Center of Research Translation (CORT) Project 2

NCT02038179 | Completed Phase 2 Results DMC

• 2 other identifiers: F130408004P50AR060772
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

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

Keywords

Pre-hypertension; JNC 7 stage I hypertension

Outcome Measures

Primary Outcomes (3)

• 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)

Study Arms (2)

Allopurinol, Then Placebo

EXPERIMENTAL

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; Drug: Placebo

Placebo, Then Allopurinol

EXPERIMENTAL

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; Drug: Placebo

Interventions

Allopurinol 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.

Allopurinol, Then Placebo; Placebo, Then Allopurinol

Placebo DRUG

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

Allopurinol, Then Placebo; Placebo, Then Allopurinol

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (2)

• 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.

  PMID: 34493347 DERIVED

• 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.

  PMID: 33779064 DERIVED

MeSH Terms

Conditions

Prehypertension

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Elizabeth Rahn
• Organization: University of Alabama at Birmingham

elizabethrahn@uabmc.edu

205-996-6552

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 20, 2013
• First Posted: January 16, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: January 11, 2021
• Results First Posted: February 26, 2020

Record last verified: 2021-01

Locations

US (1)