Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation
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| ClinicalTrials.gov Identifier: NCT01719367 |
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Recruitment Status :
Completed
First Posted : November 1, 2012
Results First Posted : June 17, 2019
Last Update Posted : June 17, 2019
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atrial Fibrillation | Drug: Atenolol | Not Applicable |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 38 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Genetically Determined Response to Atenolol in Patients With Persistent Atrial Fibrillation |
| Study Start Date : | January 2013 |
| Actual Primary Completion Date : | September 2016 |
| Actual Study Completion Date : | September 2016 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Atenolol
Patients will undergo a standardized, graded exercise protocol before and after receiving a dose of oral atenolol.
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Drug: Atenolol |
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01719367
| United States, Tennessee | |
| Vanderbilt University Medical Center | |
| Nashville, Tennessee, United States, 37232 | |
Publications:
| Responsible Party: | Vanderbilt University Medical Center |
| ClinicalTrials.gov Identifier: | NCT01719367 History of Changes |
| Other Study ID Numbers: |
130298 |
| First Posted: | November 1, 2012 Key Record Dates |
| Results First Posted: | June 17, 2019 |
| Last Update Posted: | June 17, 2019 |
| Last Verified: | June 2019 |
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Baseline (pre-atenolol) Post-atenolol |
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Atenolol Atrial Fibrillation Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Anti-Arrhythmia Agents 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 |