Uric Acid and Hypertension in African Americans
Condition: Cardiovascular Diseases; Heart Diseases; Hypertension
MeSH terms: Hypertension; Cardiovascular Diseases; Heart Diseases
Intervention: Allopurinol; Placebo; Chlorthalidone; Potassium chloride
Intervention description: 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.
Intervention MeSH terms: Allopurinol; Chlorthalidone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  African American (including black individuals born in the Caribbean, Africa, Canada,
             etc.)

          -  Are either untreated with any antihypertensive agent, with an average sitting clinic
             BP of between 140/90 and 159/99 mm Hg OR subjects with hypertension controlled (i.e.
             BP less than 140/90) or no higher than stage 1 hypertension (i.e., less than 160/100)
             on a single antihypertensive agent or two antihypertensive agents (individuals on
             fixed dose ARB-diuretic or ACEI-diuretic combinations will also be considered as being
             on monotherapy for purposes of the study. Individuals on beta blockade or calcium
             channel blockade for coronary artery disease and/or arrhythmia will not be eligible
             for the study)

          -  Random spot urine protein/creatinine ratio of less than 0.5 (approximates a 24-hour
             urinary protein excretion of 500 mg/day)

          -  Calculated MDRD GFR of greater than or equal to 60 ml/min/1.73/m^2

          -  No allopurinol or probenecid intake for at least one month prior to study entry

          -  Willing and able to cooperate with study procedures

          -  Willing to travel to the GCRC at Shands Hospital for overnight inpatient stays on two
             separate occasions

        Exclusion Criteria:

          -  History of malignant or accelerated hypertension

          -  Confirmed total white cell count of less than 2,500/mm^3, anemia, or thrombocytopenia

          -  Known history of liver disease

          -  Known secondary cause of hypertension

          -  Known presence of diabetes or fasting blood glucose greater than or equal to 126 mg/dL

          -  History of heart failure, acute myocardial infarction, or stroke or on a β-blocker or
             calcium channel blocker for cardiovascular indications other than for lowering blood
             pressure

          -  Abnormal EKG requiring medical intervention

          -  History of clinical or renal biopsy or evidence of renal parenchymal disease

          -  Acute gout attack within 2 weeks of study entry

          -  History of drug abuse in the last 2 years, including narcotics, cocaine, or alcohol
             (greater than 21 drinks/week)

          -  Arm circumference of greater than 52 cm, which precludes measurement with a 'thigh' BP
             cuff

          -  History of a reaction to allopurinol or chlorthalidone

          -  Pregnant or planning to become pregnant during the study, or breastfeeding

          -  History of noncompliance, are unable to comply with the study requirements, or who are
             currently participating in another study

          -  Not fasting prior to obtaining screening laboratory data. If a participant has clearly
             not fasted, we will exclude those individuals with casual blood glucose levels of
             greater than or equal to 200 mg/dL. In the event that a fasting blood sugar exceeds
             126 mg/dL, it will be reconfirmed on a blood glucose measurement obtained on a
             subsequent day, per American Diabetes Association criteria