Light Therapy as Treatment for Fatigue in Multiple Sclerosis

Study Protocol:

Eligible participants will be consented and randomized 1:1 to (a) white LT (10,000 lux), or
(b) dim red LT (<300 lux). Participants will be informed that this study will examine the
effect of two different light spectra on fatigue. The following assessments will be
administered by the study principal investigator at the baseline visit: (1) the Kurtzke
Extended Disability Status Scale (EDSS), (2) FSS, (3) Beck Depression Inventory II (BDI), (4)
Pittsburgh Sleep Quality Index (PSQI), (5) Berlin questionnaire for obstructive sleep apnea,
(6) Epworth Sleepiness Scale. A two-week sleep diary will be collected before enrollment in
order to screen for significant behavioral insufficient sleep or circadian rhythm disorders.
The light box used for LT is designed to stand on a desk or tabletop. It can be used in the
home or office. The light is delivered at a downward angle to maximize the effectiveness. The
box runs on 124 watts and contains full spectrum 5000k 10,000 lux bulbs. Bright light
treatment requires at least 2,500 lux to be effective.

Data Collection:

The study period will include a two-week baseline period, a four-week treatment period, and a
four-week follow up period. Throughout the study period, participants will record their
fatigue using the Visual Analogue Fatigue Scale (VAFS) four times daily, starting after
waking up, and every four hours thereafter. The VAFS is a simple, validated 10-point scale
ranging from 1 to 10 in which participants can report their fatigue as a snapshot at that
particular moment. Data collection will occur by participants in self-report fashion. A FSS
score will be collected at enrollment as well as at the end of the four week treatment period
and the end of the four week follow-up period. There will be three visits with a principal
investigators (PI), including the baseline visit described above, a visit with the PI at the
end of the treatment period in which participants will report a FSS and discuss their
experiences with LT, and a third follow-up visit at the end of the four-week follow up period
for a final FSS. At this last visit they will be queried on whether they believe the
intervention had any effect on their fatigue and whether they believe the alternative therapy
(white light or dim red light) would have been more or less beneficial. Additionally
participants will be asked to keep a LT log in which they will record daily LT exposure and
associated side effects.

Statistical Analysis:

The primary outcome measure is the change in the average FSS after the four-week study period
in the bright light "active" vs. dim light "control" groups. There are no reports on FSS in
response to bright LT in pMS. Using the conventional values of α=0.05 and β=0.80 for 2-tailed
tests of probability with equally sized groups: a difference in 10 points on FSS between
groups requires 18 people per study arm; a difference in 8 points requires 28 people per
group. If power is reduced to 70%, the sample sizes are 22 and 14 for 8-point and 10-point
differences. First, the investigators will compare the mean change in FSS scores, from
baseline to after completion of LT, in an intention to treat analysis. The secondary outcome
measure will be a change in the global VAFS scores after light therapy in both groups.
Frequencies will be used to describe baseline characteristics across treatment arms. X2
statistics or Fisher's exact test will be used to compare the differences between groups.
VAFS will be evaluated using a mixed-effects model which accounts for correlation between
repeated measurements. Participant logbooks will be used to generate summary statistics and
graphically display fatigue patterns throughout the day. Logbooks will also qualitatively
assess the safety and tolerability of LT.

Inclusion Criteria:

- Relapsing remitting Multiple Sclerosis based on the McDonald Criteria (2010)

- Over 18 years old

- Presence of fatigue defined as FSS over 36

Exclusion Criteria:

- A change in an anti-depressant up to 4 weeks prior to study screening

- A change in fatigue medication regime or MS disease modifying therapy up to 4 weeks
prior to study screening

- Shift work

- Use of photosensitizing medication

- Presence of eye trauma or acute optic neuritis within the preceding 3 months

- History of traumatic brain injury

- Probable (untreated) sleep apnea based on Berlin questionnaire

- Significant anemia

- History of mania

- MS relapse in the preceding four weeks

- Current pregnancy

- Known light sensitivity

- Other complicating illness preventing study completion.