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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).

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.

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

Research suggests that ketone bodies can provide an additional energy source for the heart, which may help improve heart function in heart failure. Studies have shown that increasing ketone levels can improve heart function in both animal models and humans with heart failure. ^{1 2 3 4 5}

Is the exogenous ketone drink safe for humans?

Research shows that exogenous ketone drinks are generally safe and well-tolerated in healthy adults, with only mild nausea reported in a few cases. A study found no negative effects on body weight, blood sugar, cholesterol, or kidney function after 28 days of use. ^{1 4 5 6 7}

How does the exogenous ketone drink treatment for heart failure differ from other treatments?

The exogenous ketone drink is unique because it provides an additional energy source for the heart by increasing ketone metabolism, which can be beneficial in heart failure where traditional energy sources are less effective. Unlike other treatments that focus on hormonal or blood flow changes, this approach directly targets the heart's energy supply. ^{1 2 3 6 8}

Research Team

Senthil Selvaraj, MD

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Acute Echocardiographic Effects of Exogenous Ketone Administration in Healthy Participants. [2023]

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

Ketone metabolism in the failing heart. [2021]

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

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Chronic exogenous ketone supplementation blunts the decline of cardiac function in the failing heart. [2022]

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

On the Metabolism of Exogenous Ketones in Humans. [2022]

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

Beneficial Effects of Ketone Ester in Patients With Cardiogenic Shock: A Randomized, Controlled, Double-Blind Trial. [2023]