Genetics of Hypertension Associated Treatments (GenHAT) (GenHAT)

• ClinicalTrials.gov Identifier: NCT00006294
• Recruitment Status: Completed
• First Posted: September 26, 2000
• Last Update Posted: April 6, 2018
• Sponsor: Donna Arnett, 257-5678
• Collaborators: University of Minnesota; 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

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 :

1. 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 :

1. 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

• 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

Locations

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536

Sponsors and Collaborators

Donna Arnett, 257-5678

University of Minnesota

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. doi: 10.1038/sj.tpj.6500113.

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.

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
• Other Study ID Numbers: 911; R01HL063082 ( U.S. NIH Grant/Contract )
• First Posted: September 26, 2000
• 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; Cardiovascular Diseases; Myocardial Infarction; Heart Diseases; Coronary Disease; Infarction; Vascular Diseases; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Amlodipine; Lisinopril; Chlorthalidone; Doxazosin; Antihypertensive Agents; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Vasodilator Agents; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Cardiotonic Agents; Protective Agents; Diuretics; Natriuretic Agents; Sodium Chloride Symporter Inhibitors