Ketones in Heart Failure With Reduced Ejection Fraction

Heart Failure With Reduced Ejection Fraction Clinical Trial

— HFrEF  

Official title:

Acute Effects of Ketones in Heart Failure With Reduced Ejection Fraction

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06195982
• Other study ID #: Pro00111539
• Secondary ID: 1K23HL161348-01
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: March 6, 2024
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 25
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Dietary Supplement:
• 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
• 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

Locations

Country	Name	City	State
United States	Duke University	Durham	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Duke University	American Heart Association, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Heart rate variability	Heart rate variability at rest	Assessed 20 minutes after the intervention
Other	Right ventricular function	Right ventricular function (tricuspid annular planar systolic excursion) assessed by echocardiography at rest	Assessed 30 minutes after the intervention
Other	Oxygen pulse	Peak oxygen pulse measured during cardiopulmonary exercise testing	Assessed 60 minutes after the intervention
Other	Cardiac output	Cardiac output measured during stress echocardiography	Assessed 60 minutes after the intervention
Other	Left ventricular filling pressures	E/e' ratio measured during stress echocardiography	Assessed 60 minutes after the intervention
Other	Pulse wave velocity	Pulse wave velocity measured by arterial tonometry	Assessed 50 minutes after the intervention
Other	VO2 efficiency	VO2 efficiency (total work performed over oxygen consumed) during submaximal cardiopulmonary exercise testing	Assessed 30 minutes after the intervention
Primary	Maximal exercise capacity	Peak VO2 assessed by cardiopulmonary exercise testing	60 minutes after the intervention
Primary	Submaximal exercise capacity	Exercise time at 75% of peak workload assessed by cardiopulmonary exercise testing	30 minutes after the intervention
Secondary	Left ventricular systolic function	Left ventricular ejection fraction measured during resting echocardiography.	Assessed 30 minutes after the intervention
Secondary	Arterial stiffness	Central augmentation index measured during arterial tonometry	Assessed 50 minutes after the intervention
Secondary	Ventilatory efficiency	VE/VCO2 measured during cardiopulmonary exercise testing	Assessed 60 minutes after the intervention
Secondary	Anaerobic threshold	Anaerobic threshold measured during cardiopulmonary exercise testing	Assessed 60 minutes after the intervention