Center of Research Translation (CORT) Project 2

Phase 2

Completed

• Conditions: JNC 7 Stage I Hypertension; Pre-hypertension
• Interventions: Drug: Allopurinol; Drug: Placebo

• Registration Number: NCT02038179
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-20
• Study First Submitted QC: 2014-01-14
• Study First Posted: 2014-01-16
• Study Start: 2014-07
• Primary Completion: 2018-08
• Study Completion: 2018-08
• Disposition First Submitted: 2019-09-06
• Disposition First Submitted QC: 2019-09-23
• Disposition First Posted: 2019-10-09
• Results First Submitted: 2019-11-27
• Results First Submitted QC: 2020-02-12
• Results First Posted: 2020-02-26
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-07
• Last Update Posted: 2021-01-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 99

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Allopurinol, Then Placebo	Placebo	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.
Placebo, Then Allopurinol	Allopurinol	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.
Placebo, Then Allopurinol	Placebo	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.
Allopurinol, Then Placebo	Allopurinol	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.

Primary Outcome Measures

Name	Time	Method
Change in Flow-mediated Arterial Vasodilation	4 weeks (pre-treatment vs. post-treatment FMD Values (%))	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.
Change in Systolic Blood Pressure (SBP)	4 weeks (pre-treatment vs. post-treatment 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.
Change in Serum Levels of High Sensitivity C-reactive Protein	4 weeks (pre-treatment vs. post-treatment serum levels)	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.

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States