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

Official title

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

Overview

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.

Interventions

• Dietary supplement KETONE-IQ 20 grams (g)
  Dietary Supplement: Ketone-IQ (1,3 Butanediol) Description: Ketone-IQ (1,3 Butanediol) 20g will be ingested (open-label) before bedtime.
• Dietary supplement KETONE-IQ 40 grams (g)
  Dietary Supplement: Ketone-IQ (1,3 Butanediol) Description: Ketone-IQ (1,3 Butanediol) 40g will be ingested (open-label) before bedtime.

Primary outcome measures

• Beta hydroxybutyrate (BHB) maximal concentration (Cmax) [Time frame: 1, 3, 5 hours, and final awakening (Night 2); and 1, 3, 5 hours, and final awakening (Night 5)]

Secondary outcome measures (5)

• Sleep quality as assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SD) short from 8a [Time frame: day 2, day 4, and day 7]
• Sleep quality as assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Related Impairment (SRI) short form 8a [Time frame: day 2, day 4, and day 7.]
• Sleep quality as assessed by Stanford Sleepiness Scale [Time frame: 3 questionnaires in 1 week on day 2, day 4, and day 7.]
• Sleep architecture as assessed by minutes of sleep in each stage [Time frame: Night 1, Night 2, Night 3, Night 6]
• Gastrointestinal tolerability as assessed by the Gastrointestinal Symptoms Questionnaire [Time frame: day 3, day 4, day 6, and day 7]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Johns Hopkins Bayview — Baltimore

Identifiers

NCT: NCT07224074 · IRB00517978

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗