Manipulating alertness using (exogenous) melatonin and light

Visible light does not only influence visual processes, but also affects
non-visual processes such as mood, performance, and alertness. These processes
show systematic changes over the course of the day and night. In a previous
experiment conducted by our department, we attempted to improve daytime
alertness using a polychromatic white light source in a dose-dependent manner.
Based on the limited amount of literature on this topic, a positive effect of
light on alertness was expected. If confirmed, this could be exploited, for
instance in a work environment. However, contrary to these expectations, we did
not find significant improvements in alertness in response to light during the
daytime. Informal contact with other labs revealed that others also
investigated the effects of daytime light on alertness, without significant
effects. This suggests to us that the limited number of earlier studies with
positive results might be chance observations. Our hypothesis is that light at
night is much more effective in increasing alertness than light in the day. We
are interested in the underlying mechanisms.

This study aims to investigate 2 factors that may explain the differences in
alerting effects of light between day and night.These are a possible ceiling
effect of alertness during daytime and a more prominent role of the hormone
melatonin in alertness regulation at night (Melatonin is only endogenously
produced at night).

This study will be a placebo controlled study, taking place at two different
times of day; daytime (11:30 - 16:00) and nighttime (23:30 - 04:00).
Intervention will comprise of encapsulated, oral melatonin administration
(empty gelatin capsule filled with 5 mg melatonin) compared to a placebo (empty
gelatin capsule).
1.5 hours after ingestion, either bright or dim light will be administered.
Half hourly alertness assessments will be made before, during and after
melatonin or placebo administration and bright- or dim light exposure, in the
form of a questionnaire, pupillary measurements, temperature measurements and a
reaction time task.

Every participants will participate four times on only one of the two choosen
timepoints.
Four different interventions will be applied, consisting of:
1) placebo + dim light
2) placebo + bright light
3) melatonin + dim light
4) melatonin + bright light

The order of intervention will be randomized per subject.

Ten participants will undergo all four interventions (placebo + dim light,
placebo + bright light, melatonin + dim light, melatonin + bright light) at one
time interval of the day (starting at 11:30. Ten different individuals will
take part in the same experiment, starting at 23:30.
This will result in a within the individual (intervention) and between the
individual (time of day) design. Although a (full) within subject design would
be preferred (meaning that individuals would participate at both times of day,
enduring all four conditions two times), we do not think that this is optimal,
when considering the burden of participating.

Intervention comprises of:

1) placebo + dim light
2) placebo + bright light
3) melatonin + dim light
4) melatonin + bright light


The light conditions are simulated with the use of a Philips EnergyUp light.
Philips EnergyUp lights are IEC certified according to IEC 62471
(photobiological hazard). Lights will be placed in front of the participants at
50 cm distance, at an intensity of either 2 lux or creating an intensity of
2000 lux (bright light). To create the dim light condition of 2 lux, 8 neutral
density filters, decreasing light intensity with 0.5 log-units each, will be
put in front of the lamp. Neutral density filters will be used to ensure that
only intensity is altered, without affecting spectral composition.

Participants will be treated with either 5 mg of oral encapsulated melatonin or
placebo. To ensure that no differences exist between placebo and intervention,
the placebo will exist of an empty gelatin capsule (Capsugel) whereas the
intervention will consist of the same gelatin capsule (Capsugel) filled with 5
mg melatonin (Melatomatine).

No risks are associated with participation. Light intensities and composition
is within the safe range.
A possible burden might be that participants have to swallow a capsule for four
times, which could be experienced as unpleasant. In addition, some sleepiness
as a consequence of melatonin administration might be expected