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Report for Clinical Trial NCT01719367

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

Atrial fibrillation (AF), the most common sustained heart rhythm disorder, is becoming increasingly prevalent in the Western world. The number of people with AF in the United States is projected to roughly double by the year 2050, to an estimated 6-12 million. For many patients with AF, rate control with atrioventricular (AV) node blockers is a widely accepted therapeutic strategy. These agents control heart rate, thus preventing symptoms and systolic heart failure associated with tachycardia due to a rapid ventricular response to AF. Beta-blockers are widely accepted as first line agents for rate control in AF, especially when patients have concomitant hypertension (HTN), coronary artery disease, cardiomyopathies, or heart failure (HF). As a class, beta-blockers are among the most commonly prescribed cardiovascular medications. Among patients with AF treated with beta-blockers, the heart rate (HR) response varies substantially. Sometimes, adequate rate control can be achieved by titration of the beta-blocker dose; but frequently, additional AV nodal blockers and/or digoxin are necessary. In some cases, adequate rate control cannot be achieved even with the simultaneous use of multiple AV nodal blockers, necessitating mechanical ablation of the AV node and permanent pacemaker implantation. Patient-specific variables that influence the response to beta-blockers include comorbid conditions, weight, age, and level of physical activity. Ethnic differences in the response to beta-blockers for the treatment of HTN and HF are well-described. However, the contribution of genetic variants to beta-blocker efficacy in AF is unknown. We propose to study whether the ADRB1 Gly389Asp SNP reduces response to beta-blockade in subjects with permanent AF.

NCT01719367 Atrial Fibrillation
MeSH: Atrial Fibrillation
HPO: Atrial fibrillation Paroxysmal atrial fibrillation

1 Interventions

Name: Atenolol

Type: Drug

Atenolol


Primary Outcomes

Description: After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.

Measure: Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise

Time: after 5minutes of exercise

Description: After baseline vital signs and ECG are recorded, patients will be asked to perform a baseline standardized (modified Bruce) exercise protocol. Heart rate will be recorded during each stage of the exercise protocol. Patients will be asked to exercise to sub-maximal exertion. After the baseline exercise protocol, patients will be given a single dose of oral atenolol. After a two hour waiting period to allow for peak effect of atenolol, patients will repeat the exercise protocol. The primary study outcome measure will be the difference in pre- and post-atenolol ventricular rate response to exercise. The primary outcome measure will be compared in patients with various polymorphisms in genes that might play a role in the inter-individual response to atenolol.

Measure: Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise

Time: after 10 amd 15 minutes of exercise

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 G389D

We propose to study whether the ADRB1 Gly389Asp SNP reduces response to beta-blockade in subjects with permanent AF. --- Gly389Asp ---



HPO Nodes


HPO:
Atrial fibrillation
Genes 70
SCN4B ANK2 RYR2 LMNA PRKAG2 MYPN SCN5A TNNT2 TNNI3K TNNI3 AGPAT2 CACNA2D1 HCN4 TTN POLG2 KCNE2 KCNQ1 SGO1 FOS MYOZ2 MYH7 LMNA CAVIN1 SCN2B PLN TNNC1 MFAP5 PRKAG2 TRDN TLL1 POLG CAV1 TAB2 TMEM43 ABCC9 SLC25A4 NKX2-5 ACTN2 XK TWNK KCNJ2 DTNA RRM2B KCNJ5 CACNB2 GJA5 FLNC TBX5 SCN5A BSCL2 CSRP3 KCNA5 CACNA1C MYL4 NEXN GATAD1 DMPK KCNQ1 NPPA PPARG KCNJ2 CAVIN1 GATA5 KCNQ1 SMAD3 CASQ2 KCNH2 NUP155 SCN1B SMAD3
Paroxysmal atrial fibrillation
Genes 12
KCNJ5 SCN5A CSRP3 KCNA5 KCNJ2 SCN2B MYL4 ABCC9 TBX5 KCNE2 SCN1B PRKAG2