Ketones in Heart Failure With Reduced Ejection Fraction

NCT ID: NCT06195982

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-06
• Study Completion Date: 2027-02-28

Brief 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 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.

Conditions

Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

ketone ester

(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester

Group Type: EXPERIMENTAL

ketone ester

Intervention Type: DIETARY_SUPPLEMENT

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

placebo

KE-free solution

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DIETARY_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

Interventions

ketone ester

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

Intervention Type: DIETARY_SUPPLEMENT

placebo

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

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

ketone drink; KE drink; KE therapy; DeltaG therapy; ketone therapy

Eligibility Criteria

Inclusion Criteria

1. Stable cardiovascular medical therapy for 2 weeks

2. 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.

Exclusion Criteria

1. Intentional ketogenic diet in the last week

2. Cirrhosis or significant alcohol consumption

3. 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).

4. 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).

5. >/= Moderate aortic stenosis, >mild mitral stenosis, > moderate aortic or mitral regurgitation

6. Type 1 diabetes mellitus

7. Implant of cardiac resynchronization therapy, cardiac contractility modulation, or barostim device within the previous 3 months.

8. Systolic blood pressure <90 mmHg

9. Pregnant women

10. Angina due to epicardial coronary disease or known presence of clinically-significant, unrevascularized epicardial coronary disease, in the investigator's opinion.

11. History of heart transplant, left ventricular assist device, or use of inotropic medication.

12. Participation in another clinical study with an investigational product in the previous 4 weeks prior to enrollment.

13. Conditions that may render the patient unable to complete the study

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

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senthil Selvaraj, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University

Durham, North Carolina, United States

Countries

United States

Other Identifiers

1K23HL161348-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00111539

Identifier Type: -

Identifier Source: org_study_id