Genetic Epidemiology of Responses to Antihypertensives

Completed

• Conditions: Hypertension; Cardiovascular Diseases; Heart Diseases
• Interventions: Drug: Hydrochlorothiazide; Drug: Candesartan

• Registration Number: NCT00005520
• Lead Sponsor: Mayo Clinic

Brief Summary

To determine whether measured variation in genes coding for components of vasoconstriction and volume regulating systems predict interindividual differences in blood pressure response to therapy with a thiazide diuretic, hydrochlorothiazide, or an angiotensin II receptor blocker, candesartan, in hypertensive African-Americans (N=300 treated with each drug) and in hypertensive European Americans (N=300 treated with each drug).

Detailed Description

BACKGROUND:

Essential hypertension is a common disorder that contributes to morbidity, mortality, and cost of health care, especially among African-Americans. Although a single-drug therapy is commonly prescribed for treatment of hypertension, blood pressure levels are controlled in some individuals but not in others. The study has the potential to identify genes contributing to the etiology of interindividual differences in blood pressure response to diuretic therapy in African-Americans and European Americans.

DESIGN NARRATIVE:

Hypertensive adults were treated with the diuretic hydrochlorothiazide, 25 mg/day, for four weeks; or with the angiotensin II receptor blocker candesartan, 16 mg/day for 2 weeks followed by 32 mg/day for 4 weeks. Interindividual variations in blood pressure responses and in candidate genes coding for components of systems regulating vasoconstriction and volume were measured. In addition, a panel of 500,000 single nucleotide polymorphisms genome-wide was measured in subsets of the most extreme responders and nonresponders to each drug for genome-wide association of analyses.

Study Timeline

• Study Start: 1997-02
• Study First Submitted: 2000-05-25
• Study First Submitted QC: 2000-05-25
• Study First Posted: 2000-05-26
• Primary Completion: 2008-01
• Study Completion: 2008-01
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-15
• Last Update Posted: 2013-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
African American hydrochlorothiazide	Hydrochlorothiazide	300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.
European American hydrochlorothiazide	Hydrochlorothiazide	300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks
African American candesartan	Candesartan	300 African American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks
European American candesartan	Candesartan	300 European American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks

Primary Outcome Measures

Name	Time	Method
Change in blood pressure	4 weeks for hydrochlorothiazide; 6 weeks for candesartan	The blood pressure response to antihypertensive drug therapy was defined by the difference between blood pressure levels prior to and at the end of drug therapy.

Secondary Outcome Measures

Name	Time	Method
Adverse metabolic changes	4 weeks for hydrochlorothiazide only	Potentially adverse metabolic changes in response to hydrochlorothiazide include changes in fasting serum glucose and insulin; serum potassium; serum lipids (triglycerides, HDL-cholesterol, total cholesterol); and serum uric acid.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States