Genetics of Hypertension Associated Treatments (GenHAT)

NCT ID: NCT00006294

Last Updated: 2024-04-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

37939 participants

Study Classification

OBSERVATIONAL

Study Start Date

1999-09-30

Study Completion Date

2005-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cardiovascular Diseases Heart Diseases Hypertension Coronary Disease Myocardial Infarction

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Chlorthalidone

Participants will take chlorthalidone at recommended doses to control hypertension

Chlorthalidone

Intervention Type DRUG

participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study

Amlodipine

Participants will take Amlodipine at recommended doses to control hypertension

Amlodipine

Intervention Type DRUG

participant's drug dose will be titrated from 10mg to 40mg over the course of the study

Lisinopril

Participants will take Lisinopril at recommended doses to control hypertension

Lisinopril

Intervention Type DRUG

participant's drug dose will be titrated from 10mg to 40mg over the course of the study

Doxazosin

Participants will take Doxazosin at recommended doses to control hypertension

Doxazosin

Intervention Type DRUG

participant's drug dose will be titrated from 2mg to 8mg over the course of the study

Interventions

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Chlorthalidone

participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study

Intervention Type DRUG

Lisinopril

participant's drug dose will be titrated from 10mg to 40mg over the course of the study

Intervention Type DRUG

Amlodipine

participant's drug dose will be titrated from 10mg to 40mg over the course of the study

Intervention Type DRUG

Doxazosin

participant's drug dose will be titrated from 2mg to 8mg over the course of the study

Intervention Type DRUG

Other Intervention Names

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Hygroton, Thalitone, Chlorthalid Zestoretic Norvasc Cardura

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Minnesota

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Donna Arnett, 257-5678

OTHER

Sponsor Role lead

Responsible Party

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Donna Arnett, 257-5678

PI

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Donna Arnett

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

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University of Kentucky

Lexington, Kentucky, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 12439737 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15967849 (View on PubMed)

Zhang X, Lynch AI, Davis BR, Ford CE, Boerwinkle E, Eckfeldt JH, Leiendecker-Foster C, Arnett DK. Pharmacogenetic association of NOS3 variants with cardiovascular disease in patients with hypertension: the GenHAT study. PLoS One. 2012;7(3):e34217. doi: 10.1371/journal.pone.0034217. Epub 2012 Mar 28.

Reference Type DERIVED
PMID: 22470539 (View on PubMed)

Other Identifiers

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R01HL063082

Identifier Type: NIH

Identifier Source: secondary_id

View Link

911

Identifier Type: -

Identifier Source: org_study_id

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