Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

June 14, 2019 updated by: Vanderbilt University Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subjects must be at least 18 years of age.
  • Subjects must have a history of persistent AF currently treated with a rate control strategy.
  • Subjects should be willing to give written, informed consent.
  • Subjects must be willing and able to participate in the exercise protocol.

Exclusion Criteria:

  • New York Heart Association Class III or IV heart failure.
  • A history of heart failure induced by tachy-arrhythmia.

  • A history of coronary artery disease and the presence of at least one of the following:

    • Canadian Class III or IV angina.
    • Recent myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention within 6 months.
  • Severe renal or hepatic impairment.
  • Subjects who have a clinically significant allergy/intolerance to atenolol, including a history of beta-blocker induced bronchospasm.
  • Females who are pregnant or nursing.
  • History of severe AV node dysfunction/pacemaker dependence.
  • Subjects who have a systolic blood pressure < 90 mm Hg or resting Ventricular Rate <50 or >120 per minute on the day of the study.
  • Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atenolol
Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.
Drug: Atenolol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Pre- and Post-atenolol Ventricular Rate Response After 5 Minutes of Exercise
Time Frame: after 5minutes of exercise
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.
after 5minutes of exercise
Change in Pre- and Post-atenolol Ventricular Rate Response After 10 and 15 Minutes of Exercise
Time Frame: after 10 amd 15 minutes of exercise
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.
after 10 amd 15 minutes of exercise

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

October 29, 2012

First Submitted That Met QC Criteria

October 31, 2012

First Posted (Estimate)

November 1, 2012

Study Record Updates

Last Update Posted (Actual)

June 17, 2019

Last Update Submitted That Met QC Criteria

June 14, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 130298

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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