Center of Research Translation (CORT) Project 2

January 7, 2021 updated by: Kenneth Saag, MD, MSc, University of Alabama at Birmingham

University of Alabama at Birmingham CORT Project 2: The Effects of Urate Lowing Therapy (ULT) in Inflammation, Endothelial Function, and Blood Pressure

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 weeks (pre-treatment vs. post-treatment SBP)
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.
4 weeks (pre-treatment vs. post-treatment FMD Values (%))
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.
4 weeks (pre-treatment vs. post-treatment serum levels)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

August 1, 2018

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

December 20, 2013

First Submitted That Met QC Criteria

January 14, 2014

First Posted (Estimate)

January 16, 2014

Study Record Updates

Last Update Posted (Actual)

January 11, 2021

Last Update Submitted That Met QC Criteria

January 7, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F130408004
  • P50AR060772 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pre-hypertension

Clinical Trials on Allopurinol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Italy

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe