Center of Research Translation (CORT) Project 2

• ClinicalTrials.gov Identifier: NCT02038179
• Recruitment Status: Completed
• First Posted: January 16, 2014
• Results First Posted: February 26, 2020
• Last Update Posted: January 11, 2021
• Sponsor: University of Alabama at Birmingham
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Information provided by (Responsible Party): Kenneth Saag, MD, MSc, University of Alabama at Birmingham

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pre-hypertension; JNC 7 Stage I Hypertension	Drug: Allopurinol; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: July 2014
• Actual Primary Completion Date: August 2018
• Actual Study Completion Date: August 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Allopurinol, Then 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.	Drug: Allopurinol; Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.; Drug: Placebo; Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.
Experimental: Placebo, Then 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.	Drug: Allopurinol; Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.; Drug: Placebo; Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.

Outcome Measures

Primary Outcome Measures :

1. Change in Systolic Blood Pressure (SBP) [ Time Frame: 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.
2. Change in Flow-mediated Arterial Vasodilation [ Time Frame: 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.
3. Change in Serum Levels of High Sensitivity C-reactive Protein [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

Sponsors and Collaborators

University of Alabama at Birmingham

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  Study Documents (Full-Text)

Documents provided by Kenneth Saag, MD, MSc, University of Alabama at Birmingham:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] April 12, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Kenneth Saag, MD, MSc, Professor of Medicine, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT02038179
• Other Study ID Numbers: F130408004; P50AR060772 ( U.S. NIH Grant/Contract )
• First Posted: January 16, 2014
• Results First Posted: February 26, 2020
• Last Update Posted: January 11, 2021
• Last Verified: January 2021

Keywords provided by Kenneth Saag, MD, MSc, University of Alabama at Birmingham:

Pre-hypertension; JNC 7 stage I hypertension

Additional relevant MeSH terms:

Hypertension; Prehypertension; Vascular Diseases; Cardiovascular Diseases; Allopurinol; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Free Radical Scavengers; Antioxidants; Protective Agents; Physiological Effects of Drugs