Analyzing How Genetics May Affect Response to High Blood Pressure Medications

Hypertension Clinical Trial

Official title:

GenHAT - Genetics of Hypertension Associated Treatments - Ancillary to ALLHAT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00563901
• Other study ID #: 1402
• Secondary ID: R01HL063082-07A1
• Status: Completed
• Phase: N/A
• First received: November 21, 2007
• Last updated: March 2, 2014
• Start date: September 2000
• Est. completion date: May 2004

Study information

• Verified date: January 2008
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

High blood pressure is one of the most common health problems in the United States. There are many medications to treat high blood pressure, but there is a large variance in how people respond to these medications. It is believed that genetic variations may contribute to the inconsistent treatment response. This study will use genetic analysis to determine whether particular genes interact with high blood pressure medications to modify the risk of certain cardiovascular diseases.

Description:

High blood pressure affects nearly one in three individuals in the Unites States. There are many factors that can cause high blood pressure, including family history and genetic traits, kidney disease, stress, diabetes, and diet. If left untreated, high blood pressure can increase one's risk for coronary heart disease (CHD), stroke, heart attack, and heart failure. While high blood pressure can be managed with medication, people receiving medication treatment for high blood pressure are still variably at risk for CHD and other cardiovascular conditions. This risk variation may stem from varying drug reactions that are likely due to genetics. This study will use genetic analysis to determine whether particular genes interact with high blood pressure medications to modify the risk of certain cardiovascular diseases.

This is a continuation study to the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), which included a randomized trial of the four high blood pressure drugs chlorthalidone, amlodipine, lisinopril, and doxazosin. Using samples from ALLHAT participants, this study will analyze the interactions of candidate gene pathways of relevance with medications from the ALLHAT study. Researchers will examine both single DNA building blocks and multiple genes in the candidate gene pathways and determine whether their interaction with the ALLHAT drugs modifies the risk of cardiovascular outcomes. Researchers will perform genetic analysis on 96 genetic markers using structured association testing (SAT) and false discovery rate (FDR) methods. These methods will control for population stratification and multiple testing. Finally, the study will establish a mechanism for other researchers to continue further analysis of the genetic variants examined in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37939
• Est. completion date: May 2004
• Est. primary completion date: May 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Participant in the ALLHAT study

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Cerebrovascular Accident
• Coronary Artery Disease
• Coronary Disease
• Hypertension
• Stroke

Locations

Country	Name	City	State
United States	University of Texas Houston	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Heart, Lung, and Blood Institute (NHLBI), University of Minnesota - Clinical and Translational Science Institute, University of Texas

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — 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 an — View Citation

Davis BR, Arnett DK, Boerwinkle E, Ford CE, Leiendecker-Foster C, Miller MB, Black H, Eckfeldt JH. Antihypertensive therapy, the alpha-adducin polymorphism, and cardiovascular disease in high-risk hypertensive persons: the Genetics of Hypertension-Associa — View Citation

Davis BR, Ford CE, Boerwinkle E, Arnett D, Eckfeldt J, Black H. Imputing gene-treatment interactions when the genotype distribution is unknown using case-only and putative placebo analyses--a new method for the Genetics of Hypertension Associated Treatment (GenHAT) study. Stat Med. 2004 Aug 15;23(15):2413-27. — View Citation

Maitland-van der Zee AH, Boerwinkle E, Arnett DK, Davis BR, Leiendecker-Foster C, Miller MB, Klungel OH, Ford CE, Eckfeldt JH. Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovas — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Candidate genes that interact with ALLHAT high blood pressure medications to modify risk of other cardiovascular conditions		Measured at completion of genetic analysis	No
Secondary	Within selected candidate genes, effect of multiple gene interactions with high blood pressure medications in modifying risk of other cardiovascular conditions		Measured at completion of genetic analysis	No

External Links

•   Click here for more information on the parent ALLHAT study