Clinical trial NCT02038179: Center of Research Translation (CORT) Project 2
Official title: University of Alabama at Birmingham CORT Project 2: The Effects of Urate Lowing Therapy (ULT) in Inflammation, Endothelial Function, and Blood Pressure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pre-hypertension
JNC 7 Stage I Hypertension
Keywords: Pre-hypertension
JNC 7 stage I hypertension
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2014-01-16
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Systolic Blood Pressure (SBP)
timeFrame: 4 weeks (pre-treatment vs. post-treatment SBP)
measure: Change in Flow-mediated Arterial Vasodilation
timeFrame: 4 weeks (pre-treatment vs. post-treatment FMD Values (%))
measure: Change in Serum Levels of High Sensitivity C-reactive Protein
timeFrame: 4 weeks (pre-treatment vs. post-treatment serum levels)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
References:
citation: Shaffer A, Rahn E, Saag K, Mudano A, Gaffo A. Variation in serum urate levels in the absence of gout and urate lowering therapy. BMC Rheumatol. 2021 Sep 8;5(1):32. doi: 10.1186/s41927-021-00202-6.
citation: Gaffo AL, Calhoun DA, Rahn EJ, Oparil S, Li P, Dudenbostel T, Feig DI, Redden DT, Muntner P, Foster PJ, Biggers-Clark SR, Mudano A, Sattui SE, Saddekni MB, Bridges SL Jr, Saag KG. Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial. Arthritis Rheumatol. 2021 Aug;73(8):1514-1522. doi: 10.1002/art.41749. Epub 2021 Jun 5.