Clinical trial NCT00837902: Genetic Determinants of Response to Beta Blockade
Official title: Genetic Determinants of Response to Beta Blockade
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Atenolol
Exercise
Genotype
Healthy volunteers
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
First posted: 2009-02-06
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Reduction in Heart Rate
timeFrame: 2 exercise periods of 6 minutes each. 6 minutes of exercise before taking atenolol, and 6 minutes of exercise starting 2.5 hours after taking 25 mg of atenolol (2.5 hours + 6 minutes)
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Charles M Stein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.