Genetics of Hypertension Associated Treatments (GenHAT) (GenHAT)

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ClinicalTrials.gov Identifier: NCT00006294

Recruitment Status : Completed

First Posted : September 26, 2000

Last Update Posted : April 6, 2018

Sponsor:

Collaborators:

University of Minnesota - Clinical and Translational Science Institute

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

Donna Arnett, 257-5678, University of Kentucky

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Cardiovascular Diseases Heart Diseases Hypertension Coronary Disease Myocardial Infarction	Drug: Chlorthalidone Drug: Lisinopril Drug: Amlodipine Drug: Doxazosin

Detailed 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.

Study Design


Study Type :	Observational
Actual Enrollment :	37939 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Pharmacological Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Anti-hypertensive Treatment
Study Start Date :	September 1999
Actual Primary Completion Date :	August 2005
Actual Study Completion Date :	August 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Pressure Medicines

Drug Information available for: Chlorthalidone Doxazosin

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Chlorthalidone Participants will take chlorthalidone at recommended doses to control hypertension	Drug: Chlorthalidone participant's drug dose will be titrated from 12.5mg to 25mg over the course of the study Other Name: Hygroton, Thalitone, Chlorthalid
Amlodipine Participants will take Amlodipine at recommended doses to control hypertension	Drug: Amlodipine participant's drug dose will be titrated from 10mg to 40mg over the course of the study Other Name: Norvasc
Lisinopril Participants will take Lisinopril at recommended doses to control hypertension	Drug: Lisinopril participant's drug dose will be titrated from 10mg to 40mg over the course of the study Other Name: Zestoretic
Doxazosin Participants will take Doxazosin at recommended doses to control hypertension	Drug: Doxazosin participant's drug dose will be titrated from 2mg to 8mg over the course of the study Other Name: Cardura

Outcome Measures

Primary Outcome Measures :

Blood Pressure [ Time Frame: baseline and six month ]
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

Secondary Outcome Measures :

Effect of genotype on event rates [ Time Frame: 6 years ]
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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	55 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Hypertensive individuals, multiple races and ethnic groups are represented in this study population

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006294

Locations


United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536

Sponsors and Collaborators

Donna Arnett, 257-5678

University of Minnesota - Clinical and Translational Science Institute

National Heart, Lung, and Blood Institute (NHLBI)

Investigators


Principal Investigator:	Donna Arnett	University of Kentucky

More Information

Publications:

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.

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. Epub 2005 Jun 20.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.


Responsible Party:	Donna Arnett, 257-5678, PI, University of Kentucky
ClinicalTrials.gov Identifier:	NCT00006294 History of Changes
Other Study ID Numbers:	911 R01HL063082 ( U.S. NIH Grant/Contract )
First Posted:	September 26, 2000 Key Record Dates
Last Update Posted:	April 6, 2018
Last Verified:	April 2018


Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Additional relevant MeSH terms:


Hypertension Infarction Cardiovascular Diseases Heart Diseases Myocardial Infarction Coronary Disease Coronary Artery Disease Vascular Diseases Ischemia Pathologic Processes Necrosis Myocardial Ischemia Arteriosclerosis Arterial Occlusive Diseases Amlodipine	Lisinopril Chlorthalidone Doxazosin Antihypertensive Agents Calcium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Vasodilator Agents Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Cardiotonic Agents Protective Agents Physiological Effects of Drugs Diuretics

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