Ketone Conferred Resiliency Against Sleep Restriction With Nutritional Intervention.

NCT06075914 | Recruiting DMC

• 2 other identifiers: 2022H0308CDMRP-PR212399-D
• 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. Ketogenic supplementation is speculated to alleviate some sleep deprivation issues via action of ketones. Ketones are small molecules that appear in the blood when following a ketogenic diet or consuming ketone supplements. The goal of this project is to find out if diet and/or ketones can improve sleep deprivation detriments over 5 days of sleep restriction (-50% from habitual sleep).

Conditions

Sleep Deprivation; Nutritional Intervention

Keywords

Ketogenic Diet; Mediterranean Diet; Ketone Esters; Placebo

Outcome Measures

Primary Outcomes (12)

• Habitual Sleep

  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. Habitual sleep will be measured using a validated Pittsburgh Sleep Index questionnaire (average time in bed in the past 30-days).

  Up to ~9-weeks

• Polysomnography

  Sleep parameters (timing, duration, and quality of sleep) will be assessed by a continuous ring-finger wearable (Oura Ring™, USA). Specific sleep monitoring variables are polysomnography sleep stages (light sleep, rapid eye-movement sleep, deep sleep, sleep latency, total sleep duration).

  Up to ~9-weeks

• Heart Rate + Variability (HRV) Monitoring

  Heart rate and heart rate variability will be assessed during sleep deprivation by wrist-based acceleration and bluetooth pairing with a chest heart rate sensor (Polar Unite™, Polar USA).

  Up to ~9-weeks

• Neuropsychological Outcome 1 - ANAM

  The first cognitive assessment will be done via 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 ~9-weeks

• Neuropsychological Outcome 2 - GRAD-CPT

  The second cognitive assessment will be Gradual-onset Continuous Performance Task (GRAD-CPT). 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 that assesses multiple metrics of executive function, including sustained attention, mind wandering, and response inhibition.

  Up to ~9-weeks

• Neuropsychological Outcome 3 - Face-Name Task

  The third task is the Face-Name Task. 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 ~9-weeks

• Shooting Performance

  Ohio State University is one of the few centers in the world equipped with a Virtual Training (VirTra) small arms indoor training simulator. 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.

  Up to ~9-weeks

• Neuromuscular Monitoring (Agility)

  We will be collecting agility measures (upper/lower body) using the QuickBoard. This 5-sensor bluetooth board is designed to capture upper- and lower-body contact reaction time and precision to randomized light prompts on an iPad. Participants will undergo 3 series of upper-lower body prompts, 20s each, with 60s rest in-between sets (1:3 work:rest ratio).

  Up to ~9-weeks

• Neuromuscular Monitoring (Strength)

  Strength performance will be monitored by using hand-grip strength, countermovement jump power, and isometric mid-thigh pull. All exercises will be performed in sets of 3.

  Up to ~9-weeks

• Continuous Intestitial Fluid Monitoring

  Continuous quantification of interstitial fluid glucose and beta-hydroxybutyrate (BHB) will be monitored using sensor-based devices developed and manufactured by Abbott Biowearables. Values are recorded non-invasively and automatically every 15-minutes. The wear period for a sensor is 14-days and thus we will have participants apply new sensors a week before beginning the second sleep deprivation trial. Sensors will be placed on the non-dominant arm (mid-triceps region) during each experimental phase.

  Up to ~9-weeks

• Daily Ketone/Glucose Monitoring

  Daily fasting glucose/ketones will be assessed using capillary finger stick lancing. A small drop of blood will be obtained once daily, while fasting, using enzymatic strips fitted for a handheld analyzer (KetoMojo). All the data will be stored in the device's internal memory.

  Up to ~9-weeks

• Venous Blood Draws

  Fasting venous blood will be collected at Day 1 and Day 5 of the sleep restriction protocol, then again after the 6-week feeding period to measure metabolites and hormones in serum and plasma (i.e., cholesterol, testosterone, growth-hormone, insulin, melatonin, epinephrine/norepinephrine).

  Up to ~9-weeks

Study Arms (3)

Ketogenic Diet Arm

EXPERIMENTAL

The goal of the KD is to have participants achieve consistent blood BHB ≥0.5 mM; preferably in the range of \>1 to 3 mM. We will measure ketones daily via finger stick to provide individual feedback and provide a quantitative measure of compliance. The KD will consist of approximately 50 g carbohydrate and 1.5 g/kg reference weight protein. These may be adjusted based on daily BHB readings. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods. A wide range of foods will be incorporated including non-starchy vegetables, fruits (berries, olives, tomatoes, lemons/limes), meats (beef, chicken, pork, fish, lamb), nuts and seeds, oils (olive, canola, coconut), cheese, butter, cream, eggs, and fatty fish (salmon, sardines). Nutritional ketosis is associated with natriuresis that will lead to sodium and fluid loss if the extra sodium excreted is not compensated, thus slightly higher sodium and potassium intakes will be required.

Other: Ketogenic Intervention

Mediterranean Diet + Placebo

PLACEBO COMPARATOR

The MD+PL arm will be modeled after a Mediterranean style eating pattern. It will contain the same amount of protein as the KD, but with slight variations in protein sources, including limiting red meat to 1x/wk. The diet will provide unprocessed, higher-fiber foods with emphasis on vegetables, fruits, nuts and seeds, legumes, tubers, whole grains, and fish and seafood. Poultry, eggs, cheese, and yogurt will be included in moderate amounts. Use of olive oil and other monounsaturated fat sources (e.g., avocados and olives) will be encouraged while keeping added sugars to a minimum and avoiding highly processed foods (refined grains, fruit juice, processed meats). Saturated fat will be \<10% of energy. We will include adequate omega-3 fats (e.g., salmon). No alcohol will be included in both diets, but we will track consumption. This group will also consume two daily doses of placebo.

Other: Mediterranean Intervention; Dietary Supplement: Placebo

Mediterranean Diet + Ketone Ester

ACTIVE COMPARATOR

The MD+KE arm will consume the exact same diet as the MD+PL group with the exception they will consume two daily doses of KE instead of the placebo.

Other: Mediterranean Intervention; Dietary Supplement: Ketone Ester

Interventions

Ketogenic Intervention OTHER

Participants will receive ready-to-eat Ketogenic Diet meals.

Ketogenic Diet Arm

Mediterranean Intervention OTHER

Participants will receive ready-to-eat Mediterranean Diet meals.

Mediterranean Diet + Ketone Ester; Mediterranean Diet + Placebo

Placebo DIETARY_SUPPLEMENT

Participants will receive twice-daily placebo servings to be consumed once in the morning and once before sleep.

Mediterranean Diet + Placebo

Ketone Ester DIETARY_SUPPLEMENT

Participants will receive twice-daily ketone ester servings to be consumed once in the morning and once before sleep.

Mediterranean Diet + Ketone Ester

Eligibility Criteria

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

You may qualify if:

• Healthy, 18-40 years old.
• BMI: 20-35 kg/m2
• Sleep at least 7h per night.
• Willing to participate in \~9-weeks of testing and provided food.
• Willing to adhere to all study procedures.

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

formic acid 4-(3-oxobutyl)phenyl ester

Condition Hierarchy (Ancestors)

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

Study Officials

• Jeff S Volek, PhD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeff S Volek, PhD, RD

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind (investigator and participants)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, random allocation, balanced 3-arm study.

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: October 10, 2023
• Study Start: May 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)