Ketones in Heart Failure With Reduced Ejection Fraction

Phase 2

• Conditions: Heart Failure With Reduced Ejection Fraction
• Interventions: Dietary Supplement: ketone ester; Dietary Supplement: placebo

• Registration Number: NCT06195982
• Lead Sponsor: Duke University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-12-14
• Study First Submitted QC: 2023-12-26
• Study First Posted: 2024-01-08
• Study Start: 2024-03-06
• Status Verified: 2025-03
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2027-02
• Study Completion: 2027-02

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ketone ester	ketone ester	(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
placebo	placebo	KE-free solution

Primary Outcome Measures

Name	Time	Method
Submaximal exercise capacity	30 minutes after the intervention	Exercise time at 75% of peak workload assessed by cardiopulmonary exercise testing
Maximal exercise capacity	60 minutes after the intervention	Peak VO2 assessed by cardiopulmonary exercise testing

Secondary Outcome Measures

Name	Time	Method
Left ventricular systolic function	Assessed 30 minutes after the intervention	Left ventricular ejection fraction measured during resting echocardiography.
Substrate utilization	60 minutes after the intervention	Substrate utilization (reflected by the respiratory exchange ratio) assessed by cardiopulmonary exercise testing.
Left ventricular filling pressures	Assessed 60 minutes after the intervention	E/e' ratio measured during stress echocardiography
Vasodilation at rest	60 minutes after the intervention	Total peripheral resistance measured at rest (calculated using cardiac output from echocardiography and brachial blood pressure)

Trial Locations

Locations (1)

Duke University; 🇺🇸 Durham, North Carolina, United States