Effects of Afternoon and Evening Light on Teenagers' Melatonin Levels, Alertness, Sleepiness and Sleep

Study Overview
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Brief Summary
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Many teenagers are familiar with this: on school days, they have to get up early; during the day, they hardly get any light exposure; in the evening, they go to bed late - and are then tired at school the next day! Around the world, teenagers are sleep deprived, with studies suggesting that almost half ( 45%) suffer from inadequate sleep. Previous investigations have shown that people's sleep-wake rhythm is related to the light conditions that they are exposed to during the day and at night. However, little is known about how different light levels in the afternoon can modulate teenagers' sleep and their bodily responses to light in the late evening. Therefore, the investigators aim to study which lighting conditions have a favourable effect on these aspects and how the potentially harmful effects of light at night can be prevented.

Detailed Description
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Light exposure during adolescence seems to be the critical component of a vicious circle. Due to the maturation of sleep-wake regulatory systems in combination with progressively ill-timed exposure to light and early school start times, teenagers suffer from the accumulation of sleep depth during school days. Therefore, the proposed study investigates whether the physiological and alerting effects of late evening light exposure in adolescents depend on the intensity of light exposure in the preceding afternoon (primary endpoint: evening melatonin concentration). The investigators aim to describe dose-response relationships, where the dose is the preceding (real-world applicable) afternoon light intensity (< 10 lx,  100 lx, or >1000 lx EDI, three-hour duration), and the responses are the adolescents' physiological and alerting responses to evening light exposure ( 100 lx melanopic EDI, 4.5-hour duration). By this route, the researchers can explore whether increasing afternoon light exposure is a feasible target for ameliorating the detrimental effects of artificial light at night and promoting healthier sleep-wake regulation during adolescence.

Official Title
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Modulating Evening Responses to Light by Afternoon Light Exposure in Adolescents

Conditions
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Healthy, Teenager, Healthy Lifestyle

Intervention / Treatment
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* Other: Low light condition
* Other: Moderate light condition
* Other: High light condition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Capable of judgment Normal BMI (Age-related Body-Mass-Index Percentile > P3 & < P97; approx. corresponding to 28.5 ≥ BMI ≤ 16) Signed consent form of participants Signed consent form of a legal representative Exclusion Criteria: Pregnancy or breastfeeding (only female) Current participation in other clinical trials Extreme chronotype (Extreme early or late chronotype/mid sleep time: mid-sleep time < 1:00 / > 7:00) Extremely short or long sleep durations during school- or work days (< 6 hours > 11 hours) Sleep disorders High myopia (< -6 diopters) High hyperopia (> +6 diopters) Non-normal best-corrected visual acuity (BCVA < 0.5 [20/40]) General health concerns or disorders, including heart and cardiovascular, neurological, nephrological, endocrinological, and psychiatric conditions Ophthalmological or optometric conditions Medication impacting visual, neuroendocrine, sleep, and circadian physiology Drug and alcohol use (urinary drug screening & breathalyzer test) Non-compliance with sleep-wake times: >1 deviation from ±60 minute window sleep and wake-up time Non-compliance with caffeine intake (> 1 times caffeine intake) Transmeridian travel (>2 time zones) <1 month prior to the first session of the study shift work <3 months prior to the beginning of the study

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

Sexes Eligible for Study
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All

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
Interventional Model Description: The protocol is a full within-subject trial (cross-over). All participants will conduct three 18-hour experiment sessions and go through the same protocol except for the sequence of the experiment sessions (counter-balanced and randomised).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crossover sequence 1: Dim, Moderate, High<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of <10 lx. In the second experimental session, they receive an intensity of  100 lx, and in the third experimental session, they receive an intensity of >1000 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|
| Experimental: Crossover sequence 2: Dim, High, Moderate<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of <10 lx. In the second experimental session, they receive an intensity of >1000 lx, and in the third experimental session, they receive an intensity of  100 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|
| Experimental: Crossover sequence 3: Moderate, Dim, High<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of  100 lx. In the second experimental session, they receive an intensity of <10 lx, and in the third experimental session, they receive an intensity of >1000 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|
| Experimental: Crossover sequence 4: Moderate, High, Dim<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of  100 lx. In the second experimental session, they receive an intensity of >1000 lx, and in the third experimental session, they receive an intensity of <10 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|
| Experimental: Crossover sequence 5: High, Moderate, Dim<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of >1000 lx. In the second experimental session, they receive an intensity of  100 lx, and in the third experimental session, they receive an intensity of <10 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|
| Experimental: Crossover sequence 5: High, Dim, Moderate<br>All participants will go through all three light conditions in the three experiment sessions: They will receive white fluorescent overhead light (given in melanopic EDI at eye level) as the 3h afternoon light intervention. In the first experimental session, they receive an intensity of >1000 lx. In the second experimental session, they receive an intensity of <10 lx, and in the third experimental session, they receive an intensity of  100 lx. | Other: Low light condition<br>* During the Dim light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (<5 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: Moderate light condition<br>* During the Moderate light condition, the three-hour afternoon light exposure at the participants' eye level will be dim ( 100 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>Other: High light condition<br>* During the High light condition, the three-hour afternoon light exposure at the participants' eye level will be dim (>1000 lx melanopic EDI). In the 4.5-hour evening light exposure, this will constitute a light intensity of  100 lx melanopic EDI at the participants' eye level.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary melatonin | Salivary melatonin. Saliva samples (>1 mL) will be taken from the participants every 30 Minutes using Salivettes. The Salivettes will be centrifuged, the cotton part removed and immediately frozen at -20°C. At a later point, melatonin [in pg] will be determined in these samples by double-antibody radioimmunoassay (RIA). To quantify melatonin suppression, the analytic team will calculate the area under the curve (AUC) for each laboratory condition. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Onset Latency (PSG-derived) | The investigators will operationalise Sleep Onset Latency according to the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events (time interval from lights out to the first PSG-derived sleep epoch in minutes). | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Slow wave activity (PSG-derived) | The investigators will examine slow-wave activity (SWA; delta power density between 0.5 and 4.5 Hz) during the first sleep cycle. EEG slow-wave activity (SWA) (i.e., delta power density between 0.5 and 4.5 Hz) will be calculated as an indicator of sleep propensity across the night within each non-rapid eye movement NREM part of a sleep cycle. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Sleep stages (PSG-derived) | The investigators will score the PSG-derived sleep stages and arousals according to the American Academy of Sleep Medicine (AASM) Manual for the Scoring of Sleep and Associated Events. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Subjective sleepiness | The investigators will assess subjective sleepiness using the single-item 9-point Karolinska Sleepiness Scale (KSS) - a well-validated, highly sensitive subjective Likert-type measurement scale for subjective sleepiness. Scores range from 1 to 9 with higher values on the scale corresponding to higher sleepiness. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Vigilant attention | Objective alertness will be measured using a modified auditory Psychomotor Vigilance Test (aPVT). After a response, the next tone will be played randomly after 2-10 s. The reaction time data will focus on mean 1/reaction time (mean 1/RT), the most sensitive measure for a slight deviation in sleep pressure. Mean 1/RT will be calculated after the removal of false starts and lapses. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Melanopsin sensitivity (pupillary light response) | The investigators will measure changes in the pupil area using silent substitution pupillography and examine the differences between melanopsin response amplitude before the afternoon light condition (pre-light treatment) and the melanopsin response amplitude after the afternoon light condition (post-light treatment). | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Skin temperature | Skin temperature will be continuously monitored with six surface temperature thermocouples placed on proximal and distal regions of the body surface. Skin temperatures (distal & proximal) and the distal-proximal skin temperature gradient (DPG) will be calculated. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Objective sleepiness 1 | The volunteers will perform a Karolinska Drowsiness Test (KDT) three times during scheduled wakefulness. During the KDT, participants fixate on a point on the wall from a one-meter distance for five minutes (eyes open). These sessions will provide EEG data with relatively few artefacts. As the first indicator for objective sleepiness, EEG-derived alpha/theta ratio will be calculated. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 
| Objective sleepiness 2 | The volunteers will perform a Karolinska Drowsiness Test (KDT) three times during scheduled wakefulness. During the KDT, participants fixate on a point on the wall from a one-meter distance for five minutes (eyes open). These sessions will provide EEG data with relatively few artefacts. As the second indicator for objective sleepiness, electro-oculogram-derived (EOG-derived) slow-eye movements will be calculated. | Through study completion, estimated 1.5 years (within 3 weeks for each participant) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melatonin, polysomnography, EEG, sleep, afternoon light, pupil size, evening light