Genetic Epidemiology of Responses to Antihypertensives (GERA)
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).
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Genetic Epidemiology of Responses to Antihypertensives|
- Change in blood pressure [ Time Frame: 4 weeks for hydrochlorothiazide; 6 weeks for candesartan ] [ Designated as safety issue: No ]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.
- Adverse metabolic changes [ Time Frame: 4 weeks for hydrochlorothiazide only ] [ Designated as safety issue: No ]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.
Biospecimen Retention: Samples With DNA
Serum, plasma, buffy coat, urine.
|Study Start Date:||February 1997|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
African American hydrochlorothiazide
300 African American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks.
European American hydrochlorothiazide
300 European American hypertensives were treated with hydrochlorothiazide 25 mg daily for 4 weeks
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
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
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005520
|United States, Minnesota|
|Rochester, Minnesota, United States|
|Principal Investigator:||Stephen T. Turner, M.D.||Mayo Foundation|