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

Not Applicable
Completed
Conditions
Placebo
Sleep Inertia
Caffeine
Interventions
Other: Placebo
Dietary Supplement: Caffeine
Registration Number
NCT04975360
Lead Sponsor
University of Zurich
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
32
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboAdministration of a placebo formulation at 22:30. Participants are kept awake until 03:00 and then given a 4-hour sleep opportunity.
CaffeineCaffeineAdministration 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.
Primary Outcome Measures
NameTimeMethod
Acute Sleep Inertia QuestionnaireAt 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 Outcome Measures
NameTimeMethod
Psychomotor vigilance taskBetween 07:15-07:30 hours after caffeine and placebo administration

Reaction-time task

Cortisol awakening responseBetween 07:00-08:00 hours after caffeine and placebo administration

Physiological awakening response to address HPA-axis function

Polysomnographic recording of nocturnal sleepBetween 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.

Caffeine Effects QuestionnaireBetween 07:15-08:00 hours after caffeine and placebo administration

Acute questionnaire to assess caffeine-related subjective effects.

Positive and Negative Affect ScheduleBetween 07:00-08:15 hours after caffeine and placebo administration

Questionnaire

N-back taskBetween 07:30-07:40 hours after caffeine and placebo administration

Working memory and brain executive function task

d2 attention taskBetween 07:40-07:45 hours after caffeine and placebo administration

Focused attention task

Polysomnographic recording of morning nap opportunityBetween 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.

Trial Locations

Locations (1)

University of Zurich

🇨🇭

Zürich, Switzerland

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