Ketone Ester for Heart Failure

(KEHeart Trial)

Overseen By Jessica Lee

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: Claustrophobia, Implanted device

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to assess how ketone esters affect the heart in people with heart failure. Researchers will use MRI scans to observe changes in heart function before and after participants take the supplement for 12 weeks. Participants will be randomly assigned to receive either the ketone ester (a nutritional ketosis supplement) or a placebo that looks and tastes the same. The trial seeks individuals with heart failure and an ejection fraction below 40%, who are not claustrophobic and do not have certain implanted devices. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on heart health.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketone esters might be safe and beneficial for people with heart failure. One study demonstrated that using ketone esters for 14 days in patients with stable heart failure improved heart health. This finding suggests that people with heart problems can tolerate ketone esters well. However, ketone salts, which differ from ketone esters, might not be suitable for those needing to limit salt intake, such as some heart failure patients. Overall, ketone esters appear safe, particularly for short-term use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for heart failure focus on improving heart muscle function with medications like ACE inhibitors, beta-blockers, and diuretics. But the ketone ester supplement works differently by providing an alternative energy source for heart cells, potentially boosting energy efficiency in a struggling heart. Researchers are excited because this new approach might enhance heart performance without the side effects typically associated with current drug therapies. Plus, since ketone esters are a natural energy source, they might offer a safer and more sustainable treatment option.

What evidence suggests that ketone ester might be an effective treatment for heart failure?

Research has shown that ketone esters could help treat heart failure. In heart failure, ketone bodies provide the heart with an alternative energy source and reduce inflammation and stress from harmful molecules. One study found that taking ketone esters for 14 days improved heart function in people with stable heart failure. In animal studies, ketone esters both prevented and treated heart failure. Ketone therapy might also enhance exercise capacity and muscle function in heart failure patients. This trial will compare the effects of ketone ester supplements with a placebo. These findings suggest that ketone esters can benefit the heart and overall health in people with heart failure. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for heart failure patients with an ejection fraction (EF) less than 40%. It's not suitable for individuals who don't meet this specific heart function criterion.

Inclusion Criteria

My heart's pumping ability is below 40%.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ketone esters or placebo daily for 12 weeks

12 weeks

Baseline and post-intervention MRI scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketone Ester
• Placebo

Trial Overview The study tests the effects of ketone esters on the heart compared to a placebo. Participants will be randomly assigned to receive either the ketone ester or placebo, and their heart health will be monitored using cardiac MRI before and after a 12-week period.

How Is the Trial Designed?

Group I: Ketone ester supplement Experimental Treatment 1 Intervention

Ketone ester given daily for 12 weeks and scanned before and after intervention with MRI.

Group II: Placebo Placebo Group 1 Intervention

Placebo given that mimics taste, weight, and size of the interventional supplement mirroring the same time points as the ketone ester supplement group. Mirrored imaging with MRI as well.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In heart failure, the heart struggles to produce enough energy due to decreased mitochondrial metabolism, but ketone bodies can serve as an alternative energy source, potentially improving heart function.

While ketogenic diets alone have shown limited benefits for heart function, intravenous ketone infusions and ketone ester cocktails may enhance cardiac performance, suggesting that boosting ketone oxidation could be a promising treatment strategy for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

The ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate effectively elevates blood ketone levels in healthy volunteers, reaching maximum plasma concentrations of 3.30 mM for β-hydroxybutyrate within 1-2 hours after ingestion.

This ketone monoester was generally well-tolerated over a 5-day period, although some gastrointestinal side effects were noted at higher doses, indicating it is a safe alternative to traditional ketogenic diets for enhancing physical and cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Clarke, K., Tchabanenko, K., Pawlosky, R., et al.[2022]

In a 28-day study involving 59 healthy adults, the novel exogenous ketone diester bis-hexanoyl-(R)-1,3-butanediol (BH-BD) was found to be well-tolerated and safe, with no significant differences in tolerability scores compared to a placebo.

BH-BD effectively increased blood ketone levels one hour after consumption, indicating its potential for promoting nutritional ketosis without adverse effects on vital signs or laboratory measures.

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]

A study involving 24 healthy adults showed that consuming a ketone monoester three times a day for 28 days safely elevated blood ketone levels without affecting body weight, blood glucose, cholesterol, or kidney function.

The only reported side effect was mild nausea in a small number of instances, indicating that the ketone monoester is well-tolerated for sustained use.

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]

Chronic oral supplementation with ketone esters (KE) significantly improved heart function in rodent models of heart failure, with the KE-1 diet preventing left ventricular dysfunction and the KE-2 diet enhancing recovery post-myocardial infarction (MI).

The KE-2 diet not only improved heart function but also normalized myocardial ATP levels and altered gene expression related to ketone metabolism, suggesting that ketone bodies can serve as an effective alternative fuel for the failing heart.

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]

Chronic supplementation of ketone bodies, specifically using a ketone ester, significantly improved heart function in mice with established heart failure, preventing further decline in cardiac performance over two weeks.

The treatment not only elevated blood levels of β-hydroxybutyrate without causing ketoacidosis but also reduced heart muscle hypertrophy and fibrosis, suggesting that ketone therapy could be a promising approach for managing heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic exogenous ketone supplementation blunts the decline of cardiac function in the failing heart. Takahara, S., Soni, S., Phaterpekar, K., et al.[2022]

In a study involving 12 participants previously hospitalized for COVID-19, a single oral dose of ketone ester did not improve left ventricular ejection fraction (LVEF), indicating no significant impact on overall heart function.

However, the ketone ester did lead to a significant increase in global longitudinal strain (GLS), suggesting potential benefits in myocardial function, even though it did not affect cardiac output or blood oxygen saturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study. Wodschow, HZ., Davidovski, FS., Christensen, J., et al.[2023]

The study demonstrated that the ketone body acetoacetate can be used as a radiotracer to assess heart failure in a rat model induced by doxorubicin, showing increased blood levels and mitochondrial uptake in the heart, indicating its potential as an alternate nutrient for cardiac function.

Kinetic analysis using [(11)C]-acetoacetate revealed decreased uptake rates in heart failure rats, correlating with a significant reduction in left ventricular ejection fraction, suggesting that this radiotracer can effectively evaluate cardiac function without the need for stress testing.

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]

Ketone metabolic modulation shows promise as a novel treatment for heart failure (HF), particularly in patients with reduced ejection fraction, as it may enhance myocardial energy use during the disease's progression.

Current evidence suggests that exogenous ketone therapy could provide beneficial effects in both animal models and humans with HF, indicating a potential new therapeutic approach alongside traditional treatments.

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]

A ketone ester supplement can induce acute nutritional ketosis, which changes how the body uses energy during exercise, particularly in elite cyclists.

This shift in energy utilization leads to reduced lactate production and improved performance in time-trial events, suggesting potential benefits for athletes during prolonged or intense exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fueling Performance: Ketones Enter the Mix. Egan, B., D'Agostino, DP.[2018]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425001010

Therapeutic Ketosis for Heart Failure: A State-of-the-Art ... In heart failure specifically, ketone bodies may provide an alternative energy source for the failing heart as well as reduce inflammation and oxidative stress.

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.067971

Cardiovascular Effects of Oral Ketone Ester Treatment in ... The results of this study demonstrate favorable cardiovascular effects of 14-day ketone ester treatment in patients with stable heart failure ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7819534/

Ketone Ester Treatment Improves Cardiac Function and ... Conclusions: Chronic oral supplementation with KE was effective in both prevention and treatment of heart failure in 2 preclinical animal models. In addition, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06398964

Effects of 2-week Ketosis on the Heart's Ketone Body ... Recent research suggests that 3-OHB might have benefits for HF patients beyond just providing energy. It seems to reduce inflammation and oxidative stress in ...

5. academic.oup.com academic.oup.com/cardiovascres/article/121/2/230/7960072

Therapeutic potential of ketone bodies on exercise intolerance ... We review the evidence suggesting how ketone therapy may be beneficial in improving cardiovascular and skeletal muscle function in HF.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11009516/

Evaluation of the safety and tolerability of exogenous ketosis ... For example, ketone salts may not be suitable for patients who should restrict their salt intake, such as those with heart failure or kidney disease. On the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394354/

Salutary Effects of Nutritional Ketosis for the Diseased Human ... Cardiovascular Effects of Oral Ketone Ester Treatment in Patients With Heart Failure ... nutritional ketosis on indices of cardiovascular disease ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04370600

NCT04370600 | Nutritional Ketosis in Heart Failure Moderate or greater valvular disease. Hemoglobin <10 g/dL. Daily insulin use; Hypertrophic, infiltrative, or inflammatory cardiomyopathy. Pericardial disease.