Pharmacogenetics and Cardiovascular Events

Cardiovascular Diseases Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094198
• Other study ID #: 1278
• Status: Completed
• Phase: N/A
• First received: October 15, 2004
• Last updated: August 20, 2008
• Start date: September 2003
• Est. completion date: August 2008

Study information

• Verified date: August 2008
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

To assess interactions between selected cardiovascular medications and genes in the incidence of heart attack, stroke, and atrial fibrillation, an irregular heartbeat.

Description:

BACKGROUND:

This complex study will collect additional genetic data for 3 ongoing case-control observational studies of drug-gene interactions in myocardial infarction, stroke, and new-onset atrial fibrillation. This study will add single nucleotide polymorphism (SNP) discovery for 16 of 36 candidate genes involving the renin-angiotensin system, sodium transport, adrenergic receptors, and G-proteins, and allow analysis of haplotype data.

The study was initiated in response to RFA HL-03-001, Ancillary Studies in Pharmacogenetics.

DESIGN NARRATIVE:

The primary aim of this study is to assess interactions between selected cardiovascular medications and the major candidate-gene variants or haplotypes on the incidence of myocardial infarction (MI), stroke and atrial fibrillation (AF). The candidate-gene sets-selected on the basis of biology, pharmacology, and information from genome-wide scans-include: (1) 10 genes in the renin-angiotensin system; (2) 10 genes involved in renal sodium transport; (3) 8 genes encoding alpha and beta adrenergic receptors; (4) 8 other genes, including G-proteins, estrogen receptors, and the alpha-1C subunit of the L-type calcium channel. The products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha agonists, calcium antagonists, and estrogens. Both hypothesis-testing and hypothesis-generating analyses are planned. For selected single nucleotide polymorphisms (SNPs) studied in vitro or in small clinical populations, several specific drug-gene interactions are plausible, and these associations will be evaluated in an hypothesis-testing manner.

The study used data from previously funded case-control studies which are expected to produce 1053 MI cases, 565 stroke cases and 800 atrial fibrillation cases and 3249 matching controls from the enrollees of Group Health Cooperative. These patients will already have had chart abstractions, pharmacy database searches, telephone interviews and phlebotomy with specimen storage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older
• Eligibility: No eligibility criteria

Study Design

N/A

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cardiovascular Diseases
• Cerebrovascular Accident
• Heart Diseases
• Myocardial Infarction
• Stroke

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (3)

Kooperberg C, Ruczinski I. Identifying interacting SNPs using Monte Carlo logic regression. Genet Epidemiol. 2005 Feb;28(2):157-70. — View Citation

Psaty BM, Furberg CD. Contemplating ACTION--long-acting nifedipine in stable angina. Lancet. 2004 Sep 4-10;364(9437):817-8. — View Citation

Smith NL, Heckbert SR, Lemaitre RN, Reiner AP, Lumley T, Weiss NS, Larson EB, Rosendaal FR, Psaty BM. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA. 2004 Oct 6;292(13):1581-7. — View Citation