Heart Failure With Reduced Ejection FractionPhase 2HFrEFNCT06195982
Ketones in Heart Failure With Reduced Ejection Fraction
A Phase 2 study testing ketone ester in people with Heart Failure With Reduced Ejection Fraction, run by Duke University at 1 site in United States.
Trial summary
The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- ketone ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2024to 27 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stable cardiovascular medical therapy for 2 weeks
- Participants will be required to have heart failure with reduced ejection fraction (left ventricular EF </= 45%) and New York Heart Association (NYHA) class II or III symptoms. In cases of ambiguity of functional status, reduced peak VO2 (<85% predicted VO2) at the baseline visit can be used to confirm reduced exercise tolerance.
Who cannot join
- Intentional ketogenic diet in the last week
- Cirrhosis or significant alcohol consumption
- 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 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: supplemental oxygen (aside from obstructive sleep apnea), chronic obstructive pulmonary disease requiring home oxygen or exacerbation within the last 2 months requiring steroids or antibiotics, severe obstructive lung disease (Gold stage 3).
- >/= Moderate aortic stenosis, >mild mitral stenosis, > moderate aortic or mitral regurgitation
- Type 1 diabetes mellitus
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- Implant of cardiac resynchronization therapy, cardiac contractility modulation, or barostim device within the previous 3 months.
- Systolic blood pressure <90 mmHg
- Pregnant women
- Angina due to epicardial coronary disease or known presence of clinically-significant, unrevascularized epicardial coronary disease, in the investigator's opinion.
- History of heart transplant, left ventricular assist device, or use of inotropic medication.
- Participation in another clinical study with an investigational product in the previous 4 weeks prior to enrollment.
- Conditions that may render the patient unable to complete the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Acute Effects of Ketones in Heart Failure With Reduced Ejection Fraction
The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur. This study is assessing whether the ketone drink can improve these symptoms. This drink has been given status by Food and Drug Administration as "generally regarded as safe".
The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.
- Being tested
- ketone ester, placebo
- Keywords
- heart failure, ketones, ketosis, metabolism, exercise
- Medical subject headings
- Heart Failure, Ketosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketone esterDietary supplement
Also called ketone drink, KE drink, KE therapy, DeltaG therapy
500 mg/kg of ketone ester administered approximately 1 hour prior to the maximal exercise testing and 250 mg/kg administered approximately 30 minutes prior to submaximal exercise testing
placeboDietary supplement
ketone-free placebo administered approximately 1 hour prior to the maximal exercise testing and ketone-free placebo administered approximately 30 minutes prior to submaximal exercise testing
| Study group | Role | What they receive |
|---|---|---|
| ketone ester | Experimental | (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester Receives: Dietary Supplement: ketone ester |
| placebo | Placebo comparator | KE-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: 60 minutes after the intervention
Submaximal exercise capacity
Exercise time at 75% of peak workload assessed by cardiopulmonary exercise testing
Measured: 30 minutes after the intervention
Secondary outcomes (4)
Left ventricular systolic function
Left ventricular ejection fraction measured during resting echocardiography.
Measured: Assessed 30 minutes after the intervention
Substrate utilization
Substrate utilization (reflected by the respiratory exchange ratio) assessed by cardiopulmonary exercise testing.
Measured: 60 minutes after the intervention
Left ventricular filling pressures
E/e' ratio measured during stress echocardiography
Measured: Assessed 60 minutes after the intervention
Vasodilation at rest
Total peripheral resistance measured at rest (calculated using cardiac output from echocardiography and brachial blood pressure)
Measured: 60 minutes after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2024
- Study start6 Mar 2024
- Primary completion27 Aug 2026
- Study completion27 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 With Reduced Ejection FractionStudies 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
- Overview: The overall study design will be a randomized, double-blind crossover comparison of ketone ester (KE) therapy vs. KE-free vehicle in 25 patients with established HF with reduced ejection fraction (HFrEF). The main outcomes will be measures of exercise performance (peak and submaximal exercise).
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Senthil Selvaraj, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06195982
- Sponsor's protocol ID
- Pro00111539
- Other IDs
- 1K23HL161348-01
- Acronym
- HFrEF
- Status last verified
- Aug 2026
- First submitted
- 14 Dec 2023
- Last updated
- 3 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 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Effects of Ketones in Heart Failure With Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT06195982
- Acronym / sponsor ID
- HFrEF / Pro00111539
- Keywords
- heart failure, ketones, ketosis, metabolism, exercise
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- American Heart Association, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 6 Mar 2024 (actual)
- Primary completion
- 27 Aug 2026 (actual)
- Study completion
- 27 Aug 2026 (actual)
- First posted
- 8 Jan 2024 (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.
The purpose of this study is to understand the effects of a ketone drink on exercise capacity and other cardiovascular parameters in patients with heart failure. In heart failure, patients are limited in their ability to do all the things they want to do, and exercise as much as they would like, due to becoming tired and short of breath early. There may be several reasons why these symptoms occur. This study is assessing whether the ketone drink can improve these symptoms. This drink has been given status by Food and Drug Administration as "generally regarded as safe".
The use of DeltaG in this study is experimental. DeltaG has not been approved by the Food and Drug Administration (FDA) for the use being evaluated in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Overview: The overall study design will be a randomized, double-blind crossover comparison of ketone ester (KE) therapy vs. KE-free vehicle in 25 patients with established HF with reduced ejection fraction (HFrEF). The main outcomes will be measures of exercise performance (peak and submaximal exercise).
| Arm | Type | Receives |
|---|---|---|
| ketone ester | Experimental | Dietary Supplement: ketone ester(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester |
| placebo | Placebo comparator | Dietary Supplement: placeboKE-free solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Stable cardiovascular medical therapy for 2 weeks
- Participants will be required to have heart failure with reduced ejection fraction (left ventricular EF </= 45%) and New York Heart Association (NYHA) class II or III symptoms. In cases of ambiguity of functional status, reduced peak VO2 (<85% predicted VO2) at the baseline visit can be used to confirm reduced exercise tolerance.
Key exclusion criteria (13 listed)
- Intentional ketogenic diet in the last week
- Cirrhosis or significant alcohol consumption
- 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 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: supplemental oxygen (aside from obstructive sleep apnea), chronic obstructive pulmonary disease requiring home oxygen or exacerbation within the last 2 months requiring steroids or antibiotics, severe obstructive lung disease (Gold stage 3).
- >/= Moderate aortic stenosis, >mild mitral stenosis, > moderate aortic or mitral regurgitation
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 |
|---|---|---|
| ketone esterAlso: ketone drink, KE drink, KE therapy, DeltaG therapy500 mg/kg of ketone ester administered approximately 1 hour prior to the maximal exercise testing and 250 mg/kg administered approximately 30 minutes prior to submaximal exercise testing | Dietary supplement | ketone ester |
| placeboketone-free placebo administered approximately 1 hour prior to the maximal exercise testing and ketone-free placebo administered approximately 30 minutes prior to submaximal exercise testing | Dietary supplement | placebo |
Primary outcome
Maximal exercise capacity
Time frame: 60 minutes after the intervention
Peak VO2 assessed by cardiopulmonary exercise testing
Submaximal exercise capacity
Time frame: 30 minutes after the intervention
Exercise time at 75% of peak workload assessed by cardiopulmonary exercise testing
4 secondary outcomes
Left ventricular systolic function
Time frame: Assessed 30 minutes after the intervention
Substrate utilization
Time frame: 60 minutes after the intervention
Left ventricular filling pressures
Time frame: Assessed 60 minutes after the intervention
Vasodilation at rest
Time frame: 60 minutes after the intervention
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 3 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Senthil Selvaraj, MD principal investigator
Duke University
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 ketone ester in people with Heart Failure With Reduced Ejection Fraction, run by Duke University 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 2 inclusion and 13 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 3 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. Some participants in this study may receive a placebo. 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?
Maximal exercise capacity (time frame: 60 minutes after the intervention). The study lists 2 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 3 Sep 2026.