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

NCT ID: NCT05588934

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-09

Study Completion Date

2026-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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. 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. 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. During the in-lab portion of the study, participants will be asked to complete more motor vigilance tests.

Researchers will be comparing the personalized caffeine recommendation group against the standard caffeine recommendation to see if it is better at addressing each of the main questions.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This clinical trial will be examining whether the 2B-Alert Caffeine Optimization algorithm provides greater performance optimization, side effect minimization, and quality of recovery sleep during sleep deprivation compared to the standard published recommendations for caffeine use. The objective of this clinical trial will be to conduct a head-to-head comparison between the 2B-Alert app versus a commonly recommended caffeine dosing regimen for sustaining optimal performance during sleep deprivation and minimizing side effects and subsequent sleep disruption. The specific aims are to: Determine the effectiveness of 2B-Alert versus standard caffeine dosing on psychomotor vigilance, subjective sleepiness, and cognition on single and multiple nights of sleep deprivation; Determine the effectiveness of 2B-Alert versus standard caffeine dosing at mitigating physiological and emotional side effects; Determine the effectiveness of 2B-Alert versus standard caffeine dosing at minimizing disruptions in recovery sleep.

This clinical trial will consist of three phases. Phase 1 includes the enrollment visit where participants will come into the lab, complete baseline personality and mood testing, and be given the actigraph watch and phone with the 2B-Alert app. Then the participant will undergo 13-days of at-home psychomotor vigilance testing and sleep data collection.

Phase 2 begins with the participant arrives at the lab for the 4-day in-lab portion of the study. During this phase the participant will complete a night of baseline sleep using polysomnography to collect sleep data. At the end of baseline sleep, the participant will begin the 62-hour sleep deprivation portion. During the deprivation portion, data will be collected periodically on the participants psychomotor vigilance. After 37-49 hours of continuous sleep deprivation participants will be administered either caffeine gum or placebo gum.

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.

After the 62-hour period of total sleep deprivation, participants will complete Phase 3, a night of recovery sleep; During this phase, participants' sleep data will be collected using polysomnography. After the night of recovery sleep participants will remain in the lab for further psychomotor vigilance testing. Once this is complete individuals will be released from the lab and their participation will be complete.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Sleep Deprivation Caffeine

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

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.
Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo Dose Both Nights

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

Group Type PLACEBO_COMPARATOR

Placebo Gum

Intervention Type OTHER

Commercially available non-caffeinated gum.

Standard Caffeine Dose Both Nights

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.

Group Type ACTIVE_COMPARATOR

Caffeine Gum

Intervention Type DIETARY_SUPPLEMENT

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

Placebo Gum

Intervention Type OTHER

Commercially available non-caffeinated gum.

Optimized Caffeine Dose Both Nights

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.

Group Type ACTIVE_COMPARATOR

Caffeine Gum

Intervention Type DIETARY_SUPPLEMENT

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

Placebo Gum

Intervention Type OTHER

Commercially available non-caffeinated gum.

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

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.

Group Type ACTIVE_COMPARATOR

Caffeine Gum

Intervention Type DIETARY_SUPPLEMENT

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

Placebo Gum

Intervention Type OTHER

Commercially available non-caffeinated gum.

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

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.

Group Type ACTIVE_COMPARATOR

Caffeine Gum

Intervention Type DIETARY_SUPPLEMENT

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

Placebo Gum

Intervention Type OTHER

Commercially available non-caffeinated gum.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Caffeine Gum

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

Intervention Type DIETARY_SUPPLEMENT

Placebo Gum

Commercially available non-caffeinated gum.

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Military Energy Gum

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

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 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)
* 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 medication for any length of time
* Self-reported use of products or drugs that cannot be safely discontinued during in-laboratory phases (determined on a case-by-case basis by the examining study physician)
* Self-reported current use of other illicit drugs (to include but not limited to benzodiazepines, amphetamines, cocaine, marijuana) or positive urine drug screen
* (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 (if a physician performs a repeat measurement, \~20 minutes after original measure, and it 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
* Inability to read and sign consent
* (Military only) 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-Psychomotor Vigilance Tests (PVTs) during Phase 1 (Days 2-13)
Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

U.S. Army Medical Research Acquisition Activity

FED

Sponsor Role collaborator

Biotechnology High Performance Computing Software Applications Institute

UNKNOWN

Sponsor Role collaborator

University of Arizona

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

University of Arizona Psychiatry Department

Tucson, Arizona, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

William D Killgore, Ph.D.

Role: CONTACT

(520) 621-0605

Lindsey Hildebrand, MA

Role: CONTACT

(520) 626-2203

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

William DS Killgore

Role: primary

520-621-0605

Camryn Wellman

Role: backup

William D Killgore, PhD

Role: primary

520-621-0605

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 26518594 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27397562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27634801 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29808510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33364521 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28436072 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16313140 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19238808 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

STUDY00001953

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Remote Guided Caffeine Reduction
NCT04560595 COMPLETED NA
Circadian Rhythm Monitoring Study
NCT07336654 NOT_YET_RECRUITING NA
Light and Sleep Fragmentation
NCT06009289 NOT_YET_RECRUITING PHASE4
Protocol PERCAF 2018
NCT03859882 COMPLETED NA