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Completed

NCT Number: NCT06195982

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.

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Key information

Conditions

Heart Failure With Reduced Ejection Fraction Acid-Base Imbalance Acidosis Behavior Cardiovascular Diseases Heart Diseases Heart Failure Ketosis Metabolic Diseases Motor Activity Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Duke University

Durham, North Carolina, 27710, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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

Treatment and study plan

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

Other names: ketone drink, KE drink, KE therapy, DeltaG therapy, ketone therapy

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

Primary outcomes

  1. Maximal exercise capacity

    Time frame: 60 minutes after the intervention

    Peak VO2 assessed by cardiopulmonary exercise testing

  2. Submaximal exercise capacity

    Time frame: 30 minutes after the intervention

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

Secondary outcomes

  1. Left ventricular systolic function

    Time frame: Assessed 30 minutes after the intervention

    Left ventricular ejection fraction measured during resting echocardiography.

  2. Substrate utilization

    Time frame: 60 minutes after the intervention

    Substrate utilization (reflected by the respiratory exchange ratio) assessed by cardiopulmonary exercise testing.

  3. Left ventricular filling pressures

    Time frame: Assessed 60 minutes after the intervention

    E/e' ratio measured during stress echocardiography

  4. Vasodilation at rest

    Time frame: 60 minutes after the intervention

    Total peripheral resistance measured at rest (calculated using cardiac output from echocardiography and brachial blood pressure)

Other outcomes

  1. Right ventricular function

    Time frame: Assessed 30 minutes after the intervention

    Right ventricular function (tricuspid annular planar systolic excursion) assessed by echocardiography at rest

  2. Cardiac output

    Time frame: Assessed 60 minutes after the intervention

    Cardiac output measured during stress echocardiography

  3. Vasodilation during exercise

    Time frame: 60 minutes after the intervention

    Total peripheral resistance measured during cardiopulmonary exercise testing

  4. Pulse wave velocity

    Time frame: Assessed 50 minutes after the intervention

    Pulse wave velocity measured by arterial tonometry

  5. VO2 efficiency

    Time frame: Assessed 30 minutes after the intervention

    VO2 efficiency (total work performed over oxygen consumed) during submaximal cardiopulmonary exercise testing

  6. Arterial stiffness

    Time frame: Assessed 50 minutes after the intervention

    Central augmentation index measured during arterial tonometry

  7. Anaerobic threshold

    Time frame: Assessed 60 minutes after the intervention

    Anaerobic threshold measured during cardiopulmonary exercise testing

  8. Pulmonary artery pressure

    Time frame: Assessed 60 minutes after the intervention

    Pulmonary artery systolic pressure assessed through echocardiography during cardiopulmonary exercise testing

  9. Ventilatory efficiency

    Time frame: Assessed 60 minutes after the intervention

    Ratio of minute ventilation to carbon dioxide production measured during cardiopulmonary exercise testing

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • American Heart Association
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Institutes of Health (NIH)

Registry information

Official study title

Acute Effects of Ketones in Heart Failure With Reduced Ejection Fraction

Acronym: HFrEF

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Jan 8, 2024
Registry last updated
Aug 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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