Exogenous Ketone Drink for Heart Failure

Overseen By Clinical Research Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Duke University

Must not be taking: GLP-1 RAs

Disqualifiers: Cirrhosis, Diabetes, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how a ketone drink affects individuals with heart failure with preserved ejection fraction, particularly regarding exercise and heart function. Participants will consume both the ketone drink and a placebo drink over two 8-week periods to compare effects. Individuals with heart failure that makes exercise difficult and who are on stable medical treatment may be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your medical therapy has been stable for at least 2 weeks before joining. This suggests you should continue your current medications as long as they are stable.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that short-term use of ketone drinks can improve heart function in some individuals with heart failure. In a 14-day study, patients with a type of heart failure similar to HFpEF (heart failure with preserved ejection fraction) experienced improved heart function after consuming a ketone drink.

However, safety concerns exist. Another study found that ketone drinks might not be suitable for individuals who need to limit salt intake, which is crucial for those with heart or kidney issues.

Overall, while the results are promising, participants should consult their doctors to determine if a ketone drink is appropriate for them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Most treatments for heart failure focus on managing symptoms and improving heart function using medications like ACE inhibitors, beta-blockers, and diuretics. However, the exogenous ketone drink, KetoneIQ, offers a novel approach by using (R)-1,3-butanediol to provide an alternative energy source for the heart. Researchers are excited about this treatment because it bypasses glucose metabolism, potentially offering a new way to improve energy efficiency in heart cells. This unique mechanism could help enhance heart function and energy levels, unlike traditional therapies that primarily focus on altering blood pressure and fluid balance.

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

Research has shown that ketone drinks might help people with heart failure. In this trial, participants will receive either an exogenous ketone drink or a placebo. Some studies have found that ketone drinks can improve heart function and reduce fluid buildup in individuals with impaired heart pumping. Ketone supplements have been linked to better heart performance and less strain, potentially allowing the heart to work more efficiently. Early evidence also suggests that ketones could support heart health by improving blood flow. These findings offer hope that ketone drinks could help people with heart failure exercise more easily. ^{1 3 5 6 7}

Who Is on the Research Team?

Senthil Selvaraj, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals with heart failure where the heart muscle pumps normally, known as HFpEF. Participants will be tested to see if they qualify and then given either a ketone drink or a placebo over two 8-week periods, switching halfway.

Inclusion Criteria

Elevated invasively-determined filling pressures previously

I've had heart failure needing strong water pills, with signs of fluid buildup.

My current medical treatment has been stable for at least 2 weeks.

Exclusion Criteria

I have type 1 diabetes.

I have chest pain due to heart artery disease or untreated significant heart artery blockage.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Treatment

Participants receive either a ketone drink or a placebo drink for 8 weeks

8 weeks

1 visit (in-person) after 8 weeks

Crossover Treatment

Participants receive the alternate drink (ketone or placebo) for another 8 weeks

8 weeks

1 visit (in-person) after 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exogenous Ketone Drink

Trial Overview The study is testing the effects of an exogenous ketone drink versus a placebo on exercise capacity and heart function in people with HFpEF. It's designed so that each participant tries both drinks in two separate 8-week phases.

How Is the Trial Designed?

Group I: Exogenous ketone drink Experimental Treatment 1 Intervention

(R)-1,3-butanediol (commercially obtained as "KetoneIQ")

Group II: Placebo Placebo Group 1 Intervention

ketone-free solution

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Published Research Related to This Trial

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]

Exogenous ketone drinks, such as ketone esters and ketone salts, effectively raise blood D-β-hydroxybutyrate (D-βHB) levels, with significant increases observed in a study of 15 participants, indicating a practical alternative to traditional ketogenic diets.

Both types of ketone drinks lowered blood glucose and triglyceride levels without causing adverse effects on blood electrolytes, suggesting they are safe and beneficial for metabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

On the Metabolism of Exogenous Ketones in Humans. Stubbs, BJ., Cox, PJ., Evans, RD., et al.[2022]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425003331

Should Exogenous Ketone Body Supplementation Be ... Short-term ketone ester supplementation for 14 days in patients with HFrEF has demonstrated improvements in cardiac function and decongestion, ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038461

Cardiovascular and Metabolic Effects of Modulating ... Oral dosing of BD led to prolonged ketosis and cardiovascular and metabolic benefits in patients with heart failure with reduced ejection fraction.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40789530/

Should Exogenous Ketone Body Supplementation Be ... Emerging evidence suggests that exogenous ketone bodies may have beneficial cardiovascular effects in patients with heart failure. The KETO-AHF ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06653725

Exogenous KETOne Supplements in Patients Hospitalized ... In AHF patients, ketone ester improved cardiac output, LVEF, and filling pressures. Emerging evidence suggests that 1,3-butanediol supplements may sustain ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1463381/full

Underlying mechanisms of ketotherapy in heart failure Ketone oxidation can effectively prevent a decrease in vascular density in failing hearts, particularly by promoting the proliferation, migration, and sprouting ...

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. clinicaltrials.gov clinicaltrials.gov/study/nct04633460

Acute Effects of Exogenous Ketone Ester Administration in ... 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.