Uric Acid and Hypertension in African Americans
Condition: Cardiovascular Diseases; Heart Diseases; Hypertension
MeSH terms: Hypertension; Cardiovascular Diseases; Heart Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      This study will test the hypothesis that the administration of a xanthine oxidase inhibitor
      (allopurinol) will prevent thiazide-induced hyperuricemia, which will result in better blood
      pressure (BP) control in African Americans.
    

Detailed description: 
      Thiazide diuretics when used in the treatment of hypertension are associated with many
      metabolic side effects, including hyperuricemia, gout, insulin resistance, and
      hyperlipidemia. Each of these conditions is already highly prevalent in African Americans.
      Our hypothesis is that thiazide-induced hyperuricemia decreases the efficacy of thiazides in
      controlling BP, leads to endothelial dysfunction, and increases the incidence of insulin
      resistance and impaired glucose tolerance. This hypothesis will be tested in a randomized,
      double-blind, placebo-controlled clinical trial of 8-10 weeks duration in which a total of
      100 African American patients with hypertension will be enrolled, randomized, and treated as
      follows:

        1. Subjects with untreated stage I hypertension will receive chlorthalidone (25 mg/day) and
           potassium chloride (40 mEq/day) for 4 weeks. Serum potassium levels will be obtained
           after four weeks on chlorthalidone. If the level is below 3.5 mEg/L, a bolus of 40 mEq
           potassium 2 to 3 times daily will be given for 2 to 3 days, or as clinically indicated.
           A maintenance dose of 50 mEq will be initiated. After at least 7 days, they will then be
           randomized to add-on allopurinol (300 mg/day) or placebo. Treatment will continue for
           8-10 weeks with the chlorthalidone, potassium chloride, and allopurinol/placebo regimen.

        2. Subjects with hypertension controlled (i.e. BP <140/90) or no higher than stage 1
           hypertension (i.e., <160/100) on a single antihypertensive agent or two antihypertensive
           agents will be switched from their prior antihypertensive agent to chlorthalidone 25
           mg/day, and potassium chloride (40mEq/day) for 4 weeks. Serum potassium levels will be
           obtained after four weeks on chlorthalidone. If the level is below 3.5 mEg/L, a bolus of
           40 mEq potassium 2 to 3 times daily will be given for 2 to 3 days, or as clinically
           indicated. A maintenance dose of 50 mEq will be initiated. After at least 7 days, they
           will then be randomized to add-on allopurinol (300 mg/day) or placebo. Treatment will
           continue for 8-10 weeks with the chlorthalidone, potassium chloride, and
           allopurinol/placebo regimen.

      The allopurinol (or placebo) dose will be adjusted to achieve serum uric acid levels between
      4 and 5.5 mg/dL after 2 weeks on drug. All subjects will receive a low-sodium diet. The
      primary endpoint is reduction in systolic BP. Secondary endpoints measure endothelial
      function, ambulatory blood pressure, body composition, systemic inflammation, metabolic
      parameters, oxidant stress, and renal hemodynamics.
    

Intervention name(s): Allopurinol; Placebo; Chlorthalidone; Potassium chloride
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Allopurinol (300 mg capsule) was given for 8-10 weeks compared to placebo group after initial baseline testing. After two weeks on the Allopurinol, a serum uric acid level was obtained. If the uric acid level was greater than 5.5, the Allopurinol dosage was increased to 600mg (two 300 mg capsules)for the duration of the trial, 6-8 weeks.; Placebo capsule (matched in appearance for Allopurinol and labeled 300mg) was given for 8-10 weeks compared to the Allopurinol group after initial baseline testing. After two weeks on the placebo, a serum uric acid level was obtained. If the uric acid level was greater than 5.5, the placebo dosage was increased to 600mg (two 300 mg capsules)for the duration of the study, 6-8 weeks.; Chlorthalidone 25 mg was given daily for 5 weeks before baseline visit for testing and continued through out the study.; Potassium Chloride 40-50meq was given daily for 5 weeks before baseline visit for testing and continued through out the study.
Other intervention name(s): Zyloprim; sugar pill
Intervention MeSH terms: Allopurinol; Chlorthalidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment