Delayed-release Bedtime Caffeine and Sleep Inertia Symptoms Immediately Upon Awakening
Condition: Sleep Inertia; Caffeine; Placebo
Study type: Interventional

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.
    

Intervention name(s): Caffeine; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 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.; Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.
Intervention MeSH terms: Caffeine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: A randomized, double-blind, placebo controlled, cross-over design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Sleep restriction; Proactive countermeasure