Ketones in Heart Failure With Reduced Ejection Fraction

NCT06195982 | Enrolling By Invitation Phase 2 FDA Drug

• 2 other identifiers: Pro001115391K23HL161348-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Keywords

heart failure; ketones; ketosis; metabolism; exercise

Outcome Measures

Primary Outcomes (2)

• Maximal exercise capacity

  Peak VO2 assessed by cardiopulmonary exercise testing

  60 minutes after the intervention

• Submaximal exercise capacity

  Exercise time at 75% of peak workload assessed by cardiopulmonary exercise testing

  30 minutes after the intervention

Secondary Outcomes (4)

• Left ventricular systolic function

  Assessed 30 minutes after the intervention

• Substrate utilization

  60 minutes after the intervention

• Left ventricular filling pressures

  Assessed 60 minutes after the intervention

• Vasodilation at rest

  60 minutes after the intervention

Other Outcomes (9)

• Right ventricular function

  Assessed 30 minutes after the intervention

• Cardiac output

  Assessed 60 minutes after the intervention

• Vasodilation during exercise

  60 minutes after the intervention

Study Arms (2)

ketone ester

EXPERIMENTAL

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

Dietary Supplement: ketone ester

placebo

PLACEBO COMPARATOR

KE-free solution

Dietary Supplement: placebo

Interventions

ketone ester 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

Also known as: ketone drink, KE drink, KE therapy, DeltaG therapy, ketone therapy

ketone ester

placebo 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

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Duke University: lead
• American Heart Association: collaborator
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Heart Failure; Ketosis; Motor Activity

Interventions

formic acid 4-(3-oxobutyl)phenyl ester

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Study Officials

• Senthil Selvaraj, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: December 14, 2023
• First Posted: January 8, 2024
• Study Start: March 6, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)