Genetic Determinants of Response to Beta Blockade

NCT ID: NCT00837902

Last Updated: 2018-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2014-12-31

Brief Summary

The overall goal of this project is to determine the genetic factors contributing to interindividual differences in response to beta-blockade.

Detailed Description

The Aim is to define the contribution of genetic variation to the interindividual variability in response to β-blockade. The rationale for the study is as follows: Beta-blockers prevent the activation of β-ARs and thus form the cornerstone of treatment of pathological states such as congestive heart failure and coronary artery disease. Functional polymorphisms in cardiac beta-receptors have been shown to determine response to β-blocker therapy. A physiologic stimulus such as exercise causes sympathetic stimulation and activation of the cardiac β-ARs and genotypic differences in response to β-blockers are magnified under states of heightened sympathetic activity. Thus, in addition to measuring the response to β-blockers at rest, we will also determine the response to β-blockade after sub-maximal exercise on a supine bicycle ergometer. Genetic variations that may alter sensitivity to a beta blocker will be sought.

Conditions

Healthy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Atenolol

There is only 1 arm to this study. Intervention: All participants received atenolol. Genotyping for GRK5 was performed to identify if participants were GLN/GLN, GLN/LEU, or LEU/LEU.

Heart rates were measured at rest, and as participants performed graded incremental exercise on a supine bicycle ergometer (at 25, 50, and 75 W for 2 minutes each) twice, once before and once 2.5 hours after taking 25 mg of atenolol.

Group Type: EXPERIMENTAL

Atenolol (β-blocker)

Intervention Type: DRUG

25 mg tablet

Interventions

Atenolol (β-blocker)

25 mg tablet

Intervention Type: DRUG

Other Intervention Names

generic atenolol is being used, so not applicable

Eligibility Criteria

Inclusion Criteria

• Subject must be willing to give written informed consent and be able to adhere to diet and study schedules.
• Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations.
• Subjects must have a clinically acceptable physical examination and ECG.
• Laboratory tests (CBC, blood chemistries, and urinalysis) must be within clinically acceptable limits.

Exclusion Criteria

• Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within one week prior to study drug administration.
• Subjects who are presently, or were formerly, narcotic addicts or alcoholics.
• Active smokers.
• Subjects who have a clinically significant allergy/intolerance to atenolol.
• Females with a positive serum/urine pregnancy test at screening.
• Females who are nursing.
• Subjects with complete heart block/ any other significant cardiovascular disease.
• Subjects with a history of asthma symptoms or medication for it within last 10 years.
• Subjects who have a systolic blood pressure < 90 mm Hg or diastolic blood pressure < 50 mm Hg or heart rate < 50/min at the screening visit or on the baseline pre drug values on the study day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

C. Michael Stein

Dan May Professor of Medicine,. Professor of Pharmacology, Assistant Director of the Division of Clinical Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Charles M Stein, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

Kurnik D, Cunningham AJ, Sofowora GG, Kohli U, Li C, Friedman EA, Muszkat M, Menon UB, Wood AJ, Stein CM. GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans. Pharmacogenomics. 2009 Oct;10(10):1581-7. doi: 10.2217/pgs.09.92.

Reference Type: RESULT

PMID: 19842931 (View on PubMed)

Other Identifiers

P01HL056693

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL065962

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1UL1RR024975

Identifier Type: NIH

Identifier Source: secondary_id

View Link

081267

Identifier Type: -

Identifier Source: org_study_id