Acute Effects of Exogenous Ketone Ester Administration in Heart Failure

Heart Failure With Preserved Ejection Fraction Clinical Trial

Official title:

Acute Effects of Exogenous Ketone Ester Administration in Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04633460
• Other study ID #: 833870
• Status: Completed
• Phase: Phase 2
• Start date: October 6, 2020
• Est. completion date: October 16, 2023

Study information

• Verified date: October 2023
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test whether a ketone ester drink will improve exercise in people with heart failure (HF) compared to a placebo. In HF, 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.

There is some evidence that in addition to problems with the heart, patients with HF also have problems with their arteries and muscles that affect their ability to exercise. Ketones have been shown to improve exercise capacity in healthy volunteers, which may be related to effects on the heart function or on muscles. An infusion of ketones through an intravenous (IV) line has also been shown to significantly improve heart function, but whether a drink can produce similar improvements in HF patients is not known. 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: Completed
• Enrollment: 20
• Est. completion date: October 16, 2023
• Est. primary completion date: October 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion criteria:

1. Left ventricular ejection fraction = 50%

2. Evidence for elevated filling pressures as follows (at least one of the following between a-d):

a. Mitral early (E)/mitral septal tissue annular (e') velocity ratio > 8 in addition to one of the following: i. Large left atrium (LA>4.0 cm width or LA volume index >34 mL/m2) ii. Chronic loop diuretic use for control of symptoms iii. Elevated natriuretic peptides within the past year (NT-proBNP>125 pg/ml or BNP>35 pg/ml) b. Mitral E/e' ratio > 1441 at rest or with exercise c. Elevated invasively-determined filling pressures previously (resting left ventricular end-diastolic pressure >16 mm Hg or pulmonary capillary wedge pressure > 15 mmHg; or PCWP/LVEDP = 25 mmHg with exercise) d. Prior episode of acute heart failure requiring IV diuretics with evidence of volume overload on exam/radiology or elevated natriuretic peptides.

Exclusion Criteria

1. Intentional ketogenic (high fat, low carbohydrate) diet in the last week or use of ketogenic medications (SGLT2 inhibitors)

2. Significant liver disease (liver function tests > 3x upper limit of normal, cirrhosis) or alcohol abuse disorder (>14 drinks/week).

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/inflammatory cardiomyopathy, clinically significant pericardial disease, joint or neuromuscular disease that precludes exercise, acute coronary syndrome within the last 2 months, estimated glomerular filtration rate<30 mL/min/1.73 m2, and hemoglobin < 9 mg/dL).

4. Clinically significant lung disease. This would be defined by severe obstructive lung disease (Gold stage 3), a requirement for supplemental oxygen, or chronic obstructive pulmonary disease with an exacerbation requiring steroids or antibiotics within the last 2 months.

5. >= Moderate aortic stenosis, >mild mitral stenosis, >= moderate aortic or mitral regurgitation on screening echocardiogram

6. Type 1 diabetes mellitus

7. Pregnant women. Due to unknown affects of nutritional ketosis in pregnant women, pregnancy will be an exclusion. Accordingly, women of childbearing age with a menstrual cycle within the past year will be asked to submit a urine specimen for pregnancy testing.

8. Angina due to epicardial coronary disease or known presence of clinically-significant, unrevascularized epicardial coronary disease, in the investigator's opinion.

9. Prior reduced LVEF to < 45%

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Dietary Supplement:
• Ketone ester
A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
• placebo drink
KE free placebo drink

Locations

Country	Name	City	State
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Heart rate variability at rest		Assessed 20 minutes after the intervention.
Other	Left ventricular global longitudinal strain (%) assessed by echocardiography strain analysis at rest.		Assessed 30 minutes after the intervention.
Other	Exercise-induced extravascular lung water (B-lines) assessed during lung ultrasound with exercise.		Assessed 60 minutes after the intervention.
Other	VO2 kinetics (Tau) during submaximal cardiopulmonary exercise testing		Assessed 30 minutes after the intervention.
Other	Tissue Doppler velocity measured during rest echocardiography.		Assessed 30 minutes after the intervention.
Other	E/e' ratio measured during stress echocardiography.		Assessed 60 minutes after the intervention.
Primary	Maximal exercise capacity (peak VO2) assessed by cardiopulmonary exercise testing		Assessed 60 minutes after the intervention.
Primary	Submaximal exercise capacity (exercise time at 75% of peak workload) assessed by cardiopulmonary exercise testing.		Assessed 30 minutes after the intervention.
Secondary	Percent change in systemic vascular resistance with exercise		Assessed 60 minutes after the intervention.
Secondary	Substrate utilization (reflected by the respiratory exchange ratio) assessed by cardiopulmonary exercise testing.		Assessed 60 minutes after the intervention.
Secondary	VO2 efficiency (total work performed over oxygen consumed) during submaximal cardiopulmonary exercise testing.		Assessed 30 minutes after the intervention.
Secondary	Presence of exercise-induced arrhythmias (significant atrial or ventricular arrhythmias)		Assessed throughout the study visit date after the intervention is given.