Genetics of Hypertension Associated Treatments (GenHAT)

Hypertension Clinical Trial

— GenHAT  

Official title:

Pharmacological Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Anti-hypertensive Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006294
• Other study ID #: 911
• Secondary ID: R01HL063082
• Status: Completed
• Start date: September 1999
• Est. completion date: August 2005

Study information

• Verified date: April 2024
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To examine whether the association between selected hypertensive genes and combined fatal coronary heart disease and nonfatal myocardial infarction in high-risk hypertensives is modified by the type of antihypertensive treatment, leading to differential risks of coronary heart disease.

Description:

BACKGROUND:

The study might shed important light on the variation in patient response to antihypertensive agents, and improve the ability to pick the right antihypertensive for specific patients. GenHAT is an ancillary study to ALLHAT (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). ALLHAT recruited 42,515 hypertensives and randomized them to one of four antihypertensive agents (lisinopril, chlorthalidone, amlodipine, and doxazosin); follow-up will be completed in March, 2002.

DESIGN NARRATIVE:

GenHAT, a prospective study ancillary to ALLHAT, will characterize hypertension genetic variants and determine their interaction with antihypertensive treatments in relation to coronary heart disease (CHD). DNA from frozen clots stored at the ALLHAT Central Laboratory will be used to genotype variants of hypertension genes (angiotensinogen -6, angiotensin converting enzyme insertion/deletion, angiotensin type- 1 receptor, alpha-adducin, beta2 adrenergic receptor, lipoprotein lipase, and 10 new hypertension variants expected to be discovered during the course of the study). In addition to the primary aim, a number of secondary aims will be undertaken to evaluate gene- treatment interactions in relation to other endpoints, including all-cause mortality, stroke, heart failure, left ventricular hypertrophy, decreased renal function, peripheral arterial disease, and blood pressure lowering. Because of the ethnic and gender diversity of ALLHAT, an assessment will be made of the effects of these variants on outcomes in key subgroups (age >65 years, women, African Americans, Type II diabetics), and whether the gene-treatment interactions in relation to outcomes are consistent across subgroups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37939
• Est. completion date: August 2005
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

• not taking anti-hypertensive medication

• use of anti-hypertensives for less than two months with a baseline blood pressure between 140/90 and 180/110

• use of anti-hypertensives for greater than two months with a blood pressure not greater than 160/100

• at least one additional cardiovascular risk factor such as previous MI, stroke, type 2 diabetes, smoking, left ventricular hypertrophy or dyslipidemia

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Coronary Disease
• Heart Diseases
• Hypertension
• Infarction
• Myocardial Infarction

Intervention

Drug:
• Chlorthalidone
participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study
• Lisinopril
participant's drug dose will be titrated from 10mg to 40mg over the course of the study
• Amlodipine
participant's drug dose will be titrated from 10mg to 40mg over the course of the study
• Doxazosin
participant's drug dose will be titrated from 2mg to 8mg over the course of the study

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (3)

Lead Sponsor	Collaborator
Donna Arnett, 257-5678	National Heart, Lung, and Blood Institute (NHLBI), University of Minnesota

Country where clinical trial is conducted

United States, 

References & Publications (2)

Arnett DK, Boerwinkle E, Davis BR, Eckfeldt J, Ford CE, Black H. Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study. Pharmacogenomics J. 2002;2(5):309-17. doi: 10.1038/sj.tpj.6500113. — View Citation

Arnett DK, Davis BR, Ford CE, Boerwinkle E, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study. Circulation. 2005 Jun 28;111(25):3374-83. doi: 10.1161/CIRCULATIONAHA.104.504639. Epub 2005 Jun 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood Pressure	Blood pressure will be measured to determine the effect of the prescribed anti-hypertensive . Data will be presented as the change in blood pressure over the course of six months	baseline and six month
Secondary	Effect of genotype on event rates	The rate of fatal myocardial infarction (MI) was evaluated in relation to the ACE I/D genotype and anti-hypertensive used. Data are presented as the incidence of fatal MI after six years of follow up	6 years