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Pharmacogenomic Evaluation of Antihypertensive Responses 2

Information source: University of Florida
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hypertension

Intervention: Metoprolol (Drug); Chlorthalidone (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University of Florida

Official(s) and/or principal investigator(s):
Julie A Johnson, PharmD, Principal Investigator, Affiliation: University of Florida


There are many medications available for the treatment of high blood pressure (hypertension), but finding the right one for a specific patient can be challenging. In fact, it is estimated that less than 50% of people with hypertension have their blood pressure under control. The hypothesis is that genetic differences between individuals influence their response to antihypertensive medications. This study is aimed at determining the genetic factors that may influence a person's response to either a beta-blocker or a thiazide diuretic. The hope is that through this research, the investigators may someday be able to use an individual's genetic information to guide the selection of their blood pressure medicine, leading to better control of blood pressure, and less need for the current trial and error process.

Clinical Details

Official title: Pharmacogenomic Evaluation of Antihypertensive Responses 2

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Antihypertensive Response

Secondary outcome: Adverse Metabolic Effects

Detailed description: The proposed work should help move toward the long-term goal of selection of antihypertensive drug therapy based on a patient's genetic make-up. Hypertension (HTN) is the most common chronic disease for which drugs are prescribed, and the most prevalent risk factor for heart attack, stroke, renal failure and heart failure. Responses to antihypertensive drug therapy exhibit considerable interpatient variability, contributing to poor rates of HTN control (currently about 40-50% in the US), and frequent nonadherence and dropout from therapy. We propose to identify genetic predictors of the antihypertensive and adverse metabolic responses to two preferred and pharmacodynamically contrasting drugs, a beta-blocker (metoprolol) and a thiazide diuretic (chlorthalidone) in a sequential monotherapy design in 400 hypertensive individuals. Data collected will include home and clinic blood pressure, blood samples for testing for adverse metabolic effects and other biomarkers, RNA, and DNA and urine sample. We will conduct genome-wide association single nucleotide polymorphism (SNP) genotyping and data from the study will be used for replication of findings from the previous PEAR trial, along with new discoveries. The primary aims are to define the genetic determinants of the antihypertensive response and adverse metabolic responses (e. g. changes in glucose, triglycerides and uric acid). The proposed research is significant because genetically-targeted antihypertensive therapy could lead to dramatically higher response rates and fewer adverse effects than the usual trial-and-error approach. This would likely lead to higher rates of HTN control, less need for polypharmacy, reduced health care costs, and improved outcomes.


Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.


Inclusion Criteria:

- An average seated home diastolic blood pressure (DBP) > 85 mmHg and < 110 mmHg and

home systolic blood pressure (SBP) < 180 mmHg.

- Subjects must also have an average seated (> 5 minutes) clinic DBP between 90 mmHg

and 110 mmHg and SBP < 180 mmHg Exclusion Criteria:

- Secondary forms of hypertension (HTN) (including sleep apnea)

- Isolated systolic HTN

- Other diseases requiring treatment with BP lowering medications

- Heart rate < 55 beats/min (for metoprolol only)

- Known cardiovascular disease (including history of angina pectoris, heart failure,

presence of a cardiac pacemaker, history of myocardial infarction or revascularization procedure, or cerebrovascular disease, including stroke and TIA)

- Diabetes mellitus (Type 1 or 2)

- Renal insufficiency (serum creatinine > 1. 5 in men or 1. 4 in women)

- Primary renal disease

- Pregnancy or lactation

- Liver enzymes > 2. 5 upper limits of normal

- Current treatment with NSAIDS, cyclooxygenase-2 (COX2) inhibitors, oral

contraceptives or estrogen.

Locations and Contacts

University of Florida, Gainesville, Florida 32610, United States

Emory University School of Medicine, Atlanta, Georgia 30322, United States

Mayo Clinic, Division of Hypertension, Rochester, Minnesota 55905, United States

Additional Information

PEAR study website

Starting date: August 2010
Last updated: April 29, 2015

Page last updated: August 23, 2015

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