SNPMiner Trials (Home Page)
Report for Mutation C3435T
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 15 clinical trials
Clinical Trials
1 Influence of MDR1 Genotype on Indinavir and Saquinavir Pharmacokinetics in Healthy Volunteers
This study will examine whether a particular type of gene (MDR1) in the body can affect blood levels of two protease inhibitors, indinavir and saquinavir, which are used to treat people with HIV. If blood levels of these drugs are too low or too high, they may not work well or may cause side effects in patients. This study will determine how MDR1 genes might affect absorption of these medicines. Healthy normal volunteers between 18 and 50 years of age may be eligible for this study. Candidates will be screened with a medical history and blood and urine tests. The blood will be tested for: - Routine laboratory values for assessing general health - HIV - MDR1 gene type - Amount of P-glycoprotein (a protein made by the MDR1 gene) on T cells. Participants will have blood drawn three more times, as follows: - After one dose of the sedative midazolam (Versed(Registered Trademark)): Participants will take an 8-milligram dose of midazolam syrup by mouth. Four hours later, a single blood sample will be drawn through a needle in an arm vein. This part of the study will assess the efficiency of a certain enzyme involved in metabolizing (breaking down) indinavir and saquinavir. - After four doses of indinavir: About a week after taking the midazolam, participants will take 800 mg of indinavir (two capsules) 3 times a day (every 8 hours) for 1 day. The following morning they will come to the clinic, where a catheter (flexible plastic tube) will be placed in an arm vein for repeated blood draws. A blood sample will be drawn, and a fourth and final dose of indinavir will be given. Seven blood samples of about a teaspoon each will then be collected through the catheter over an 8-hour period to measure blood levels of the drug. - After 10 doses of saquinavir: About a week after the last dose of indinavir, participants will start taking 1,200 mg (6 capsules) of saquinavir soft-gelatin capsules 3 times a day for 3 days. On the fourth day, participants will come to the clinic. A catheter will be inserted into an arm vein and about 4 teaspoons of blood will be collected for routine laboratory tests and to measure saquinavir levels. A urine sample will also be collected for routine tests. Participants will then receive the tenth and final dose of saquinavir, and eight blood samples of about a teaspoon each will be collected through the catheter over an 8-hour period.
NCT00050180 Healthy HIV Infections Drug: Midazolam Drug: Indinavir Drug: Saquinavir MeSH:HIV Infections
Healthy HIV Infections HIV Infections The expression of P-glycoprotein, a transporter protein present in enterocytes as well as other cells involved in the absorption and distribution of HIV protease inhibitors, has been linked to a single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T. --- C3435T ---
2 The Pharmacogenetics of Oxycodone Analgesia in Postoperative Pain
Patients undergoing surgery (thyroidectomy and hysterectomy) will postoperatively receive oxycodone intravenously (IV) as pain management with morphine as an escape medicine, if there is insufficient pain relief with oxycodone. Patients' pain and side effects will be registered and after 24 hours they will answer a questionnaire. All included patients will be genotyped accordingly to CYP2D6 and relevant single nucleotide polymorphisms (SNPs), and measures of plasma levels of oxycodone will be performed.
NCT00260260 Postoperative Pain Drug: Oxycodone MeSH:Pain, Postoperative
Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G --- --- C3435T ---
Primary Outcomes
Measure: Responder (satisfaction with pain treatment in questionnaire and no escape medication)Measure: Non-responder (dissatisfaction with pain management in questionnaire and/or escape medication)
Measure: Responder status compared to CYP2D6 genotype
Secondary Outcomes
Measure: Registration of pain, side effects and total amount of oxycodone given compared to CYP2D6 genotype and SNPs3 The Pharmacogenetics of Oxycodone Analgesia in Human Experimental Pain Models
Thirty-two healthy volunteers will be submitted to experimental pain and on the 2 study days receive Oxycodone 20 mg po vs. placebo. Half of the volunteers will be poor metabolizers according to CYP2D6 genotype and half will be extensive metabolizers (EM) and have an enzyme with normal function. The study hypothesis is that PM will experience less pain relief than EM.
NCT00271973 Healthy Drug: Oxycodone
Among these are the A118G SNP in the μ-receptor gene OPRM1 and the C3435T and G2677T/A SNPs in the MDR-1 gene of P-glycoprotein. --- A118G --- --- C3435T ---
Primary Outcomes
Measure: Pain threshold and tolerance measured by electrical stimulation and pain intensity measured by cold pressor test.Secondary Outcomes
Measure: The above compared to SNPs. Plasma levels of oxycodone and metabolites.4 Prospective Study of the Influence of CYP3A4/CYP3A5 and MDR1 Gene Single Nucleotide Polymorphisms on Long-Term Tacrolimus Disposition in Renal Allograft Recipients: a Five Year Follow-up Study Using Abbreviated Concentration-Time Measurements.
An evaluation of the effects of genetically determined variant metabolizing and transporting proteins involved in the disposition of the immunosuppressive drug tacrolimus in renal transplant recipients. In a five year follow-up study tacrolimus dose-corrected exposure changes significantly and the effect(s) of single nucleotide polymorphisms of the CYP3A4/CYP3A5 and MDR1 genes on the latter is assessed in this study.
NCT00411944 Renal Transplantation
The effects of the CYP3A5*1, CYP3A4*1B, MDR1 G2677T/A and C3435T single nucleotide polymorphisms on the evolution of tacrolimus disposition are studied over 5 years in order to clarify the interrelationship between CYP3A5, CYP3A4 and MDR1 genotypes, time-dependent exposure and tacrolimus-related toxicity. --- G2677T --- --- C3435T ---
5 A Controlled, Randomized, Parallel, Multicentre Study to Assess Safety and Tolerability of the Oral Direct Thrombin Inhibitor AZD0837, Given as an Extended-release Formulation, in the Prevention of Stroke and Systemic Embolic Events in Patients With Atrial Fibrillation
The main purpose of this study is to provide dose-guiding information by assessing the safety and tolerability of 4 different dosing regimens of an extended-release (ER) formulation of AZD0837 compared with well-controlled, dose-adjusted Vitamin-K antagonists (VKA) (aiming for an international normalized ratio (INR) 2.0 to 3.0) in patients with non-valvular atrial fibrillation (AF) with one or more additional risk factors for stroke.
NCT00684307 Nonvalvular Atrial Fibrillation Drug: AZD0837 Drug: Vitamin-K antagonist at INR 2-3 Drug: AZD0837 MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T. --- C3435T ---
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T. --- C3435T ---
Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC. --- C3435T ---
Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T. --- C3435T ---
Primary Outcomes
Description: Number of patients with a bleeding event while on study drug. Patients with multiple events are counted once
Measure: Bleeding Events Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)Description: Change in Creatinine values from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measure: Creatinine Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Number of patients while on study drug with ALAT>=3 times upper limit of normal.l
Measure: Alanine Aminotransferase (ALAT) Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)Description: Number of patients while on study drug with Bilirubin>=2 times upper limit of normal
Measure: Bilirubin Time: 36 weeks according to protocol. For patients who discontinued treatment the time frame was <36 weeks. Mean number of weeks was 21 weeks (baseline to end of treatment visit)Secondary Outcomes
Description: Change in D-Dimer values from enrolment to week 12 visit for VKA naïve patients while on study drug (week 12 visit-enrolment)
Measure: D-Dimer Time: 14 weeks according to protocol.(enrolment to week 12 visit)Description: Change in Activated partial thromboplastin time (APTT) from baseline to week 12 visit for VKA naïve patients while on study drug (week 12 visit-baseline)
Measure: Activated Partial Thromboplastin Time (APTT) Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Change in Ecarin clotting time (ECT) from baseline to week 12 visit for patients while on study drug (week 12 visit-baseline)
Measure: Ecarin Clotting Time (ECT) Time: 12 weeks according to protocol.(baseline to week 12 visit)Description: Assessment made on the week 12 visit
Measure: Plasma Concentration of AZD0837 (Prodrug) Time: 12 weeks after baseline according to protocolDescription: Assessment made on the week 12 visit
Measure: Plasma Concentration of AR-H067637XX (Active Metabolite) Time: 12 weeks after baseline according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype TT for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TT Time: 36 weeks according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype TC for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype TC Time: 36 weeks according to protocolDescription: Oral clearance of AR-H067637XX in subgroup of patients with genotype CC for gene polymorphism ABCB1 C3435T
Measure: Oral Clearance (CL/F) of AR-H067637XX (Active Metabolite) for C3435T Genotype CC Time: 36 weeks according to protocol6 Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care
Dosing methods for digoxin, a drug used to treat heart failure, have not been updated in decades despite evidence in recent years suggesting that blood levels of digoxin achieved with traditional dosing practices may increase the risk of adverse events. We developed a simple dosing tool that targets lower blood levels of digoxin that have been associated with improved outcomes compared to higher blood levels. The aim of this study is to determine if this simplified dosing tool is more effective than standard digoxin dosing practices at achieving lower blood levels and also to determine if digoxin dosing may be further optimized by incorporating patients' genetic information believed to influence the drug's properties.
NCT01005602 Heart Failure Other: Digoxin Dosing per Nomogram Drug: Digoxin MeSH:Heart Failure
HPO:Congestive heart failure Left ventricular dysfunction Right ventricular failure
We compared serum digoxin concentrations by ABCB1 genotype.. Serum Digoxin Concentration by ABCB1 SNP C3435T. --- C3435T ---
Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T. --- C3435T ---
Primary Outcomes
Measure: Percent of Patients Achieving a Desired Steady-state Serum Digoxin Concentration Between 0.5 - 0.9ng/ml Time: Steady-state (2 - 4 weeks after initiation)Secondary Outcomes
Measure: Mean Serum Digoxin Concentration Time: Steady-state (2 - 4 weeks after initiation)Measure: Serum Digoxin Concentration < 1.0 ng/ml Time: Steady-state (2 - 4 weeks after initiation)
Description: 55 patients in the Digoxin Dosing per Nomogram group consented to the Pharmacogenetic substudy and provided blood samples to perform pharmacogenetic analyses. We compared serum digoxin concentrations by ABCB1 genotype.
Measure: Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T Time: Steady-state (2 - 4 weeks after initiation)Description: Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T
Measure: Serum Digoxin Concentration by ABCB1 SNP C3435T Time: Steady-state (2 - 4 weeks after initiation)Description: Serum digoxin concentration by ABCB1 SNP genotypes
Measure: Serum Digoxin Concentration by ABCB1 SNP G2677T/A Time: Steady-state (2 - 4 weeks after initiation)7 CYP2D6 Screening for Adverse Drug Reactions to Codeine in Breast Milk
The purpose of this study is to determine if non-invasive salivary genetic screening of breastfeeding mothers taking codeine will allow for the successful identification of mother-infant pairs susceptible to adverse events and to prevent these adverse events by personalizing their medication to their genetics.
NCT01050400 Cytochrome P450 2D6 Ultra-rapid Metabolism Genetic: Cytochrome P450 2D6 (CYP2D6) genetic screening. MeSH:Drug-Related Side Effects and Adverse Reactions
Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment.. null. --- C3435T ---
Primary Outcomes
Measure: Incidence of maternal and neonatal CNS depression in the prospective pharmacogenetic screening group to that of a retrospectively screened population Time: 5-8 days post c-section surgerySecondary Outcomes
Measure: Incidence of the phase II uridine diphosphate glucuronyltransferase 2B7 (UGT2B7)*2/*2 variant which has been associated with higher morphine 6-glucuronide to morphine ratios. Time: Minimum 1 week prior to c-sectionMeasure: Incidence of the C3435T polymorphism in the multi-drug resistance gene (MDR1) which has been associated with significantly greater pain relief from morphine treatment. Time: Minimum 1 week prior to c-section
Measure: Incidence of the A118G polymorphism in the opioid receptor 1 (OPRM1) which has been associated with reduced response to morphine treatment. Time: Minimum 1 week prior to c-section
8 An Open Non Randomized Comparative Study Exploring Drug Interaction Between Colchicine and Calcineurin Inhibitors in 2 Groups (Ciclosporin Group and Tacrolimus Group) of Renal Graft Recipients
Ciclosporin inhibits P-glycoprotein should increase colchicine bioavailability whereas tacrolimus should not influence colchicine disposition. This is a prospective, controlled, open labeled study performed in renal graft recipients comparing colchicine single dose (1mg) pharmacokinetics in 14 patients treated with tacrolimus and 14 patients treated with cyclosporin.
NCT01160276 Renal Replacement Therapies Drug: cyclosporine+colchicine Drug: tacrolimus
ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T.. null. --- C3435T ---
Primary Outcomes
Measure: Area under the curve of plasma concentration of colchicine over time 0-∞ Time: 4 weeksSecondary Outcomes
Measure: Half-life of colchicine (T1/2). Time: 4 weeksMeasure: AUC0-3h colchicine to focus the analysis on the absorption phase (argument in favor of an interaction-dependent P-gp) Time: 4 weeks
Measure: Cmax observed colchicine. Time: 4 weeks
Measure: Residual tacrolimus or cyclosporine concentrations Time: 4 weeks
Measure: ABCB1 genotype at position 3435 (rs 1045642) or 3435 cc, 3435TT, heterozygotes could not be included in the tacrolimus group. Time: 4 weeks
Measure: ABCB1 Haplotypes composed of 3 SNPs: C3435T, G2677T / A and C1236T. Time: 4 weeks
Measure: CYP3A5 Genotype: search for the allele * 1 (rs 776746): 3 possible genotypes CYP3A5 * 3 / * 3 - CYP3A5 * 3 / * 1 - CYP3A5 * 1 / * 1. Time: 4 weeks
Measure: GFR calculated by MDRD formula. Time: 4 weeks
Measure: BMI Time: 4 weeks
Measure: Drug related (azathioprine, mycophenolic acid, diuretics, ACE inhibitors, ARAII) Time: 4 weeks
9 Utilizing Pharmacogenetics to Predict Drug Interactions in Kidney Transplant Recipients
Solid organ transplant recipients would greatly benefit from pharmacogenetic evaluation since immunosuppressive drug regimens consist of multiple medications with narrow therapeutic ranges and toxic adverse event profiles. Tacrolimus is a potent immunosuppressive agent utilized for rejection prophylaxis. Intensive pharmacokinetic monitoring must be performed following organ transplantation to ensure therapeutic drug concentrations due to its highly variable pharmacokinetics profile and narrow therapeutic index. Tacrolimus is a substrate for CYP450 3A and for the membrane transporter p-glycoprotein (Pgp). Polymorphisms in the gene encoding for CYP3A5 have been extensively studied and have been found to influence the dosing of tacrolimus. The effect of ABCB1 gene polymorphisms (which encodes for Pgp) upon tacrolimus pharmacokinetics has been more difficult to establish. This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene (C1236T, G2677T, C3435T) can predict the degree of drug interaction between tacrolimus (CYP3A5/Pgp substrate) and ketoconazole (CYP3A5/Pgp inhibitor) in patients who are CYP3A5 nonexpressors. This prospective pharmacokinetic and pharmacogenomic study will enroll 20 stable renal transplant recipients with the CYP3A5 *3/*3 genotype and grouped by ABCB1 haplotype (CGC vs TTT). Pharmacokinetics of tacrolimus will be assessed on 2 occasions with and without ketoconazole coadministration separated by 1 week. The order of study occasions will be randomized in a crossover design. The results of this study may identify a genomic marker for predicting drug-drug interactions. Knowing this information a priori will aid clinicians in modifying drug dosing and alleviate patients of the burden of significant drug toxicities.
NCT01288521 Kidney Transplantation Drug: Tacrolimus + Ketoconazole, Then Tacrolimus alone Drug: Tacrolimus alone, Then Tacrolimus + Ketoconazole
This study will determine if haplotypes derived from three frequent polymorphisms in the ABCB1 gene (C1236T, G2677T, C3435T) can predict the degree of drug interaction between tacrolimus (CYP3A5/Pgp substrate) and ketoconazole (CYP3A5/Pgp inhibitor) in patients who are CYP3A5 nonexpressors. --- C1236T --- --- G2677T --- --- C3435T ---
Primary Outcomes
Description: Tac bioavailability alone vs. Tac bioavailability with Keto. To determine F we took the ratio of area under the curve of the oral dose divided by the area under the curve of the IV dose. F was determined by fitting a model that considered the plasma concentration of tac with IV vs. oral dosing.
Measure: Tacrolimus Bioavailability (F) Time: baseline and 2 weeks10 Investigation Drug-drug Interaction Between Dabigatran and Clarithromycin
Dabigatran (Pradaxa ®) is a new oral anticoagulant. It is used to prevent venous thromboembolism in orthopedic surgery and has recently demonstrated efficacy and safety at least as good as anticoagulants in the prevention of thromboembolism in atrial fibrillation and the treatment of venous thromboembolism. It is administered with fixed dose and does not require laboratory monitoring because of the low inter and intra individual pharmacokinetic (PK) and pharmacodynamics (PD) of dabigatran. However, the bioavailability of dabigatran is very low (6.5%) and is controlled by an efflux protein, P-GP. This molecule has a genetic polymorphism. The inhibition of this protein can cause a significant increase in intestinal absorption of dabigatran and expose patients to a risk of bleeding by overdose. Two major drug interactions have been identified : quinidine (cons-indication) and amiodarone (precautions). It is likely that other interactions exist and can be clinically significant in patients not selected such as testing. The development of tools to study the influence of P-GP on the PK and PD of dabigatran is therefore interesting. As the P-GP has a genetic polymorphism, the study of the latter is an important element in the detection of drug interactions. In this sense, clarithromycin, a potent inhibitor of P-GP is a good model to evaluate the primary mechanism of drug interaction of dabigatran and optimize the experimental design of studies to be conducted.
NCT01385683 Healthy Drug: Dabigatran then dabigatran and clarithromycin Drug: Clarithromycin and dabigatran then dabigatran
Genotyping of MDR-1 (gene for P-GP): C3435T SNP of exon 26, SNP G2677T / A of exon 21 and C1236T SNP of exon 12. Inclusion Criteria: - affiliated or beneficiary of a social security category - having signed the inform consent form - having signed the genetic consent form - weight between 60 and 85 kg - normal clinical exam - normal biological exam Exclusion Criteria: - contra-indication to dabigatran - contra-indication to clarithromycin - previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease - smoker - peptic ulcer - severe liver disease - severe kidney failure - previous surgery within one month Inclusion Criteria: - affiliated or beneficiary of a social security category - having signed the inform consent form - having signed the genetic consent form - weight between 60 and 85 kg - normal clinical exam - normal biological exam Exclusion Criteria: - contra-indication to dabigatran - contra-indication to clarithromycin - previous history of psychiatric disease, or antidepressant treatment, or convulsion, or hemorrhagic disease - smoker - peptic ulcer - severe liver disease - severe kidney failure - previous surgery within one month Healthy null --- C3435T ---
Primary Outcomes
Description: Calculating the area under the curve (AUC) from plasma concentrations of dabigatran versus time by the trapezoidal method. Determination of maximum concentration (Cmax)
Measure: Determination of dabigatran and its metabolites in plasma by LC/MS-MS method Time: At Day 4 and Day 11Secondary Outcomes
Description: Measures activated Partial Thromboplastin Time (aPTT)and measures ECarin Time (ECT),
Measure: Pharmacodynamic parameters Time: At Day 4 and Day 11Description: Genotyping of MDR-1 (gene for P-GP): C3435T SNP of exon 26, SNP G2677T / A of exon 21 and C1236T SNP of exon 12
Measure: Genotyping Time: At Day 111 A Phase II Trial of Induction Chemotherapy With ND-420, Cisplatin and Fluorouracil Followed by Surgery in the Treatment of Patients With Localized Squamous Cell Carcinoma of the Esophagus
Investigator will assign 53 patients who had been histologically proven localized squamous cell carcinoma of esophagus to receive the induction chemotherapy regimen of ND-420 50 mg/m2 on day 1, cisplatin 70 mg/m2 on day1, plus fluorouracil 700 mg/m2 daily, day1 to day4, every 3 weeks for 2 cycles and then followed by surgical resection. The successful rate of complete treatment per protocol and complete resection will be the primary variant to evaluate in our study.
NCT02017600 Localized Squamous Cell Carcinoma of the Esophagus Drug: ND-420 Procedure: Surgery Drug: Cisplatin Drug: fluorouracil MeSH:Carcinoma Carcinoma, Squamous Cell Esophageal Neoplasms Esophageal Squamous Cell Carcinoma
HPO:Carcinoma Esophageal neoplasm Squamous cell carcinoma
the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response. --- C938A --- --- C3435T ---
Primary Outcomes
Measure: the R0 resection rate of participants Time: up to three monthsSecondary Outcomes
Measure: the response rate (RECIST) of participants Time: up to three monthsMeasure: Number of participants with adverse events as a measure of safety and tolerability Time: up to one year
Measure: the population pharmacokinetic parameters (Cmax, AUC... )of ND-420 in the participants Time: 0, 30min, 1hr of ND-420 infusion. selected randomly form one of 3hr, 7hr, 11hr and 23hr after the end of ND-420 infusion.
Measure: the correlation between clinical outcomes and the potential predictive genomic biomarkers(B-tubulin mutation, p53-Arg 72Pro, Bcl2-C938A, MDR1-C3435T polymorphism, TNFRSF1B-1466, GSTP1-l105V, CYP1B1, TS-5'UTR) for tumor response Time: up to one year
Measure: 1-year survival rate of participants Time: up to one year
Measure: pathologic complete response rate of participants Time: up to one year
Measure: 1-year progression free survival rate of participants Time: up to one year
Measure: 1-year overall survival rate of participants Time: up to one year
12 A Prospective Pilot Study to Evaluate the Effect of Systemic Adjuvant Therapy on the Cognitive and Brain Function of Breast Cancer Patients
The purpose of the study is to examine cognitive and brain function in stage I-III breast cancer patients who have undergone adjuvant systemic therapy (chemotherapy or chemotherapy plus anti-hormonal therapy) in comparison to a group of healthy controls. Our hypothesis is that systemic adjuvant therapy in the form of chemotherapy or chemotherapy and anti-hormonal therapy given to primary breast cancer patients can cause cognitive impairment. We hypothesize that the use of simultaneous PET/MRI will allow us to determine key regions in the brain that show metabolic, structural, and functional deficits in a semi-quantitative manner and reveal subtle changes that are often missed during neuropsychological tests due to the low sensitivity of neuropsychological batteries.
NCT02078531 Breast Cancer MeSH:Breast Neoplasms
HPO:Breast carcinoma Neoplasm of the breast
For example, several genetic polymorphisms of multidrug resistance 1 (MDR1) have been identified that may influence P-glycoprotein (P-gp) function, one of the most studied polymorphisms being C3435T in exon26.P-gp which is present in the blood brain barrier affects the amount of drug uptake into the brain by actively transporting them out of the cells. --- C3435T ---
Primary Outcomes
Description: We hope to gain a better understanding of the complex and currently poorly understood relationship between chemotherapy/anti-hormonal therapy and possible cognitive decline in patients undergoing such therapy. In current practice, a large number of patients with primary breast cancer are offered adjuvant chemotherapy after surgery, followed by hormonal therapy in patients whose tumours are hormone receptor-positive. The management of many adverse effects of chemotherapy, such as nausea, vomiting and febrile neutropenia has improved, and concern has shifted to more subtle and potentially chronic problems such as cognitive dysfunction, which may affect patients' quality of life.
Measure: Change the relationship between chemotherapy/anti-hormonal therapy and possible cognitive decline in patients undergoing such therapy Time: 1 year13 Role of Genetic Factors in the Response to Digoxin in the Acute Treatment of Atrial Fibrillation
This study tested the hypothesis that response to digoxin is modulated by single Nucleotid Polymorphism (SNP): - Multi Drug Resistance (MDR1) gene haplotypes and Solute carrier organic anion transporter family member 1B3 (SLCO1B3) gene Polymorphism and their role in the response to treatement. - Aldosterone synthase (CYP11B2) gene and sodium channel, voltage-gated, type V alpha subunit gene (SCN5A) correlated with atrial fibrillation and their roles in response to digoxin.
NCT02167165 Atrial Fibrillation Drug: Digoxin Injection MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation
The aim of the current study is to analyze the ABCB1: C1236T (Gly412Gly), G2677>T⁄A (Ala893Ser/ Thr) and C3435T (Il1145Ile) polymorphisms. --- C1236T --- --- Ala893Ser --- --- C3435T ---
Primary Outcomes
Description: In the current study we aimed at outlining the different MDR-1, SLCO1B3, CYP11B12 and SCN5A genotypes in a sample of Tunisian patients, suffering from AF and taking digoxin, to assess the role of SNPs in affecting serum digoxin concentrations, and studying the consequences on patients' clinical outcome. Patients will be monitored for 24 hours in an intensive care unit;
Measure: Correlation between the response to digoxin and the genotypes of the patients Time: 24 hoursSecondary Outcomes
Description: Rhythm control: rate and delay of return to sinusal rhythm. Rate control: reduction of heart rate : HR <100 bpm or 20% reduction from baseline
Measure: Rhythm and Rate control Time: 24 hoursOther Outcomes
Description: hypotension during hospitalisation, bradycardia, chest pain, allergic reaction
Measure: Arterial hypotension Bradycardia (HR <45 bpm) Other (chest pain, allergic reaction……) Time: 24 hours14 Conversion Pharmacodynamic Study in Stable Renal Transplant Patients Receiving Tacrolimus Two Times a Day to a New Formulation of Tacrolimus - LCP Tacro - 1 Time a Day.
LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability than twice-daily tacrolimus capsules and no new safety concerns. - Stable kidney transplant patients can be safely converted from Adoport® twice-daily to LCP-Tacro®. - The greater bioavailability of LCP-Tacro after once-daily dosing results in similar (AUC) exposure, at a dose approximately 30% less, than the total daily dose of Adoport®. - LCP-Tacro provides a slow drug release and this results in flatter kinetics characterized by significantly lower peak-trough fluctuations. - CN is the major cellular target of the calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus. The ability of these drugs to inhibit CN activity is dependent on their binding to the respective immunophilins, cyclophilins A and B for CsA and FKBP12 for tacrolimus. - CN inhibition is a rate limiting phenomenon. Over concentrations of tacrolimus does not correlate with an increase in the CN activity.
NCT02961608 Kidney Transplant; Complications Drug: Drug conversion from Tacrolimus (Prograf® or Adoport®) to LCP-Tacrolimus (Envarsus®)
Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T ---
Set TAC trough concentrations for optimal inhibition of CN.. drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.. Inclusion Criteria: - Adult patients (≥ 18 years). --- C3435T --- --- C3435T ---
Primary Outcomes
Description: The main objective of this study is to compare the area under the curve (AUC) of CN activity after administration of a sustained release formulation (LCP- Tacro, Envarsus®) compared to an immediate release formulation (Prograf®) of TAC in renal transplant patients.
Measure: Area under the curve (AUC) of CN activity Time: Baseline and 35 days post conversionSecondary Outcomes
Description: Pharmacokinetic study AUC 0-24 h of each TAC formulation 12h (Prograf®) and the new formulation of TAC every 24h (LCP- Tacro, Envarsus®).
Measure: Area Under the curve 0-24 h of each TAC formulation Time: Baseline and 35 days post conversionDescription: Study PK / PD: relationship PK TAC (drug exposure) and PD (activity CN) of both formulations. Set TAC trough concentrations for optimal inhibition of CN.
Measure: TAC trough concentrations for optimal inhibition of CN Time: Baseline and 35 days post conversionDescription: Analysis of drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism.
Measure: drug exposure according to CYP3A (CYP3A4 and CYP3A5 * 22 * 3) and ABCB1 (C3435T) polymorphism. Time: Baseline and 35 days post conversion15 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. --- C3435T ---
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