Caffeine Optimization Versus Standard Caffeine Dosage (2B-2)

NCT05588934 | Recruiting

• 1 other identifier: STUDY00001953
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

This clinical trial will be a comparison between personalized recommended caffeine dosing regimen versus the standard recommended caffeine dosing regimen for sustaining performance during sleep deprivation and minimizing side effects and subsequent sleep disruption. The questions this study aims to answer are: Whether the personalized caffeine recommendations improve vigilance, sleepiness, and cognition after total sleep deprivation, compared to standard recommendations; Whether the personalized caffeine recommendation better addresses the physical and emotional side effects of total sleep deprivation, compared to standard recommendations; And whether personalized caffeine recommendations aids in better recovery sleep after total sleep deprivation, compared to standard recommendations. Participants will be asked to:

1. 1.Complete a 13-day at-home portion, wearing an actigraph watch to measure activity and sleep, and complete motor vigilance tests up to six times a day.
2. 2.Complete a 4-day in-lab portion, where participants will have to complete one night of baseline sleep, undergo 62-hours of total sleep deprivation, and then complete one night of recovery sleep.
3. 3.During the in-lab portion of the study, participants will be asked to complete more motor vigilance tests.

Conditions

Sleep Deprivation; Caffeine

Keywords

SLEEP; CAFFEINE

Outcome Measures

Primary Outcomes (1)

• Mean psychomotor vigilance test reaction time

  The mean response time to psychomotor vigilance tests during the Peak Alertness Window.

  Peak Alertness Window: During each overnight sleep deprivation period from 3:00am to 9:00am

Study Arms (5)

Placebo Dose Both Nights

PLACEBO COMPARATOR

Participants will be administer non-caffeinated, placebo gum during both nights of Phase 2.

Other: Placebo Gum

Standard Caffeine Dose Both Nights

ACTIVE COMPARATOR

Participants will be administer the standard caffeine recommendation (200mg/2 hr. up to 800mg/24 hr.) using caffeinated and non-caffeinated gum during both nights of Phase 2.

Dietary Supplement: Caffeine Gum; Other: Placebo Gum

Optimized Caffeine Dose Both Nights

ACTIVE COMPARATOR

Participants will be administer the optimized caffeine recommendation (0-300mg/2 hr. up to 800mg/24 hr.) potentially using caffeinated and non-caffeinated gum, depending on optimized dosage, during both nights of Phase 2.

Dietary Supplement: Caffeine Gum; Other: Placebo Gum

Placebo Dose 1st Night/Standard Caffeine Dose 2nd Night

ACTIVE COMPARATOR

Participants will be administer non-caffeinated, placebo gum during the first night of Phase 2. Then, participants will be administer the standard caffeine recommendation (200mg/2 hr. up to 800mg/24 hr.) using caffeinated and non-caffeinated gum during the second night of Phase 2.

Dietary Supplement: Caffeine Gum; Other: Placebo Gum

Placebo Dose 1st Night/Optimized Caffeine Dose 2nd Night

ACTIVE COMPARATOR

Participants will be administer non-caffeinated, placebo gum during the first night of Phase 2. Then, participants will be administer the optimized caffeine recommendation (0-300mg/2 hr. up to 800mg/24 hr.) potentially using caffeinated and non-caffeinated gum, depending on optimized dosage, during the second night of Phase 2.

Dietary Supplement: Caffeine Gum; Other: Placebo Gum

Interventions

Caffeine Gum DIETARY_SUPPLEMENT

Commercially available caffeinated gum that contains 100mg of caffeine per piece of gum.

Also known as: Military Energy Gum

Optimized Caffeine Dose Both Nights; Placebo Dose 1st Night/Optimized Caffeine Dose 2nd Night; Placebo Dose 1st Night/Standard Caffeine Dose 2nd Night; Standard Caffeine Dose Both Nights

Placebo Gum OTHER

Commercially available non-caffeinated gum.

Optimized Caffeine Dose Both Nights; Placebo Dose 1st Night/Optimized Caffeine Dose 2nd Night; Placebo Dose 1st Night/Standard Caffeine Dose 2nd Night; Placebo Dose Both Nights; Standard Caffeine Dose Both Nights

Eligibility Criteria

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

You may qualify if:

• Age 18-39 years of age
• Must demonstrate adequate comprehension of the protocol by achieving a score of at least 80% correct on a short multiple-choice quiz

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 bedtimes 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)
• 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, rapid eye movement (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
• History of neurologic disorder (e.g., seizure disorder, amnesia for any reason, hydrocephalus, multiple sclerosis)
• Self-reported caffeine use \> 400 mg per day on average
• Score of 14 or above on the Beck Depression Inventory (BDI)
• Score of 41 or above on the Spielberger Trait Anxiety Inventory (STAI-T)
• Score below 31 or above 69 on the Morningness-Eveningness Questionnaire
• Self-reported regular nicotine use (\> 1 cigarette or equivalent per week) within the last 1 year) or positive nicotine/cotinine result during screening visit
• Self-reported heavy alcohol use (≥14 drinks per week or as determined by the examining study physician) or positive saliva alcohol result during screening visit
• 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)

Sponsors & Collaborators

• University of Arizona: lead
• U.S. Army Medical Research Acquisition Activity: collaborator
• Biotechnology High Performance Computing Software Applications Institute: collaborator

Study Sites (2)

University of Arizona

Tucson, Arizona, 85719, United States

RECRUITING

University of Arizona Psychiatry Department

Tucson, Arizona, 85724, United States

RECRUITING

Related Publications (8)

• Kamimori GH, Johnson D, Thorne D, Belenky G. Multiple caffeine doses maintain vigilance during early morning operations. Aviat Space Environ Med. 2005 Nov;76(11):1046-50.

  PMID: 16313140 BACKGROUND

• Killgore WD, Kahn-Greene ET, Grugle NL, Killgore DB, Balkin TJ. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep. 2009 Feb;32(2):205-16. doi: 10.1093/sleep/32.2.205.

  PMID: 19238808 BACKGROUND

• Killgore WDS, Kamimori GH. Multiple caffeine doses maintain vigilance, attention, complex motor sequence expression, and manual dexterity during 77 hours of total sleep deprivation. Neurobiol Sleep Circadian Rhythms. 2020 May 31;9:100051. doi: 10.1016/j.nbscr.2020.100051. eCollection 2020 Nov.

  PMID: 33364521 BACKGROUND

• Liu J, Ramakrishnan S, Laxminarayan S, Balkin TJ, Reifman J. Real-time individualization of the unified model of performance. J Sleep Res. 2017 Dec;26(6):820-831. doi: 10.1111/jsr.12535. Epub 2017 Apr 24.

  PMID: 28436072 BACKGROUND

• Ramakrishnan S, Wesensten NJ, Balkin TJ, Reifman J. A Unified Model of Performance: Validation of its Predictions across Different Sleep/Wake Schedules. Sleep. 2016 Jan 1;39(1):249-62. doi: 10.5665/sleep.5358.

  PMID: 26518594 BACKGROUND

• Ramakrishnan S, Wesensten NJ, Kamimori GH, Moon JE, Balkin TJ, Reifman J. A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine. Sleep. 2016 Oct 1;39(10):1827-1841. doi: 10.5665/sleep.6164.

  PMID: 27397562 BACKGROUND

• Reifman J, Kumar K, Wesensten NJ, Tountas NA, Balkin TJ, Ramakrishnan S. 2B-Alert Web: An Open-Access Tool for Predicting the Effects of Sleep/Wake Schedules and Caffeine Consumption on Neurobehavioral Performance. Sleep. 2016 Dec 1;39(12):2157-2159. doi: 10.5665/sleep.6318.

  PMID: 27634801 BACKGROUND

• Vital-Lopez FG, Ramakrishnan S, Doty TJ, Balkin TJ, Reifman J. Caffeine dosing strategies to optimize alertness during sleep loss. J Sleep Res. 2018 Oct;27(5):e12711. doi: 10.1111/jsr.12711. Epub 2018 May 28.

  PMID: 29808510 BACKGROUND

MeSH Terms

Conditions

Sleep Deprivation

Condition Hierarchy (Ancestors)

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

Central Study Contacts

William D Killgore, Ph.D.

CONTACT

(520) 621-0605; killgore@psychiatry.arizona.edu

Lindsey Hildebrand, MA

CONTACT

(520) 626-2203; hildebrandll@arizona.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants will not have any knowledge of which of the five condition groups they are apart of during or after the study. The investigator will not have any knowledge of which of the five condition groups the participant is apart of during or after the study. A third party will prepare the caffeine dosing and not participate in the administration to avoid knowledge of what participants are in what categories.
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There are four different experimental conditions and one control condition that determines the ratio of caffeine gum to placebo gum that is administered to participants. 1. Standard Caffeine Dose Both Nights (200mg/2 hr. up to 800mg/24 hr.) 2. Optimized Caffeine Dose Both Nights (0-300mg/2 hr. up to 800mg/24 hr.) 3. Placebo Dose 1st Night/Standard Caffeine Dose 2nd Night (0mg) / (200mg/2 hr. up to 800mg/24 hr.) 4. Placebo Dose 1st Night/Optimized Caffeine Dose 2nd Night (0mg) / (0-300mg/2 hr. up to 800mg/24 hr.) 5. Placebo Dose Both Nights (0mg) Participants will be randomly assigned to 1 of the 5 conditions, so 20% of the study population will be in each condition.

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: October 20, 2022
• Study Start: June 9, 2023
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 4, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)