Effects of Caffeine on Sleep-wake Regulation in Teenagers

Study Overview
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Brief Summary
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The aim is to quantify the effects of one dose of caffeine (compared to placebo) on sleep and wakefulness in adolescents.

Official Title
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Caffeine-induced Effects on Sleep, Cognitive Performance, and Underlying Cerebral Correlates During Adolescence - a Randomised, Placebo-controlled, Double-blind Clinical Study

Conditions
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Adolescence, Caffeine

Intervention / Treatment
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* Other: Placebo
* Other: Caffeine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self-reported habitual caffeine consumption: min. 80 mg per month until max 300 mg per week as estimated from mean caffeine content per serving of caffeine containing beverages and food Body-Mass-Index: 16.2-25.4 Informed Consent as documented by signature of participant Informed Consent as documented by signature of legal representative Exclusion Criteria: Previous enrollment into the current study Investigators' family members, employees or other dependent persons Left-handedness No normal current health as based on questionnaires, screenings of urine, and examination by the physician in charge Drug use: Volunteers must be drug-free for the entire duration of the study, with no history of drug or alcohol dependency. 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 (Munich Chronotype Questionnaire [17], MCTQ <2 or >7) Short or long sleep duration: subjective sleep duration during schooldays not between 6-10 h (based on MCTQ) Inability to follow procedures Insufficient knowledge of project language (German) Circumstances endangering MRI safety Non-compliance with sleep/wake times during ambulatory part (deviation of more than ±1.5 hour from scheduled times)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* placebo capsule (mannitol)<br>|
| Experimental: Caffeine<br> | Other: Caffeine<br>* caffeine capsule (80 mg of caffeine plus mannitol)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of sleep after caffeine intake (vs. placebo) | Structure and intensity of sleep is measured by polysomnography. We focus on changes in deep sleep. | Nighttime sleep recordings start around 4 hours after caffeine/placebo intake | 
| Change of brain blood-oxygen-level-dependent activity after caffeine intake (vs. placebo) | Using magnetic resonance imaging (MRI), we measure blood-oxygen-level-dependent activity in the brain during a working memory task. How higher blood-oxygen-level-dependent activity can be interpreted depends on behavioral performance. | Start of measurements around 45 minutes once after placebo, once after caffeine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hormonal profile after caffeine intake (vs. placebo) | Hormonal levels are measured in saliva samples. We focus on time of melatonin onset (higher values indicate later time). | Per condition (caffeine and placebo) 8 saliva samples (taken around 250 minutes, 230 minutes, 165 minutes, 115 minutes, 65 minutes and 15 minutes before bedtime, and 490 minutes and 520 minutes after bedtime) | 
| Change in subjective sleepiness after caffeine intake (vs. placebo) | Sleepiness is measured by a questionnaire (Karolinska Sleepiness Scale, KSS). Higher scores on KSS (range between 1 and 9) represent higher sleepiness. | Per condition (caffeine and placebo) 8 times (around 250 minutes, 230 minutes, 165 minutes, 115 minutes, 65 minutes and 15 minutes before bedtime, and 490 minutes and 520 minutes after bedtime) | 
| Change in subjective sleep quality after caffeine intake (vs. placebo) | Subjective sleep quality is measured by the Leeds Sleep Evaluation Questionnaire (LSEQ). Four different scales are evaluated: a) Getting to Sleep (range: 1-100, where lower values represent more difficulties to fall asleep), b) Quality of Sleep (range: 1-100, where lower values represent lower quality), c) Awake Following Sleep (range: 1-100, where lower values represent problems to wake up), and d) Behavior Following Wakening (range: 1-100, where lower values represent more sleepiness after awakening). | Per condition around 480 minutes after bedtime | 
| Change in working memory performance after caffeine intake (vs. placebo) | Working performance is measured by accuracy in an n-back task (%of correct responses in 2-back versus 0-back) | Performance is measured 3 times in each condition (around 45 minutes, 180 minutes and 780 minutes after treatment) | 
| Change in viglance performance after caffeine intake (vs. placebo) | Vigilance performance is measured by reaction time patterns in a psychomotor vigilance task | Performance is measured 3 times in each condition (around 85 minutes, 200 minutes and 730 minutes after treatment) | 
| Change in declarative memory performance after caffeine intake (vs. placebo) | Performance is quantified by assessing the course of the number of words recalled from a list of words (learned before treatment) | Performance is measured 3 times in each condition (around before 40 minutes before treatment and 210 and 760 minutes after treatment) | 
| Change in pattern separation performance after caffeine intake (vs. placebo) | Cognitive performance is measured by the lure discrimination index and the recognition performance for repeat items. | Performance is measured 3 times in each condition (around 20 minutes before treatment and 220 minutes and 770 minutes) | 
| Change in mental effort during cognitive performance (working memory) after caffeine intake (vs. placebo) | Mental effort is measured by visual analogue scales targeting satisfaction, concentration, exhaustion and motivation. Scores range from 0-100. Higehr scores indicate higher levels on these scales. | Mental effort is measured 3 times in each condition (around 70 minutes, 200 minutes and 800 minutes after treatment) | 
| Change in well-being after caffeine intake (vs. placebo) | Well-being is quantified as mean of three visual analogue scales targeting tension, mood and physical comfort. Scores range from 0-100. Higher scores indicate better well-being. | Per condition (caffeine and placebo) 8 times (around 250 minutes, 230 minutes, 165 minutes, 115 minutes, 65 minutes and 15 minutes before bedtime, and 490 minutes and 520 minutes after bedtime) | 
| Change in cerebral blood flow | Using magnetic resonance imaging (MRI), we measure levels of cerebral blood flow in the brain during rest. | once after placebo, once after caffeine (start of measurements around 60 minutes after treatment once after placebo, once after caffeine) |