Pharmacogenomic Evaluation of Antihypertensive Responses 2
Overview[ - collapse ][ - ]
| 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. |
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| Condition | Hypertension |
| Intervention | Drug: metoprolol or chlorthalidone |
| Phase | Phase 4 |
| Sponsor | National Institute of General Medical Sciences (NIGMS) |
| Responsible Party | 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 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 15, 2010 |
|---|---|
| Last Updated Date | October 15, 2013 |
| Start Date | August 2010 |
| Estimated Primary Completion Date | March 2014 |
| Current 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 |
| Current Secondary Outcome Measures | adverse metabolic effects [Time Frame: after 6-8 weeks treatment] [Designated as safety issue: Yes] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Pharmacogenomic Evaluation of Antihypertensive Responses 2 |
|---|---|
| Official Title | Pharmacogenomic Evaluation of Antihypertensive Responses 2 |
| 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. |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Hypertension |
| Intervention | 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. |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 400 |
| Estimated Completion Date | March 2014 |
| Estimated Primary Completion Date | March 2014 |
| Eligibility 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. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01203852 |
|---|---|
| Other Study ID Numbers | U01 GM074492-06 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | National Institute of General Medical Sciences (NIGMS) |
| Study Sponsor | National Institute of General Medical Sciences (NIGMS) |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Julie A Johnson, PharmD University of Florida |
| Verification Date | October 2013 |
Locations[ + expand ][ + ]
| University of Florida | Gainesville, Florida, United States, 32610 |
|---|---|
| Emory University | Atlanta, Georgia, United States |
| Mayo Clinic | Rochester, Minnesota, United States |