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Pharmacogenomic Evaluation of Antihypertensive Responses 2 (PEAR2)
This study has been completed.
Sponsor:
University of Florida
Collaborator:
National Institute of General Medical Sciences (NIGMS)
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01203852
First received: September 15, 2010
Last updated: March 24, 2017
Last verified: March 2017
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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 Drug: Chlorthalidone | Phase 4 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | Pharmacogenomic Evaluation of Antihypertensive Responses 2 |
Resource links provided by NLM:
MedlinePlus related topics:
Blood Pressure Medicines
Drug Information available for:
Chlorthalidone
Metoprolol
Metoprolol tartrate
Metoprolol fumarate
Metoprolol succinate
U.S. FDA Resources
Further study details as provided by University of Florida:
Primary Outcome Measures:
- 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:
- Adverse Metabolic Effects [ Time Frame: after 6-8 weeks treatment ]Change in glucose after treatment with study medication
| Enrollment: | 839 |
| Study Start Date: | August 2010 |
| Study Completion Date: | April 2014 |
| Primary Completion Date: | April 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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:
Drug: Chlorthalidone
Chlorthalidone 25 mg 4 times per week titrated to 25 mg daily
Other Name: Thalitone
|
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
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For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01203852
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 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)
Investigators
| Principal Investigator: | Julie A Johnson, PharmD | University of Florida |
More Information
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | University of Florida |
| ClinicalTrials.gov Identifier: | NCT01203852 History of Changes |
| Other Study ID Numbers: |
IRB201700661 U01GM074492-06 ( U.S. NIH Grant/Contract ) |
| Study First Received: | September 15, 2010 |
| Results First Received: | April 29, 2015 |
| Last Updated: | March 24, 2017 |
| Studies a U.S. FDA-regulated Drug Product: | No | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Keywords provided by University of Florida:
|
hypertension antihypertensive drug pharmacogenetics |
genetics blood pressure glucose |
Additional relevant MeSH terms:
|
Hypertension Vascular Diseases Cardiovascular Diseases Metoprolol Antihypertensive Agents Chlorthalidone Anti-Arrhythmia Agents Sympatholytics 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 Diuretics Natriuretic Agents Sodium Chloride Symporter Inhibitors Membrane Transport Modulators |
ClinicalTrials.gov processed this record on September 21, 2017