Real-Time Caffeine Optimization During Total Sleep Deprivation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Arizona
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 1 at home monitoring
Study Overview
Brief Summary
Sleep deprivation (SD) has a powerful degrading effect on cognitive performance, particularly psychomotor vigilance (PV) and reaction time. Caffeine is well known to be an effective countermeasure to the effects of SD. However, individuals differ in both their response to SD and to the administration of caffeine. This has made it difficult to provide individualized recommendations regarding the use of caffeine to sustain alertness when needed. For the past two decades, the Army's Biotechnology HPC Institute (BHSAI), in collaboration with the Walter Reed Army Institute of Research, have been developing statistical models to predict individual performance during prolonged SD. Recently, this resulted in the publication of the 2B-Alert app, a computer algorithm based on large datasets that can learn an individual's response to SD by combining actigraphic sleep data with simultaneously acquired PV performance data. The 2B-Alert algorithm can predict an individual's sleep need and performance after ~2 weeks of training the model. Recently, the model has been extended to incorporate individualized responses to caffeine. This was recently validated in a retrospective study published by BHSAI in 2019. The present study is designed to test the predictive capacity of the 2B-Alert app in real time. During Phase 1 a total of 21 healthy participants will wear an actigraph & complete multiple daily PV tests on a personal cell phone. After 2 weeks, these individuals will attend Phase 2 involving an in-laboratory stay & SD. Participants will have an 8-hour period of sleep in the laboratory, followed by 62 hours of continuous wakefulness. During these 62 hours, participants will complete PV and mood testing every 3 hours. The 2B-Alert app will be used to predict individual caffeine need to sustain performance at near-baseline levels based on the statistical model. At 44 hours SD, participants will undergo a 6-hour "alertness window" where they may receive individualized doses of caffeine based on the recommendations of the model. After 62 hours of SD, Phase 3 begins, involving a night of monitored recovery sleep and additional sessions of PV and mood testing until release from the study at 6 pm on the final day. It is hypothesized that the 2B-Alert app will be effective at providing caffeine dosing recommendations that return PV and mood performance to normal levels during the alertness window.
Detailed Description
The first objective of the present study is to determine whether the 2B-Alert Caffeine Optimization Model (2BAlert) can create individualized caffeine schedules that effectively recover PVT performance during a specified window of time. The 2BAlert model is the linchpin of the comprehensive fatigue management system being developed by Walter Reed Army Institute of Research (WRAIR) and Biotechnology High Performance Computing Software Applications Institute (BHSAI). It is a software tool that "learns" (quantifies) the relationship between an individual's sleep/wake parameters (as objectively measured via wrist actigraphy) and his/her psychomotor performance (as objectively measured on a PVT). It quantifies the extent to which an individual is sensitive/resilient to the effects of sleep loss, and produces individualized performance predictions that can be used to inform decisions regarding current and future readiness, as well as the application of fatigue countermeasures such as naps or caffeine. The most recent version of 2BAlert can apply fatigue countermeasures directly to an individual based on their individualized performance prediction. This model gives recommendations for when and how much caffeine to use in order to optimize performance during a specified period of time. While this model has been applied post-hoc to previously collected data, it has yet to be tested in real-time. This study will provide the first opportunity to directly test if the model can be effectively used, in real-time, to recover PVT performance to a desired level (i.e., 275ms) when required (i.e., a six hour period following 44 hours of sleep loss).
A second objective of the present study is to investigate if 2BAlert can not only recover PVT performance during a specified period, but also recover increases in self-reported stress and anxiety related to sleep-loss. Data from a previous study by WRAIR shows that self-reported stress and anxiety increase after 1 night of sleep loss and continues to increase after a second night of continuous sleep deprivation. These measures return to baseline following 12 hours of recovery sleep and map directly onto PVT performance. Therefore, the investigators hypothesize that if PVT performance can be recovered by caffeine, self-reported stress and anxiety can also return close to baseline levels with caffeine.
A tertiary objective of the study is to assess whether images acquired using a smartphone camera are suitable for developing a passive, non-intrusive computer-vision system that could substitute the PVT for assessing alertness. Currently, the algorithm uses PVT data because: (a) compared to other performance measures, the PVT is relatively sensitive to sleep loss and the circadian rhythm of alertness; and (b) there are no learning effects on the PVT. However, the PVT requires an individual to actively engage in a 3- to 10-min long test, which must be performed at least a dozen times during sleep deprivation, making it a sensitive but impractical test to measure a Soldier's alertness in operational settings.
All participants will participate in the following continuous study phases. Caffeine gum may be administered during this study.
Phase 1: At Home Sleep/Wake Measurement: All participants will be instructed to maintain their normal sleep/wake schedule for the 13 days/12 nights immediately preceding phase 2 (the in-laboratory portion of the study). Compliance will be verified objectively via wrist actigraphy. Participants will be given a smartphone and asked to complete a PVT on it every 3 hours while awake and log their normal caffeine use as well as daily sleep duration.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 39 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy men and non-pregnant, non-lactating women.
- •Must demonstrate adequate comprehension of the protocol by achieving a score of at least 80% correct on a short multiple-choice quiz. Individuals who fail to achieve a passing score on the initial quiz will be given one opportunity to retest after a review of protocol information. Individuals who fail the comprehension assessment for the second time will be disqualified
Exclusion Criteria
- •Self-reported habitual nightly sleep amounts outside the target range of approximately 6-9 hours (i.e., less than 6 hours per night or more than 9 hours per night, on average)
- •Self-reported nighttime lights-out times earlier than approximately 2100 hours on average during weeknights (Sunday through Thursday)
- •Self-reported morning wake-up times later than approximately 0900 on average during weekdays (Monday through Friday)
- •Self-reported habitual napping (> 3 times per week) in conjunction with normal sleep habits
- •Self-reported symptoms suggestive of a sleep disorder (to include but not limited to sleep disordered breathing/sleep apnea, narcolepsy, idiopathic hypersomnia, restless leg syndrome, parasomnias, REM behavior disorder, etc.)
- •History of a sleep disorder (to include all of the above)
- •Any use of prescription or over-the-counter sleep aids during the 6 month period prior to screening indicative of a potential sleep disorder as determined by the examining study physician (e.g., use of a sleep aid for several nights following time zone travel, or the occasional use of a sleep inducing medication (e.g. 1-2 times per month), would not necessarily constitute evidence of a sleep disorder and result in disqualification)
- •Self-reported caffeine use in excess of 400 mg (e.g., approximately 8 caffeinated sodas or approximately 3-4 12-oz cups of coffee) per day on average
- •History of neurologic disorder (to include but not limited to epilepsy or another seizure disorder, amnesia for any reason, hydrocephalus, MS). An infrequent or resolved single neurological event (e.g., childhood seizure, rare sporadic migraine headaches, resolved meningeal infection with no sequelae) may be deemed non-exclusionary at the discretion of the examining study physician.
- •Score of 14 or above on the Beck Depression Inventory
- •Score of 41 or above on the Spielberger Trait Anxiety Inventory
- •Score of lower than 31 or higher than 69 on the Morningness-Eveningness Questionnaire
- •Self-reported or suspected regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent per week) within the last 1 year)
- •Self-reported or suspected heavy alcohol use (minimum limit to define heavy alcohol use is 14 drinks per week or as determined by the examining study physician)
- •History of cardiovascular disease (to include but not limited to arrhythmias, valvular heart disease, congestive heart failure, history of sudden cardiac death or myocardial infarction)
- •Underlying acute or chronic pulmonary disease requiring daily inhaler use
- •Kidney disease or kidney abnormalities
- •Liver disease or liver abnormalities
- •Self-reported history of psychiatric disorder requiring hospitalization or use of psychiatric product for any length of time
- •Self-reported or suspected use of products or drugs that cannot be safely discontinued during in-laboratory phases, to be determined on a case-by-case basis by the examining study physician
- •Self-reported or suspected current use of other illicit drugs (to include but not limited to benzodiazepines, amphetamines, cocaine, marijuana)
- •(Females only) Positive urine pregnancy result
- •(Females only) Self-reported or suspected current breast-feeding or collecting breast-milk
- •Resting blood pressure above 140/90 or resting pulse > 110 beats per minute Note that if a repeat measurement is within range, volunteer will not be excluded.
- •BMI ≥ 30 (Obese Class I or greater)
- •Clinically significant values (as determined by the reviewing study physician) for any hematology or chemistry parameter. Reviewing study physician may opt to repeat any clinically significant tests and include participants whose repeat test values are not clinically significant.
- •Positive urine nicotine/cotinine result during screening visit
- •Positive urine drug result during screening visit
- •Positive saliva alcohol results during screening visit
- •Inability to read and sign consent
- •Failure to obtain required approved official leave to participate.
- •Failure to cooperate with requirements of the study, e.g. failure to complete 80% of Smart-PVTs during Phase 1 (Days 2-13)
Arms & Interventions
Single Arm
Intervention: Caffeine (Dietary Supplement)
Outcomes
Primary Outcomes
Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 1 at home monitoring
Time Frame: Task duration is 5 minutes. Every 3 hours during Phase 1 (Days 2 - 13: at 0800, 1100, 1400, 1700, 2000, and 2300 hrs)
Assesses the effects of sleep loss on visual reaction time as a behavioral measure of sleepiness Subjects continuously monitor a blank display and touch the smart phone screen as quickly as possible in response to a visual stimulus (i.e. a millisecond counter that begins at zero and stops when you press the button). Outcome measures: Mean RT (ms), Mean Speed (s-1), Lapses (#)
Changes in Psychomotor Vigilance Tests (PVT) Reaction Time During Peak Alertness Window following 44 hours of continuous wake
Time Frame: Task duration is 5 minutes. Task will occur hourly from 2130 on Day 15 to 0930 on Day 16.
Assesses the effects of sleep loss on visual reaction time as a behavioral measure of sleepiness Subjects continuously monitor a blank display and touch the smart phone screen as quickly as possible in response to a visual stimulus (i.e. a millisecond counter that begins at zero and stops when you press the button). Outcome measures: Mean RT (ms), Mean Speed (s-1), Lapses (#) The primary objective of this study is to determine if the real-time 2B-Alert Caffeine Optimization algorithm can produce personalized recommendations that will keep individual performance at or below 275 ms (milliseconds) for all study participants throughout a 6-hour Peak Alertness Window following 44 hours of continuous wake
Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 2 sleep deprivation not including Peak Alertness Window
Time Frame: Task duration is 5 minutes. Every 3 hours Phase 2 Day 14 at 0930, 1230, 1530, 1830, 2130; Day 15 at 0000, 0330, 0630, 0930, 1230, 1530, 1830; Day 16 at 1230, 1530, 1830
Assesses the effects of sleep loss on visual reaction time as a behavioral measure of sleepiness Subjects continuously monitor a blank display and touch the smart phone screen as quickly as possible in response to a visual stimulus (i.e. a millisecond counter that begins at zero and stops when you press the button). Outcome measures: Mean RT (ms), Mean Speed (s-1), Lapses (#)
Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 3 recovery
Time Frame: Task duration is 5 minutes. Every 3 hours Phase 3 Day 17 at 0930, 1230 and 1530.
Assesses the effects of sleep loss on visual reaction time as a behavioral measure of sleepiness Subjects continuously monitor a blank display and touch the smart phone screen as quickly as possible in response to a visual stimulus (i.e. a millisecond counter that begins at zero and stops when you press the button). Outcome measures: Mean RT (ms), Mean Speed (s-1), Lapses (#)
Secondary Outcomes
- Video Face Recording Phase 3 Recovery(3 minute recording every 3 hours on Day 17 at 0930, 1230, and 1530.)
- Stress Visual Analog Scale Phase 2 Sleep Deprivation(Task duration ~15 seconds. Every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Spielberger State-Trait Anxiety Inventory - State (STAI-S) Phase 2 Sleep Deprivation(Task duration ~3 minutes. Every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Karolinska Sleepiness Scale (KSS) Phase 2 Sleep Deprivation(Task duration ~15 seconds, every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Actigraphy(Throughout the entire study (~17.5 days))
- Spielberger State-Trait Anxiety Inventory - State (STAI-S) Phase 3 Recovery(Task duration ~3 minutes. Every 3 hours on Day 17 at 0930, 1230, and 1530.)
- Stress Visual Analog Scale Phase 3 Recovery(Task duration ~15 seconds. Every 3 hours on Day 17 at 0930, 1230, and 1530.)
- Self-Assessment Manikin (SAM) Phase 2 Sleep Deprivation(Task duration: ~30 seconds every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Self-Assessment Manikin (SAM) Phase 3 Recovery(Task duration: ~30 seconds every 3 hours on Day 17 at 0930, 1230, and 1530.)
- Video Face Recording Phase 2 Sleep Deprivation(3 minute recording every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Karolinska Sleepiness Scale (KSS) Phase 3 Recovery(Task duration ~15 seconds, every 3 hours on Day 17 at 0930, 1230, and 1530.)
- Fatigue Visual Analog Scale (FVAS) Phase 2 Sleep Deprivation(Task duration ~15 seconds, every 3 hours starting Day 14 at 0930 until Day 16 1830.)
- Fatigue Visual Analog Scale (FVAS) Phase 3 Recovery(Task duration ~15 seconds, every 3 hours on Day 17 at 0930, 1230, and 1530.)
Investigators
William D. Killgore
Professor
University of Arizona