BLUE LIGHT THERAPY FOR SLEEP IMPAIRMENT IN PARKINSON*S DISEASE - Pilot Study -

Parkinson*s disease (PD) is a neurodegenerative disorder characterized by the
coexistence of motor and non-motor features. Sleep disturbances are among the
most common (non-motor) symptoms occurring inup to 90% of PD patients and
reducing quality of life and daytime functioning. Sleep impairment may refer to
diurnal or nocturnal symptoms with extensive daytime sleepiness (EDS), sudden
sleep attacks during daytime as well as insomnia and restless leg syndrome
(RLS). Potential underlying causes of sleep disorders include motor symptoms
(rigidity and bradykinesia), autonomic dysfunction (nocturia, diaphoresis),
abnormal REM sleep behaviour (RBD), sleep apnoea, medication influence,
neurodegeneration itself of central sleep regulatory areas such as the
hypothalamus as well as age-related sleep changes. Increasing evidence suggests
that the suprachiasmatic nuclei (SCN), functioning as the circadian pacemaker
and responsible for the endogenous physiologic cycles occurring on
approximately a 24-hour cycle, is perturbed in PD. These circadian cycles are
synchronized to the environmental light or dark and to social activity cycles
by zeitgebers (cues indicating environmental time). Light represents the most
effective zeitgeber of the circadian timing system and supplementary exposure
to light has beneficial effects on sleep quality and daytime vigilance in
healthy older people and patients suffering from dementia. In addition,
dopamine neurotransmission plays an essential role in circadian rhythm
regulation especially in promoting wakefulness. Dopamine is involved in retinal
light adaptation, melanopsin and clock gene expression and influences circadian
rhythmicity through selected central nervous system structures (raphe nuclei,
locus coeruleus, hypothalamus and thalamus).
Several rodent models of PD have clearly demonstrated the pathological
involvement of the SCN in PD, offering a potentially powerful and novel
therapeutic target. The disturbance of circadian timing in PD also seems to
have an impact on several other non-motor symptoms, including depressive
symptoms and autonomic functions, as well as motor functions such as rigidity
and bradykinesia. As medication prescribed for sleep disturbances often
results in side effects, there is a great need to develop and evaluate
nonpharmacological approaches to manage not only sleep disorders in patients,
but also many other symptoms which are related to the perturbation of circadian
disruption.
Bright light therapy (BLT) was introduced to improve circadian
rhythmicity as well as mood and sleep disorders. Firstly, a positive effect on
sleep and mood was observed in the healthy general population but also in
seasonal affective disorder and depression. BLT was also found to be useful in
neurodegenerative disorders like PD. In previous studies patients diagnosed
with PD received BLT with a light intensity of 1000 - 6000 Lux for 30- 90
minutes in the morning or prior to bedtime. Results indicated noticeable
improvement in mood, sleep and interestingly, in motor functions. Based on
recommendation 10000 Lux should be used for 30 minutes and the time of
administration should depend on the type of symptoms or patient*s chronotype.
BLT is considered as a safe treatment option and only minor side effects have
been reported such as: headache, eye or vision-related complains and nausea.
The effectiveness of BLT may be attributed to its zeitgeber function, which
resets circadian rhythmicity reflected in a shift in serum melatonin
concentrations. Studies have shown that blue light with a wave length in the
range of 460-480 nm is more effective in entraining the SCN compared to
monochromatic light with a wave length around 555 nm. In addition, it has been
observed that blue light around the 460 nm range is more effective in
phase-shifting circadian output than exposure to white light of longer duration
and higher irradiance. Blue light therapy has been, for example, studied in
otherwise healthy subjects in whom it increased alertness and improved
cognitive functioning.
So far, five previous studies have used BLT (white light) in PD
patients showing improvements in sleep and other non-motor symptoms after two
weeks of therapy. Two studies have also shown an improvement in motor function.
These studies were, however, limited by either a small number of patients,
retrospective design and most have made use of unwieldy light boxes. Also the
option of blue light instead of white light as a treatment option has not been
explored in PD. In our study we propose a novel approach to light therapy using
Propeaq light therapy glasses with integrated LED lights emitting blue light
with a 468 nm wavelength more specifically targeting retinal melanopsin and the
retinohypothalamic tract and thereby more likely to effectively reset the SCN
in PD patients. Moreover, replacement of light boxes with glasses might
positively influence the study compliance and repeatability of results as well
as give further insights to underlying mechanisms of circadian disruption in
PD.

1. Primary Objective:

The primary objective is to evaluate the efficacy of Propeaq light therapy
glasses with integrated blue LED lights on sleep disorders in patients with PD
using the PSQI.

2. Secondary Objectives:

The secondary objective of the study is to evaluate efficacy of Propeaq light
therapy glasses with integrated blue LED lights on a wide range of other
domains such as motor symptoms as well as other non-motor symptoms (e.g. mood,
cognition).

The study design will be a placebo controlled single-blind study. All
participants will be randomly allocated to receive either blue light therapy
(intervention) or red light therapy (placebo).During or prior to the pilot
trial, participants will not receive any information relating to which colour
of glasses concerns the intervention and which colour the placebo.

Intervention group:
Intervention will consist of blue light therapy being administered.
Participants will wear the Propeaq light therapy glasses for one hour twice
daily (total two hours each day). During the first daily session the
participants will wear the glasses for one hour after they wake up in the
morning and during the second session they will wear the glasses for one hour
starting two hours before preferred bed time.

Control group:
Placebo will consist of red light therapy being administered using the same
glasses as the blue therapy but with red coloured glass instead of blue
coloured glass. The red light protocol will be identical to the blue light
protocol again requiring the participants to wear the glasses twice daily for
one hour (total two hours each day).

Each participant will use the blue light therapy for a total of two weeks or
the red light therapy for two weeks as well.

Light therapy was well tolerated in all studies with PD patients. The rate of
adverse events was around 6%. Reported side effects include mild headache,
sleepiness and itchy eyes. These adverse effects all resolved spontaneously
after secession of the intervention. The same amount and nature of side effects
have been reported in the red light placebo therapy. In terms of benefit, based
on previous studies with white light BLT, we expect that the participants
receiving the blue light therapy will show significant improvements in e.g.
daytime sleepiness, sleep quality and several self-reported subjective sleep
metrics, such as sleep fragmentation, sleep quality ease of falling asleep. In
addition we expect improvement of depressive mood and motor scores, reflected
by better scores on the UPDRS scale.