CaffeineCICAFFNCT05409339
Influence of Caffeine Consumption on the Human Circadian System
A study testing Caffeine in people with Caffeine and Caffeine Withdrawal, run by Psychiatric Hospital of the University of Basel at 1 site in Switzerland.
Trial summary
Surveys indicate that 85% of the adult population consume caffeine on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Caffeine, Caffeine Withdrawal, Sleep
- What is being tested?
- Caffeine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteSwitzerland
- Study dates
- 9 May 2016to 17 Dec 2017
- 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 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Self-reported caffeine consumption: 300 mg - 600 mg daily
- 18-35 years old
- Healthiness
- Exclusion criteria based on chronic or debilitating medical conditions:
- Normal current health was established based on questionnaires, screenings of urine, and examination by the physician in charge. Given the wide range of illnesses encountered in medical practice, we only list those that were certainly reasons of exclusion:
- Diseases of somatic origin: Cardiovascular-, respiratory-, gastrointestinal-, hematopoietic- visual- and immune system diseases, kidney and urinary tract, endocrine and metabolic diseases, neurologic diseases, infectious diseases, allergies (e.g. skin allergies, acute hay fever), thrombocytopenia or other dysfunction of the blood platelets.
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- Sleep disorders: Narcolepsy, sleep apnea (apnea index >10), periodic limb movements (PLMS >15), insomnia (polygraphically recorded sleep efficiency <70 %), hypersomnia, usual time in bed not between 6-9 h (assessed by [101]).
- Chronobiologic disorders: Hypernychthemeral sleep/wake cycle, delayed sleep phase syndrome (waketime >2 h later than desired, or habitually after 10 am), advanced sleep phase syndrome (waketime >2 h earlier than desired or habitually before 5 am).
- Drug/alcohol use, except caffeine: Volunteers must be drug-free (including nicotine and alcohol) for the entire duration of the study, with no history of drug (excluding caffeine) or alcohol dependency.
Who cannot join
- Self-reported caffeine consumption: < 300 mg and > 600 mg daily (as estimated from mean caffeine content per serving of caffeine containing beverages and food)
- Body Mass Index (BMI) range: <18 and >26
- Participation in other clinical trials <3 months prior to study begin
- Shift work <3 months prior to study begin
- Transmeridian travel (>2 time zones) <1 month prior to study begin
- Extreme chronotype (Morningness-Eveningness Questionnaire <30 or >70)
Show all 13Show fewer
- Inability to follow procedures
- Insufficient knowledge of project language (German)
- Metallic prosthesis or metallic implants or non-removable objects on the body (e.g. splinters, piercings)
- Tattoos with larger diameter than 10 cm
- Tattoos above the shoulder area
- Claustrophobia
- Contraceptive coil
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Caffeine Consumption on the Human Circadian System: Neurobehavioral, Hormonal and Cerebral Mechanisms
Surveys indicate that 85% of the adult population consume caffeine on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. This study quantifies the influence of regular caffeine intake and its cessation on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being, neurobehavioral performance and associated cerebral mechanisms. The knowledge is expected to contribute important insights on recent societal changes in sleep-wake behavior (e.g., shorter sleep duration and delayed sleep phase) and the related increase in people suffering from sleep problems.
Read the detailed description
Surveys indicate that 85% of the adult population consume caffeine, often on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. The circadian timing system promotes wakefulness at the end of the biological day ("wake maintenance zone") and promotes sleep after the onset of the endogenous melatonin secretion ("opening of sleep gate"). There is mounting evidence that circadian and sleep homeostatic mechanisms continuously interact at the neurobehavioral, hormonal and cerebral level. Furthermore, earlier evidence has shown that the strength of circadian wake-promotion and the timing of circadian rhythmicity differs according to a genetic predisposition in the adenosinergic system. Thus, it was assumed that the daily consumption of caffeine may substantially impact on both circadian and homeostatic sleep-wake processes at different systemic levels.
This study aimed at quantifying the influence of regular caffeine intake and its cessation on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being, neurobehavioral performance and associated cerebral mechanisms. Specifically, the study investigated the effects of sleep-wake regulatory adaptations to regular caffeine consumption and acute caffeine cessation a) on night-time sleep structure and sleep intensity (electroencephalography, EEG), b) on circadian wake-promotion (nap sleep during the biological day) and circadian timing of hormonal rhythms, and c) on waking quality, as indexed by subjective ratings, objective measures of neurobehavioral performance, and cerebral mechanisms (EEG and functional magnetic resonance imaging [MRI]).
Twenty young healthy regular caffeine consumers were examined in a double-blind, placebo-controlled within-subjects design with three conditions: Regular caffeine intake, regular placebo intake, and cessation of regular caffeine intake. In the laboratory, circadian sleep-wake promotion was assessed by combining EEG and multimodal MRI techniques. Circadian timing was assessed by salivary melatonin and cortisol rhythms. Sleep and waking quality were quantified by continuous polysomnography (during sleep at night and during a nap in the evening), waking EEG, subjective ratings (sleepiness, mood, craving, withdrawal symptoms) and cognitive performance (vigilance and working memory). Each of the three laboratory parts lasted more than 40 h under strictly controlled conditions (i.e., dim light, constant ambient temperature etc.). Subsequent to each laboratory condition, actimetry and sleep diaries served to assess sleep- and waking patterns in the field under caffeine vs. placebo conditions.
The aim was to substantially advance the knowledge about the impact of the commonly encountered caffeine consumption on the sleep-wake regulatory system. Furthermore, the project was intended to substantially contribute to the understanding of complex interplay between sleep-wake regulatory mechanisms in response to acute or long-term changes in the adenosinergic system.
- Conditions
- Caffeine, Caffeine Withdrawal, Sleep, Circadian Rhythm
- Being tested
- Caffeine, Placebo
- Keywords
- Caffeine, Withdrawal, Sleep, Circadian rhythm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
150 mg caffeine, 3 times/day (wakeup + 45 min, +255 min, and +475 min)
PlaceboDrug
Also called Mannitol
Mannitol, 3 times/day (wakeup + 45 min, +255 min, and +475 min)
| Study group | Role | What they receive |
|---|---|---|
| Caffeine-Caffeine (Condition "Caffeine") | Experimental | Through the 9-day pre-ambulatory, 2-day laboratory, and 7-day post-ambulatory parts, participants received 150 mg caffeine x 3 times daily. Receives: Drug: Caffeine |
| Caffeine-Placebo (Condition "Withdrawal") | Experimental | During the 9-day ambulatory part, participants received 150 mg caffeine x 3 times daily, followed by a switch to placebo (150 mg mannitol) from the 2nd intake of the 9th day onward, through the laboratory and the post-ambulatory parts. Receives: Drug: Caffeine; Drug: Placebo |
| Placebo (Condition "Placebo") | Placebo comparator | Through the 9-day ambulatory and 2-day laboratory, and 7-day post-ambulatory parts, participants received 150 mg mannitol x 3 times daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sleep polysomnography in normal baseline sleep
Electrophysiological activities were measured by electroencephalography during sleep. Spectral analysis was performed using a Fast-Fourier transformation to quantify delta (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and sigma (12 - 16 Hz), and beta (16 - 32 Hz) power density . Sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring per 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).Sleep stages were reported relative to total sleep time. Duration of sleep latencies was also reported.
Measured: First 8-hour nighttime sleep on the laboratory evening (Day 9)
Sleep polysomnography in an evening nap
Electrophysiological activities were measured by electroencephalography during the sleep. Spectral analysis was performed using a Fast-Fourier transformation to quantify delta (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and sigma (12 - 16 Hz), and beta (16 - 32 Hz) power density . Sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring per 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).Sleep stages were reported relative to total sleep time. Duration of sleep latencies was also reported.
Measured: approx. 13.5-hour after wake-up time on the laboratory day (Day 10)
Sleep polysomnography in a recovery sleep
Electrophysiological activities were measured by electroencephalography during the sleep. A Fast-Fourier Transformation was used to quantify slow wave activities (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and beta (12 - 16 Hz), and sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring through each 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).
Measured: Second 8-hour nighttime sleep following 20-hour wakefulness on the laboratory day (Day 10)
Wake-EEG
Electrophysiological activities during wakefulness measured by electroencephalography during the sleep. A Fast-Fourier Transformation was used to quantify slow wave activities (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and beta (12 - 16 Hz).
Measured: 14 measurements: (Day 9) -130, -20 minutes to the bedtime. (Day 10) +20, +140, +260, +370, +490, +600, +725, +867, +945, +1065, +1180, +1250 minutes after awakening.
Melatonin levels
The oscillation of melatonin levels across 43-hour laboratory stay were measured from the 33 salivary samples. The dim-light melatonin onset (DLMO) and average secretion level were analyzed and compared among three conditions.
Measured: 33 samples: (Day 9) -310,-250,-190,-140,-110,-80,-50,-10 minutes to the bedtime. (Day 10) + 50,+110,+170,+230,+290,+350,+400,+460,+515,+580,+610,+670,+700,+735,+765,+935,+965,+995,+1055,+1075,+1115,+1145,+1170, +1190,+1250 after awakening.
Subjective sleepiness
Participants were asked to assess their perceived sleepiness by Karolinska Sleepiness Scale (KSS), where they answered 1 for very alert and 9 for very sleepy.
Measured: 33 samples: (Day 9) -310,-250,-190,-140,-110,-80,-50,-10 minutes to the bedtime. (Day 10) + 50,+110,+170,+230,+290,+350,+400,+460,+515,+580,+610,+670,+700,+735,+765,+935,+965,+995,+1055,+1075,+1115,+1145,+1170, +1190,+1250 after awakening.
Vigilance
Vigilance was assessed by psychomotor vigilance tasks (PVT). Participants were asked to respond to each stimulus showing on a screen as soon as they can by keying down. The reaction times and lapses were used to indicate the vigilance.
Measured: 7 measurements: (Day 9) -160 minutes to the bedtime. (Day 10) +95, +335, +560, +795, +1040, +1235 minutes after awakening.
Vigilance-related blood oxygen level-dependent activities
Regional brain activation is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during a psychomotor vigilance task (PVT).
Measured: +795 minutes after waking up on the laboratory day (Day 10)
Working memory-related blood oxygen level-dependent activities
Regional brain activation is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during a working memory task (N-back).
Measured: +775 after waking up on the laboratory day (Day 10)
Blood oxygen level-dependent activities in resting state
Functional connectivity is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during an eye-open resting state.
Measured: approx.13.7 hours after waking up on the laboratory day (Day 10)
Secondary outcomes (5)
Cerebral blood flow
Arterial Spin Labeling sequence was used to measure the changes in cerebral blood flow induced by caffeine intake and caffeine cessation.
Measured: approx. 13.5 hours after waking up on the laboratory day (Day 10)
Caffeine concentrations
Caffeine concentrations were measured from salivary and perspiratory samples.
Measured: 12 samples: (Day 9) -185 minutes to the bedtime. (Day 10) +15, +120, +240, +300, +480, +590, +735, +825, +975, +1085, +1195 minutes after awakening.
Working memory
Working memory capacity was measured by N-Back tasks, where participants had a high workload condition (3-back) and a low workload condition (0-back).
Measured: 7 measurements: (Day 9) -140 minutes to the bedtime. (Day 10) +75, +315, +540, +775, +1020, +1215 minutes after awakening.
Sleep diary
A daily log was used to record the participant's bed- and wakeup time, self-report sleep quality, tiredness, and activities during the day including caffeine intake.
Measured: Upon wake-up and bedtime during the ambulatory parts (Day1 to Day8 and Day11 to Day17)
Actimetry
Participants wore an actiwatch to record the muscle tone in order to track the body movement and sleep-wake behaviors constantly throughout the entire study.
Measured: Constant recording from Day1 to Day17.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2022
- Study start9 May 2016
- Primary completion8 Oct 2017
- Study completion17 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for CaffeineStudies 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
- The project adopted a double blind, placebo-controlled, randomized within-subjects design. Screenings took place at the Centre for Chronobiology at the Psychiatric University Hospital Basel (UPK, single center). Data collection took place at Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital of Basel. Each participant went through three study sessions, i.e. caffeine, placebo, withdrawal. Each of the session consisted of 9 days of pre-ambulatory part, 2 days of laboratory visit, and 7 days of post-ambulatory part.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Psychiatric Hospital of the University of Basel
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Principal investigator, Carolin Reichert, Psychiatric Hospital of the University of Basel
- Investigators
- Carolin Reichert, Dr., Principal investigator, UPK Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05409339
- Sponsor's protocol ID
- CChronobiology
- Acronym
- CICAFF
- Status last verified
- Jun 2022
- First submitted
- 25 May 2022
- Last updated
- 8 Jun 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Weibel J, Lin YS, Landolt HP, Garbazza C, Kolodyazhniy V, Kistler J, Rehm S, Rentsch K, Borgwardt S, Cajochen C, Reichert CF. Caffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109851. doi: 10.1016/j.pnpbp.2019.109851. Epub 2019 Dec 19.
PubMed 31866308Weibel J, Lin YS, Landolt HP, Kistler J, Rehm S, Rentsch KM, Slawik H, Borgwardt S, Cajochen C, Reichert CF. The impact of daily caffeine intake on nighttime sleep in young adult men. Sci Rep. 2021 Feb 25;11(1):4668. doi: 10.1038/s41598-021-84088-x.
PubMed 33633278Weibel J, Lin YS, Landolt HP, Berthomier C, Brandewinder M, Kistler J, Rehm S, Rentsch KM, Meyer M, Borgwardt S, Cajochen C, Reichert CF. Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men. J Biol Rhythms. 2021 Aug;36(4):384-394. doi: 10.1177/07487304211013995. Epub 2021 May 23.
PubMed 34024173Lin YS, Weibel J, Landolt HP, Santini F, Garbazza C, Kistler J, Rehm S, Rentsch K, Borgwardt S, Cajochen C, Reichert CF. Time to Recover From Daily Caffeine Intake. Front Nutr. 2022 Feb 2;8:787225. doi: 10.3389/fnut.2021.787225. eCollection 2021.
PubMed 35187019Lin YS, Weibel J, Landolt HP, Santini F, Meyer M, Brunmair J, Meier-Menches SM, Gerner C, Borgwardt S, Cajochen C, Reichert C. Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial. Cereb Cortex. 2021 May 10;31(6):3096-3106. doi: 10.1093/cercor/bhab005.
PubMed 33585896
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Caffeine Consumption on the Human Circadian System: Neurobehavioral, Hormonal and Cerebral Mechanisms
- ClinicalTrials.gov ID
- NCT05409339
- Acronym / sponsor ID
- CICAFF / CChronobiology
- Conditions
- Caffeine, Caffeine Withdrawal, Sleep, Circadian Rhythm
- Keywords
- Caffeine, Withdrawal, Sleep, Circadian rhythm
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Psychiatric Hospital of the University of BaselUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- 9 May 2016 (actual)
- Primary completion
- 8 Oct 2017 (actual)
- Study completion
- 17 Dec 2017 (actual)
- First posted
- 8 Jun 2022 (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.
Surveys indicate that 85% of the adult population consume caffeine on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. This study quantifies the influence of regular caffeine intake and its cessation on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being, neurobehavioral performance and associated cerebral mechanisms. The knowledge is expected to contribute important insights on recent societal changes in sleep-wake behavior (e.g., shorter sleep duration and delayed sleep phase) and the related increase in people suffering from sleep problems.
Detailed description
Surveys indicate that 85% of the adult population consume caffeine, often on a daily basis. Caffeine acts on sleep homeostatic mechanisms by antagonizing the sleep factor adenosine. Whether and how caffeine also impacts on the circadian regulation of sleep and -wakefulness is fairly unexplored. The circadian timing system promotes wakefulness at the end of the biological day ("wake maintenance zone") and promotes sleep after the onset of the endogenous melatonin secretion ("opening of sleep gate"). There is mounting evidence that circadian and sleep homeostatic mechanisms continuously interact at the neurobehavioral, hormonal and cerebral level. Furthermore, earlier evidence has shown that the strength of circadian wake-promotion and the timing of circadian rhythmicity differs according to a genetic predisposition in the adenosinergic system. Thus, it was assumed that the daily consumption of caffeine may substantially impact on both circadian and homeostatic sleep-wake processes at different systemic levels.
This study aimed at quantifying the influence of regular caffeine intake and its cessation on circadian promotion of sleep and wakefulness, on circadian hormonal markers, well-being, neurobehavioral performance and associated cerebral mechanisms. Specifically, the study investigated the effects of sleep-wake regulatory adaptations to regular caffeine consumption and acute caffeine cessation a) on night-time sleep structure and sleep intensity (electroencephalography, EEG), b) on circadian wake-promotion (nap sleep during the biological day) and circadian timing of hormonal rhythms, and c) on waking quality, as indexed by subjective ratings, objective measures of neurobehavioral performance, and cerebral mechanisms (EEG and functional magnetic resonance imaging [MRI]).
Twenty young healthy regular caffeine consumers were examined in a double-blind, placebo-controlled within-subjects design with three conditions: Regular caffeine intake, regular placebo intake, and cessation of regular caffeine intake. In the laboratory, circadian sleep-wake promotion was assessed by combining EEG and multimodal MRI techniques. Circadian timing was assessed by salivary melatonin and cortisol rhythms. Sleep and waking quality were quantified by continuous polysomnography (during sleep at night and during a nap in the evening), waking EEG, subjective ratings (sleepiness, mood, craving, withdrawal symptoms) and cognitive performance (vigilance and working memory). Each of the three laboratory parts lasted more than 40 h under strictly controlled conditions (i.e., dim light, constant ambient temperature etc.). Subsequent to each laboratory condition, actimetry and sleep diaries served to assess sleep- and waking patterns in the field under caffeine vs. placebo conditions.
The aim was to substantially advance the knowledge about the impact of the commonly encountered caffeine consumption on the sleep-wake regulatory system. Furthermore, the project was intended to substantially contribute to the understanding of complex interplay between sleep-wake regulatory mechanisms in response to acute or long-term changes in the adenosinergic system.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- The project adopted a double blind, placebo-controlled, randomized within-subjects design. Screenings took place at the Centre for Chronobiology at the Psychiatric University Hospital Basel (UPK, single center). Data collection took place at Clinical Trial Unit, Department of Clinical Research, University of Basel and University Hospital of Basel. Each participant went through three study sessions, i.e. caffeine, placebo, withdrawal. Each of the session consisted of 9 days of pre-ambulatory part, 2 days of laboratory visit, and 7 days of post-ambulatory part.
| Arm | Type | Receives |
|---|---|---|
| Caffeine-Caffeine (Condition "Caffeine") | Experimental | Drug: CaffeineThrough the 9-day pre-ambulatory, 2-day laboratory, and 7-day post-ambulatory parts, participants received 150 mg caffeine x 3 times daily. |
| Caffeine-Placebo (Condition "Withdrawal") | Experimental | Drug: Caffeine, Drug: PlaceboDuring the 9-day ambulatory part, participants received 150 mg caffeine x 3 times daily, followed by a switch to placebo (150 mg mannitol) from the 2nd intake of the 9th day onward, through the laboratory and the post-ambulatory parts. |
| Placebo (Condition "Placebo") | Placebo comparator | Drug: PlaceboThrough the 9-day ambulatory and 2-day laboratory, and 7-day post-ambulatory parts, participants received 150 mg mannitol x 3 times daily. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Self-reported caffeine consumption: 300 mg - 600 mg daily
- 18-35 years old
- Healthiness
- Normal current health was established based on questionnaires, screenings of urine, and examination by the physician in charge. Given the wide range of illnesses encountered in medical practice, we only list those that were certainly reasons of exclusion:
- Diseases of somatic origin: Cardiovascular-, respiratory-, gastrointestinal-, hematopoietic- visual- and immune system diseases, kidney and urinary tract, endocrine and metabolic diseases, neurologic diseases, infectious diseases, allergies (e.g. skin allergies, acute hay fever), thrombocytopenia or other dysfunction of the blood platelets.
Key exclusion criteria (13 listed)
- Self-reported caffeine consumption: < 300 mg and > 600 mg daily (as estimated from mean caffeine content per serving of caffeine containing beverages and food)
- Body Mass Index (BMI) range: <18 and >26
- Participation in other clinical trials <3 months prior to study begin
- Shift work <3 months prior to study begin
- Transmeridian travel (>2 time zones) <1 month prior to study begin
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 |
|---|---|---|
| Caffeine150 mg caffeine, 3 times/day (wakeup + 45 min, +255 min, and +475 min) | Drug | Caffeine-Caffeine (Condition "Caffeine"), Caffeine-Placebo (Condition "Withdrawal") |
| PlaceboAlso: MannitolMannitol, 3 times/day (wakeup + 45 min, +255 min, and +475 min) | Drug | Caffeine-Placebo (Condition "Withdrawal"), Placebo (Condition "Placebo") |
Primary outcome
Sleep polysomnography in normal baseline sleep
Time frame: First 8-hour nighttime sleep on the laboratory evening (Day 9)
Electrophysiological activities were measured by electroencephalography during sleep. Spectral analysis was performed using a Fast-Fourier transformation to quantify delta (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and sigma (12 - 16 Hz), and beta (16 - 32 Hz) power density . Sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring per 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).Sleep stages were reported relative to total sleep time. Duration of sleep latencies was also reported.
Sleep polysomnography in an evening nap
Time frame: approx. 13.5-hour after wake-up time on the laboratory day (Day 10)
Electrophysiological activities were measured by electroencephalography during the sleep. Spectral analysis was performed using a Fast-Fourier transformation to quantify delta (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and sigma (12 - 16 Hz), and beta (16 - 32 Hz) power density . Sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring per 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).Sleep stages were reported relative to total sleep time. Duration of sleep latencies was also reported.
Sleep polysomnography in a recovery sleep
Time frame: Second 8-hour nighttime sleep following 20-hour wakefulness on the laboratory day (Day 10)
Electrophysiological activities were measured by electroencephalography during the sleep. A Fast-Fourier Transformation was used to quantify slow wave activities (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and beta (12 - 16 Hz), and sleep stages, i.e., non-rapid eye-movement (NREM) stage 1, NREM2, NREM3, NREM4, and REM sleep were determined by visual scoring through each 30-second epoch in accordance with the guideline of American Academy of Sleep Medicine (AASM).
Wake-EEG
Time frame: 14 measurements: (Day 9) -130, -20 minutes to the bedtime. (Day 10) +20, +140, +260, +370, +490, +600, +725, +867, +945, +1065, +1180, +1250 minutes after awakening.
Electrophysiological activities during wakefulness measured by electroencephalography during the sleep. A Fast-Fourier Transformation was used to quantify slow wave activities (0.75 - 4.5 Hz), theta (4.5 - 8 Hz), alpha (8 - 12 Hz), and beta (12 - 16 Hz).
Melatonin levels
Time frame: 33 samples: (Day 9) -310,-250,-190,-140,-110,-80,-50,-10 minutes to the bedtime. (Day 10) + 50,+110,+170,+230,+290,+350,+400,+460,+515,+580,+610,+670,+700,+735,+765,+935,+965,+995,+1055,+1075,+1115,+1145,+1170, +1190,+1250 after awakening.
The oscillation of melatonin levels across 43-hour laboratory stay were measured from the 33 salivary samples. The dim-light melatonin onset (DLMO) and average secretion level were analyzed and compared among three conditions.
Subjective sleepiness
Time frame: 33 samples: (Day 9) -310,-250,-190,-140,-110,-80,-50,-10 minutes to the bedtime. (Day 10) + 50,+110,+170,+230,+290,+350,+400,+460,+515,+580,+610,+670,+700,+735,+765,+935,+965,+995,+1055,+1075,+1115,+1145,+1170, +1190,+1250 after awakening.
Participants were asked to assess their perceived sleepiness by Karolinska Sleepiness Scale (KSS), where they answered 1 for very alert and 9 for very sleepy.
Vigilance
Time frame: 7 measurements: (Day 9) -160 minutes to the bedtime. (Day 10) +95, +335, +560, +795, +1040, +1235 minutes after awakening.
Vigilance was assessed by psychomotor vigilance tasks (PVT). Participants were asked to respond to each stimulus showing on a screen as soon as they can by keying down. The reaction times and lapses were used to indicate the vigilance.
Vigilance-related blood oxygen level-dependent activities
Time frame: +795 minutes after waking up on the laboratory day (Day 10)
Regional brain activation is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during a psychomotor vigilance task (PVT).
Working memory-related blood oxygen level-dependent activities
Time frame: +775 after waking up on the laboratory day (Day 10)
Regional brain activation is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during a working memory task (N-back).
Blood oxygen level-dependent activities in resting state
Time frame: approx.13.7 hours after waking up on the laboratory day (Day 10)
Functional connectivity is measured by echo-planar-imaging (EPI) sequence in a 3T fMRI scanner during an eye-open resting state.
5 secondary outcomes
Cerebral blood flow
Time frame: approx. 13.5 hours after waking up on the laboratory day (Day 10)
Caffeine concentrations
Time frame: 12 samples: (Day 9) -185 minutes to the bedtime. (Day 10) +15, +120, +240, +300, +480, +590, +735, +825, +975, +1085, +1195 minutes after awakening.
Working memory
Time frame: 7 measurements: (Day 9) -140 minutes to the bedtime. (Day 10) +75, +315, +540, +775, +1020, +1215 minutes after awakening.
Sleep diary
Time frame: Upon wake-up and bedtime during the ambulatory parts (Day1 to Day8 and Day11 to Day17)
Actimetry
Time frame: Constant recording from Day1 to Day17.
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 8 Jun 2022.
- Results publication: PubMed 31866308Weibel J, Lin YS, Landolt HP, Garbazza C, Kolodyazhniy V, Kistler J, Rehm S, Rentsch K, Borgwardt S, Cajochen C, Reichert CF. Caffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109851. doi: 10.1016/j.pnpbp.2019.109851. Epub 2019 Dec 19.
- Results publication: PubMed 33633278Weibel J, Lin YS, Landolt HP, Kistler J, Rehm S, Rentsch KM, Slawik H, Borgwardt S, Cajochen C, Reichert CF. The impact of daily caffeine intake on nighttime sleep in young adult men. Sci Rep. 2021 Feb 25;11(1):4668. doi: 10.1038/s41598-021-84088-x.
- Results publication: PubMed 34024173Weibel J, Lin YS, Landolt HP, Berthomier C, Brandewinder M, Kistler J, Rehm S, Rentsch KM, Meyer M, Borgwardt S, Cajochen C, Reichert CF. Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men. J Biol Rhythms. 2021 Aug;36(4):384-394. doi: 10.1177/07487304211013995. Epub 2021 May 23.
- Results publication: PubMed 35187019Lin YS, Weibel J, Landolt HP, Santini F, Garbazza C, Kistler J, Rehm S, Rentsch K, Borgwardt S, Cajochen C, Reichert CF. Time to Recover From Daily Caffeine Intake. Front Nutr. 2022 Feb 2;8:787225. doi: 10.3389/fnut.2021.787225. eCollection 2021.
- Results publication: PubMed 33585896Lin YS, Weibel J, Landolt HP, Santini F, Meyer M, Brunmair J, Meier-Menches SM, Gerner C, Borgwardt S, Cajochen C, Reichert C. Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial. Cereb Cortex. 2021 May 10;31(6):3096-3106. doi: 10.1093/cercor/bhab005.
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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.
Carolin Reichert, Dr. principal investigator
UPK Basel
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 Caffeine and Caffeine Withdrawal, run by Psychiatric Hospital of the University of Basel 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 9 inclusion and 13 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 8 Jun 2022. 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?
Sleep polysomnography in normal baseline sleep (time frame: First 8-hour nighttime sleep on the laboratory evening (Day 9)). The study lists 10 primary outcomes in all. 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 NCT05409339, which also lists 5 linked publications.
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 8 Jun 2022.