Sleep InertiaNCT04975360
Delayed-release Bedtime Caffeine and Sleep Inertia Symptoms Immediately Upon Awakening
A study testing Caffeine in people with Sleep Inertia and Caffeine, run by University of Zurich at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 34 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sleep Inertia, Caffeine, Placebo
- What is being tested?
- Caffeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteSwitzerland
- Study dates
- 8 Feb 2019to 30 Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 34 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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,
Show all 11Show fewer
- 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)
Who cannot join
- Failure to meet inclusion criteria
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of a Time-delayed, Pulsatile Caffeine Formula on Sleep Inertia, Morning Cognition, Affect and Sleepiness in Healthy Volunteers
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.
Read the 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.
- Conditions
- Sleep Inertia, Caffeine, Placebo
- Being tested
- Caffeine, Placebo
- Keywords
- Sleep restriction, Proactive countermeasure
- Medical subject headings
- Idiopathic Hypersomnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDietary supplement
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.
PlaceboOther
Identical hydroxypropylmethylcellulose capsules without containing caffeine micropellets.
| Study group | Role | What they receive |
|---|---|---|
| Caffeine | Experimental | 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. Receives: Dietary Supplement: Caffeine |
| Placebo | Placebo comparator | Administration of a placebo formulation at 22:30. Participants are kept awake until 03:00 and then given a 4-hour sleep opportunity. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Sleep Inertia Questionnaire
Modified questionnaire to assess subjective ratings of sleep inertia on physiological, emotional, cognitive and behavioral levels.
Measured: At 07:00 hours after caffeine and placebo administration
Secondary outcomes (8)
Polysomnographic recording of nocturnal sleep
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.
Measured: Between 03:00-07:00 hours after caffeine and placebo administration
Caffeine Effects Questionnaire
Acute questionnaire to assess caffeine-related subjective effects.
Measured: Between 07:15-08:00 hours after caffeine and placebo administration
Positive and Negative Affect Schedule
Questionnaire
Measured: Between 07:00-08:15 hours after caffeine and placebo administration
Psychomotor vigilance task
Reaction-time task
Measured: Between 07:15-07:30 hours after caffeine and placebo administration
N-back task
Working memory and brain executive function task
Measured: Between 07:30-07:40 hours after caffeine and placebo administration
d2 attention task
Focused attention task
Measured: Between 07:40-07:45 hours after caffeine and placebo administration
Cortisol awakening response
Physiological awakening response to address HPA-axis function
Measured: Between 07:00-08:00 hours after caffeine and placebo administration
Polysomnographic recording of morning nap opportunity
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.
Measured: Between 08:00-09:00 hours after caffeine and placebo administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2021
- Study start8 Feb 2019
- Primary completion30 Aug 2019
- Study completion30 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sleep InertiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- A randomized, double-blind, placebo controlled, cross-over design.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Collaborators
- Lokman Hekim University, Elixir Pharmaceuticals
- Responsible party
- Principal investigator, Hans-Peter Landolt, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04975360
- Sponsor's protocol ID
- Caff-Clock
- Status last verified
- Jul 2021
- First submitted
- 3 Feb 2021
- Last updated
- 29 Jul 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34611208
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a Time-delayed, Pulsatile Caffeine Formula on Sleep Inertia, Morning Cognition, Affect and Sleepiness in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04975360
- Acronym / sponsor ID
- Caff-Clock
- Conditions
- Sleep Inertia, Caffeine, Placebo
- Keywords
- Sleep restriction, Proactive countermeasure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Collaborators
- Lokman Hekim University, Elixir Pharmaceuticals
- Study start
- 8 Feb 2019 (actual)
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 30 Aug 2019 (actual)
- First posted
- 23 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, double-blind, placebo controlled, cross-over design.
| Arm | Type | Receives |
|---|---|---|
| Caffeine | Experimental | Dietary Supplement: CaffeineAdministration 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. |
| Placebo | Placebo comparator | Other: PlaceboAdministration of a placebo formulation at 22:30. Participants are kept awake until 03:00 and then given a 4-hour sleep opportunity. |
Who may qualify
- Ages
- 18 to 34 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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,
Key exclusion criteria (1 listed)
- Failure to meet inclusion criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CaffeineThe 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. | Dietary supplement | Caffeine |
| PlaceboIdentical hydroxypropylmethylcellulose capsules without containing caffeine micropellets. | Other | Placebo |
Primary outcome
Acute Sleep Inertia Questionnaire
Time frame: At 07:00 hours after caffeine and placebo administration
Modified questionnaire to assess subjective ratings of sleep inertia on physiological, emotional, cognitive and behavioral levels.
8 secondary outcomes
Polysomnographic recording of nocturnal sleep
Time frame: Between 03:00-07:00 hours after caffeine and placebo administration
Caffeine Effects Questionnaire
Time frame: Between 07:15-08:00 hours after caffeine and placebo administration
Positive and Negative Affect Schedule
Time frame: Between 07:00-08:15 hours after caffeine and placebo administration
Psychomotor vigilance task
Time frame: Between 07:15-07:30 hours after caffeine and placebo administration
N-back task
Time frame: Between 07:30-07:40 hours after caffeine and placebo administration
d2 attention task
Time frame: Between 07:40-07:45 hours after caffeine and placebo administration
Cortisol awakening response
Time frame: Between 07:00-08:00 hours after caffeine and placebo administration
Polysomnographic recording of morning nap opportunity
Time frame: Between 08:00-09:00 hours after caffeine and placebo administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2021.
- Derived from this study: PubMed 34611208Dornbierer 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Caffeine in people with Sleep Inertia and Caffeine, run by University of Zurich at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Sleep Inertia Questionnaire (time frame: At 07:00 hours after caffeine and placebo administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04975360, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2021.