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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Obstructive Sleep Apnea (OSA) is a common medical disorder that is associated with reduced quality of life and higher risk of cardiovascular disease. Treatments for OSA and limited and not well tolerated. 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 ketogenic diet, the investigators propose that ingesting exogenous ketones can be an alternative method to improve OSA. Specifically the investigators will examine the effect of taking a commercially available product (Ketone-IQ) at bedtime on overnight ketones and sleep quality. The investigators will also examine the effect of Ketone-IQ on sleep apnea severity, compared to placebo. This project will examine the the preliminary efficacy of ingesting exogenous ketones before sleep on sleep apnea.

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.

What data supports the effectiveness of the treatment Ketone-IQ for sleep apnea?

Research suggests that ketone bodies, which are increased by ketogenic diets, may improve sleep quality and have shown positive effects on sleep disorders, including obstructive sleep apnea. Additionally, ketone bodies have been found to improve sleep efficiency and counteract sleep disruptions after strenuous exercise. ^{1 2 3 4 5}

Is Ketone-IQ safe for human use?

Research shows that ketone esters, including those similar to Ketone-IQ, are generally safe and well-tolerated in humans, with some reports of mild gastrointestinal effects at high doses. Studies have found no significant changes in vital signs or lab measurements, indicating good safety profiles for these compounds. ^{4 6 7 8 9}

How does the treatment Ketone-IQ differ from other treatments for sleep apnea?

Ketone-IQ is unique because it involves the use of ketone bodies, which are alternative energy sources for the brain, potentially improving sleep disorders like sleep apnea by altering brain metabolism. Unlike traditional treatments, Ketone-IQ may offer a novel approach by leveraging the metabolic effects of ketosis, which is typically achieved through a ketogenic diet or ketone supplements. ^{1 7 10 11 12}

Research Team

Jonathan Jun, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

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.

I do not use supplemental oxygen.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Is there a relationship between the ketogenic diet and sleep disorders? [2022]

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

Ketogenic diet improves sleep quality in children with therapy-resistant epilepsy. [2007]

3. England 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. [2023]

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

Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise. [2023]

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

Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis. [2022]

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

Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. [2022]

8. Switzerland 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. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Nutritional ketosis delays the onset of isoflurane induced anesthesia. [2019]

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

A Metabolic Intervention for Improving Human Cognitive Performance During Hypoxia. [2022]

12. England 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. [2023]