A Dose Selection Trial of Light Therapy for Impaired Sleep in Parkinson's Disease
Phase: NA
Conditions: Parkinson Disease, Sleep Disorder, Fatigue
Sponsor: Massachusetts General Hospital

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FULL PROTOCOL TITLE 
A Dose Selection Trial of Light Therapy for Impaired Sleep in Parkinson’s Disease 
 
Protocol Version: 7.0 
Protocol Date: November 8, 2022 
 
SHORT PROTOCOL TITLE 
ENLITE PD 
 
Protocol Principal Investigator (PPI): 
Aleksandar Videnovic, MD, MSc 
Director, Program on Sleep, Circadian Biology, and Neurodegeneration 
Director, Division of Sleep Medicine 
Massachusetts General Hospital 
 
Associate Professor of Neurology 
Harvard Medical School 
 
MGH Neurological Clinical Research Institute 
165 Cambridge Street, Suite 600 
Boston, MA 02114 
 
Supported by: 
The National Institute of Neurological Disorders and Stroke (NINDS) 
 
Study Intervention Provided by: 
The SunBox Co., Gaithersburg, MD, USA 
 
Sponsor of IND/IDE: 
n/a 

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SYNOPSIS 
Study Title 
A Dose-selection Trial of Light Therapy for Impaired Sleep in Parkinson’s Disease 
Primary Objectives 
The primary aims of this trial are to (i) determine whether once- or twice-daily bright-white light 
therapy (BWLT) improves sleep in Parkinson’s disease (PD) sufficiently to carry forward in a 
phase III efficacy trial and, if so, (ii) to select the superior dose frequency to carry forward. Only 
dose frequencies judged to be safe will be considered for selection. 
Secondary Objectives 
The key secondary aim is to determine whether once-weekly BWLT is a non-inferior control 
condition relative to twice-daily dim-red light therapy (DRLT). Additional secondary aims will (i) 
estimate the effect of daily BWLT on fatigue in PD, and (ii) determine whether patients adhere to 
light therapy (LT). 
Design and Outcomes 
This is a 16-week, randomized, phase II, parallel-group, placebo-controlled, dose-selection 
clinical trial of LT in participants with PD and co-existing sleep disruption using a comparative 
selection trial design.  
At baseline, the mid-treatment visit, and at completion of the treatment and wash-out periods, 
the following assessments/instruments will be completed: Parkinson’s Disease Sleep Scale, 2nd 
version (PDSS-2), Parkinson’s Disease Fatigue Scale (PFS-16), Epworth Sleepiness Scale 
(ESS), Non-Motor Symptoms Scale (NMSS), MDS Unified Parkinson’s Disease Rating Scale 
(MDS-UPDRS), Parkinson’s Disease Questionnaire-39 (PDQ-39), Geriatric Depression Scale 
(GDS-15), and Montreal Cognitive Assessment (MoCA). Participants will complete daily sleep 
logs and wear a wrist activity and light exposure monitor throughout the study. The PDSS-2 will 
be the primary outcome variable  
Interventions and Duration 
After a 4-week baseline period that will incorporate sleep hygiene education, eligible participants 
will be randomized 1:1:1:1 to 8 weeks of one of four treatment conditions: (i) BWLT twice daily 
(morning and evening), (ii) BWLT once daily (evening only), (iii) BWLT once weekly (evening 
only), and (iv) DRLT twice daily (morning and evening). Participants randomized to the once-
weekly BWLT and twice-daily DRLT groups will serve as controls of dose frequency and of 
wavelength and illuminance, respectively. Participants randomized to BWLT will receive one 
hour of full-spectrum white light (10,000 lux) in direction of gaze, in the morning and evening 
(twice daily) or in the evening only, daily or weekly, for eight weeks. Participants randomized to 
DRLT will receive one hour of filtered red light (300 lux) in direction of gaze, in the morning and 
evening (twice daily), for eight weeks. SunRay light boxes (The SunBox Co., Gaithersburg, MD, 
USA) will be used for LT administration. Dimensions of the box are 15.5" (H) x 23" (W) x 3.25" 
(D). SunRay light boxes are equipped with a spectrally transparent prismatic diffuser or a red 
filter, both of which block UV rays. After the intervention period, all participants will complete a 
4-week wash-out period to assess carry-over effects of LT. Each participant will be on-study for 

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16 weeks. Total enrollment time is estimated to be 20 months. Estimated time from enrollment 
to the completion of data analysis is 30 months.  
Sample Size and Population 
Approximately up to 158 participants with PD will be randomized from 25 PD and Movement 
Disorders Centers in the United States. 
Inclusion Criteria: 
1) Diagnosis of idiopathic PD as defined by the Movement Disorder Society Clinical 
Diagnostic Criteria for Parkinson's disease; 
2) PD Hoehn and Yahr stage 2-4; 
3) A score of 2 (mild) or above on the Sleep Problems question of the MDS-UPDRS Part 1; 
4) Stable dose of all PD medications for at least 30 days prior to randomization; 
5) Willingness to wear an Actiwatch and complete daily sleep logs;  
6) Age 45 or above 
Exclusion Criteria: 
1) Atypical or secondary forms of parkinsonism; 
2) Co-existent significant sleep apnea at screening, as determined by the PI’s clinical 
assessment; adequately treated sleep apnea, as assessed by sleep apnea machine 
download (CPAP download) will be permitted; 
3) Co-existent symptomatic restless legs syndrome (RLS) (as assessed by the 
International Classification of Sleep Disorders (ICDS) diagnostic criteria for RLS) at 
screening; 
4) Cognitive impairment as determined by a Mini Mental State Examination score <25 at 
screening; 
5) Presence of moderate depression defined as a Beck Depression Inventory II (BDI-II) 
score ≥20 at screening; 
6) Current untreated hallucinations or psychosis (drug-induced or spontaneous) with a 
score of 2 or above on the Hallucinations and Psychosis question of the MDS-UPDRS 
Part 2; 
7) Use of hypno-sedative drugs or melatonin for sleep or stimulants, unless the participant 
has been on a stable dose for at least 60 days prior to the screening; 
8) Ongoing or recent (within 30 days prior to screening) Cognitive Behavioral Therapy for 
Insomnia; 
9) Use of antidepressants, unless the participant has been on a stable dose for at least 60 
days prior to the screening; 
10) Work hours between 10 PM and 6 AM, within 60 days prior to randomization or 
anticipated during the 16 weeks after screening; 
11) Travel between 3 or more time zones within 45 days prior to study screening or 
anticipated such travel during the 16 weeks after screening; 
12) Unstable or serious medical illness; 
13) History of significant eye trauma or disease, retinopathy, or cataract Grade 4 that would 
significantly affect transmission or processing of light through either eye; 
14) Current use, use at any time during study participation, or use within the 30 days prior to 
screening of photosensitizing or other medications that in the opinion of the investigator 
would interfere with the safety of the participant during the trial, including: amiodarone, 
porfimer, psoralens, chlorpromazine, quinidine, demeclocycline, temoporfin, tetracycline, 
fleroxacin, oral isoretinoin, voriconazole, nalidixic acid, thioridazine, St. John’s wort, 
ofloxacin, and piroxicam; 

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15) Pregnant women will be excluded from participation; if a participant is pre-menopausal, a 
urine pregnancy test will be conducted at randomization to determine eligibility. 
16) Individuals currently enrolled in another interventional trial will be excluded from 
participation; individuals may be screened for the study after a 12-week washout period 
following their completion of the other trial. Individuals currently enrolled in an 
observational study may be enrolled if in the opinion of the investigator the observational 
study will not impact the participant’s ability to meet the requirements of this trial. 
 
Schedule of Activities 
Evaluation 
Screening/ 
Sleep 
Hygiene 
Education 
Baseline/ 
Randomizati
on 
Mid-
Treatment 
Assessment  
End of 
Intervention 
Assessment  
Wash-out 
Assessment  
 
V1 
Screening 
V2 
Week 0 
V3 
Week 4 
V4 
Week 8 
V5 
Week 12 
Written Informed 
Consent 
x 
 
 
 
 
Inclusion/Exclusion 
Review 
x 
x 
 
 
 
Medical History/ 
Demographics 
x 
 
 
 
 
HT, WT, Vital Signs 
(HR,BP) 
x 
 
 
 
 
Physical 
Examination 
x 
 
 
 
 
Neurological 
Examination 
x 
 
 
 
 
BDI-II 
x 
 
 
 
 
MMSE 
x 
 
 
 
 
Berlin questionnaire 
x 
 
 
 
 
Eye Exam 
x 
 
 
 
 
Concomitant 
Medication Review  
x 
x 
x 
x 
x 
MDS-UPDRS (I-IV) 
x1 
x 
x 
x 
x 
PDSS-2 
 
x 
x 
x 
x 

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PFS-16 
 
x 
x 
x 
x 
NMSS 
 
x 
x 
x 
x 
PDQ-39 
 
x 
x 
x 
x 
GDS-15 
 
x 
x 
x 
x 
MoCA 
 
x 
x 
x 
x 
Randomization  
 
x 
 
 
 
Dispense / Return 
Study Device  
 
x 
 
x 
 
Dispense / Collect 
LT Log 
x 
x 
x 
x 
x 
Dispense / Collect 
Actiwatch 
x 
x 
x 
x 
x 
Mail Actiwatch to 
Actigraphy Core 
 
x 
x 
x 
x 
Dispense / Collect 
Sleep Logs 
x 
x 
x 
x 
x 
Adverse Event 
Review  
 
x 
x 
x 
x 
1Only the Sleep question of the MDS-UPDRS Part 1 will be administered at the Screening visit.