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Trial record 1 of 2 for:    NCT01203852
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Pharmacogenomic Evaluation of Antihypertensive Responses 2 (PEAR2)

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: NCT01203852
Recruitment Status : Completed
First Posted : September 16, 2010
Results First Posted : May 19, 2015
Last Update Posted : April 6, 2018
National Institute of General Medical Sciences (NIGMS)
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 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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Metoprolol Drug: Chlorthalidone 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 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 839 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacogenomic Evaluation of Antihypertensive Responses 2
Study Start Date : August 2010
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Arm Intervention/treatment
Experimental: Metoprolol + Chlorthalidone
Study participants in this group had their current hypertension treatment withdrawn, baseline labs drawn and hypertension documented. Participants were initiated on metoprolol tartrate 50 mg twice daily for two weeks, followed by dose titration to 100 mg twice daily for six additional weeks if blood pressure (BP) > 120/70 mmHg. BP measures were again recorded. Participants entered a washout where metoprolol was titrated, then discontinued, and the patient's hypertension was re-established. After another set of identical baseline labs, study participants were initiated on chlorthalidone 25 mg four days per week (Monday, Wednesday, Thursday, Saturday) 15 mg daily for two weeks, followed by 25 mg daily for an additional six weeks.
Drug: Metoprolol

Metoprolol 50 mg twice daily titrated to 100 mg twice daily

Note: due to discontinuation of the manufacture of chlorthalidone 15 mg, effective Jan 1, 2013; the starting dose of chlorthalidone will be 25 mg 4 times per week (Mon, Wed, Thur, Sat) with subsequent titration to 25 mg daily.

Other Names:
  • Lopressor
  • Toprol XL

Drug: Chlorthalidone
Chlorthalidone 25 mg 4 times per week titrated to 25 mg daily
Other Name: Thalitone

Primary Outcome Measures :
  1. Change in Blood Pressure From Baseline to Treatment [ Time Frame: after 6-8 weeks of treatment ]
    Response to blood pressure medication will be assessed by measuring blood pressure before and after treatment

Secondary Outcome Measures :
  1. Adverse Metabolic Effects [ Time Frame: after 6-8 weeks treatment ]
    Change in glucose after treatment with study medication

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (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 < 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.

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): NCT01203852

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United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, Minnesota
Mayo Clinic, Division of Hypertension
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
University of Florida
National Institute of General Medical Sciences (NIGMS)
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Principal Investigator: Julie A Johnson, PharmD University of Florida
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: University of Florida Identifier: NCT01203852    
Other Study ID Numbers: IRB201700661-N
U01GM074492-06 ( U.S. NIH Grant/Contract )
First Posted: September 16, 2010    Key Record Dates
Results First Posted: May 19, 2015
Last Update Posted: April 6, 2018
Last Verified: April 2018

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