Ketone-IQ for Sleep Apnea

(KETO-SLEEP 2 Trial)

Overseen By Athena Mavronis

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Johns Hopkins University

Must not be taking: Opiates, Acetazolamide, SGLT2 inhibitors

Disqualifiers: Concomitant sleep disorder, Respiratory impairment, others

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

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Ketone-IQ, a type of exogenous ketone (a substance produced by the body during a keto diet), can improve sleep quality and reduce the severity of obstructive sleep apnea (OSA), a condition that disrupts breathing during sleep. Participants will use Ketone-IQ and a placebo (a substance with no active ingredient) on different nights to observe any differences. The trial targets individuals with moderate to severe OSA who regularly use a CPAP machine (a device that keeps airways open during sleep). As a Phase 1, Phase 2 trial, the research aims to understand how Ketone-IQ works in people and to measure its effectiveness in an initial, smaller group.

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

The trial requires you to stop using nightly medications that affect breathing and Sodium-glucose cotransporter-2 (SGLT2) inhibitors. If you are taking these, you will need to stop before participating.

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

Earlier studies have shown that Ketone-IQ, which contains 1,3 butanediol, may benefit brain function and overall health. This suggests it has been generally well-received in past uses. Although specific safety information for sleep apnea is limited, current research is examining short-term responses to Ketone-IQ. As a purchasable product, many have used it without major issues. However, since testing for sleep apnea is still in early stages, participation in studies is crucial to confirm its safety and effectiveness for this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sleep apnea?

Unlike the standard treatments for sleep apnea, such as CPAP machines and oral appliances, Ketone-IQ offers a novel approach by utilizing ketone bodies to potentially improve sleep quality. Researchers are keen to explore this treatment because ketone bodies might enhance brain energy metabolism during sleep, which is a different mechanism than simply mechanically supporting airways. This innovative angle could lead to better patient compliance and offer benefits beyond what's currently available.

What evidence suggests that Ketone-IQ might be an effective treatment for sleep apnea?

This trial will evaluate the effects of Ketone-IQ on sleep apnea. Research has shown that a low-carb, high-fat ketogenic diet can reduce the severity of obstructive sleep apnea (OSA). Since following this diet can be challenging, supplements like Ketone-IQ might offer a useful alternative. Studies have found that these supplements can improve sleep quality, especially after intense exercise. The idea is that taking Ketone-IQ before bed could raise ketone levels overnight, potentially alleviating OSA symptoms. Although human research on Ketone-IQ for OSA is limited, early studies suggest a positive effect. Participants in this trial will experience both Ketone-IQ and placebo treatments in a crossover design to assess its impact on OSA. ^{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 individuals with Obstructive Sleep Apnea (OSA), a condition that disrupts sleep and increases heart disease risk. Participants should be interested in trying an alternative to the challenging ketogenic diet by taking Ketone-IQ at bedtime to potentially improve their sleep quality and reduce OSA severity.

Inclusion Criteria

I use my CPAP machine regularly, at least 4 hours on 70% of days.

I have been diagnosed with moderate to severe sleep apnea.

I am between 18 and 65 years old with a BMI between 18 and 35.

Exclusion Criteria

I am currently taking medication for diabetes that includes drugs like Invokana, Farxiga, Jardiance, or Steglatro.

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

I do not use supplemental oxygen.

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 effects on sleep apnea and related symptoms

2 weeks

4 nights total (2 nights Ketone-IQ, 2 nights Placebo)

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 drinking Ketone-IQ, an exogenous ketone product, before sleeping can help manage OSA better than a placebo. It aims to see whether this approach can increase overnight ketones and enhance sleep quality without adhering strictly to a ketogenic diet.

How Is the Trial Designed?

Group I: Placebo first Experimental Treatment 2 Interventions

This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Placebo first, then Ketone-IQ.

Group II: Ketone-IQ first Experimental Treatment 2 Interventions

This is a crossover study where participants will ingest either Ketone-IQ for 2 nights, or placebo for 2 nights before sleep. This arm will ingest Ketone-IQ first, then placebo.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

HVMN Inc

Industry Sponsor

Trials

3

Recruited

80+

KETONE-IQ

Collaborator

Trials

2

Recruited

60+

Published Research Related to This Trial

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 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]

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 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]

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]

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 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]

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]

Ketone bodies, particularly β-hydroxybutyrate (BOHB) and acetone, can significantly increase in concentration during certain diseases or therapeutic interventions, providing valuable metabolic insights for managing conditions like heart failure and obesity-related diseases.

Monitoring ketone body levels can help optimize weight loss strategies and improve disease management by promoting the use of ketones as an alternative fuel source when glucose utilization is impaired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis. Anderson, JC., Mattar, SG., Greenway, FL., et al.[2022]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06687655

Impact of Exogenous Ketones on Sleep Apnea

The specific ketone product to be tested for its impact on sleep and breathing is 1,3 butanediol (1,3BD) in a commercially available formulation called "Ketone ...

2.

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.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06655649

Impact of Exogenous Ketones on Sleep Disruption ...

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 ...

4.

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.

5.

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

The investigator's 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 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9473641/

Ketogenic dietary lifestyle intervention effects on sleep ...

The MCI Sleep Study assesses longitudinal changes in objective and subjective measures of sleep between two investigational diet groups.

7.

help.ketone.com

help.ketone.com/article/h6u6uxy44a-effects-of-ketone-iq

What's the research behind Ketone-IQ?

Learn about the effects of Ketone-IQ®. Research shows benefits for cognition, endurance, metabolic health, and appetite regulation.