Modafinil to Optimize the Performance of Cold-Stressed Sleep-Deprived Personnel

200 mg Microcrystalline Cellulose

Placebo intervention to compare to modafinil intervention.

200 mg Modafinil

Evaluating the effect of Modafinil under both sleep deprivation and acute cold exposure on thermoregulation, cognitive flexibility/performance, and dexterity.

Height will be measured in inches using a stadiometer.

Body weight will be measured in kilograms using a calibrated electronic scale.

Fat mass will be measured in kilograms via dual x-ray absorptiometry and used to calculate body fat percentage (fat mass/body weight).

Lean mass will be measured in pounds using dual x-ray absorptiometry.

Bone mineral content (BMC) will be measured in pounds using dual x-ray absorptiometry.

Physical activity and sleep duration will be recorded in minutes per day with a wrist actigraphy monitoring system (Actiwatch Spectrum Plus, Koninklijke Philips N.V., Amsterdam, NL or equivalent device). The accelerometer will be placed on the volunteer's wrist on the first familiarization day, worn continuously throughout the entirety of study participation (11 days total), and returned after a 2-day washout period after the second overnight collection. Activity and sleep measurements recorded by the accelerometer will be utilized to determine sleep/wake times of volunteers throughout the study duration.

Core temperature will be measured continuously at baseline (room temperature) and during cold exposure using a telemetric thermometer capsule (e-Celsius® Performance Capsule, BodyCap, Saint-Clair, France, or similar). Volunteers will either insert the capsule as a rectal suppository the morning of testing, or opt to ingest orally the night (at least 12 hours) prior to data collection to ensure deep core body temperature is accurately monitored. Volunteers will be removed from testing if core temperature decreases to 35 degrees Celcius or lower.

Skin temperature will be continuously measured in Celcius at baseline (room temperature) and during cold exposure using Thermochron iButtons attached at the volunteer's chest, triceps, hand, thigh, calf, and foot.

The FTT is an approximately 10 minute test used to assess manual dexterity and visuomotor coordination. Volunteers are asked to follow simply motor commands using their hands and fingers while seated using a standard 8-finger QWERTY keyboard position (left fingers resting on ASDF, right fingers resting on JKL;). Volunteers are presented varying finger tap sequences on a computer displaying spatially compatible keys matching the standard position (ASDFJKL;) and asked to press the corresponding key while wearing Army issued contact gloves. The presentation time of cues will be adjusted throughout the task at variable difficulties to assess visuomotor response thresholds. Volunteers are scored based on how quickly finger taps are correctly executed in the presented sequence without errors of omission, commission, or excursions.

Volunteers will continuously scan a computer screen to detect stimuli that are present in irregular intervals approximately every 1 minute. Volunteers will be scored based on whether a stimulus is correctly detected (max score of 30), falsely detected, and the response time in milliseconds when detected. This task is sensitive to low doses of stimulants, nutritional factors, environmental conditions, and sleep loss.

PVT is a 10-minute test of simple visual reaction time used to assess alertness. Volunteers will be scored based on reaction time, correct responses, and lapses (failure to detect stimuli).

Matching to Sample assesses short-term spatial memory (working memory) and pattern recognition. Volunteers are presented with a series of 8x8 matrices. Each matrix is displayed for 4 seconds, volunteers see a blank screen for 8 to 16 seconds, and then 2 matrices will be presented: one matrix identical to the original, and another slightly different to the original. Volunteers have 15 seconds to select the correct comparison matrix. Volunteers will be scored by correct responses, reaction time, and time-out errors.

Grammatical reasoning assesses language-based logical reasoning. Volunteers will be presented with either the letters "AB" or "BA" followed by a statement that describes the order of the two letters (e.g. "A precedes B"). The volunteer must select whether the statement is true or false. Volunteers are scored based on accuracy and reaction time, with a max score of 32 correct responses.

The Go/No-Go Task is a 10 minute test that assesses response inhibition. Volunteers will randomly be presented with with a "+" or "x" on their screen during moderate exercise on a stationary bike. Volunteers will be instructed to press a button as quickly as possible in response to one visual stimulus, and withhold a response to the other visual stimulus. Number of correct responses, incorrect responses, and reaction time will be scored.

The N-Bask Task is a 10 minute assessment of working memory. Volunteers will be shown a series of letters on a screen while performing moderate exercise on a stationary bike and asked to mentally take note of the letters shown. Volunteers will then be asked to respond "yes" or "no" by pressing the respective button if the letters currently displayed are the same letters that were displayed either 1, 2, and/or 3 letters back. Correct and incorrect responses will be recorded as a volunteer score.

Task-Switching is a 10 minute assessment of cognitive flexibility. Volunteers will switch back and forth randomly between determining if the number presented on the screen is odd or even or if the number presented is above or below 5 while performing moderate exercise on a stationary bike. Volunteers will decipher which task is being performed based on the color of the number presented (pink or blue), and press the corresponding button on their keypad (odd/even or greater than/less than). Volunteers will be scored based on number of correct responses.

Grip strength will be measured in both hands to evaluate manual performance under cold stress using a hand dynamometer. Volunteers were asked to hold the dynamometer in a neutral position (shoulder adducted, elbow flexed to 90 degrees, forearm and wrist neutral) and instructed to squeeze the handle as hard as possible while maintaining a neutral position. Three repetitions will be completed for each hand, alternating hands between each trial. Grip strength for each hand was scored as the mean of the 3 trials, recorded in kilograms.

The BART is used to assess risk-taking behavior, reportedly altered by sleep loss. Volunteers will repeatedly fill simulated balloons with air, and points are awarded each time the balloon inflates with air without "popping it". The more the balloon is inflated, the more points are earned. Volunteers can bank their points at any time. All points accumulated that are not banked will be lost if the balloon pops. Simulated balloons will randomly pop after either 8, 32, or 128 puffs. Volunteers will be scored based on how many balloons are popped in each of these categories.

Volunteers will complete a single item exit survey at the end of the second experimental visit to assess the potential of the placebo effect on cognitive and physical performance during cold exposures. Volunteers will be asked to report which experimental session they believe they consumed Modafinil, answering either: session 1, session 2, or not sure.

Volunteers will be prescribed a standardized diet (1.2 g/kg protein, 6 g/kg carbohydrate, 1 g/kg fat) to moderate the potential influence of diet on performance during the experimental visits. Diet prescription will be based on volunteer body mass measured at the first familiarization visit. Volunteers will start diet prescription 48 hours prior to the first experimental visit at baseline assessment, and continue study diet through completion of second experimental visit (8 days total). Study dieticians will prepare individual diets derived from military combat rations (MRE; Meal, Ready-to-Eat) and commercially available food items. Dietary intake will be verified by collecting wrappers/containers and any food or drink that is not entirely consumed will be weighed and accounted for.

The ESQ was used to determine the effects of exposure to environmental extremes. A modified version of the ESQ was used to assess the effects relevant to cold exposure only. Volunteers were asked to rate statements on a scale from 1 (not at all) to 5 (extreme). Higher scores indicate that the volunteer is experiencing more severe symptoms of cold exposure.

The POMS is a 65-item inventory of mood states that asks volunteers to rate each mood-related adjective on a 5-point scale (0-4) based on how the volunteer is currently feeling. Mood states will be measured on 7 sub-scales: 1) tension/anxiety [TA], 2) depression/dejection [DD], 3) anger/hostility [AH], 4) vigor/activity [VA], 5) fatigue/inertia [FI], 6) confusion/bewilderment [CB], and 7) friendliness. Subscales 1-6 have a potential score of 0-44, while the friendliness subscale has a potential score of 0-40. Total mood disturbance is calculated as: [(TA + DD + AH + FI + CB) - VA] with a potential score of 0-176 . Higher scores indicate that the individual experiences more intense or more frequent negative mood states compared to the general population.

The Buss-Perry Aggression Questionnaire is a 29-item questionnaire that assesses aggressive impulses and thought patterns. Volunteers rank statements on a 5-point scale from "extremely uncharacteristic of me (1)" to "extremely characteristic of me (5)." Aggression is scored on 4 scales: 1) physical aggression, 2) verbal aggression, 3) anger, and 4) hostility. Volunteers are scored for each subscale: physical (scored 9-45), verbal (scored 5-25), anger (scored 7-35), and hostility (scored 8-40), as well as a total score of all items (scored 29-145). Higher scores indicate greater overall aggression.

The FAS is a one-item inventory measuring feelings of arousal ranging from 1 (low arousal) to 6 (high arousal). Volunteers will be asked to rate their current level of arousal in the final minute of the 15-minute bout of moderate exercise on a stationary bike. Higher scores indicate higher levels of arousal.

The FS is a one-item inventory measuring the extent to which pleasant or unpleasant feelings are currently experiencing. The FS ranges from 5 (very good) to -5 (very bad). Volunteers will complete the FS in the final minute of the 15 minute bout of moderate exercise on a stationary bike. Higher scores indicate the volunteer is experiencing more pleasant feelings while lower scores indicate the volunteer is experiencing more unpleasant feelings.

The CD-RISC-25 was administered at the start of the first familiarization day to assess volunteer resilience as a potential moderating psychological factor. Volunteers were asked to rate 25 items on a scale from "not true at all" (0) to "true nearly all the time" (4). Scores can range from 0-100, with higher scores reflecting greater resilience.

A background survey will be administered at the start of the first familiarization day. Volunteers will be asked to report basic demographic information, tobacco and supplement use, military service, recent physical activity habits, and previous experience with cold exposure as potential moderating variables of cognitive and physical performance during experimental visits.

Participants were asked to report any adverse events they may have experienced in the 24 hours following completion of 26-hour overnight cold exposures. Study staff met with volunteers to complete an in-person assessment the morning after overnight collection (Days 4 and 8) and provided a list of expected adverse events associated with Modafinil and sleep deprivation, as well as asked to report any other events/symptoms. Volunteers were asked to report whether they had experienced: trouble sleeping, nausea/other GI issues, headache, numbness or pain in fingers, numbness or pain in toes, other (specify), or no adverse event.