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

University of Zurich (UZH)

Status: Completed

Conditions: Caffeine; Sleep Inertia; Placebo

Treatments: Other: Placebo; Dietary Supplement: Caffeine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04975360

Caff-Clock

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: Male

Ages: 18 to 34 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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32 participants in 2 patient groups, including a placebo group

Caffeine

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Caffeine

Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: Placebo