Ketone Ester for Frail Elderly

(TAKEOFF Trial)

Recruiting at 2 trial locations

Overseen By Brianna Stubbs, DPhil

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Buck Institute for Research on Aging

Must not be taking: Immunosuppressants, Chemotherapy, Chronic antibiotics, others

Disqualifiers: Non ambulatory, Frailty, Cancer, others

Compensation: Varies

Number of Visits: 6

Duration: 20 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a food supplement with ketones, known as Ketone Ester, can improve strength and overall wellness in adults aged 65 and older who are experiencing a slight decline in physical abilities. Participants will be divided into two groups to take either a ketone supplement or a placebo (a non-active substance) daily for 20 weeks. This trial may suit individuals who can walk at a normal speed and experience some loss in physical function but can generally manage daily activities independently. Participants will visit the study site to provide samples and complete physical tests and questionnaires. The trial is taking place in California, Ohio, and Connecticut. As an unphased trial, this study offers participants the chance to contribute to valuable research on dietary supplements and aging.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must maintain your usual medication routine during the study.

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

Research shows that ketone esters can safely increase blood ketone levels, potentially enhancing physical and mental performance. In past studies, many participants used ketone esters without major issues, though some experienced stomach problems, such as nausea or diarrhea. While ketone esters have not been studied in older adults for frailty, they have generally been well-tolerated in other contexts.

Prospective participants in a clinical trial with ketone esters should be aware of possible stomach-related side effects. Overall, research suggests that ketone esters hold promise in terms of safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for frailty in the elderly, which typically focus on physical therapy and nutritional support, ketone ester offers a unique approach by utilizing its active ingredient, C8 ketone di-ester. This compound provides an alternative energy source for the body, potentially improving muscle function and energy levels. Researchers are excited because ketone esters might enhance physical performance and cognitive function more effectively than traditional methods, offering hope for a more dynamic improvement in overall quality of life for frail elderly individuals.

What evidence suggests that ketone ester supplements might be an effective treatment for improving strength and wellness in frail elderly adults?

Research has shown that ketone esters, which participants in this trial may receive, can improve strength and health in older adults. Studies have found that these supplements safely trigger ketosis, a state where the body uses fat for energy, which has been linked to better physical performance and overall well-being. In a recent small study, older adults took daily doses of ketone ester without any major problems. Although data on very frail elderly people is limited, the mechanism of ketone esters suggests they might enhance physical function. ^{1 2 3 6 7}

Who Is on the Research Team?

Jenna Bartley, PhD

Principal Investigator

University of Connecticut

John Newman, MD, PhD

Principal Investigator

Buck Institute

Jeff Volek, Phd

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for adults aged 65 or older who are experiencing a decline in physical function. Participants must be able to attend five study visits over 20 weeks and provide blood, stool, and urine samples. The key exclusion criteria have not been provided.

Inclusion Criteria

I am 65 years old or older.

I can walk at a required speed.

I weigh at least 50 kg.

Exclusion Criteria

I cannot walk by myself.

I am considered very frail according to a clinical assessment.

I was in the hospital within the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person), phone screening

Baseline

Baseline assessments including medical history, physical assessment, and cognitive and physical function testing

1 day

1 visit (in-person)

Treatment

Participants consume either a ketone drink or placebo daily for 20 weeks, with regular assessments and sample collections

20 weeks

4 visits (in-person), bi-weekly phone check-ins

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 Comparator

Trial Overview The study tests if a ketone ester drink can improve strength and wellness in frail elderly individuals compared to a non-ketone placebo drink. Participants will consume their assigned drink daily for 20 weeks with random assignment into two groups.

How Is the Trial Designed?

Group I: Ketone ester Active Control 1 Intervention

Ketone ester (KE) (Chemical name: Bis-octanoyl-(R)-1,3-butanediol, Common name: C8 ketone di-ester) formulated as a dietary supplement. KE 12.5 g per day for 1 week; followed by KE 25 g per day for 1 week; followed by KE 37.5 g per day split into two doses for 1 week; followed by KE 50 g per day split into two doses for 17 weeks

Group II: Non-ketone placebo Placebo Group 1 Intervention

Placebo oil (non-ketogenic canola oil) formulated as a dietary supplement. Placebo oil 12.5 g per day for 1 week; followed by Placebo oil 25 g per day for 1 week; followed by Placebo oil 37.5 g per day split into two doses for 1 week; followed by Placebo oil 50 g per day split into two doses for 17 weeks

Who Is Running the Clinical Trial?

Buck Institute for Research on Aging

Lead Sponsor

Trials

6

Recruited

1,200+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

University of Connecticut

Collaborator

Trials

194

Recruited

162,000+

California Pacific Medical Center Research Institute

Collaborator

Trials

44

Recruited

10,600+

Published Research Related to This Trial

In a study involving 80 healthy older adults, the medium-chain triglyceride GSK2981710 increased plasma β-hydroxybutyrate (BHB) levels but did not lead to significant improvements in cognitive function or memory-related neuronal activity over 14 days.

The most common side effect was diarrhea, affecting 100% of participants in the initial part of the study, indicating that while GSK2981710 is generally well-tolerated, it may cause gastrointestinal discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of GSK2981710, a medium-chain triglyceride, on cognitive function in healthy older participants: A randomised, placebo-controlled study. O'Neill, BV., Dodds, CM., Miller, SR., et al.[2020]

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 a study with conscious dogs, the ingestion of R,S-1,3-butanediol diacetoacetate induced ketosis, but the achieved level (0.8 mM) was lower than the levels (1-3 mM) seen in children on a ketogenic diet for epilepsy.

The study suggests that while the ketosis level in dogs was lower, humans might experience higher ketone body concentrations from the same doses of the ester, potentially making it a viable option for managing seizures in children with intractable epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dog model of therapeutic ketosis induced by oral administration of R,S-1,3-butanediol diacetoacetate. Puchowicz, MA., Smith, CL., Bomont, C., et al.[2022]

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]

Oral administration of the ketone ester (KE) significantly increases ketosis levels in non-fasted mice, reaching a peak of 6.83 mmol/L within 30 minutes, indicating its rapid effectiveness in generating ketone bodies.

The study reveals that KE enhances brain metabolism by increasing acetyl-CoA and citric cycle intermediates, which may inhibit glycolysis and suggest a potential therapeutic role for KE in acute neurological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice. Suissa, L., Kotchetkov, P., Guigonis, JM., et al.[2021]

Two validated LC-MS methods were developed to accurately measure ketone ester and its metabolites in human plasma, ensuring reliable pharmacokinetic profiling for potential therapeutic use.

The study found that ketone ester undergoes non-saturable metabolism in human plasma, indicating its metabolic stability at high concentrations, and that human serum albumin plays a role in its metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Determination of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate (Ketone Ester) and Its Metabolites Beta-hydroxybutyrate, 1-3-Butanediol, and Acetoacetate in Human Plasma Using LC-MS. Panse, N., Halquist, M., Gerk, PM.[2023]

Oral administration of exogenous ketone supplements over 28 days effectively induced sustained nutritional ketosis in male rats, achieving ketone levels greater than 0.5 mM without the need for carbohydrate restriction.

The study showed that these supplements led to a rapid increase in β-hydroxybutyrate (βHB) levels and a decrease in blood glucose, while having minimal impact on lipid levels, indicating their potential safety and efficacy for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Kesl, SL., Poff, AM., Ward, NP., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06645847

Targeting Aging With a Ketone Ester for Function in Frailty This study aims to find out if a food supplement that contains a naturally occurring substance, ketones, can help to improve strength and general wellness ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10635199/

Rationale and protocol for a safety, tolerability and feasibility ... Ketone esters (KEs) induce ketosis without dietary changes, but KEs have not been studied in an older adult population. Our long-term goal is to examine if KEs ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1279770724004160

Daily consumption of ketone ester, bis-octanoyl (R) The results of this pilot study demonstrate that this cohort of healthy older adults tolerably and safely consumed up to 25 g per day of the ketone ester, bis- ...

4. withpower.com withpower.com/trial/phase-frail-elderly-10-2024-2154c

Ketone Ester for Frail Elderly (TAKEOFF Trial) Trial Overview The study tests if a ketone ester drink can improve strength and wellness in frail elderly individuals compared to a non-ketone placebo drink.

5. mdedge.com mdedge.com/content/are-ketogenic-supplements-key-healthy-aging

Are ketogenic supplements the key to healthy aging? Although scientists still don't know why the ketogenic diet was effective for controlling seizures, they have documented the effectiveness of ketogenic diets ...

6. medrxiv.org medrxiv.org/content/10.1101/2024.09.17.24313811v1.full.pdf

1,3-butanediol i endpoints as primary and secondary outcomes in a larger trial of pre-frail older adults. ... Ketone ester supplementation. 646 blunts overreaching ...

7. reporter.nih.gov reporter.nih.gov/project-details/10908375

Targeting Aging with Ketone Ester in Older adults ... This collaborative project will carry out the first clinical trial of a ketone ester compound in frailty, in order to generate the first robust safety data for ...