Ketone Supplement for Heart Failure

Recruiting in Palo Alto (17 mi)

Overseen by Yuchi Han, MD, MMSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Ohio State University

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type I diabetes, Severe kidney disease, Recent myocardial infarction, others

Trial Summary

What is the purpose of this trial?

This study is being done to evaluate how a ketone ester (KE) beverage affects heart function and health in people with heart failure compared to a placebo beverage (a beverage made with standard food ingredients that do not contain ketone esters).

Will I have to stop taking my current medications?

The trial requires that your current heart and diabetes medications have been stable for at least 3 months before joining, and the dosage should not change for 1 month before starting. However, you can reduce or stop these medications during the study if needed. Changes in oral diuretics are allowed but must be stable for 1 week before starting the trial.

What data supports the effectiveness of the treatment Ketone Ester for heart failure?

Research suggests that ketone esters can improve heart function in heart failure by providing an additional energy source for the heart, which is often energy-starved in this condition. Studies in animals and some human trials have shown that increasing ketone levels can help the heart work better, especially in heart failure with reduced ejection fraction (a measure of how well the heart pumps blood). ^{1 2 3 4 5}

Is the ketone supplement safe for humans?

Research shows that ketone supplements, like ketone esters, are generally safe and well-tolerated in healthy adults, with no significant changes in vital signs or lab tests, although mild nausea was occasionally reported. ^{1 6 7 8 9}

How is the ketone ester treatment different from other heart failure treatments?

Ketone ester treatment is unique because it provides an additional energy source for the heart by increasing ketone body levels, which can improve heart function in heart failure. Unlike traditional treatments that focus on neurohormonal and hemodynamic factors, this approach targets the heart's metabolism directly, potentially offering benefits in cases where other treatments may not be as effective. ^{1 2 3 4 10}

Research Team

Yuchi Han, MD, MMSc

Principal Investigator

Ohio State University

Eligibility Criteria

Adults aged 18-80 with heart failure, BMI of 25-50 or Type II Diabetes/prediabetes, stable heart and diabetes medications for at least 3 months, and able to do treadmill tests. Excludes those with recent major surgeries, certain heart conditions like transplants or severe arrhythmias, pregnant women, drug/alcohol abuse history, severe kidney disease, uncontrolled blood pressure or life expectancy less than a year.

Inclusion Criteria

I have had heart condition symptoms that are not the most severe for at least 3 months.

I have a BMI between 25 and 50, or I have Type II Diabetes, prediabetes, or metabolic syndrome.

Your heart function and blood pressure in your lungs are not within normal range.

Exclusion Criteria

Criterion: You are allergic to Gadolinium-based contrast agents.

You have metal implants or aneurysm clips that are not safe for MRI scans.

Your heart's pumping ability is less than 50%.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants consume the Ketone Ester or Placebo beverage twice daily for 6 weeks

6 weeks

Daily monitoring of blood markers, blood pressure, heart rate, and overall health

Washout

Participants undergo a 4-week washout period before crossing over to the other group

4 weeks

Treatment Phase 2

Participants crossover to the other group and consume the Ketone Ester or Placebo beverage twice daily for another 6 weeks

6 weeks

Daily monitoring of blood markers, blood pressure, heart rate, and overall health

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ketone Ester (Other)

Trial Overview The trial is testing the effects of a ketone ester beverage on exercise tolerance and cardiac function in people with heart failure. Participants will be randomly assigned to receive either the ketone ester drink or a placebo (a non-ketone standard beverage) to compare outcomes.

Participant Groups

Group I: Ketone Ester Experimental Treatment 1 Intervention

This arm will provide a Keto Ester Beverage for consumption.

Group II: Keto Ester Acute Experimental Treatment 1 Intervention

This arm will provide a Keto Ester Beverage for consumption.

Group III: Placebo Placebo Group 1 Intervention

This arm will provide a Placebo Beverage for consumption.

Group IV: Placebo Acute Placebo Group 1 Intervention

This arm will provide a Placebo Beverage for consumption.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The Ross Heart Hospital Columbus, OH

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Patients Recruited

2,659,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure. Yurista, SR., Matsuura, TR., Silljé, HHW., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone metabolism in the failing heart. Lopaschuk, GD., Karwi, QG., Ho, KL., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal Changes in Circulating Ketone Body Levels in Patients With Acute Heart Failure: A Post Hoc Analysis of the EMPA-Response-AHF Trial. Voorrips, SN., Boorsma, EM., Beusekamp, JC., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Selvaraj, S., Kelly, DP., Margulies, KB.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketones regulate endothelial homeostasis. Lopaschuk, GD., Hess, DA., Verma, S.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. Chen, O., Blonquist, TM., Mah, E., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Soto-Mota, A., Vansant, H., Evans, RD., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(11)C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure. Croteau, E., Tremblay, S., Gascon, S., et al.[2016]

In a study involving 10 recreational endurance runners, ingestion of a commercially available oral ketone supplement (β-hydroxybutyrate-salt + MCT) did elevate plasma ketone levels but did not significantly improve 5-km running performance compared to a placebo.

No notable differences were found in other physiological or perceptual measures during the exercise, suggesting that while the supplement increased ketone levels, it did not enhance exercise performance or related responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an Exogenous Ketone Supplement on Five-Kilometer Running Performance. Prins, PJ., Koutnik, AP., D'Agostino, DP., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone bodies and the heart. Papazafiropoulou, AK., Georgopoulos, MM., Katsilambros, NL.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ketone Ester Treatment Improves Cardiac Function and Reduces Pathologic Remodeling in Preclinical Models of Heart Failure. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Ketone metabolism in the failing heart. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Longitudinal Changes in Circulating Ketone Body Levels in Patients With Acute Heart Failure: A Post Hoc Analysis of the EMPA-Response-AHF Trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Ketones regulate endothelial homeostasis. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

[(11)C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure. [2016]

9. Poland pubmed.ncbi.nlm.nih.gov

Effects of an Exogenous Ketone Supplement on Five-Kilometer Running Performance. [2020]

10. Poland pubmed.ncbi.nlm.nih.gov

Ketone bodies and the heart. [2022]