Impact of Exogenous Ketones on Sleep and Breathing in Healthy Volunteers (K-SLEEP)

Not Applicable

Not yet recruiting

• Conditions: Healthy Participants; Sleep

• Registration Number: NCT07224074
• Lead Sponsor: Johns Hopkins University

Brief Summary

Ketones are molecules generated by the body during the metabolism of fat. Exogenous ketones (EK) are substances that can raise the level of ketones in the circulation without changing diet. In this research study, the investigators are testing the tolerability, sleep effects, and dose effects of a commercially available EK product called Ketone-IQ.

The investigators will administer Ketone-IQ open-label to healthy volunteers (n=20, 10 men, 10 women) before sleep in the participant's home setting and collect information about subjective sleep and GI symptoms, as well as objective data about beta-hydroxybutyrate (BHB) levels and sleep architecture using a headband-EEG device (Sleep Profiler). Participants will measure capillary BHB levels before ingestion and at 1, 3, and 5 hours post-ingestion, as well as upon awakening.

Questionnaires will be used to gather feedback on the palatability of EK, GI side effects, and sleep quality. Higher scores indicate better sleep quality. 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 a separate night to allow for uninterrupted sleep.

Detailed Description

There is growing interest leveraging ketone metabolism for human health and performance. Exogenous ketones (EK) are substances that directly increase circulating ketones in the body without requiring a change in diet. While EK have been studied in the contexts of energy metabolism and exercise, few studies have examined EKs impact on sleep, a critical window for repair and rest. A mouse study showed that wakefulness increased brain ketones, while injection of acetoacetate increased slow wave sleep, suggesting a homeostatic sleep-promoting role of ketones. In humans, strenuous exercise reduced rapid eye movement (REM) sleep, which was prevented by ingestion of a ketone ester before sleep. Otherwise, few studies have systematically evaluated the effects of EK on sleep architecture and quality.

To examine the potential of EK to affect sleep, the investigators are conducting the K-SLEEP study. The investigators will examine sleep architecture and quality and BHB levels when EK are ingested prior to sleep (n=20). Healthy volunteers will ingest EK or placebo 30 minutes before sleep. Participants will measure capillary BHB levels before ingestion and at 1, 3, 5, hours post-ingestion as well as upon awakening. Questionnaires will solicit feedback about EK palatability, GI side effects, and sleep quality. Two doses will be examined, 20 g or 40 g with 1-2 days of washout between doses.

EK come in several forms including 1,3BD, ketone esters (beta-hydroxybutyrate + 1,3BD), fatty acid esters (C6 or C8 medium chain fatty acids + 1,3 BD), free acid ketones (beta-hydroxybutyric acid), and ketone salts (combination of ketone body with a mineral salt such as sodium or potassium). 1,3BD can be ingested in isolation or in a combination formulation (5, 6) whereupon it is absorbed and converted by hepatic enzymes into gamma-hydroxybutyrate and then oxidized to the ketone body BHB. In this study, the investigators will utilize a commercially available formulation of 1,3BD called Ketone IQ. This product has a more gradual onset and prolonged period of ketosis than ketone salt ingestion, making it more suitable for inducing sustained ketosis during several hours of sleep.

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-30
• Study First Submitted QC: 2025-10-30
• Last Update Submitted: 2025-10-30
• Study First Posted: 2025-11-03
• Last Update Posted: 2025-11-03
• Study Start: 2026-01-01
• Primary Completion: 2028-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Adults aged 18-50 years old with a BMI of 18 - 30 kg/m^2

Exclusion Criteria

• No concomitant sleep disorder (e.g. sleep apnea, insomnia, restless leg syndrome, narcolepsy, idiopathic hypersomnia). If there is no known diagnosis of sleep apnea, a STOP-BANG score of 5 or higher is an exclusion.
• No current daytime respiratory impairment such as uncontrolled asthma, or uncontrolled Chronic Obstructive Pulmonary Disease (COPD), pneumonia, interstitial lung disease.
• No known history of chronic renal disease or diabetes (type 1 or type 2).
• No use of supplemental oxygen.
• Cannot be on a low carbohydrate (<130 g carbohydrate/day) or ketogenic diet, intermittent fasting, or consuming exogenous ketones
• Cannot be pregnancy or breastfeeding
• Cannot be on medications: acetazolamide or Sodium-glucose cotransporter-2 (SGLT2) inhibitor (10), daily opioid use.
• K-BREATHE: no history of claustrophobia or panic disorder
• Frequent alcohol intake (more than 1 drink per day on average, or > 10 drinks per week).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Beta hydroxybutyrate (BHB) maximal concentration (Cmax)	1, 3, 5 hours, and final awakening (Night 2); and 1, 3, 5 hours, and final awakening (Night 5)	Participants will measure their capillary BHB levels at home at 4 time points after ingestion (1, 3, 5 hours, and final awakening). The investigators will derive the maximal BHB concentration (mmol) of these timepoints. Measured on two occasions: Night 2 (Ketone IQ 20 g) and Night 5 (Ketone IQ 40 g).

Secondary Outcome Measures

Name	Time	Method
Sleep quality as assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) short from 8a	day 2, day 4, and day 7	Modified PROMIS-SD short form 8a: Uses a Likert-type response scale. The raw score range is 8 to 40 with a higher score indicating greater severity of sleep disturbance.
Sleep quality as assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Related Impairment (SRI) short form 8a	day 2, day 4, and day 7.	Modified PROMIS-SRI short form 8a: uses a Likert-type response scale. The raw score range is 8 to 40 with a higher score indicating greater severity of sleep related impairment.
Sleep quality as assessed by Stanford Sleepiness Scale	3 questionnaires in 1 week on day 2, day 4, and day 7.	Stanford Sleepiness Scale; Total score range: 0-7. 7 Sleep quality 7 being the worst
Sleep architecture as assessed by minutes of sleep in each stage	Night 1, Night 2, Night 3, Night 6	Measured using a Sleep Profiler device, the Sleep Profiler provides automated sleep staging validated against polysomnography (PSG), using EEG signals to quantify time spent in each sleep stage. Worn for about 8 hours each night.
Gastrointestinal tolerability as assessed by the Gastrointestinal Symptoms Questionnaire	day 3, day 4, day 6, and day 7	Questionnaire about GI tolerability of product; 0-8, 8 being "unbearable"

Trial Locations

Locations (1)

Johns Hopkins Bayview; 🇺🇸 Baltimore, Maryland, United States