Clinical trial NCT05513547: Beneficial Effects of Daytime Light Exposure and Physical Activity on the Human Circadian Clock and Sleep
Official title: Beneficial Effects of Daytime Light Exposure and Physical Activity on the Human Circadian Clock and Sleep
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Circadian System
Keywords: daytime light exposure
human circadian clock
Dim-Light Melatonin Onset (DMLO)
nocturnal light exposure
intrinsically photosensitive retinal ganglion cells (ipRGCs)
retinal photoreceptors
photopic illuminance
melanopic illuminance
melanopic equivalent daylight illuminance (EDI)
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2022-08-24
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential Bayes Factor approach: spectral characteristics of daytime LE varied in a within-subject manner in three sequential 7-hour LE protocols (P1, P2, P3).

Physical activity varied between subjects in two subgroups: one 'resting' group and one 'hiking' group. The latter will hike (P2/3) or walk on a treadmill (P1) for 4 hours during LE.
Primary purpose: BASIC_SCIENCE

Brief summary: This study is to examine the circadian phase-shifting effects of daylight and physical activity (primary endpoint: shift in dim-light melatonin onset (DLMO)) as well as their effects on sleep the ensuing night and analyzes how different spectral characteristics of daylight and physical activity affect the biological clock and sleep.

There are two types of interventions in a within-between study plan: - Within participants: light conditions will be varied during daytime in three 7-hour light exposure protocols (usual office lighting, natural daylight, natural daylight with "blue"-light filtering glasses). - Between participants: physical activity levels (rest vs. 4 hours of moderate activity, i.e., hiking) will be varied. Eligible volunteers are invited to partake in the three-week study schedule, including three experimental visits and in-between ambulatory sleep-wake and light exposure tracking. On study intake, participants are randomly assigned to either the 'hike' or 'rest' activity subgroup. The 'resting subgroup' will be allowed to study, read, etc. during the experimental conditions, whereas the 'hiking subgroup' will have 4 hours of scheduled moderate physical activity during each LE condition starting 3 hours after waking up.

Following the screening procedure and an adaptation night to screen for sleep disorders, eligible participants will be matched with a 'partner'. One will be assigned to the rest (A), the other to the hiking (B) subgroup. LE protocols within each subgroup are identical and participants from each pair will undergo all light conditions on the same day to minimize variability due to e.g., weather conditions.

Detailed description: While phylogenetically, life on earth has developed under the cyclic changes of sunlight and darkness, human life in modern societies is usually characterized by a markedly different light environment: spending most of the waking day indoors in relatively low light levels, whereas exposing ourselves to relatively high levels of artificial light in the evening. This decrease in day-night contrast has detrimental effects on the human circadian system and sleep. The pathways that mediate these effects have functionally been mapped using evening or nocturnal light exposure (LE). It has been shown that light with increased short-wavelength proportions suppresses melatonin, delays the biological clock, and impairs sleep. These consequences are thought to be mainly mediated by the effects of short-wavelength light on intrinsically photosensitive retinal ganglion cells (ipRGCs), which express melanopsin that has its peak spectral sensitivity at around 480nm. Little is known about the contributions of the other retinal photoreceptors, particularly the cones, which encode colour and brightness under daylight viewing conditions. Thus, the precise contributions of melanopic and photopic illuminance remain to be established. Besides the negative effects of evening artificial LE, exposure to higher levels of daylight is associated with beneficial consequences for sleep and circadian rhythms. However, also in this respect, the precise photopic and melanopic contributions remain to be established. Beyond this, daylight exposure is often confounded with physical activity, which can act as a zeitgeber itself. Specifically, physical activity in the morning and the afternoon has been shown to acutely phase-advance the biological clock and positively affect sleep. The possible contributions of an interaction with LE remain to be established. This study aims at delineating the effects of (i) photopic and melanopic illuminance during daytime LE and (ii) physical activity on the biological clock and sleep. The spectral characteristics of daytime LE will be varied in a within-subject manner in three 7-hour LE protocols. Physical activity will be varied between subjects in two subgroups (i.e., 'hike' and 'rest'). This study investigates the relative importance of daytime and its precise spectral characteristics as well as physical activity for healthy circadian rhythms and sleep.

Eligibility criteria: Inclusion Criteria:

* Age: 18-35 years
* Body Mass Index: 18.5-24.9 (i.e., normal weight according to World Health Organization (WHO) criteria)
* Moderate cardiorespiratory fitness levels, moderate level of endurance training according to the category "moderate physical activity" (category 2) of the International Physical Activity Questionnaire (IPAQ) short form
* Informed consent as documented by signature of the participant

Exclusion Criteria:

* Self-reported pregnancy
* Investigator's family members, employees, or other dependent persons
* Chronic or debilitating medical (including psychiatric) conditions; normal state of health will be established on the basis of questionnaires and the examination by the physician in charge. Illnesses that would be a reason for exclusion are:

  * Sleep disorders: Narcolepsy, sleep apnea (apnea index \> 10), periodic limb movements (PLM index \> 15), insomnia (polygraphically recorded sleep efficiency \< 70% or Pittsburgh Sleep Quality Index (PSQI) index \> 5), hypersomnia
  * Chronobiological disorders: hypernychthemeral sleep-wake cycle, delayed or advanced sleep phase syndrome
  * Psychiatric disorders
  * Somatic diseases: cardiovascular, respiratory, gastrointestinal, haemopoietic, visual and immune system diseases, neurological disorders, infectious diseases, allergies (e.g., skin allergies, acute hay fever), thrombocytopenia or other dysfunctions of blood platelets
* Drug use: volunteers must not consume any drugs (including nicotine and alcohol) for the entire duration of the study with no history of drug or alcohol dependency. This will be ensured by the use of a urine multi-drug screen at every experimental visit.
* Medication that could affect outcome parameters
* Shift work \< 3 months prior to study intake
* Transmeridian travel (\> 2 time zones) \< 1 month prior to study intake
* Extreme chronotype (Munich Chronotype Questionnaire \[MCTQ\] \<2 or \>7)
* Extremely long/short sleep duration (subjective sleep duration on workdays outside 6-10h according to the MCTQ)
* Abnormal colour vision, vision disorders (other than e.g., mild myopia corrected with contact lenses)
* Inability to understand and/or follow procedures
* Non-adherence to the circadian stabilization protocol during the five days prior to and between the experimental visits (deviation of \>30min form scheduled times more than twice or on the day of the study visit)

Primary outcomes:
measure: Difference in salivary DLMO (in minutes, phase advance) between the first and the second night (Shift in dim-light melatonin onset (DLMO))
timeFrame: On the evenings of each LE protocol (from 5 hours before habitual bedtime (HBT) (every 30 minutes)) and in the mornings during the first hour after wake-up (8h later) on day 8-10, day 15-17, day 22-24.
Secondary outcomes:
measure: EEG slow-wave activity (SWA) (i.e., delta power density between 0.5 and 4.5 Hz) as an indicator of sleep propensity within each NREM part of a sleep cycle
timeFrame: On day 8-10, day 15-17, day 22-24.
measure: Change in Karolinska Sleepiness Scale (KSS) for subjective sleepiness
timeFrame: On the evenings of each LE protocol, from 5 hours before HBT on day 8-10, day 15-17, day 22-24.
measure: Change in Visual Comfort Scale (VCS) for mood, visual comfort and physical well-being.
timeFrame: On the evenings of each LE protocol, from 5 hours before HBT on day 8-10, day 15-17, day 22-24.
measure: Change in Psychomotor Vigilance Task (PVT) for objective alertness
timeFrame: On the evenings of each LE protocol, from 5 hours before HBT on day 8-10, day 15-17, day 22-24.
measure: Change in Self-Assessment of Sleep and Awakening Quality Scale (SSA) for subjective sleep quality
timeFrame: Throughout the three weeks of the study protocol
measure: Change in Polysomnography (PSG)-derived sleep stages and arousals according to the AASM Manual for the Scoring of Sleep and Associated Events for objective sleep quality
timeFrame: During the nights of each experimental protocol (on day 8-10, day 15-17, day 22-24).
measure: Change in actimetry (sleep-wake schedules) measured by actimetry devices
timeFrame: Throughout the three weeks of the study protocol
measure: Change in participants' light exposure, measured by lightweight light sensor
timeFrame: Throughout the three weeks of the study protocol
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Centre for Chronobiology, Psychiatric Hospital of the University of Basel
Study officials:
affiliation: Centre for Chronobiology, Psychiatric Hospital of the University of Basel
name: Christine Blume, Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: