Heart Failure With Preserved Ejection Fraction (HFPEF)Phase 2NCT06937320
Chronic Exogenous Ketosis in HFpEF
A Phase 2 study testing Exogenous Ketone Drink in people with Heart Failure With Preserved Ejection Fraction (HFPEF) and Heart Failure With Normal Ejection Fraction, run by Duke University at 1 site in United States.
Trial summary
The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction (HFPEF), Heart Failure With Normal Ejection Fraction, Heart Failure, Diastolic
- What is being tested?
- Exogenous Ketone Drink
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jul 2025to Jun 2027
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older
- Stable medical therapy for at least 2 weeks
- New York Heart Association (NYHA) class symptoms II or III
- Left ventricular ejection fraction ≥ 50%
- Evidence for elevated filling pressures as follows (at least one of the following between a-d):
- Mitral early (E)/mitral septal tissue annular (e') velocity ratio > 8 on echocardiography in addition to one of the following:
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- Enlarged left atrium (LA>4.0 cm width or LA volume index >34 mL/m2)
- Chronic loop diuretic use for control of symptoms
- Elevated natriuretic peptides within the past year (NT-proBNP>125 pg/ml or BNP>35 pg/ml)
- Mitral E/e' ratio > 14 at rest or with exercise on echocardiography
- Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure >16 mm Hg or pulmonary capillary wedge pressure > 14 mmHg; or PCWP or LVEDP ≥ 25 mmHg with exercise)
- Prior episode of acute heart failure requiring IV diuretics with evidence of volume overload on exam or radiology, or evidence of elevated natriuretic peptides.
Who cannot join
- Intentional ketogenic (high fat, low carbohydrate) diet in the last week
- Cirrhosis or alcohol use disorder (>14 drinks/week).
- Contraindications to stress testing, conditions that limit exercise, and other clinically-significant causes of exertional limitation (claudication with peripheral artery disease, atrial fibrillation and heart rate >110 at rest, systolic blood pressure>180 mmHg or diastolic blood pressure>110 mmHg, infiltrative/hypertrophic/inflammatory cardiomyopathy, clinically significant pericardial disease, joint or neuromuscular disease that precludes exercise, acute coronary syndrome within the last 2 months, estimated glomerular filtration rate<20 mL/min/1.73 m2, and hemoglobin < 9 mg/dL).
- Clinically significant lung disease, defined as severe obstructive lung disease (Gold stage 3), a requirement for supplemental oxygen, or chronic obstructive pulmonary disease with an exacerbation requiring steroids or antibiotics within the last 2 months.
- > Moderate aortic stenosis, >mild mitral stenosis, > moderate aortic or mitral regurgitation on screening echocardiogram, or presence of a prosthetic valve in the mitral position.
- Type 1 diabetes mellitus
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- Start of a GLP-1 RA within the past 6 months.
- Pregnant women.
- Angina due to epicardial coronary disease or known presence of clinically-significant, unrevascularized epicardial coronary disease, in the investigator's opinion.
- Prior reduced LVEF to < 45% by echocardiography or cardiac MRI
- Participation in another clinical study with an investigational product in the previous 4 weeks prior to enrollment (or longer if deemed necessary by the investigator).
- Conditions that may render the patient unable to complete the study, in the opinion of the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Chronic Effects of Exogenous Ketone Administration in Heart Failure With Preserved Ejection Fraction
The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).
- Conditions
- Heart Failure With Preserved Ejection Fraction (HFPEF), Heart Failure With Normal Ejection Fraction, Heart Failure, Diastolic
- Being tested
- Exogenous Ketone Drink, Placebo
- Keywords
- heart failure, ketosis, exercise, chronic, ketones, metabolism, echocardiography, cardiopulmonary exercise test
- Medical subject headings
- Heart Failure, Diastolic, Heart Failure, Ketosis, Motor Activity, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exogenous Ketone DrinkDietary supplement
Also called (R)-1,3-butanediol, KetoneIQ, ketone
(R)-1,3-butanediol (BD, commercially available as "KetoneIQ") initially dosed 300 mg/kg BID (target dose 400 mg/kg grams BID if tolerated) for 8 weeks
PlaceboDietary supplement
equi-volume placebo administered for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Exogenous ketone drink | Experimental | (R)-1,3-butanediol (commercially obtained as "KetoneIQ") Receives: Dietary Supplement: Exogenous Ketone Drink |
| Placebo | Placebo comparator | ketone-free solution Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal exercise capacity
Peak VO2 assessed by cardiopulmonary exercise testing
Measured: 8 weeks
Secondary outcomes (6)
Respiratory exchange ratio
Respiratory exchange ratio (RER) during cardiopulmonary exercise testing at 25 watts
Measured: 8 weeks
Vasodilatory reserve
Percent change in total peripheral resistance from rest to peak exercise
Measured: 8 weeks
Left atrial volume index
Left atrial volume index measured by echocardiogram
Measured: 8 weeks
Resting E/e'
Resting E/e' on echocardiogram
Measured: 8 weeks
Heart failure-related health status
Heart failure-related health status using Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). Score range is from 0 to 100, with higher scores indicating better health status and lower scores indicating poorer health status.
Measured: 8 weeks
NT-proBNP
N-terminal pro-B-type natriuretic peptide levels measured in peripheral blood.
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 posted22 Apr 2025
- Study start28 Jul 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection Fraction (HFPEF)Studies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Randomised
- Intervention model
- Crossover
- Model description
- This is an 8-week randomized, crossover, double-blind, placebo-controlled trial to evaluate the effects of an exogenous ketone drink on peak VO2 in 20 patients with heart failure with preserved ejection fraction (HFpEF).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Senthil Selvaraj, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06937320
- Sponsor's protocol ID
- Pro00117625
- Status last verified
- Oct 2026
- First submitted
- 15 Apr 2025
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No