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

NCT ID: NCT04975360

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-08
• Study Completion Date: 2019-08-30

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.

Detailed Description

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, the investigators developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening.

The investigators comprehensively test this formulation in two placebo-controlled, double-blind, cross-over studies. First, the investigators establish the in vivo caffeine release profile in young men. Subsequently, they investigate the formulation's ability to improve sleep inertia in sleep-restricted volunteers. Following oral administration of 160 mg caffeine at habitual bedtime [22:30], the investigators keep the participants awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening [at 07:00]. Immediately upon awakening, the investigators quantify subjective state, psychomotor vigilance, cognitive performance, and the cortisol awakening response. They also record polysomnography during nocturnal sleep and a 1-hour nap opportunity at 08:00.

Conditions

Sleep Inertia; Caffeine; Placebo

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Caffeine

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.

Group Type: EXPERIMENTAL

Caffeine

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.

Interventions

Caffeine

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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 34 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Lokman Hekim University

OTHER_GOV

Sponsor Role: collaborator

Elixir Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Hans-Peter Landolt

Research Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Zurich

Zurich, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 34611208 (View on PubMed)

Other Identifiers

Caff-Clock

Identifier Type: -

Identifier Source: org_study_id