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

Overview

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.

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.