Allopurinol Improves Heart Function in African Americans With Resistant Hypertension

NCT05888233 | Completed Phase 2 FDA Drug

• 2 other identifiers: F4655-PI21RX004655-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

African American adults in the United States have the highest prevalence rate of high blood pressure (hypertension) and heart failure in the world. African Americans with treatment resistant hypertension have higher levels of the enzyme - xanthine oxidase compared to Caucasians. This trial will test if administration of the xanthine oxidase inhibitor - Allopurinol (commonly used in the treatment of gout), given over a period of 8 weeks, will improve heart function, exercise ability and quality of life in African American Veterans with resistant hypertension.

Conditions

Resistant Hypertension; Heart Failure Preserved Ejection Fraction

Keywords

Hypertension; Xanthine Oxidase; African American; Black; Heart Failure

Outcome Measures

Primary Outcomes (9)

• Normalized peak early diastolic filling rate (E)

  Change from baseline in left ventricular diastolic function index: Normalized peak early diastolic filling rate (E) after 8-weeks of treatment with Allopurinol. (Range 1.5 - 3.0 end-diastolic velocity (EDV)/second)

  8 weeks

• Six minute walk test

  Change in exercise capacity by six minute walk test after 8-weeks of Allopurinol. Timed activity for distance walked (Distance range approximately 400-800 meters (m); Further distance = better outcome)

  8 weeks

• Self Reported health survey for Heart Failure

  Change in self reported quality of life measures using Kansas City Heart Failure Questionnaire (KCCQ-12) after 8-weeks of Allopurinol. Scale (Minimum - 0 ; Maximum - 100; High score = worse outcome)

  8 weeks

• Self reported Health Survey

  Change in self reported quality of life measures using the Quality of Life Medical Outcomes Study Questionnaire (SF 36 QOL) after 8-weeks of Allopurinol. Scale (Minimum - 0; Maximum - 100; High score = worse outcome)

  8 weeks

• Left ventricular end-diastolic volume index

  Change from baseline in left ventricular diastolic function index: left ventricular end diastolic volume normalized to body surface area after 8-weeks of treatment with Allopurinol. (Range 40 - 100 milliliters per square meter (mL/m2)

  8 weeks

• Left ventricular (LV) end-diastolic mass index

  Change from baseline in left ventricular diastolic function index: LV end-diastolic mass indexed to body surface area after 8-weeks of treatment with Allopurinol. (Range: 40-100 grams/square meter (m2)

  8 weeks

• Left ventricular (LV) end-diastolic fractional shortening

  Change from baseline in left ventricular diastolic function index: LV end-diastolic fractional shortening after 8-weeks of treatment with Allopurinol. (Range: 15-80%)

  8 weeks

• Left ventricular (LV) end-diastolic mid-wall radius to wall thickness ratio

  Change from baseline in left ventricular diastolic function index: LV end-diastolic mid-wall radius to wall thickness ratio. Ratio (no units; Range: 1.5-4.0).

  8 weeks

• Normalized peak late diastolic filling rate (A), EDV/s

  Change from baseline in left ventricular diastolic function index: Normalized peak late diastolic filling rate (A) after 8-weeks of treatment with Allopurinol. (Range 1.3 - 4.5 end-diastolic velocity (EDV)/second)

  8 weeks

Secondary Outcomes (5)

• Systolic Blood Pressure

  8 weeks

• Xanthine Oxidase

  8 weeks

• mitochondrial DNA damage-associated molecular patterns

  8 weeks

• Brain Natriuretic Peptide

  8 weeks

• Diastolic Blood Pressure

  8 weeks

Study Arms (1)

Allopurinol - African American Veterans

EXPERIMENTAL

Subjects will receive Allopurinol (300mg/daily) for 4 weeks. If tolerated, dose may be increased to 600 milligrams (mg)/daily for an additional 4 weeks. Subjects will take Allopurinol (300-600 milligrams (mg)/daily) for 8 weeks total

Drug: Allopurinol

Interventions

Allopurinol DRUG

Single arm of Allopurinol treatment for 300mg/daily for 4 weeks then may be increased to 600mg/daily for an additional 4 weeks.

Allopurinol - African American Veterans

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Veteran
• African American
• Resistant hypertension diagnosis (defined as blood pressure greater than 140/90 millimeters of mercury (mmHg) at 2 clinic visits despite the use of 3 antihypertensive medications at pharmacologically effective doses)
• Locale - Birmingham, AL and surrounding areas

You may not qualify if:

• History of heart failure
• Chronic kidney disease (estimated creatinine clearance \< 60 milliliters per minute (ml/min)
• Chronic steroid therapy
• Known coronary artery disease
• Known causes of secondary hypertension
• Already taking Allopurinol
• Claustrophobia
• Cardiac implantable electronic device (permanent pacemaker and/or intracardiac defibrillator)
• Metal clips and/devices or other item that specifically prohibit safe cardiovascular magnetic resonance imaging (CMR)

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

Location

MeSH Terms

Conditions

Heart Failure, Diastolic; Hypertension; Heart Failure

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Louis J Dell'Italia, MD

  Birmingham VA Medical Center, Birmingham, AL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This is an open label unblinded drug pilot study to determine whether Allopurinol improves left ventricular diastolic function, exercise capacity, and quality of life in African American Veterans with resistant hypertension after 8-weeks of treatment.

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: June 5, 2023
• Study Start: September 30, 2024
• Primary Completion: April 30, 2026
• Study Completion: August 31, 2026
• Last Updated: September 4, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)