Clinical trial NCT06195982: Ketones in Heart Failure With Reduced Ejection Fraction
Official title: Acute Effects of Ketones in Heart Failure With Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: heart failure
ketones
ketosis
metabolism
exercise
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2024-01-08
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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).
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximal exercise capacity
timeFrame: 60 minutes after the intervention
measure: Submaximal exercise capacity
timeFrame: 30 minutes after the intervention
Secondary outcomes:
measure: Left ventricular systolic function
timeFrame: Assessed 30 minutes after the intervention
measure: Substrate utilization
timeFrame: 60 minutes after the intervention
measure: Left ventricular filling pressures
timeFrame: Assessed 60 minutes after the intervention
measure: Vasodilation at rest
timeFrame: 60 minutes after the intervention
Other outcomes:
measure: Right ventricular function
timeFrame: Assessed 30 minutes after the intervention
measure: Cardiac output
timeFrame: Assessed 60 minutes after the intervention
measure: Vasodilation during exercise
timeFrame: 60 minutes after the intervention
measure: Pulse wave velocity
timeFrame: Assessed 50 minutes after the intervention
measure: VO2 efficiency
timeFrame: Assessed 30 minutes after the intervention
measure: Arterial stiffness
timeFrame: Assessed 50 minutes after the intervention
measure: Anaerobic threshold
timeFrame: Assessed 60 minutes after the intervention
measure: Pulmonary artery pressure
timeFrame: Assessed 60 minutes after the intervention
measure: Ventilatory efficiency
timeFrame: Assessed 60 minutes after the intervention
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Senthil Selvaraj, MD
role: PRINCIPAL_INVESTIGATOR
References: