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Center of Research Translation (CORT) Project 2

Primary Purpose

Pre-hypertension, JNC 7 Stage I Hypertension

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Allopurinol

Placebo

About this trial

This is an interventional treatment trial for Pre-hypertension focused on measuring Pre-hypertension, JNC 7 stage I hypertension

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

University of Alabama at Birmingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Allopurinol, Then Placebo

Placebo, Then Allopurinol

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02038179

First Posted

December 20, 2013

Last Updated

January 7, 2021

Sponsor

University of Alabama at Birmingham

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02038179

Brief Title

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

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

July 2014 (undefined)

Primary Completion Date

August 2018 (Actual)

Study Completion Date

August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Alabama at Birmingham

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pre-hypertension, JNC 7 Stage I Hypertension

Keywords

Pre-hypertension, JNC 7 stage I hypertension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

99 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Allopurinol, Then Placebo

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo, Then Allopurinol

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Allopurinol

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in Systolic Blood Pressure (SBP)

Description

Time Frame

4 weeks (pre-treatment vs. post-treatment SBP)

Title

Change in Flow-mediated Arterial Vasodilation

Description

Time Frame

4 weeks (pre-treatment vs. post-treatment FMD Values (%))

Title

Change in Serum Levels of High Sensitivity C-reactive Protein

Description

Time Frame

4 weeks (pre-treatment vs. post-treatment serum levels)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

University of Alabama at Birmingham

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34493347

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.

Results Reference

derived

PubMed Identifier

33779064

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.

Results Reference

derived

Learn more about this trial

Center of Research Translation (CORT) Project 2

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