Exogenous Ketones for Obstructive Sleep Apnea

(KETO-SLEEP 1 Trial)

Overseen By Athena Mavronis

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Opiates, Acetazolamide, SGLT2 inhibitors

Disqualifiers: Concomitant sleep disorder, Respiratory impairment, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking exogenous ketones (a type of chemical the body can use for energy) before bedtime can improve sleep quality and reduce the severity of obstructive sleep apnea (OSA), a condition where breathing stops and starts during sleep. Many people find it challenging to adhere to a ketogenic diet, so the trial explores if a ketone supplement, specifically Ketone-IQ, could serve as an easier alternative. The study involves participants with moderate to severe OSA who regularly use a CPAP machine (a device that helps keep the airway open during sleep). Individuals with moderate to severe OSA who consistently use a CPAP machine may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use nightly medications that affect breathing or SGLT2 inhibitors.

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

Research has shown that taking extra ketones, such as those in Ketone-IQ, is generally safe. Studies have found that they are usually well-tolerated with few side effects. These ketones have been studied for their potential to aid brain function in low oxygen situations and appear safe to use. As this trial is in an early stage, it primarily aims to understand how the body processes the ketones and their safety for individuals with sleep apnea. While the treatment is expected to be safe, the trial will confirm this by closely monitoring participants for any issues. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for sleep apnea?

Most treatments for obstructive sleep apnea, like CPAP machines, work by keeping the airway open during sleep. But Ketone-IQ works differently, offering a new approach by using exogenous ketones. These ketones may influence energy metabolism, potentially improving sleep quality without relying solely on mechanical devices. Researchers are excited because this could provide a more natural, ingestible option that might enhance sleep efficiency and reduce apnea episodes.

What evidence suggests that ingesting exogenous ketones might be an effective treatment for obstructive sleep apnea?

Research has shown that a ketogenic diet, low in carbohydrates and high in fat, can reduce the severity of obstructive sleep apnea (OSA). Due to the challenges of maintaining this diet, scientists are exploring exogenous ketones, like Ketone-IQ, as an alternative. In this trial, participants with sleep apnea using CPAP will ingest either nothing, Ketone-IQ 20 g, or Ketone-IQ 40 g before bedtime to assess its effects. Early findings suggest that taking Ketone-IQ before bed might improve sleep quality and reduce OSA symptoms. Some studies have found that ketone supplements can enhance sleep efficiency and quality, especially after exercise. While the exact effects on OSA are still under investigation, the potential for exogenous ketones to improve sleep is promising. ^{1 2 3 6 7}

Who Is on the Research Team?

Jonathan Jun, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for people with Obstructive Sleep Apnea (OSA), a condition that disrupts sleep and can lead to health problems. Participants should be currently receiving treatment for OSA but are looking for additional ways to improve their sleep quality.

Inclusion Criteria

I have been diagnosed with moderate to severe sleep apnea.

I use my CPAP machine regularly, at least 4 hours on most nights.

My CPAP is set at or below 10 cm water pressure.

Exclusion Criteria

I do not have any sleep disorders.

Currently on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants ingest exogenous ketones (Ketone IQ) or placebo before sleep to assess pharmacokinetics, tolerability, and sleep impacts

2 weeks

Multiple nights of in-home monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketone-IQ

Trial Overview The study tests if taking Ketone-IQ, an exogenous ketone supplement, at bedtime can improve overnight ketones and sleep quality in OSA patients. It compares the effects of this supplement to a placebo on how severe the sleep apnea is.

How Is the Trial Designed?

Group I: Ketone Intervention Experimental Treatment 1 Intervention

Participants with sleep apnea using CPAP will undergo open-label procedures. They will ingest (1) nothing, (2) Ketone IQ 20 g or (3) Ketone IQ 40 g before bedtime and undergo objective and subjective sleep assessments.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

KETONE-IQ

Collaborator

Trials

2

Recruited

60+

HVMN Inc

Industry Sponsor

Trials

3

Recruited

80+

Published Research Related to This Trial

In a study involving 14 healthy young adults, both ketone monoester (KME) and ketone monoester/salt (KMES) formulations significantly increased circulating R-beta-hydroxybutyrate (R-βHB) levels in a dose-dependent manner, with KME10 reaching a peak concentration of 2.4 mM after 15 minutes.

Both formulations were well-tolerated, but KMES was slightly more acceptable due to a better taste, while KME was associated with a more frequent decrease in appetite, indicating that user experience may vary between different ketone products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans. Bolyard, ML., Graziano, CM., Fontaine, KR., et al.[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]

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 pilot study with 11 subjects, consuming a ketone ester drink helped mitigate cognitive decline during hypoxia, as indicated by improved performance on cognitive tasks compared to a placebo.

Hypoxia significantly affected cognitive performance, leading to longer blink durations and lower blink rates, but the ketone ester consumption showed potential in reducing these negative effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Metabolic Intervention for Improving Human Cognitive Performance During Hypoxia. Coleman, K., Phillips, J., Sciarini, M., et al.[2022]

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]

A hypocaloric ketogenic diet (KD) significantly increased levels of beta-hydroxybutyrate (BHB) in participants, and this effect was enhanced by the addition of exogenous ketone salts (KS), leading to a 26% increase in ketonemia compared to a placebo.

The combination of the KD and KS not only augmented ketonemia but also resulted in a 6% reduction in fasting glucose levels, suggesting that the hypoglycemic effects of a ketogenic diet may be further improved with exogenous ketones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts. Buga, A., Kackley, ML., Crabtree, CD., et al.[2023]

A ketogenic diet (KD) and exogenous ketone supplements significantly increased blood ketone levels in rodent models, which correlated with a delayed onset of isoflurane-induced anesthesia, indicating that ketosis may influence anesthetic induction.

The study, involving chronic and sub-chronic feeding of KD and ketone supplements to different rodent models, suggests that elevated ketone levels could alter the effectiveness of anesthetics, potentially requiring adjustments in surgical anesthetic dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional ketosis delays the onset of isoflurane induced anesthesia. Ari, C., Kovács, Z., Murdun, C., et al.[2019]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06687655

Impact of Exogenous Ketones on Sleep Apnea Two doses (20 g and 40 g) of Ketone-IQ will be tested each for two nights, with one night used to measure BHB levels and separate night to allow for ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06655649

Impact of Exogenous Ketones on Sleep Disruption in ... Our lab has shown that a low carbohydrate, high fat ketogenic diet (KD) can reduce OSA severity. Since it can be challenging to adhere to a ketogenic diet, the ...

3. withpower.com withpower.com/trial/phase-1-sleep-apnea-syndromes-11-2024-5c57f

Exogenous Ketones for Obstructive Sleep Apnea · Info ... Trial Overview The study tests if taking Ketone-IQ, an exogenous ketone supplement, at bedtime can improve overnight ketones and sleep quality in OSA patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10581428/

Exogenous Ketosis Improves Sleep Efficiency and ... These data indicate that KE ingestion improves sleep efficiency and quality after high-intensity exercise.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07224074

Impact of Exogenous Ketones on Sleep and Breathing ... In this research study, the investigators are testing the tolerability, sleep effects, and dose effects of a commercially available EK product ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11442756/

Ketone monoester attenuates declines in cognitive ... Exogenous ketone supplements are a potential augmentation strategy for cognitive resilience during acute hypoxic exposure due to their capacity to attenuate ...

7. trial.medpath.com trial.medpath.com/clinical-trial/aa694acebdd47abc/nct06687655-impact-exogenous-ketones-sleep-disruption-vulnerable-populations

Impact of Exogenous Ketones on Sleep Apnea | MedPath Specifically the investigators will examine the effect of taking a commercially available product (Ketone-IQ) at bedtime on overnight ketones and sleep quality.