Modafinil to Optimize the Performance of Cold-Stressed Sleep-Deprived Personnel
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Height (in)
研究概览
简要总结
Environmental and workplace stressors are common and often unavoidable in military operations. Two critical stressors are cold stress and sleep loss. They both can substantially degrade operational effectiveness. Various countermeasures are available to mitigate the adverse effects of these stressors, but due to operational requirements many are of limited use in the field. Modafinil is a drug that mitigates the effects of sleep deprivation and potentially cold stress, and modafinil may prevent performance degradation due to the combination of these stressors. This study will help determine if modafinil alters body-heat production and prevents cognitive and physical performance degradation due to cold stress in rested and sleep-deprived volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 17 Years 至 39 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, men and women aged 18-39 years old. Active-duty military personnel who are 17 years of age will also be allowed to participate.
- •Willing to refrain from the use of caffeine - including dietary supplements that contain caffeine - alcohol, and nicotine 24 hours prior to data collection.
- •Willing to refrain from vigorous physical activity 24 hours prior to data collection.
- •Willing to refrain from any dietary supplement use within one week of initial screening and at any time while enrolled in the study (except a multi-vitamin containing up to 100% RDA).
- •Willing to consume study diets throughout the course of the study.
- •Supervisory approval for participation if permanent party military or a federal employee.
排除标准
- •Use of modafinil or armodafinil in the last 3 months.
- •Known allergy to modafinil or armomodafinil.
- •Current medical profile, or condition, that limits, compromises, or is likely to render inconsistent performance with Grip Strength, Finger Tapping, or cardiovascular exercise on an exercise bike.
- •a. Individuals taking substances that directly interact with modafinil, alertness/attention/concentration, or sympathetic tone: stimulants; decongestants, barbiturates, bronchodilators; SNRIs; opioids; appetite suppressants; anti-obesity medications; b. Individuals taking substances which inhibit CYP3A4 (penicillins; macrolide antibiotics; fluoroquinolones; lomitapide; goldenseal) or MAO inhibitors.
- •c. Individuals taking substances which induce CYP3A4 (carbamazepine, phenobarbital, rifampin) to a greater than minimal degree: systemic steroids; anti-gout agents (Exceptions can be recommended to PI for CYP3A4 inducers which do not fall into other listed categories).
- •d. Individuals taking substances which are metabolized by CYP450 enzymes 1A2, 2B6, 2C19, or 3A4: immune-suppressant/-modulatory drugs; SSRIs; TCAs; anti-coagulants; antituberculosis agents; antimalarials; antineoplastic agents; antibody-derived drugs; antivirals; azole antifungals; anti-parasitic agents; abortive migraine medications; muscle relaxants; sex hormones or modulators; ibrexafungerp; lefamulin; palovarotene; propranolol.
- •Females who are pregnant or breastfeeding, have a positive- pregnancy test, or plan on becoming pregnant in the next 3 months.
- •Individuals currently taking/using contraceptives (i.e., oral contraceptive pill, intrauterine device, contraceptive implant, contraceptive injection, etc.) other than condoms.
- •Current or history of mental health issues, illness, or condition (i.e., attention deficit hyperactivity disorder, autism spectrum disorder, diagnosed depression or anxiety disorders) that OMSO physician/healthcare provider believes puts the volunteers at increased risk.
- •Current or history of psychosis, or history of suicidal or homicidal ideations within the past 2 years.
- •History of cold injuries or cold-induced asthma.
- •Raynaud's syndrome.
- •Previous hand/finger injuries that impair dexterity and hand function.
- •Metal hardware (plates/screws) in the upper extremities (arm/hands).
- •Abnormal blood count (For example: hemoglobin (Hb) outside of the typical normal values reported by LabCorp in accordance with OMSO (Normal [Hb] Males = 12.6-17.7 g/dL; Females = 11.1-15.9 g/dL) or hematocrit (Hct) outside of the normal ranges (Normal Hct Males = 37.5-51.0%; Females = 34.0-46.6%) levels, presence of abnormal blood laboratory measures (e.g., hemoglobin S or sickle cell traits).
- •Current or history of alcohol abuse (defined as Harmful Use by the World Health Organization), those who meet criteria for alcohol abuse disorder (as outlined in the DSM-5), or other substance abuse (i.e., the use of illegal drugs or the use of prescription or over-the-counter drugs for purposes other than those for which they are meant to be used, or in excessive amounts).
- •Diagnosed sleep disorders (i.e., sleep-apnea, narcolepsy, etc.).
- •Diseases and disorders of the metabolic, cardiovascular, endocrine, neurological, or gastrointestinal systems that in determination of OMSO are expected to interfere with safe conduct of the study.
- •A medical diagnosis of high blood pressure (hypertension).
- •Heart problems or prior heart attack.
- •Regular daily use of medication that may significantly interfere with the study drug or outcomes, as determined by the OMSO physician/healthcare provider.
- •Known allergies to medical adhesives.
- •Difficulty swallowing large pills (self-reported) for those individuals unwilling to utilize the rectal suppository of the telemetric pill.
- •History of obstructive disease of the gastrointestinal tract including (but not limited to) diverticulosis, diverticulitis and inflammatory bowel disease, peptic ulcer disease, Crohn's disease, ulcerative colitis, or previous gastrointestinal surgery, etc. that OMSO physician/healthcare provider believes puts the volunteers at increased risk.
- •Donated blood within 8 weeks prior to study participation.
研究组 & 干预措施
Placebo
200 mg Microcrystalline Cellulose
干预措施: 200 mg Microcrystalline Cellulose (Drug)
Modafinil
200 mg Modafinil
干预措施: Modafinil (M) (Drug)
结局指标
主要结局
Height (in)
时间窗: Familiarization 1 (Day -2)
Height will be measured in inches using a stadiometer.
Body Weight (kg)
时间窗: Familiarization 1 (Day -2)
Body weight will be measured in kilograms using a calibrated electronic scale.
Body Composition: DXA Fat Mass (lbs)
时间窗: Familiarization 1 (Day -2)
Fat mass will be measured in kilograms via dual x-ray absorptiometry and used to calculate body fat percentage (fat mass/body weight).
Body Composition: DXA Lean Mass (lbs)
时间窗: Familiarization 1 (Day -2)
Lean mass will be measured in pounds using dual x-ray absorptiometry.
Body Composition: DXA Bone Mineral Content (lbs)
时间窗: Familiarization 1 (Day -2)
Bone mineral content (BMC) will be measured in pounds using dual x-ray absorptiometry.
Sleep & Physical Activity
时间窗: Familiarization 1 to Study Completion (11 Days)
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.
Cold Exposure: Core Temperature
时间窗: Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cold Exposure: Skin Temperature
时间窗: Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Dexterity: Finger Tapping Task (FTT)
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: Scanning Visual Vigilance
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: Psychomotor Vigilance Test (PVT)
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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).
Cognitive Assessment: Matching to Sample
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: Grammatical Reasoning
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: Go/No-Go Task
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: N-Back Task
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Cognitive Assessment: Task-Switching Task
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
Physical Performance: Grip Strength
时间窗: Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7)
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.
次要结局
- Cognitive Assessment: Balloon Analogue Risk Task (BART)(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Assessment of Blinding(Cold Exposure (Day 7))
- Dietary Intake(Baseline Assessment (Day 0) to Cold Exposure (Day 7))
- Cold Exposure: Environmental Symptoms Questionnaire (ESQ)(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Mood Assessment: Profile of Mood States Questionnaire (POMS 2-A)(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Mood Assessment: Buss-Perry Aggression Questionnaire(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Mood Assessment: Felt Arousal Scale (FAS)(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Mood Assessment: Feeling Scale (FS)(Familiarization 1 (Day -2), Familiarization 2 (Day -1), Baseline Assessment (Day 0), Cold Exposure (Days 2 & 3), Cold Exposure (Days 6 & 7))
- Resilience: Connor-Davidson Resilience Scale (CD-RISC-25)(Familiarization 1 (Day -2))
- Background Survey(Familiarization 1 (Day -2))
- Adverse Events(Post Overnight Chamber Exposures (Days 5 & 8))
研究者
Harris R. Lieberman
Research Psychologist
United States Army Research Institute of Environmental Medicine