Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Matt Kolek, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01719367
First received: October 29, 2012
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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, using a candidate gene approach, the effect of genetic variants on heart rate response to beta-blockade in patients with AF.


Condition Intervention
Atrial Fibrillation
Drug: Atenolol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Ventricular rate response during exercise. [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 200
Study Start Date: January 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atenolol
Patients will undergo a standardized, graded exercise protocol before ank after receiving a dose of oral atenolol.
Drug: Atenolol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 VR <50 or >120 per minute on the day of the study.
  • Patients currently taking Vaughan-Williams Class I or III anti-arrhythmic drugs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01719367

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Matt J Kolek, M.D.    615-936-1713    matt.kolek@vanderbilt.edu   
Principal Investigator: Dawood Darbar, M.D.         
Sub-Investigator: Matt J Kolek, M.D.         
Sponsors and Collaborators
Vanderbilt University
  More Information

Additional Information:
Publications:
European Heart Rhythm Association; Heart Rhythm Society; Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines; Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol. 2006 Aug 15;48(4):854-906. No abstract available.

Responsible Party: Matt Kolek, Fellow in Cardiovascular Disease, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01719367     History of Changes
Other Study ID Numbers: Kolek 01
Study First Received: October 29, 2012
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Baseline (pre-atenolol)
Post-atenolol

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Atenolol
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 29, 2014