Allopurinol Improves Heart Function in African Americans With Resistant Hypertension

NCT ID: NCT05888233

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2026-05-31

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.

Detailed Description

Hypertension among African American adults in the United States has one of the highest prevalence rates in the world and is related to adverse changes in left ventricular (LV) structure and function. Hypertension is an underlying factor in greater than 50% of African American adults with heart failure and is the strongest risk factor in that population. African American adults have a 50% increased incidence of heart failure, due in large part due to the greater prevalence and severity of hypertension.

Heart failure occurs 8 years earlier in African American adults compared with Caucasians. Further, African American adults with heart failure have worse quality of life and depressive symptoms and have a 5-year mortality rate that is 34% higher than in Caucasians. Although African American adults have the highest death rate for heart failure, they are consistently under-represented in clinical trials. The greater heart failure burden among African Americans calls for further work to discover effective preventive and therapeutic strategies for this higher-risk population with heart failure preserved ejection fraction (HFpEF).

An estimated 10-20% of hypertensive patients have resistant hypertension (RHTN), defined as having controlled or uncontrolled blood pressure with the use of 3 or more medications that includes a diuretic. A recent study reported increased plasma xanthine oxidase (XO) activity and mitochondrial DNA damage associated molecular products (mtDAMPs) levels in African American adults with RHTN, compared with Caucasian adults with RHTN. This supports the consensus that oxidative stress is higher in African American adults. Increased xanthine oxidase in heart muscle cells causes a breakdown of muscle structure and a decrease in calcium sensitivity, resulting in left ventricular (LV) dysfunction. A recent study shows that diastolic blood pressure, and other indices of LV diastolic function positively relate to xanthine oxidase activity among African American but not Caucasian RHTN patients.

Given the higher level of xanthine oxidase activity and mtDAMPs in African Americans, the purpose of this clinical trial is to test whether blockade with Allopurinol (for 8 weeks) will improve LV diastolic function, exercise capacity and quality of life metrics in 50 African American Veterans with resistant hypertension.

Conditions

Heart Failure Preserved Ejection Fraction; Resistant Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Allopurinol - African American Veterans

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

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

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

Interventions

Allopurinol

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Veteran

2. African American

3. Resistant hypertension diagnosis (defined as blood pressure greater than 140/90 mmHg at 2 clinic visits despite the use of 3 antihypertensive medications at pharmacologically effective doses)

4. Locale - Birmingham, AL and surrounding areas

Exclusion Criteria

1. History of heart failure

2. Chronic kidney disease (estimated creatinine clearance < 60 ml/min)

3. Chronic steroid therapy

4. Known coronary artery disease

5. Known causes of secondary hypertension

6. Already taking Allopurinol

Magnetic Resonance Imaging Exclusion

1. Claustrophobia

2. Cardiac implantable electronic device (permanent pacemaker and/or intracardiac defibrillator)

3. Metal clips and/devices or other item that specifically prohibit safe CMR

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Louis J Dellitalia, MD

Role: PRINCIPAL_INVESTIGATOR

Birmingham VA Medical Center, Birmingham, AL

Locations

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Louis J Dellitalia, MD

Role: CONTACT

Louis.Dellitalia@va.gov

(205) 933-8101 ext. 4729

Betty M Pat, PhD

Role: CONTACT

Betty.Pat@va.gov

(205) 612-7339

Facility Contacts

Kallie Chauncey

Role: primary

kallie.chauncey@va.gov

205-933-8101 ext. 5211

Betty M Pat, PhD

Role: backup

Betty.Pat@va.gov

(205) 612-7339

Other Identifiers

I21RX004655-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

F4655-P

Identifier Type: -

Identifier Source: org_study_id