Center of Research Translation (CORT) Project 2

Study Overview
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Brief Summary
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We propose a novel intervention for reducing BP that could have a preferential impact in patients with hyperuricemia and gout. There is a great need for new anti-hypertensives, particularly among those with gout. The proposed study is novel in its plans to investigate the physiologic mechanisms through which urate contributes to vascular disease and by which ULT may contribute to BP reduction. Also innovative, we will: 1) determine to what extent the described benefit of lowering serum urate extends beyond the adolescent population previously studied into young adults, 2) test whether a urate-lowering approach will benefit individuals that do not yet meet the current definition of hyperuricemia and do not have gout, and 3) begin to explore potential mechanisms for the higher prevalence of hypertension among African-Americans. If successful, this work could translate to the standard of clinical care and to health care recommendations for the population as a whole.

Official Title
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University of Alabama at Birmingham CORT Project 2: The Effects of Urate Lowing Therapy (ULT) in Inflammation, Endothelial Function, and Blood Pressure

Conditions
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Pre-hypertension, JNC 7 Stage I Hypertension

Intervention / Treatment
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* Drug: Allopurinol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-hypertension or stage I hypertension, defined as the following after the mean of two clinic measurements: Systolic blood pressure (SBP) ≥ 120 and <160 or; Diastolic blood pressure (DBP) ≥ 80 and < 100 Serum urate ≥ 5.0 mg/dL for men or ≥ 4.0 mg/dL for women Age 18-40 Exclusion Criteria: Any current pharmacological treatment for hypertension, including diuretics (calcium channel blockers at stable doses were later allowed) Estimated glomerular filtration rate < 60 mL/min/1.73m2 Current use of any urate-lowering therapy or statins Prior diagnosis of gout or past use of urate-lowering therapy for gout Prior diagnosis of diabetes Pregnancy, or recent delivery or last trimester pregnancy loss more recent than 3 months Active smokers Immune-suppressed individuals including transplant recipients or current use of azathioprine. Leucopenia with absolute white cell count < 3000 /mL, anemia with hemoglobin < 12 g/dL, or thrombocytopenia with platelet count < 150,000/mL Individuals of Han Chinese or Thai descent with HLAB5801 genetic phenotype Serious medical condition that at investigator's judgment precludes utilization of a fixed dose of allopurinol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allopurinol, Then Placebo<br>Participants will be asked to take 4 weeks of allopurinol (300 mg oral per day), then will crossover (after 2-4 week washout period) and take placebo for an additional 4 weeks. | Drug: Allopurinol<br>* Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.<br>Drug: Placebo<br>* Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.<br>|
| Experimental: Placebo, Then Allopurinol<br>Participants will be asked to take 4 weeks of placebo, then will crossover (after 2-4 week washout period) and take allopurinol (300 mg oral per day) for an additional 4 weeks. | Drug: Allopurinol<br>* Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.<br>Drug: Placebo<br>* Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Systolic Blood Pressure (SBP) | Compare systolic blood pressure (SBP) captured by wearing a 24 hour ambulatory blood pressure monitor during each phase of treatment (allopurinol 300 mg/day PO or placebo). Change in systolic blood pressure is calculated by comparing SBP at the end of each treatment phase to pre-treatment values. | 4 weeks (pre-treatment vs. post-treatment SBP) | 
| Change in Flow-mediated Arterial Vasodilation | Compare endothelial function as indexed by flow-mediated arterial vasodilation (FMD) within each phase of treatment (allopurinol 300 mg/day PO or placebo). Percent (%) change in FMD is calculated by comparing FMD (%) at the end of each treatment phase to pre-treatment values. | 4 weeks (pre-treatment vs. post-treatment FMD Values (%)) | 
| Change in Serum Levels of High Sensitivity C-reactive Protein | Serum level of high sensitivity C-reactive protein will be reported as a change during treatment phase (allopurinol 300 mg/day PO or placebo). Change in serum level of C-reactive protein is calculated by comparing serum values at the end of each treatment phase to pre-treatment levels. | 4 weeks (pre-treatment vs. post-treatment serum levels) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-hypertension, JNC 7 stage I hypertension