Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT05519644

Strategies to Augment Ketosis: Ketone Conferred Resiliency Against Sleep Restriction

Sleep deprivation is a major problem in military populations. Some major consequences of sleep loss are inability to concentrate, poor work efficiency, and increase in errors during daily tasks. There is some evidence that ketone ester supplements may lessen the adverse effects of sleep restriction. The main purpose of these supplements is to raise your blood concentration of ketones, which are safe, small molecules that appear in the blood during fasting, when following a ketogenic diet, or consuming ketone supplements.

The main purpose of this study is to examine if ingesting a ketone ester supplement, twice daily, can improve cognitive and physical performance during short-term sleep restriction.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Sleep Deprivation Dyssomnias Mental Disorders Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms Sleep Wake Disorders

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

The Ohio State University

Columbus, Ohio, 43210, United States

About this study

Only 1 in 3 U.S. Army Active Component Soldiers are estimated to get the target =7-hr of sleep on duty days, and ~14% have a sleep disorder. Insufficient sleep has profound effects on human performance that include deficits in working memory, creativity, innovative thinking, strategic planning, mood disturbances, lapses in attention and vigilance, and impaired physical performance. In a classic dose-response sleep study performed at Walter Reed Army Institute of Research, it was demonstrated that limiting sleep to 3-hr per night for 7-days resulted in a steady deterioration on a psychomotor vigilance task across the week of sleep restriction. Sleep restriction over 3-days has been shown to adversely affect marksmanship performance, including significantly longer time to make decisions, misidentifying friends versus foes, and believing performance did not change over time. Short-term sleep restriction is linked with impaired glucose metabolism and decreased whole body insulin sensitivity, and increases the risk of developing T2D. Military personnel have few good options to counteract physical and cognitive detriments attributed to insufficient sleep. Warfighters increasingly turn to caffeine and sugar-containing energy drinks to combat sleep loss and fatigue, especially during deployment. At best, these nutritional countermeasures provide a transient performance gain, and may trigger a 'rebound' hypoglycemia that exacerbates performance detriments that can increase the risk of obesity and related problems. Ketosis could improve tolerance to sleep restriction and sleep abnormalities through multiple mechanisms. We have reported that a 1-yr KD improved sleep quality and the proportion of people categorized as poor sleepers. Ketones are a preferred brain fuel that may enhance neurocognitive function. The ability to metabolize a lipid-derived substrate (ketones) capable of sustaining the brain's high energy demands during periods with limited access to carbohydrate was a central adaptation in human evolution, that is also associated with a remarkable protection from the adverse signs of hypoglycemia. At the low end of nutritional ketosis (0.5 mM), ~5% of whole brain energy metabolism is provided by ketones. At ketone concentrations of 1.5 mM (typical of KDs), ketones supply nearly 20%; at the higher end of nutritional ketosis 4-5 mM [achievable with ketone esters (KE)], half of the brain energy demands are met by ketones. Importantly in situations where brain glucose metabolism is impaired, uptake and utilization of ketones remain fully intact, suggesting a hierarchy of importance placed on ketones as the preferred fuel for human brains.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant is willing and able to comply with all study procedures including the following prior to Test Days: fasting (>10 h; water only), no alcohol (>24 h), no exercise (>24 h), no acute illness and controlled feeding before each Test Day, maintain diet, exercise, medication, and supplement habits throughout the study.
  • Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history.
  • Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator.

Exclusion criteria

  • <18 or >40 years of age
  • >35 body mass index (BMI).
  • Diagnosed sleeping disorders (i.e., sleep apnea, insomnia).
  • Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements.
  • Drink alcohol in excess of 3 drinks/day or 14 drinks/week
  • Have any conditions or contraindications to blood draws.
  • Have been diagnosed with diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or use diabetic medications other than metformin
  • Currently consume a low carbohydrate or ketogenic diet or have done so in the last 3 months
  • Have experienced weight loss of >10% of your body weight within the last 6 months
  • Are pregnant, lactating, or planning on becoming pregnant during the study
  • Have any major psychiatric disorders (e.g., schizophrenia, bipolar disorder)

Treatment and study plan

Sleep deprivation

Other

The sleeping protocol will be monitored by investigators and personnel with experience in sleep medicine. Participants will be required to reduce sleep by 50% of normal, for 4 consecutive nights, to observe potential deficits in physical and cognitive performance

Heart Rate

Other

HR will be assessed by wrist-based acceleration with cloud technology (Polar Unite™, Polar USA). This monitor is less burdensome than other sleep monitoring technologies and less likely to interfere with normal sleep and activity demands of the cadets. Each participant will be fitted with the watch for acclimatization and then establish 3-day baseline patterns for 3 nights before the sleep loss protocol.

Sleep monitoring

Other

Sleep will be assessed by wrist-based acceleration with cloud technology (Polar Unite™, Polar USA). This monitor is less burdensome than other sleep monitoring technologies and less likely to interfere with normal sleep and activity demands of the cadets.Each participant will be fitted with the watch for acclimatization and then establish 3-day baseline patterns for 3 nights before the sleep loss protocol.

Diet

Other

Diet will be included and the same meals will be available for all subjects while controlling for caffeine. Participants will be given food during each intervention week.

Exercise Performance

Other

Since weight training is now a crucial part of any warfighter's physical preparation, we will have subjects perform weight training workouts emphasizing all major muscle groups on Days 2, 3 and 4

Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index

Behavioral

These will be administered on Days 1 and 5 of each intervention trial to assess different behavioral outcomes.

Cognitive performance

Other

Automated Neuropsychological Assessment Metrics (ANAM), Cambridge Neuropsychological Test Automated Battery. (CANTAB),Gradual-onset Continuous Performance Task (GRAD-CPT),Face-Name Task will be used to assess cognitive function and performance.

Marksmanship Performance

Other

The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Multiple metrics of marksmanship (total number of shots fired/silhouette target presentation, percentage of targets successfully hit/min, the radial distance of a shot from the center on target, shot group tightness, and time from target presentation to trigger pull) will be collected during each visit.

Other names: VirTra

Quick Board

Other

Upper body and lower body reaction tests will be assess using Quick Board Analysis on days 1 and 5 of the sleep restriction intervention.

Other names: Response Time

Advanced Medical Technologies Inc, Jump Test

Other

Whole body power will be assessed with a repetitive jump test. Power (peak, average, curve functions) will be assessed using an AMTI force plate with Accupower 2.0 software (Advanced Mechanical Technology Inc, Watertown, MA).

Other names: Whole Body Power

CGM/CKM

Other

Continuous Ketone/Glucose Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at ~2- week intervals during the study. The sensor will be removed at the end of the final test day.

Blood Draw

Biological

Blood samples will be collected according to the schedule in Figure 1.

Ketone Supplement

Dietary Supplement

Participants will take a diester of hexanoic acid (a ketogenic medium chain fatty acid) and (R)-1,3 butanediol (C6 Di-ester) during one of the trial interventions

Primary outcomes

  1. Automated Neuropsychological Assessment Metrics (ANAM)

    Time frame: Up to ~ 4 weeks

    This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.

  2. Cambridge Neuropsychological Test Automated Battery. (CANTAB)

    Time frame: Up to ~ 4 Weeks

    This iPad delivery assessment will include an Information Sampling Task to test impulsivity and decision making, response time (in msec), which provides a level of sensitivity not available with traditional paper and pencil tasks, processing speed, executive functioning, and spatial memory. We have also incorporated tasks which assess the ability to rapidly identify expressed facial emotions, which may index one's ability to accurately respond to overtly threatening or non-threatening stimuli

  3. Gradual-onset Continuous Performance Task (GRAD-CPT

    Time frame: Up to ~4 weeks

    This test measures endogenous attentional control by using smooth (rather than abrupt) transitions between visual images. Scene stimuli are visually presented and smoothly transition from one scene to another. Subjects press a button when one type of scene is presented (e.g., city scene) and withhold the button press when another type of scene (e.g., mountain scene) is presented. It is a Go/No-Go test and assesses multiple metrics of executive function, including sustained attention, mind wandering, and response inhibition.

  4. Face-Name Task

    Time frame: Up to ~4 weeks

    We will implement a face-name relational memory task, known to activate the hippocampus (along with prefrontal and parietal cortices) in humans using face-name pairs presented for 3-sec with an interval of 750-msec. Participants will judge which name was previously presented with the face. After a 15-min delay, participants will complete an associative face-name recognition task to assess episodic memory performance.

  5. Total number of shots fired

    Time frame: Up to ~4 weeks

    The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Total number of shots fired, a metric of marksmanship, will be collected during each visit, to assess reaction time and accuracy.

  6. Percentage of targets successfully hit per minute

    Time frame: Up to ~4 weeks

    The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Percentage of targets successfully hit/min, a metric of marksmanship, will be collected during each visit to assess accuracy.

  7. Radial distance of a shot from the center on target

    Time frame: Up to ~4 weeks

    The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. The radial distance of a shot from the center on target, a metric of marksmanship, will be collected during each visit to assess shot accuracy.

  8. Shot Group Tightness

    Time frame: Up to ~4 weeks

    The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Shot group tightness, a metric of marksmanship, will be collected during each visit to assess multi-shot accuracy.

  9. Time from target presentation to trigger pull

    Time frame: Up to ~4 weeks

    The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Time from target presentation to trigger pull, a metric of marksmanship , will be collected during each visit to assess reaction time.

  10. Power Outcome (QuickBoard)

    Time frame: Up to ~4 weeks

    Upper body and lower body reaction tests will be assess using Quick Board Analysis on days 1 and 5 of the sleep restriction intervention.

Secondary outcomes

  1. CGM/CKM

    Time frame: Up to ~ 4 weeks

    Diurnal concentrations of ketones and glucose via a continuous monitor. The ketone sensor in this CKM device is similar to the FreeStyle Libre continuous glucose monitoring (CGM). The sensor adheres to the back of the arm where it continuously samples interstitial fluid for quantification of BHB concentration. The sensor is worn for a period of 2-wk, two sensors will be used to cover all test days in this study (4 weeks including 2 week washout)

  2. Heart Rate

    Time frame: Up to ~ 4 weeks

    HR will be assessed by wrist-based acceleration with cloud technology (Polar Unite™, Polar USA). This will allow for assessment of changes in HR.

  3. Short Form- McGill Pain Questionnaire

    Time frame: Up to ~ 4 weeks

    The Short Form McGill pain questionnaire (SF-MPQ) will be used to assess pain in individuals. Clinically important change (CIC): mean improvement in total scores >5 on the 0-45 SF-MPQ scale. Minimum detectable change (MDC) for total, sensory, affective, average, and current pain: 5.2cm, 4.5cm, 2.8cm, 1.4cm, and 1.4cm, respectively. The SF-MPQ will be examined around the sleep restriction/exercise intervention on Days 1 and 5 to assess pain change.

  4. Profile of Mood States- Short Form

    Time frame: Up to ~ 4 weeks

    Shortened Profile of Mood States- Short Form (POMS-SF) measures six different dimensions of mood swings over a period of time. These include: Tension or Anxiety, Anger or Hostility, Vigor or Activity, Fatigue or Inertia, Depression or Dejection, Confusion or Bewilderment. For each word and statement, they must circle the number on a Likert scale from 0= Not at all to 4=Extremely for how often they have felt those feelings today and over the past week. The POMS-SF will be examined around the sleep restriction/exercise intervention on Days 1 and 5 to assess mood.

  5. Pittsburgh Sleep Quality Index

    Time frame: Up to ~ 4 weeks

    The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. PSQI will be examined around the sleep restriction/exercise intervention on Days 1 and 5 to assess sleep quality.

  6. Insulin

    Time frame: Up to ~ 4 weeks

    Differences in blood hormones insulin after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).

  7. Ghrelin

    Time frame: Up to ~ 4 weeks

    Differences in blood hormones insulin after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).

  8. CRP

    Time frame: Up to ~ 4 weeks

    Differences in blood proteins after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).

  9. Brain Derived Neurotropic Factor

    Time frame: Up to ~4 weeks

    Differences in neurotrophins after supplementation will be analyzed using commercially available ELISA assay kits (Cayman Chemical, USA).

Sponsors and collaborators

Lead sponsor

Ohio State University

Other

Registry information

Acronym: STAK-Sleep

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Aug 29, 2022
Registry last updated
Jun 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.