risk of cardiotoxicity and response to therapy Time: 2 years3 Federal Cardiomonitoring System. Determination of the Efficiency of a Single-lead ECG Recorded With CardioQVARK Cardiac Monitor in Order to Detect Atrial Fibrillation in Primary Health Centers.
This interventional prospective multicenter nonrandomized clinical and epidemiological study is the first Russian study aimed at evaluating the effectiveness of a single-lead electrocardiography device (CardioQVARK) in screening for atrial fibrillation in primary health care.
NCT04204330 Atrial Fibrillation Device: CardioQvark cardiac monitor and software, single-lead ECG MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation
For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.. Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Inclusion Criteria: Men and women aged 18 to 96 years who have one or more of the following risk factors: - hypertonic disease - history of ischemic stroke or transient ischemic attacks - type 1 and type 2 diabetes - 1-3 degrees obesity - heart failure or the presence of a clinic to reduce exercise tolerance associated with shortness of breath - coronary heart disease or the presence of symptoms of chest pain, in the absence of an established diagnosis of coronary heart disease - the presence of peripheral arterial atherosclerosis - the presence of a clinic of interruptions in the work of the heart (bouts of rapid, irregular heartbeats, pauses in work of heart) Non-inclusion criteria: - Acute coronary syndrome - Acute ischemic or hemorrhagic stroke - Acute psychosis - The presence of severe concomitant diseases with an expected life expectancy of less than 2 years Exclusion Criteria: Refusal of further participation in the study Atrial Fibrillation Atrial Fibrillation This is an interventional, prospective, multicenter, nonrandomized clinical and epidemiological study.
Primary Outcomes
Description: Total number of AF cases newly diagnosed during the study period.
Measure: Total number of AF cases newly diagnosed during the study period. Time: Through study completion, an average of 1 yearDescription: Number of patients who, for the first time ever, were assigned to anticoagulation therapy.
Measure: Number of patients who, for the first time ever, were assigned to anticoagulation therapy. Time: Through study completion, an average of 1 yearDescription: Assessed using data obtained from pharmacokinetic analysis. International normalised ratio (INR) - target range from 2 to 3.
Measure: Compliance to anticoagulation therapy for warfarin. Time: 6 months after administration of anticoagulantsDescription: Assessed using data obtained from pharmacokinetic analysis. Quantitative determination of the concentration of drugs in the blood (blood sampling three hours after taking the drug).
Measure: Compliance to anticoagulation therapy for new oral anticoagulants. Time: 6 months after administration of anticoagulantsDescription: Evaluated as incremental cost-effectiveness ratio of screening per quality adjusted life year gained, and per stroke avoided.
Measure: Cost-effectiveness of using the single-lead CardioQVARK ECG device in screening for AF in primary health care. Time: Through study completion, an average of 1 yearSecondary Outcomes
Description: Mean time to diagnosis.
Measure: Mean time to diagnosis. Time: Through study completion, an average of 1 yearDescription: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1.
Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 1. Time: Through study completion, an average of 1 yearDescription: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2.
Measure: Number of patients with a CHA₂DS₂-VASc score (the CHA2DS2-VASc Score is the most commonly utilized method to predict thromboembolic risk in atrial fibrillation) of ≥ 2. Time: Through study completion, an average of 1 yearDescription: Defined as frequency of ischemic stroke or transient ischemic attack in patients with newly diagnosed AF and assigned anticoagulants.
Measure: Incidence of ischemic stroke or transient ischemic attack after enrollment in the study. Time: Through study completion, an average of 1 yearDescription: Defined as frequency of massive hemorrhage in patients with newly diagnosed AF and assigned anticoagulants.
Measure: Incidence of massive hemorrhage after enrollment in the study. Time: Through study completion, an average of 1 yearDescription: Defined as frequency of hemorrhagic stroke in patients with newly diagnosed AF and assigned anticoagulants.
Measure: Incidence of hemorrhagic stroke after enrollment in the study. Time: Through study completion, an average of 1 yearDescription: For warfarin - CYP2C9 (CYP2C9 * 2, CYP2C9 * 3), VKORC1 (1 marker), CYP4F2 (1 marker), GGCX (1 marker). For new oral anticoagulants - rs2244613 of the gene CES1, rs1045642 (C3435T), rs1128503 (C1236T), rs2032582 (G2677T / А) of the gene ABCB1, rs2231142 (С421А, Q141K) of the gene ABCG2, rs776746 (A6986G * 399 CYP3 CYP3) CYP3A4.
Measure: Pharmacogenetic testing by polymorphic markers Time: 6 months after administration of anticoagulants