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