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Completed

NCT Number: NCT04975360

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

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.

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Key information

Conditions

Sleep Inertia Caffeine Disorders of Excessive Somnolence Dyssomnias Idiopathic Hypersomnia Mental Disorders Nervous System Diseases Placebo Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year–34 year

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

University of Zurich

Zurich, 8057, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Exclusion criteria

  • Failure to meet inclusion criteria

Treatment and study plan

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.

Placebo

Other

Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.

Primary outcomes

  1. Acute Sleep Inertia Questionnaire

    Time frame: At 07:00 hours after caffeine and placebo administration

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

Secondary outcomes

  1. Polysomnographic recording of nocturnal sleep

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

    All-night polysomnographic recordings of nocturnal sleep: electrical bio-signals include simultaneous, standardized recordings of brain waves (electroencephalogram), muscle tone on the chin (electromyogram), and slow and rapid eye movements (electrooculogram). The information will be aggregated for visual scoring of sleep stages according to standardized criteria specified by the American Academy of Sleep Medicine.

  2. Caffeine Effects Questionnaire

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

    Acute questionnaire to assess caffeine-related subjective effects.

  3. Positive and Negative Affect Schedule

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

    Questionnaire

  4. Psychomotor vigilance task

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

    Reaction-time task

  5. N-back task

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

    Working memory and brain executive function task

  6. d2 attention task

    Time frame: Between 07:40-07:45 hours after caffeine and placebo administration

    Focused attention task

  7. Cortisol awakening response

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

    Physiological awakening response to address HPA-axis function

  8. Polysomnographic recording of morning nap opportunity

    Time frame: Between 08:00-09:00 hours after caffeine and placebo administration

    Polysomnographic recordings of sleep during one-hour nap opportunity: electrical bio-signals include simultaneous, standardized recordings of brain waves (electroencephalogram), muscle tone on the chin (electromyogram), and slow and rapid eye movements (electrooculogram). The information will be aggregated for visual scoring of sleep stages according to standardized criteria specified by the American Academy of Sleep Medicine.

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Collaborators

  • Elixir Pharmaceuticals
  • Lokman Hekim University

Registry information

Official study title

Effects of a Time-delayed, Pulsatile Caffeine Formula on Sleep Inertia, Morning Cognition, Affect and Sleepiness in Healthy Volunteers

Important dates

Study start
2019
Primary completion
2019
Study completion
2019
First posted
Jul 23, 2021
Registry last updated
Jul 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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