Clinical trial NCT05888233: Allopurinol Improves Heart Function in African Americans With Resistant Hypertension
Official title: Allopurinol Improves Diastolic Function in African Americans With Resistant Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Failure Preserved Ejection Fraction
Resistant Hypertension
Keywords: Hypertension
Xanthine Oxidase
African American
Black
Heart Failure
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2023-06-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Normalized peak early diastolic filling rate (E)
timeFrame: 8 weeks
measure: Six minute walk test
timeFrame: 8 weeks
measure: Self Reported health survey for Heart Failure
timeFrame: 8 weeks
measure: Self reported Health Survey
timeFrame: 8 weeks
measure: Left ventricular end-diastolic volume index
timeFrame: 8 weeks
measure: LV end-diastolic mass index
timeFrame: 8 weeks
measure: LV end-diastolic fractional shortening
timeFrame: 8 weeks
measure: LV end-diastolic mid-wall radius to wall thickness ratio
timeFrame: 8 weeks
measure: Normalized peak late diastolic filling rate (A), EDV/s
timeFrame: 8 weeks
Secondary outcomes:
measure: Systolic Blood Pressure
timeFrame: 8 weeks
measure: Xanthine Oxidase
timeFrame: 8 weeks
measure: mitochondrial DNA damage-associated molecular patterns
timeFrame: 8 weeks
measure: Brain Natriuretic Peptide
timeFrame: 8 weeks
measure: Diastolic Blood Pressure
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham VA Medical Center, Birmingham, AL
state: Alabama
Study officials:
affiliation: Birmingham VA Medical Center, Birmingham, AL
name: Louis J Dellitalia, MD
role: PRINCIPAL_INVESTIGATOR
References: