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Pharmacogenomic Evaluation of Antihypertensive Responses 2 (PEAR2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dr. Julie A Johnson, National Institute of General Medical Sciences (NIGMS)
ClinicalTrials.gov Identifier:
NCT01203852
First received: September 15, 2010
Last updated: October 15, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Hypertension
Drug: metoprolol or chlorthalidone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacogenomic Evaluation of Antihypertensive Responses 2

Resource links provided by NLM:


Further study details as provided by National Institute of General Medical Sciences (NIGMS):

Primary Outcome Measures:
  • antihypertensive response [ Time Frame: after 6-8 weeks of treatment ] [ Designated as safety issue: No ]
    antihypertensive response will be assessed by measuring blood pressure before and after treatment


Secondary Outcome Measures:
  • adverse metabolic effects [ Time Frame: after 6-8 weeks treatment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 400
Study Start Date: August 2010
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: metoprolol Drug: metoprolol or chlorthalidone
metoprolol 50 mg twice daily titrated to 100 mg twice daily chlorthalidone 15 mg daily titrated to 25 mg 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.
Experimental: chlorthalidone Drug: metoprolol or chlorthalidone
metoprolol 50 mg twice daily titrated to 100 mg twice daily chlorthalidone 15 mg daily titrated to 25 mg 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.

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 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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An average seated home DBP > 85 mmHg and < 110 mmHg and home 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 (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, COX2-inhibitors, oral contraceptives or estrogen.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01203852

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Emory University
Atlanta, Georgia, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States
Sponsors and Collaborators
Investigators
Principal Investigator: Julie A Johnson, PharmD University of Florida
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. Julie A Johnson, Principal Investigator, National Institute of General Medical Sciences (NIGMS)
ClinicalTrials.gov Identifier: NCT01203852     History of Changes
Other Study ID Numbers: U01 GM074492-06
Study First Received: September 15, 2010
Last Updated: October 15, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of General Medical Sciences (NIGMS):
hypertension
antihypertensive drug
pharmacogenetics
genetics
blood pressure
glucose

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases
Antihypertensive Agents
Chlorthalidone
Metoprolol
Metoprolol succinate
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Autonomic Agents
Cardiovascular Agents
Diuretics
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Sympatholytics
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014