Heart Failure Preserved Ejection FractionPhase 2RESISTNCT05888233
Allopurinol Improves Heart Function in African Americans With Resistant Hypertension
A Phase 2 study testing Allopurinol in people with Heart Failure Preserved Ejection Fraction and Resistant Hypertension, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Failure Preserved Ejection Fraction, Resistant Hypertension
- What is being tested?
- Allopurinol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2024to 31 Aug 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- Magnetic Resonance Imaging Exclusion
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233-1927
About this study
Official title: Allopurinol Improves Diastolic Function in African Americans With Resistant Hypertension
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.
Read the 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.
- Being tested
- Allopurinol
- Keywords
- Hypertension, Xanthine Oxidase, African American, Black, Heart Failure
- Medical subject headings
- Heart Failure, Diastolic, Hypertension, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AllopurinolDrug
Single arm of Allopurinol treatment for 300mg/daily for 4 weeks then may be increased to 600mg/daily for an additional 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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%)
Measured: 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).
Measured: 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)
Measured: 8 weeks
Secondary outcomes (5)
Systolic Blood Pressure
Change in systolic blood pressure after 8 weeks of Allopurinol. Range: 120-200 millimeters of mercury (mmHg)
Measured: 8 weeks
Xanthine Oxidase
Change in systemic levels of xanthine oxidase (range - Xanthine oxidase activity, U/mg protein - Range 0 - 0.1)
Measured: 8 weeks
mitochondrial DNA damage-associated molecular patterns
Change in systemic levels of mitochondrial DNA damage-associated molecular patterns (range 0-5000 copies/uL)
Measured: 8 weeks
Brain Natriuretic Peptide
Change in systemic levels of brain natriuretic peptide (BNP) after 8 weeks of Allopurinol (Scale 0 to > 100 pgmL; Minimum 0; Maximum >100).
Measured: 8 weeks
Diastolic Blood Pressure
Change in diastolic blood pressure after 8 weeks of Allopurinol. Range: 70-110 millimeters of mercury (mmHg)
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2023
- Study start30 Sep 2024
- Primary completion30 Apr 2026
- Study completion31 Aug 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Louis J Dell'Italia, MD, Principal investigator, Birmingham VA Medical Center, Birmingham, AL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05888233
- Sponsor's protocol ID
- F4655-P
- Other IDs
- I21RX004655-01
- Acronym
- RESIST
- Status last verified
- Aug 2026
- First submitted
- 2 May 2023
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allopurinol Improves Diastolic Function in African Americans With Resistant Hypertension
- ClinicalTrials.gov ID
- NCT05888233
- Acronym / sponsor ID
- RESIST / F4655-P
- Keywords
- Hypertension, Xanthine Oxidase, African American, Black, Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 30 Sep 2024 (actual)
- Primary completion
- 30 Apr 2026 (actual)
- Study completion
- 31 Aug 2026 (actual)
- First posted
- 5 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Allopurinol - African American Veterans | Experimental | Drug: AllopurinolSubjects 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AllopurinolSingle arm of Allopurinol treatment for 300mg/daily for 4 weeks then may be increased to 600mg/daily for an additional 4 weeks. | Drug | Allopurinol - African American Veterans |
Primary outcome
Normalized peak early diastolic filling rate (E)
Time frame: 8 weeks
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)
Six minute walk test
Time frame: 8 weeks
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)
Self Reported health survey for Heart Failure
Time frame: 8 weeks
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)
Self reported Health Survey
Time frame: 8 weeks
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)
Left ventricular end-diastolic volume index
Time frame: 8 weeks
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)
Left ventricular (LV) end-diastolic mass index
Time frame: 8 weeks
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)
Left ventricular (LV) end-diastolic fractional shortening
Time frame: 8 weeks
Change from baseline in left ventricular diastolic function index: LV end-diastolic fractional shortening after 8-weeks of treatment with Allopurinol. (Range: 15-80%)
Left ventricular (LV) end-diastolic mid-wall radius to wall thickness ratio
Time frame: 8 weeks
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).
Normalized peak late diastolic filling rate (A), EDV/s
Time frame: 8 weeks
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)
5 secondary outcomes
Systolic Blood Pressure
Time frame: 8 weeks
Xanthine Oxidase
Time frame: 8 weeks
mitochondrial DNA damage-associated molecular patterns
Time frame: 8 weeks
Brain Natriuretic Peptide
Time frame: 8 weeks
Diastolic Blood Pressure
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Individual participant dataSharing planned: No
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Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis J Dell'Italia, MD principal investigator
Birmingham VA Medical Center, Birmingham, AL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allopurinol in people with Heart Failure Preserved Ejection Fraction and Resistant Hypertension, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normalized peak early diastolic filling rate (E) (time frame: 8 weeks). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.