Optimized Caffeine for Sleep Deprivation

(2B-2 Trial)

Recruiting at 1 trial location

Overseen By William D Killgore, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Arizona

Must not be taking: Sleep aids, Psychiatric meds, Illicit drugs, others

Disqualifiers: Sleep disorders, Neurologic disorders, Cardiovascular disease, others

Compensation: Varies

Number of Visits: 2

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a personalized caffeine plan can help people stay alert and think clearly when very tired, compared to a standard caffeine plan. The researchers aim to determine if the personalized plan reduces caffeine's side effects and improves sleep recovery after sleep deprivation. Participants will try different doses of caffeine gum to identify the most effective dose. This trial suits individuals who sleep 6-9 hours a night and do not heavily rely on caffeine or have sleep disorders. As an unphased trial, it offers participants the chance to contribute to innovative research that could enhance personalized caffeine use for better alertness and sleep recovery.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you use products or drugs that cannot be safely discontinued during the in-laboratory phases, you may be excluded from participating. This will be determined on a case-by-case basis by the examining study physician.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that caffeine is relatively safe for healthy adults, though it can cause issues in certain groups. Most people tolerate caffeine well, but it may lead to sleep problems if consumed too close to bedtime. This study explores how different caffeine amounts can help with sleep loss without causing unwanted side effects.

For personalized caffeine dosing, research indicates it can range from no caffeine to a maximum of 800 mg, depending on individual needs. This method aims to boost alertness while minimizing side effects, though some increase in stress and anxiety may occur after sleep loss.

Standard caffeine dosing, which can include up to 800 mg in 24 hours, has similar safety data. However, it might reduce total sleep time and efficiency, affecting how quickly someone falls asleep and how long they stay asleep.

Overall, caffeine in these amounts is generally well-tolerated, but it can impact sleep, which is important to consider in a sleep deprivation study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to combat sleep deprivation using caffeine in a more personalized and potentially effective manner. Unlike the typical one-size-fits-all caffeine dosing, this study investigates both a standard dosing regimen and an optimized dosing approach, which adjusts the caffeine amount between 0-300mg every two hours, tailored to individual needs. This personalized method could enhance alertness and performance more effectively than current methods, which often rely on fixed caffeine doses that don't consider individual differences in response. By using caffeine gum, the trial also introduces an alternative delivery method that could offer faster absorption and convenience compared to traditional caffeine sources like coffee or pills.

What evidence suggests that this trial's treatments could be effective for sleep deprivation?

Research shows that caffeine helps maintain alertness when sleep is insufficient. Studies have found that doses between 150 and 600 mg can enhance thinking and focus in sleep-deprived individuals. In this trial, participants will be assigned to different treatment arms to evaluate various caffeine dosing strategies. One arm will receive a Standard Caffeine Dosing Regimen, while another will follow an Optimized Caffeine Dosing Regimen, potentially using tools like the 2B-Alert app to tailor caffeine intake. Meanwhile, a Placebo arm will help assess the effects of caffeine compared to no active treatment. This personalized approach aims to balance alertness with minimal negative effects on sleep. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-39 who understand the study protocol, as shown by scoring at least 80% on a quiz. It's designed for those experiencing sleep deprivation and will test if personalized caffeine dosing can improve alertness, mood, cognition during wakefulness, and enhance recovery sleep.

Inclusion Criteria

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 morning wake-up times later than approximately 0900 on average during weekdays (Monday through Friday)

Score of 41 or above on the Spielberger Trait Anxiety Inventory (STAI-T)

I have kidney disease or abnormalities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

At-home Testing

Participants 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.

13 days

In-lab Sleep Deprivation

Participants complete a 4-day in-lab portion, including one night of baseline sleep, 62 hours of total sleep deprivation, and one night of recovery sleep. Caffeine or placebo gum is administered during sleep deprivation.

4 days

Continuous in-lab stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including further psychomotor vigilance testing.

1 day

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine Gum
• Personalized Caffeine Dosing Regimen
• Placebo Gum
• Standard Caffeine Dosing Regimen

Trial Overview

Participants will compare two caffeine dosing regimens: one tailored to their personal needs (using caffeine gum) versus a standard dose (placebo gum). They'll track sleep with an actigraph watch at home and undergo tests in-lab after staying awake for over two days.

How Is the Trial Designed?

Group I: Standard Caffeine Dose Both Nights Active Control 2 Interventions

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 II: Optimized Caffeine Dose Both Nights Active Control 2 Interventions

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 III: Placebo Dose 1st Night/Standard Caffeine Dose 2nd Night Active Control 2 Interventions

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 IV: Placebo Dose 1st Night/Optimized Caffeine Dose 2nd Night Active Control 2 Interventions

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 V: Placebo Dose Both Nights Placebo Group 1 Intervention

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

Caffeine Gum is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Caffeine for:

• Fatigue
• Sleep deprivation
• Alertness

Approved in European Union as Caffeine for:

• Fatigue
• Sleep deprivation
• Alertness

Approved in Canada as Caffeine for:

• Fatigue
• Sleep deprivation
• Alertness

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

Biotechnology High Performance Computing Software Applications Institute

Collaborator

Trials

3

Recruited

210+

U.S. Army Medical Research Acquisition Activity

Collaborator

Trials

26

Recruited

10,500+

Published Research Related to This Trial

A study involving 24 healthy volunteers showed that 300 mg of slow-release caffeine significantly improved vigilance and performance during periods of sleep deprivation, lasting up to 13 hours after intake.

The research indicated that while both 300 mg and 600 mg doses were effective, the 300 mg dose was optimal for maximizing benefits without side effects, and there was no difference in performance during recovery after sleep.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slow-release caffeine: a new response to the effects of a limited sleep deprivation. Lagarde, D., Batéjat, D., Sicard, B., et al.[2015]

A new optimization algorithm has been developed to guide caffeine consumption, helping individuals maximize their neurobehavioural performance during sleep loss, based on a validated model of performance.

Simulations showed that this algorithm could enhance performance by up to 64% using the same caffeine amount as in previous studies, or maintain performance while reducing caffeine intake by up to 65%, promoting safer consumption practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caffeine dosing strategies to optimize alertness during sleep loss. Vital-Lopez, FG., Ramakrishnan, S., Doty, TJ., et al.[2019]

The Evodia rutaecarpa aqueous extract (ERAE) and its main component, evodiamine, effectively reduce caffeine-induced sleep disturbances and excitatory effects in mice, as shown through various behavioral tests.

Evodiamine appears to work by reversing the reduction of GABAA receptor subunits caused by caffeine, suggesting a mechanism that involves the GABAergic system, making it a promising candidate for mitigating caffeine's adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evodiamine Reduces Caffeine-Induced Sleep Disturbances and Excitation in Mice. Ko, YH., Shim, KY., Lee, SY., et al.[2020]

A study involving 48 healthy participants showed that Stay Alert chewing gum effectively delivers caffeine in a dose-dependent manner, with higher doses resulting in higher plasma caffeine levels.

The pharmacokinetics of caffeine from the gum demonstrated linearity across multiple doses, indicating that it can be a reliable method for maintaining alertness in sleep-deprived individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteers. Syed, SA., Kamimori, GH., Kelly, W., et al.[2013]

Caffeine from Stay Alert chewing gum is absorbed significantly faster than from capsules, with peak absorption times (Tmax) ranging from 44.2 to 80.4 minutes for gum compared to 84.0 to 120.0 minutes for capsules, indicating a quicker onset of effects.

Both the gum and capsule formulations provide similar amounts of caffeine to the bloodstream, but the gum's faster absorption may be beneficial for quickly improving alertness and performance after sleep loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers. Kamimori, GH., Karyekar, CS., Otterstetter, R., et al.[2019]

Caffeine citrate injection remains stable in various intravenous admixtures and parenteral nutrition solutions when stored at room temperature for up to 24 hours.

This stability suggests that caffeine citrate can be safely used in clinical settings without concerns of degradation during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of caffeine citrate injection in intravenous admixtures and parenteral nutrition solutions. Nahata, MC., Zingarelli, J., Durrell, DE.[2019]

In food-limited rats, caffeine showed a proportional relationship between dose and serum levels, indicating predictable pharmacokinetics for caffeine itself, while its metabolites displayed disproportionality, suggesting complex metabolism.

Chronic administration of caffeine led to steady-state concentrations by day 11, with differences in clearance and volume of distribution between administration routes, highlighting the importance of understanding caffeine's pharmacokinetics for its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral and IP caffeine pharmacokinetics under a chronic food-limitation condition. Lau, CE., Ma, F., Falk, JL.[2019]

A new pulsatile-release caffeine formulation was tested in 22 sleep-restricted volunteers and showed significant improvements in reducing sleep inertia symptoms upon awakening, including faster reaction times and better mood.

This innovative caffeine delivery method, taken before planned awakening, effectively enhances the transition from sleep to wakefulness, suggesting it could be beneficial for individuals experiencing severe grogginess after waking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening. Dornbierer, DA., Yerlikaya, F., Wespi, R., et al.[2023]

Sustained-release CaffXtend® capsules (SR-Caffeine) provide a longer duration of caffeine release, with a mean time to peak concentration (tmax) of 4.08 hours compared to just 0.83 hours for immediate-release caffeine (IR-Caffeine), indicating a more gradual absorption.

Participants taking SR-Caffeine reported significantly better mood and alertness, along with lower feelings of jitteriness and tiredness over an 8-12 hour period, with no adverse events reported, suggesting it may be a safer and more effective option for sustained cognitive enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Bioavailability and Benefits on Mental Functions of Novel Extended-Release Caffeine Capsules against Immediate-Release Caffeine Capsules: An Open-Label, Randomized, Cross-over, Single-Dose Two-Way Crossover Study. Thanawala, S., Shah, R., Abiraamasundari, R., et al.[2023]

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We report that, for healthy adults, caffeine consumption is relatively safe, but that for some vulnerable populations, caffeine consumption could be harmful.

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