NCT05519644

Strategies to Augment Ketosis: Ketone Conferred Resiliency Against Sleep Restriction

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Ohio State University · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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.

Conditions

• Sleep Deprivation

Interventions

Type	Name	Description
OTHER	Sleep Deprivation	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
OTHER	Heart Rate	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.
OTHER	Sleep Monitoring	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.
OTHER	Diet	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.
OTHER	Exercise Performance	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
BEHAVIORAL	Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index	These will be administered on Days 1 and 5 of each intervention trial to assess different behavioral outcomes.
OTHER	Cognitive performance	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.
OTHER	Marksmanship Performance	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	Quick Board	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	Advanced Medical Technologies Inc, Jump Test	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	CGM/CKM	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.
BIOLOGICAL	Blood Draw	Blood samples will be collected according to the schedule in Figure 1.
DIETARY_SUPPLEMENT	Ketone 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

Timeline

• Start date: 2023-06-20
• Primary completion: 2026-08-01
• Completion: 2026-08-01
• First posted: 2022-08-29
• Last updated: 2025-05-29

Locations

1 site across 1 country: United States