GERA: Genetic Epidemiology of Responses to Antihypertensives

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00005520

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

1,200

Enrollment

Location

131

Duration (Months)

9.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases Heart Diseases Hypertension	Drug: Hydrochlorothiazide Drug: Candesartan

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 Design

Study Type:

Observational

Actual Enrollment :

1200 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Genetic Epidemiology of Responses to Antihypertensives

Study Start Date :

Feb 1, 1997

Actual Primary Completion Date :

Jan 1, 2008

Actual Study Completion Date :

Jan 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
African American hydrochlorothiazide 300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.	Drug: Hydrochlorothiazide
European American hydrochlorothiazide 300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks	Drug: Hydrochlorothiazide
African American candesartan 300 African American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks	Drug: Candesartan
European American candesartan 300 European American hypertensives were treated with candesartan 16 mg daily for 2 weeks followed by 32 mg daily for 4 weeks	Drug: Candesartan

Outcome Measures

Primary Outcome Measures

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

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.