Ketones in Heart Failure With Reduced Ejection Fraction (HFrEF)

Duke University

Status and phase: Invitation-only; Phase 2

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Dietary Supplement: ketone ester; Dietary Supplement: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06195982

1K23HL161348-01 (U.S. NIH Grant/Contract)

Pro00111539

Details and patient eligibility

About

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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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25 participants in 2 patient groups, including a placebo group

ketone ester

Experimental group

Description:

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

Treatment:

Dietary Supplement: ketone ester

placebo

Placebo Comparator group

Description:

KE-free solution

Treatment:

Dietary Supplement: placebo