Strategies to Augment Ketosis: Ketone Conferred Resiliency Against Sleep Restriction

NCT05519644 | Recruiting DMC

• 2 other identifiers: 2022H0169CDMRP-PR212399-C
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sleep Deprivation

Outcome Measures

Primary Outcomes (10)

• Automated Neuropsychological Assessment Metrics (ANAM)

  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.

  Up to ~ 4 weeks

• Cambridge Neuropsychological Test Automated Battery. (CANTAB)

  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

  Up to ~ 4 Weeks

• Gradual-onset Continuous Performance Task (GRAD-CPT

  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.

  Up to ~4 weeks

• Face-Name Task

  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.

  Up to ~4 weeks

• Total number of shots fired

  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.

  Up to ~4 weeks

• Percentage of targets successfully hit per minute

  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.

  Up to ~4 weeks

• Radial distance of a shot from the center on target

  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.

  Up to ~4 weeks

• Shot Group Tightness

  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.

  Up to ~4 weeks

• Time from target presentation to trigger pull

  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.

  Up to ~4 weeks

• Power Outcome (QuickBoard)

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

  Up to ~4 weeks

Secondary Outcomes (9)

• CGM/CKM

  Up to ~ 4 weeks

• Heart Rate

  Up to ~ 4 weeks

• Short Form- McGill Pain Questionnaire

  Up to ~ 4 weeks

• Profile of Mood States- Short Form

  Up to ~ 4 weeks

• Pittsburgh Sleep Quality Index

  Up to ~ 4 weeks

Study Arms (2)

Placebo First

ACTIVE COMPARATOR

Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.

Other: Sleep Deprivation; Other: Heart Rate; Other: Sleep Monitoring; Other: Diet; Other: Exercise Performance; Behavioral: Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index; Other: Cognitive performance; Other: Marksmanship Performance; Other: Quick Board; Other: Advanced Medical Technologies Inc, Jump Test; Other: CGM/CKM; Biological: Blood Draw; Dietary Supplement: Ketone Supplement

Ketone Ester First

EXPERIMENTAL

Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo

Other: Sleep Deprivation; Other: Heart Rate; Other: Sleep Monitoring; Other: Diet; Other: Exercise Performance; Behavioral: Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index; Other: Cognitive performance; Other: Marksmanship Performance; Other: Quick Board; Other: Advanced Medical Technologies Inc, Jump Test; Other: CGM/CKM; Biological: Blood Draw; Dietary Supplement: Ketone Supplement

Interventions

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

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

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

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

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.

Also known as: VirTra

Ketone Ester First; Placebo First

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.

Also known as: Response Time

Ketone Ester First; Placebo First

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).

Also known as: Whole Body Power

Ketone Ester First; Placebo First

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.

Ketone Ester First; Placebo First

Blood Draw BIOLOGICAL

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

Ketone Ester First; Placebo First

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

Ketone Ester First; Placebo First

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \<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)

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• OSU Office of Responsible Research Practices

MeSH Terms

Conditions

Sleep Deprivation

Interventions

Heart Rate; Diet; Surveys and Questionnaires; Reaction Time; Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Psychological Techniques; Behavioral Disciplines and Activities; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative

Study Officials

• Jeff S Volek, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeff S Volek, PhD

CONTACT

6146881701; volek.1@osu.edu

Madison L Kackley, PhD

CONTACT

7408171622; kackley.19@osu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Study product will be distributed in a blinded manner by people not involved with testing.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A double-blind, placebo-controlled, two-period cross-over study

Study Record Dates

• First Submitted: August 18, 2022
• First Posted: August 29, 2022
• Study Start: June 20, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 29, 2025

Record last verified: 2025-05

Locations

US (1)