SNPMiner Trials by Shray Alag


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Report for Clinical Trial NCT02347111

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Prospective, Multi-Center, Randomized, Open Label Trial to Determine if a Common Atrial Fibrillation Risk Locus Modulates Differential Response to Antiarrhythmic Drugs

In this pilot and feasibility study, the investigators will enroll patients with frequent symptomatic episodes of atrial fibrillation (AF) in a cross-over study testing two different classes of anti arrhythmic drugs (AADs). This pilot and feasibility study will provide preliminary data for a larger study in which the investigators will test the hypothesis that a common AF genetic risk allele modulates response to different AADs.

NCT02347111 Atrial Fibrillation
MeSH:Atrial Fibrillation
HPO:Atrial fibrillation Paroxysmal atrial fibrillation

2 Interventions

Name: Flecainide

Description: flecainide up to 150mg twice daily for the control of atrial fibrillation
Type: Drug
Group Labels: 2

flecainide 1st sotalol 1st

Name: Sotalol

Description: sotalol up to 120mg twice daily for the control of atrial fibrillation
Type: Drug
Group Labels: 2

flecainide 1st sotalol 1st


Primary Outcomes

Description: Subjects will be monitored with the Medtronic Reveal LINQ Insertable Cardiac Monitor (ICM) system to assess AF burden. The device will be programmed to optimize the memory for storing AF episode..

Measure: AF burden (Percent of time subject is in atrial fibrillation)

Time: 12 months

Secondary Outcomes

Description: Quality of life assessment: Patients will be asked to fill out the AFEQT quality of life questionnaire baseline (study randomization), two, four, six, eight, ten, and 12 months (completion of the study). The questionnaire at the end of the 6rd month will be administered just prior to stopping the first study drug. The validated questionnaire is comprised of 20 questions about AF symptoms with answers given on a Likert scale. The questionnaire will be provided to the patients in paper format either in person or by mail, as applicable. A follow-up phone call will be made to each patient to ensure that the questionnaire is completed and returned.

Measure: AF Effect on QualiTy-of-life [AFEQT]

Time: 12 months

Purpose: Treatment

Allocation: Randomized

Crossover Assignment


There are 4 SNPs

SNPs


1 rs10033464

However, a SNP at the 4q25 locus (rs10033464) was significantly associated with successful symptom control (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.42-6.21,

As the minor allele frequency (MAF) of rs10033464 is ~12%, the ratio of carriers to non-carriers is ~1:8.

For the primary analysis, we will test the hypothesis that the chr4q25 AF risk allele (rs10033464) modulates the treatment effect difference between flecainide and sotalol.


2 rs17570669

Blood processing, DNA extraction, and genotyping: Blood samples will be drawn into ethylenediamenetetraacetic acid (EDTA) tubes and immediately refrigerated at 4° C. Plasma will be separated by centrifugation and stored at -80° C. DNA will be extracted from the buffy coat using a commercially available kit (Qiagen Puregene, Valencia, California) and stored at -20° C. Study participants will be genotyped for three common chr4q25 SNPs (rs2200733, rs17570669, and rs3853445) using Sanger sequencing.

[In addition, a number of exploratory analyses will be performed on other AF risk alleles, particularly the other 3 most common chr4q25 AF SNPs (rs2200733, rs17570669, rs3853445) associated with AF in EAs26 to determine if any of them modulate response to flecainide and sotalol, using the same test for the primary analysis based on the AF burden scores.


3 rs2200733

Blood processing, DNA extraction, and genotyping: Blood samples will be drawn into ethylenediamenetetraacetic acid (EDTA) tubes and immediately refrigerated at 4° C. Plasma will be separated by centrifugation and stored at -80° C. DNA will be extracted from the buffy coat using a commercially available kit (Qiagen Puregene, Valencia, California) and stored at -20° C. Study participants will be genotyped for three common chr4q25 SNPs (rs2200733, rs17570669, and rs3853445) using Sanger sequencing.

[In addition, a number of exploratory analyses will be performed on other AF risk alleles, particularly the other 3 most common chr4q25 AF SNPs (rs2200733, rs17570669, rs3853445) associated with AF in EAs26 to determine if any of them modulate response to flecainide and sotalol, using the same test for the primary analysis based on the AF burden scores.


4 rs3853445

Blood processing, DNA extraction, and genotyping: Blood samples will be drawn into ethylenediamenetetraacetic acid (EDTA) tubes and immediately refrigerated at 4° C. Plasma will be separated by centrifugation and stored at -80° C. DNA will be extracted from the buffy coat using a commercially available kit (Qiagen Puregene, Valencia, California) and stored at -20° C. Study participants will be genotyped for three common chr4q25 SNPs (rs2200733, rs17570669, and rs3853445) using Sanger sequencing.

[In addition, a number of exploratory analyses will be performed on other AF risk alleles, particularly the other 3 most common chr4q25 AF SNPs (rs2200733, rs17570669, rs3853445) associated with AF in EAs26 to determine if any of them modulate response to flecainide and sotalol, using the same test for the primary analysis based on the AF burden scores.



HPO Nodes


HPO: