Real-Time Caffeine Optimization During Total Sleep Deprivation

NCT04399083 | Completed

• 1 other identifier: 1912215022
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Caffeine; Sleep Deprivation; Shift-Work Related Sleep Disturbance

Outcome Measures

Primary Outcomes (4)

• Changes in Psychomotor Vigilance Tests (PVT) Reaction Time During Peak Alertness Window following 44 hours of continuous wake

  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

  Task duration is 5 minutes. Task will occur hourly from 2130 on Day 15 to 0930 on Day 16.

• Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 1 at home monitoring

  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 (#)

  Task duration is 5 minutes. Every 3 hours during Phase 1 (Days 2 - 13: at 0800, 1100, 1400, 1700, 2000, and 2300 hrs)

• Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 2 sleep deprivation not including Peak Alertness Window

  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 (#)

  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

• Changes in Psychomotor Vigilance Tests (PVT) Reaction Time Phase 3 recovery

  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 (#)

  Task duration is 5 minutes. Every 3 hours Phase 3 Day 17 at 0930, 1230 and 1530.

Secondary Outcomes (13)

• Stress Visual Analog Scale Phase 2 Sleep Deprivation

  Task duration ~15 seconds. Every 3 hours starting Day 14 at 0930 until Day 16 1830.

• Stress Visual Analog Scale Phase 3 Recovery

  Task duration ~15 seconds. Every 3 hours on Day 17 at 0930, 1230, and 1530.

• 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.

• 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.

• Video Face Recording Phase 2 Sleep Deprivation

  3 minute recording every 3 hours starting Day 14 at 0930 until Day 16 1830.

Other Outcomes (9)

• Sleep period polysomnographic (PSG) measurements with video

  During scheduled TIB periods (~2300 Day 13 to ~0700 Day 14 and ~2100 hrs on Day 16 to ~0900 hrs on Day 17) = ~20 hours of PSG recording per participant

• Caffeine Use Tracking

  ~30 seconds or less per entry as needed across Phase 1

• Sleep Tracking

  ~1 minute, once per day during Phase 1

Study Arms (1)

Single Arm

EXPERIMENTAL

Dietary Supplement: Caffeine

Interventions

Caffeine DIETARY_SUPPLEMENT

Caffeine will be administered to each participant following an individualized optimal dosing schedule created by the 2B-Alert app. Individualized caffeine dosing schedules will be created by the 2BAlert app on the smartphone the participant uses to do Smart-PVT tests. Study staff will run the optimization at 1900 on Day 15. The algorithm will recommend caffeine dosing to optimize performance during the Peak Alertness window (e.g. from 0300-0900 on Day 16, 44-50 hours of continuous sleep loss). Doses could be recommended at any hour from 2000 on Day 15 to 0800 on Day 16. HOWEVER, the algorithm will not exceed 800 mg of caffeine across the entire study AND it will not dose more than 300 mg of caffeine at a time. Gum will be chewed for a total of 10 minutes by each participant and then discarded. As there will be no placebo in this protocol, randomization and blinding procedures are not necessary. IT IS IMPORTANT TO NOTE THAT SOME PARTICIPANTS MAY NOT RECEIVE CAFFEINE AT ALL.

Single Arm

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Arizona: lead
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Related Publications (1)

• Subramaniyan M, Vital-Lopez FG, Doty TJ, Anlap I, Killgore WDS, Reifman J. Personalized alertness prediction using video-based ocular and facial features. Sleep. 2025 Nov 10;48(11):zsaf149. doi: 10.1093/sleep/zsaf149.

  PMID: 40457721 DERIVED

MeSH Terms

Conditions

Sleep Deprivation

Interventions

Caffeine

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)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 4, 2020
• First Posted: May 22, 2020
• Study Start: February 19, 2021
• Primary Completion: July 31, 2021
• Study Completion: July 31, 2021
• Last Updated: September 17, 2021

Record last verified: 2021-09

Locations

US (1)