Pharmacogenomic Evaluation of Antihypertensive Responses 2
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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 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.
    

Intervention name(s): Metoprolol; Chlorthalidone
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Chlorthalidone 25 mg 4 times per week titrated to 25 mg daily
Other intervention name(s): Lopressor; Toprol XL; Thalitone
Intervention MeSH terms: Metoprolol; Chlorthalidone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hypertension; antihypertensive drug; pharmacogenetics; genetics; blood pressure; glucose