Ketone Supplement for Sleep Deprivation

(STAK-Sleep Trial)

Overseen By Madison L Kackley, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Diabetic medications

Disqualifiers: Sleeping disorders, Diabetes, Liver dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketone ester supplement can improve thinking skills and physical performance during sleep deprivation. It targets individuals who frequently experience sleep deprivation, such as military personnel, where lack of sleep can impair concentration and increase errors. Participants will use both the ketone supplement and a placebo (a non-active substance) to compare effects. This study is for individuals without sleep disorders, who do not follow a low-carb or ketogenic diet, and who are not dealing with major medical issues. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on sleep deprivation and cognitive performance.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does require you to maintain your medication habits throughout the study.

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

Research has shown that ketone supplements are generally safe for people. One study found that when healthy adults drank a ketone beverage several times, it was safe, with participants reporting no serious side effects. Ketones naturally occur in the blood during fasting or when following a ketogenic diet, indicating they are a normal part of bodily function. This suggests they could be a safe option for addressing sleep deprivation. Although this trial is an early study with limited safety data, previous research provides a solid basis for considering ketone supplements as relatively safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for sleep deprivation focus on improving sleep hygiene or using medications like melatonin and prescription sleep aids. However, the ketone supplement being studied works differently. Unlike the standard approaches, which often aim to induce sleep or regulate sleep cycles, ketone esters provide an alternative energy source for the brain, potentially enhancing mental clarity and reducing the negative effects of sleep deprivation. Researchers are excited about this treatment because it could help people function better despite lack of sleep, offering a novel solution for managing sleep deprivation beyond just promoting sleep.

What evidence suggests that ketone supplements might be an effective treatment for sleep deprivation?

Research suggests that ketone supplements, which participants in this trial may receive, might improve sleep quality by enhancing sleep efficiency. One study found that people who took ketone supplements slept better after intense exercise. Another study showed that these supplements could reduce tiredness and improve performance when sleep is limited. Ketone supplements increase ketone levels in the blood, helping the brain and body function better even with less sleep. Although more research is needed, early findings are promising for those experiencing sleep deprivation. ^{1 3 6 7 8}

Who Is on the Research Team?

Jeff S Volek, PhD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-40, with a BMI of ≤35, who can follow study procedures like fasting and controlled feeding. It's not for those with psychiatric disorders, recent significant weight loss, sleep or gastrointestinal disorders, heavy alcohol use, metabolic diseases (except metformin users), current/recent ketogenic dieters, or pregnant/lactating women.

Inclusion Criteria

Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator

Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history

Participant is willing and able to comply with all study procedures including fasting (>10 h; water only), no alcohol (>24 h), no exercise (>24 h), no acute illness and controlled feeding before each Test Day, maintain diet, exercise, medication, and supplement habits throughout the study

Exclusion Criteria

Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements

You drink more than 3 drinks a day or 14 drinks a week.

Have any major psychiatric disorders (e.g., schizophrenia, bipolar disorder)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a ketone ester or placebo supplement twice daily during short-term sleep restriction

4 weeks

Multiple visits for assessments and interventions

Washout

A 2-week washout period between crossover interventions

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketone Supplement

Trial Overview

The study tests if a ketone ester supplement taken twice daily can boost cognitive and physical performance when sleep is restricted. Participants will undergo various assessments including sleep monitoring, heart rate tracking, diet control and performance tests while experiencing short-term sleep deprivation.

How Is the Trial Designed?

Group I: Ketone Ester First Experimental Treatment 13 Interventions

Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo

Group II: Placebo First Active Control 13 Interventions

Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

In a study involving seven male military personnel, a ketogenic diet (KD) significantly increased levels of D-β-hydroxybutyrate and decreased blood glucose compared to a carbohydrate-based diet, indicating a metabolic advantage during sleep deprivation.

The KD improved cognitive performance, mood, and reduced sleepiness during 36 hours of extended wakefulness, showing better results in tasks measuring attention and memory compared to the carbohydrate diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a 2 week ketogenic diet, versus a carbohydrate-based diet, on cognitive performance, mood and subjective sleepiness during 36 h of extended wakefulness in military personnel: An exploratory study. Henderson, LR., van den Berg, M., Shaw, DM.[2023]

The medium-chain triglyceride ketogenic diet (MCT-KD) increased blood ketone levels without causing carbohydrate starvation, indicating that ketosis can occur independently of a fasting state.

While the MCT-KD did not significantly alter circadian rhythms or core clock gene expression, it was associated with a reduction in REM sleep duration and slightly decreased wheel-running activity in mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A ketogenic diet containing medium-chain triglycerides reduces REM sleep duration without significant influence on mouse circadian phenotypes. Zhuang, H., Fujikura, Y., Ohkura, N., et al.[2023]

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]

Sleep deprivation in mice led to increased levels of ketone bodies, particularly acetoacetate, which suggests a link between energy metabolism and sleep regulation.

Injecting acetoacetate into the brain significantly enhanced slow-wave sleep activity and reduced glutamate release, indicating that acetoacetate may play a crucial role in maintaining sleep homeostasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone body metabolism and sleep homeostasis in mice. Chikahisa, S., Shimizu, N., Shiuchi, T., et al.[2015]

Both powdered and ready-to-drink (RTD) formulations of the novel ketone ester BH-BD effectively induce ketosis in healthy adults, increasing blood beta-hydroxybutyrate (BHB) levels within approximately 15 minutes after consumption.

The study found that a higher dose of the powdered formulation (25g) resulted in significantly greater BHB concentrations compared to lower doses and the RTD version, but both formulations were equally effective in raising BHB levels without affecting blood glucose concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Powder Formulation of the Ketone Ester, Bis Hexanoyl (R)-1,3-Butanediol, Rapidly Increases Circulating ß-Hydroxybutyrate Concentrations in Healthy Adults. Nieman, KM., Anthony, JC., Stubbs, BJ.[2023]

In a study involving 10 well-trained cyclists, ketone ester (KE) intake significantly improved sleep efficiency and quality after strenuous exercise, counteracting disruptions like reduced REM sleep and increased wakefulness.

The positive effects of KE on sleep were linked to increased dopamine excretion, suggesting that KE may enhance sleep regulation mechanisms following high-intensity workouts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise. Robberechts, R., Albouy, G., Hespel, P., et al.[2023]

Sleep disorders are often overlooked and can include a variety of conditions such as insomnia and sleep apnea, highlighting the need for better recognition and treatment.

The ketogenic diet (KD), which is high in fats and low in carbohydrates, has shown promise in treating sleep disorders, particularly obstructive sleep apnea, by potentially influencing sleep homeostasis through the effects of ketone bodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a relationship between the ketogenic diet and sleep disorders? Barrea, L., Pugliese, G., Frias-Toral, E., 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]

In a 24-month study involving two patients with Alzheimer's disease, the administration of (R)-3-oxobutyl 3-hydroxybutanoate (OBHB) was well tolerated with no adverse effects, suggesting its safety as a treatment option.

Both patients showed significant improvements in mood, behavior, and cognitive performance, alongside a reduction in cholesterol levels, indicating that OBHB may effectively manage hyperketonemia and enhance quality of life in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(R)-3-oxobutyl 3-hydroxybutanoate (OBHB) induces hyperketonemiain Alzheimer's disease. Chu, CB., Jiao, LD.[2020]

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