Delayed-release Bedtime Caffeine and Sleep Inertia Symptoms Immediately Upon Awakening

NCT04975360 | Completed

• 1 other identifier: Caff-Clock
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Sleep inertia (sometimes also referred to as sleep drunkenness) is a disabling state of increased sleepiness, impaired mood and reduced vigilance immediately upon awakening. Sleep inertia is highly prevalent in various neurological diseases, including neurodegenerative, affective and circadian sleep-wake rhythms disorders, as well as in frequent societal conditions such as chronic sleep restriction, jetlag and shiftwork. Reactive countermeasures against sleep inertia, i.e., strategies implemented upon wake-up, are not sufficiently effective, yet current recommendations are limited to proactive strategies, including long enough sleep at optimal times of day. These recommendations are not always easy and sometimes impossible to apply. To address this unmet medical need, the investigators developed an innovative, time-controlled, pulsatile-release formulation of 160 mg caffeine targeting an efficacious dose briefly before planned awakening.

Conditions

Sleep Inertia; Caffeine; Placebo

Keywords

Sleep restriction; Proactive countermeasure

Outcome Measures

Primary Outcomes (1)

• Acute Sleep Inertia Questionnaire

  Modified questionnaire to assess subjective ratings of sleep inertia on physiological, emotional, cognitive and behavioral levels.

  At 07:00 hours after caffeine and placebo administration

Secondary Outcomes (8)

• Polysomnographic recording of nocturnal sleep

  Between 03:00-07:00 hours after caffeine and placebo administration

• Caffeine Effects Questionnaire

  Between 07:15-08:00 hours after caffeine and placebo administration

• Positive and Negative Affect Schedule

  Between 07:00-08:15 hours after caffeine and placebo administration

• Psychomotor vigilance task

  Between 07:15-07:30 hours after caffeine and placebo administration

• N-back task

  Between 07:30-07:40 hours after caffeine and placebo administration

Study Arms (2)

Caffeine

EXPERIMENTAL

Administration of a time-controlled, pulsatile-release caffeine formulation (160 mg caffeine) at 22:30. Participants are kept awake until 03:00 and then given a 4-hour sleep opportunity.

Dietary Supplement: Caffeine

Placebo

PLACEBO COMPARATOR

Administration of a placebo formulation at 22:30. Participants are kept awake until 03:00 and then given a 4-hour sleep opportunity.

Other: Placebo

Interventions

Caffeine DIETARY_SUPPLEMENT

The 160 mg caffeine pulsatile-release formulation was manufactured using a drug layering process. Caffeine and the excipients are dispersed in the coating media and then sprayed onto inert microcrystalline cellulose spheres using a fluid bed through a Wurster tube with continuous inlet air that dries the liquid in the dispersion, to obtain various layers consisting of caffeine and release-controlling polymers. The applied release-controlling polymeric system is based on methacrylate copolymers, which control the release of caffeine in pH-dependent and pH-independent manner. The release mechanism of the polymeric system is mainly driven by the swellability and permeability of the copolymers. The final micropellets are then encapsulated into hydroxypropylmethylcellulose capsules.

Caffeine

Placebo OTHER

Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.

Placebo

Eligibility Criteria

• Age: 18 Years - 34 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• male sex in order to avoid the potential impact of menstrual cycle on sleep physiology or HPA axis activity,
• age within the range of 18 to 34 years,
• a body-mass-index below 25,
• an Epworth Sleepiness Score (ESS) below 10,
• habitual sleep onset latency below 20 minutes,
• regular sleep-wake rhythm with bedtime between 11 pm and 1 am,
• absence of any somatic or psychiatric disorders,
• no acute or chronic medication intake,
• non-smoking,
• no history of drug abuse (lifetime use \> 5 occasions, except occasional cannabis use)
• caffeine consumption of less than 4 units per day (coffee, tea, chocolate, cola, energy drinks)

Sponsors & Collaborators

• University of Zurich: lead
• Lokman Hekim University: collaborator
• Elixir Pharmaceuticals: collaborator

Study Sites (1)

University of Zurich

Zurich, 8057, Switzerland

Location

Related Publications (1)

• Dornbierer DA, Yerlikaya F, Wespi R, Boxler MI, Voegel CD, Schnider L, Arslan A, Baur DM, Baumgartner MR, Binz TM, Kraemer T, Landolt HP. A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening. Sci Rep. 2021 Oct 5;11(1):19734. doi: 10.1038/s41598-021-98376-z.

  PMID: 34611208 DERIVED

MeSH Terms

Conditions

Idiopathic Hypersomnia

Interventions

Caffeine

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Director

Model Details: A randomized, double-blind, placebo controlled, cross-over design.

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: July 23, 2021
• Study Start: February 8, 2019
• Primary Completion: August 30, 2019
• Study Completion: August 30, 2019
• Last Updated: July 29, 2021

Record last verified: 2021-07

Locations

CH (1)