Center of Research Translation (CORT) Project 2

NCT ID: NCT02038179

Last Updated: 2021-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2018-08-31

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.

Conditions

Pre-hypertension; JNC 7 Stage I Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.

Placebo

Intervention Type: DRUG

Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.

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.

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Participants who received allopurinol as urate lowering therapy, at a daily dose of 300 mg once daily by mouth for a 4 week duration.

Placebo

Intervention Type: DRUG

Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.

Interventions

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.

Intervention Type: DRUG

Placebo

Participants who received placebo tablet (matching Allopurinol 300 mg) daily by mouth for a 4 week duration.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

NIH

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Kenneth Saag, MD, MSc

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34493347 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33779064 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

P50AR060772

Identifier Type: NIH

Identifier Source: secondary_id

View Link

F130408004

Identifier Type: -

Identifier Source: org_study_id