Clinical trial NCT04975360: Delayed-release Bedtime Caffeine and Sleep Inertia Symptoms Immediately Upon Awakening
Official title: Effects of a Time-delayed, Pulsatile Caffeine Formula on Sleep Inertia, Morning Cognition, Affect and Sleepiness in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Inertia
Caffeine
Placebo
Keywords: Sleep restriction
Proactive countermeasure
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Lokman Hekim Üniversitesi
name: Elixir Pharmaceuticals
First posted: 2021-07-23
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A randomized, double-blind, placebo controlled, cross-over design.
Primary purpose: BASIC_SCIENCE

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.

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)

Exclusion Criteria:

- Failure to meet inclusion criteria

Primary outcomes:
measure: Acute Sleep Inertia Questionnaire
timeFrame: At 07:00 hours after caffeine and placebo administration
Secondary outcomes:
measure: Polysomnographic recording of nocturnal sleep
timeFrame: Between 03:00-07:00 hours after caffeine and placebo administration
measure: Caffeine Effects Questionnaire
timeFrame: Between 07:15-08:00 hours after caffeine and placebo administration
measure: Positive and Negative Affect Schedule
timeFrame: Between 07:00-08:15 hours after caffeine and placebo administration
measure: Psychomotor vigilance task
timeFrame: Between 07:15-07:30 hours after caffeine and placebo administration
measure: N-back task
timeFrame: Between 07:30-07:40 hours after caffeine and placebo administration
measure: d2 attention task
timeFrame: Between 07:40-07:45 hours after caffeine and placebo administration
measure: Cortisol awakening response
timeFrame: Between 07:00-08:00 hours after caffeine and placebo administration
measure: Polysomnographic recording of morning nap opportunity
timeFrame: Between 08:00-09:00 hours after caffeine and placebo administration
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: University of Zurich
Study officials:
References:
citation: 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.