Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Pharmacogenomic Evaluation of Antihypertensive Responses

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00246519
Recruitment Status : Completed
First Posted : October 30, 2005
Results First Posted : July 10, 2013
Last Update Posted : May 7, 2018
Information provided by (Responsible Party):
University of Florida

Brief 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 only 34% 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, we 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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Hydrochlorothiazide Drug: Atenolol Phase 4

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 34% 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 (atenolol) and a thiazide diuretic (hydrochlorothiazide) given initially as monotherapy, and subsequently in combination, to 800 individuals with uncomplicated hypertension. High quality phenotype data, including both home and ambulatory measures of blood pressure (BP) response, and lipid and insulin sensitivity measures of adverse metabolic responses will be related to genetic variation through two approaches. First, testing 7 single nucleotide polymorphisms (SNPs) in each of 70 candidate genes, we will examine the influence of these genes' variation on responses to beta-blockers and diuretics (Specific Aim 1). This will include assessment of genetic associations with: antihypertensive responses to monotherapy (Aim 1a), addition of a second drug to monotherapy (Aim 1b), and combination therapy (Aim 1c); and adverse metabolic responses to mono and combination therapy (Aim 1d). This candidate gene approach will be supplemented by discovery of novel genes involved in variable BP and metabolic responses to beta-blockers and diuretics through testing of 20,000 putative functional SNPs that span the human genome (Specific Aim 2). As in Aim 1, Aim 2 will include testing for associations with antihypertensive and adverse metabolic responses to monotherapy and combination therapy. The proposed research will substantially increase our understanding of the pharmacogenetics of mono- and combination antihypertensive drug therapy. It will also lead to creation of data sets and samples that can be used by others in the field, through deposit of data to PharmGKB, and creation of immortalized cell lines from all study participants to share data and biological samples with other researchers. 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1701 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR)
Study Start Date : October 2005
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Atenolol
atenolol 50 mg, then 100 mg if BP < 120/70, then add HCTZ 12.5 mg if BP < 120/70, then HCTZ 25 mg if BP < 120/70
Drug: Atenolol
atenolol 50 mg, then 100 mg if BP < 120/70, then add HCTZ 12.5 mg if BP < 120/70, then HCTZ 25 mg if BP < 120/70
Other Names:
  • Lopressor
  • Aquazide H or HydroDIURIL or Microzide

Experimental: Hydrochlorothiazide (HCTZ)
HCTZ 12.5 mg then HCTZ 25 mg if BP < 120/70, then add atenolol 50 mg if BP < 120/70, then atenolol 100 mg if BP < 120/70.
Drug: Hydrochlorothiazide
atenolol 50 or 100 mg hydrochlorothiazide 12.5 or 25 mg
Other Names:
  • Aquazide H or HydroDIURIL or Microzide
  • Lopressor

Primary Outcome Measures :
  1. Blood Pressure Response (Delta BP (After 18 Weeks of Medication - Baseline)). [ Time Frame: baseline to 18 weeks of treatment ]

Secondary Outcome Measures :
  1. Adverse Metabolic Responses [ Time Frame: 9-18 weeks of treatment ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   17 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

An average seated home diastolic blood pressure (DBP) > 85 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 HTN, patients currently treated with three or more antihypertensive drugs, isolated systolic HTN, other diseases requiring treatment with BP lowering medications, heart rate < 55 beats/min, 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.

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 identifier (NCT number): NCT00246519

Layout table for location information
United States, Florida
University of Florida Department of Community Health and Family Medicine
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
University of Florida
Layout table for investigator information
Principal Investigator: Julie A Johnson, PharmD University of Florida
Additional Information:
Publications of Results:

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

Layout table for additonal information
Responsible Party: University of Florida Identifier: NCT00246519    
Other Study ID Numbers: U01GM074492 ( U.S. NIH Grant/Contract )
First Posted: October 30, 2005    Key Record Dates
Results First Posted: July 10, 2013
Last Update Posted: May 7, 2018
Last Verified: April 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Florida:
blood pressure
metabolic adverse effects
Additional relevant MeSH terms:
Layout table for MeSH terms
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents