TWILIGHT: Effect of Light Exposure During Acute Rehabilitation on Sleep After TBI.
Phase: NA
Conditions: Traumatic Brain Injury, TBI, Sleep
Sponsor: University of Washington

1 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
TWILIGHT Study: Treatment with Light Therapy 
Effect of light exposure during acute rehabilitation on sleep after traumatic brain injury 
 
Protocol Version 1.2 
 
Funded by National Institute on Disability and Rehabilitation Research (NIDRR) 
H133A120028 
H133G120055 
H133A120084 
 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential investigators, 
consultants, study staff, and applicable independent ethics committees or institutional review boards.  The 
contents of this document shall not be disclosed to others without written authorization unless  it  is  necessary  
to  obtain  informed  consent  from  potential  study participants. 
 
University of Washington TBI Model System (TBIMS) Group:  
Jeanne M. Hoffman, Ph.D.  
 
Principal Investigator   
jeanneh@uw.edu 
Donald Fogelberg, Ph.D., OTR/L  
Investigator  
 
 
fogelber@uw.edu  
Jennifer Zumsteg, M.D.  
 
Investigator  
 
 
zumsteg@uw.edu  
Sureyya Dikmen, Ph.D.  
 
Investigator  
 
 
dikmen@uw.edu  
Rena Reyes, M.D.  
 
 
Data Safety Monitor  
 
rreyes@uw.edu  
Jason Barber, M.S.  
 
 
Data Analyst/Statistician  
barber@uw.edu  
Erica Wasmund   
 
 
Research Coordinator   
ericaw8@uw.edu  
 
University of Texas Southwestern 
Kathleen R. Bell, M.D. 
 
Investigator 
 
 
Kathleen.Bell@UTSouthwestern.edu 
 
Mount Sinai, New York TBIMS Group: 
Jason Krellman  
 
 
Principal Investigator 
Anne F. Ambrose, M.D.  
 
Investigator 
Tausif Billah, B.A. 
 
 
Research Coordinator 
Michelle Urman 
 
 
Research Coordinator 
  
Baylor Institute for Rehabilitation, North Texas TBIMS Group: 
Randi Dubiel, D.O.  
 
 
Principal Investigator 
Shahid Shafi, M.D., MPH  
 
Investigator 
Cindy Dunklin, B.S., CCRC  
 
Project Coordinator   
 
James A. Haley Veterans Hospital 
Risa Nakase-Richardson, Ph.D.  
Study Consultant/Investigator  
 
 
Project Officer, NIDRR: 
Cate Miller, Ph.D.  
 
 
 
 
 
 
 
Cate.Miller@ed.gov  
 
 
 
 
 

2 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
TABLE OF CONTENTS 
 
 
 
 
 
 
 
 
Page 
Title/Investigators 
 
 
 
 
 
 
 
 
 
1 
Table of Contents 
 
 
 
 
 
 
 
 
 
2 
Background and Significance  
 
 
 
 
 
 
 
3-4 
Target Population 
 
 
 
 
 
 
 
 
 
4 
Potential benefit to this population 
 
 
 
 
 
 
 
4 
Research Hypotheses and Specific Aims 
 
 
 
 
 
 
5 
Study Description 
 
 
 
 
 
 
 
 
 
5-6 
 
Figure 1:  Summary Overview of Study Procedures for TWILIGHT 
 
6 
Screening/Study Sample 
 
 
 
 
 
 
 
 
6 
 
 
 
Inclusion Criteria  
 
 
 
 
 
 
 
 
 
7 
Exclusion Criteria 
 
 
 
 
 
 
 
 
 
7 
Rationale for Study Population 
 
 
 
 
 
 
 
7 
 
 
 
Data Collection and Measures 
 
 
 
 
 
 
 
7-10 
 
Table 1: Data Collection Measures and Areas Assessed 
 
 
 
8 
Study Procedures 
 
 
 
 
 
 
 
 
 
10-12 
Data Analysis  
 
 
 
 
 
 
 
 
 
12 
 
 
 
Data Management 
 
 
 
 
 
 
 
 
 
13-14  
 
Table 2:  Performance Measures 
 
 
Safety and Adverse Events 
 
 
 
 
 
 
 
 
14 
Definitions 
 
 
 
 
 
 
 
 
 
14-15  
 
Recording of Adverse Events  
 
 
 
 
 
 
16 
 
 
Ethical Considerations/Protection of Human Subjects 
 
 
 
 
17-18 
Potential Risks, Potential Benefits, Intent to Benefit, and Risk/Benefit Ratio 
 
18-19 
Importance of Knowledge to be Gained 
 
 
 
 
 
 
19 
Overall Project Evaluation 
 
 
 
 
 
 
 
 
20 
List of Acronyms and Abbreviations  
 
 
 
 
 
 
21 
 
 
References and Works Cited  
 
 
 
 
 
 
 
22-30  
 
 
 
 
 
 
Appendix 
 
 
 
 
 
 
 
 
 
 
31-44  
 
 
 
 
 
 
 
 
  
 
 

3 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
I. 
 Background and Significance: 
Sleep disturbance is a common clinical problem after Traumatic Brain Injury (TBI). Disrupted 
sleep exacerbates other symptoms after TBI such as fatigue and can impede overall recovery after TBI 
(Castriotta RJ W. M., June 15, 2007) (Mathias JL, 2012;13).  Trouble falling or staying asleep 
(insomnia) and reversal of sleep/wake cycles (circadian rhythm disorders) are two categories of sleep 
disturbance occurring frequently after TBI. Insomnia affects roughly one-third of TBI survivors  and 
reports of overall sleep disturbances are as high as 70% (Mathias JL, 2012;13). In a study by Ayalon et 
al. (Ayalon L, 2007), 36% of individuals with TBI who reported suffering from insomnia met the 
diagnostic criteria for a circadian rhythm sleep disorder. Sleep disturbances are also common during 
inpatient rehabilitation. Makley et al. (Makley MJ E. J., 2008) found that 68% of patients with a closed 
head injury demonstrated disturbed sleep during inpatient rehabilitation. The clinical utility of 
diagnosing sleep disorders using criteria from the Diagnostic and Statistical Manual or International 
Classification of Sleep Disorders is limited in clinical situations such as the first weeks of recovery after 
TBI as these diagnostic criteria require the presence of symptoms for at least a month, rely heavily on 
subjective report and can be confusing given the frequency of co-occurring medical and psychiatric 
disorders (Ohayon MM, 2009). In these clinical situations, other tools for assessing sleep quality may be 
especially useful. These tools include sleep logs, measurements of movement with actigraphy and 
overall clinical assessment of sleep patterns. 
 
Most studies looking at treatment of sleep disturbances and wakefulness after TBI have focused 
on pharmacologic interventions and have reported limited efficacy in improving sleep.  The sedative-
hypnotic medications typically used in the treatment of sleep disorders in the general population are 
often not appropriate for use after TBI given concerns about cognitive and behavioral side effects 
(Flanagan SR, 2007) (Larson EB, 2010). There are case reports of improved sleep in the chronic phase 
of TBI recovery with cognitive behavioral therapy (Ouellet MC M. C., 2007) and light exposure (Carter 
KA, 2010) (Chesson AL, 1999) but these treatments have not been studied in the acute rehabilitation 
phase. BWL exposure is considered an appropriate option for some sleep disorders in a variety of 
clinical populations including those with dementia (Mishima K, 1994) (Riemersma-van der Lek RF, 
2008). The proposed study will help elucidate both the effects of BWL exposure after TBI in the 
inpatient rehabilitation setting as well as clinical feasibility of delivering light exposure in this case 
setting. 
 
Sleep disturbance may hinder the rehabilitation process. Clinically significant sleep disturbances 
after TBI correlate with higher rates of depression, anxiety, pain (Fogelberg DJ, 2012) and fatigue 
(Englander J, 2010), all conditions which could deter full engagement in rehabilitation. Even in a 
healthy population a moderate reduction in the amount of quality sleep over time can negatively impact 
cognitive functions such as behavioral alertness and working memory (Banks S, 2007).  BWL exposure 
has been shown to be effective in both reducing agitated behavior and improving cognition in older 
adults with dementia (Mishima K, 1994) (Riemersma-van der Lek RF, 2008) (Forbes D, 2011). After 
TBI, there is an association of sleep problems with more functional limitations, higher reliance on other 
people for care, and diminished satisfaction with quality of life at one year after injury (Fogelberg DJ, 
2012). Improved sleep in the acute recovery phase after TBI may positively impact other rehabilitation 
outcomes. In the study by Makley, et al. (Makley MJ J.-G. L., 2009) sleep disturbance was associated 
with longer average length of stay for both acute trauma center (22 days vs. 9 days) and inpatient 
rehabilitation (37 days vs. 21 days). In non-TBI populations BWL exposure has shown efficacy in the 
treatment of mood symptoms and improving alertness even with small doses and durations of treatment, 
such as a single one-hour session (Reeves GM, 2012) (Riemersma-van der Lek RF, 2008) (Revell VL, 
Jan 2006) (Chang AM, 2012) (Terman M, 2005) (Wirz-Justice A, 2012) (Friedman L, May 2012) 

4 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
(Neikrug AB, 2012). These additional effects of BWL exposure may provide clinical benefit beyond 
improved sleep in persons recovering from TBI and will be assessed in the proposed study.  
 
Research and clinical evaluation of sleep often employ actigraphy, which allows for the 
evaluation of subject movement over time and can be extrapolated to wake/rest cycles (Morgenthaler TI, 
2007). Use of actigraphy for sleep evaluation with subjects after brain injury has been successful in both 
inpatient (Zollman FS C. C., 2010) and outpatient settings (Ayalon L, 2007).  Additionally, 
considerations regarding movements and sleep specific to TBI and actigraph placement, including 
spasticity and paresis (Zollman FS C. C., 2010), are important and will be considered in the execution of 
this study.  
 
Our study group has extensive experience with the inpatient Rehabilitation brain injured population, 
research experience in regards to sleep after brain injury, and demonstrated use of light therapy and 
actigraphy in individuals with TBI (Fogelberg DJ, 2012) (Watson NF, 2007) . The University of 
Washington investigators have current IRB permission to conduct a pilot study of BWL exposure on the 
acute rehabilitation unit to allow for the current study protocol to be refined early in the research process 
and demonstrate logistics and feasibility to collaborating TBIMS centers. In the current health care 
climate, low cost treatments with low staff burden are valued and we will evaluate these factors in this 
study (Wood RL, 1999) (Whitmore RG, 2012).  
 
II. 
 Target Population:   
Individuals aged 18-70 years with moderate to severe traumatic brain injury (TBI), 30 days or 
less out from TBI hospitalized on acute inpatient rehabilitation. Moderate to severe TBI will be 
determined using the TBI Model System (TBIMS) case definition (Traumatic Brain Injury Model 
Systems, 2013): damage to brain tissue caused by an external mechanical force, post-traumatic amnesia 
(PTA) greater than 24 hours, or loss of consciousness greater than 30 minutes or Glasgow Coma Scale 
(GCS) score in the Emergency Department of 3-12, or intracranial abnormalities on imaging (Cuthbert 
JP, 2012).   
 
Exclusion parameters for age and time since injury are needed in this study since sleep patterns 
and light effects change with aging and the focus of this study is in the early recovery phase of TBI. 
Potential subjects will be excluded from the study if they have a past medical history of bipolar disorder 
(Terman M, 2005);  retinal pathology, complete blindness, or light sensitivity; absence of eye opening; 
tetraplegia with less than antigravity strength in all myotomes caudal to C6 level given the limitations on 
measuring movements with; or confirmed or suspected diagnosis of obstructive sleep apnea (Zollman 
FS C. C., 2010). BWL exposure is unlikely to change the underlying pathology for obstructed sleep and 
therefore potential subjects with a known history of sleep apnea treated with continuous positive 
pressure device, a body mass index > 40 kg/m2 at eligibility assessment, or who are classified as being 
“high risk” for sleep apnea based on the Berlin questionnaire (Netzer NC, 1999) will be excluded from 
the study. The Berlin questionnaire evaluates risks factors for sleep apnea including snoring, breathing 
pauses and daytime sleepiness. We are utilizing multiple criteria for exclusion for obstructive sleep 
apnea given the potential limitations of subjective questionnaires in subjects with TBI. 
 
III. 
 Potential benefit to this population:  
Bright White Light (BWL) exposure has potential to clinically impact care for persons with 
Traumatic Brain Injury, especially given the prevalence of co-occurring conditions such as sleep and 
mood disorders. Investigations into the use and tolerance of Bright White Light exposure in this 
population are limited, especially in the acute recovery phase and in the inpatient setting. This study will 
improve our understanding of therapeutic and functional effects of light therapy and the relationship 

5 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
with sleep efficiency. There is interest in non-pharmacologic treatment options for complications arising 
from patients experiencing a Traumatic Brain Injury (TBI), and this study investigates a treatment 
option and feasibility of integrating into usual care in the inpatient rehabilitation unit setting.  If our 
hypothesis is correct, and there is clinically significant benefit from Bright White Light exposure, some 
study participants may have direct benefit from this study.  
IV. 
 Research Hypothesis’s and Specific Aims 
Specific Aims: 
Aim 1: In persons with TBI, prospectively compare overnight sleep efficiency in a cohort exposed to 
morning Bright White Light with a comparison group exposed to Red Light in an acute inpatient 
rehabilitation setting. 
 
Aim 2: Explore the relationship between Bright White Light exposure during inpatient rehabilitation 
after TBI and mood, therapy participation, attention, rate of functional recovery and length of stay. 
Aim 3: Develop and describe sleep study procedures on the inpatient rehabilitation unit for persons with 
TBI to support optimal and feasible design of future studies in this important area. 
 
 
Research Hypothesis: 
In persons with TBI, prospectively compare overnight sleep in a cohort exposed to morning Bright 
White Light with a comparison group exposed to Red Light in an acute inpatient rehabilitation setting. 
 
Hypothesis 1: Individuals exposed to Bright White Light for 30 minutes each morning will have better 
sleep compared to the Red Light exposure group, as measured by sleep efficiency. 
 
Hypothesis 2: Individuals with daily morning Bright White Light exposure will have better mood (as 
measured by the Positive and Negative Affective Schedule, PANAS), therapy participation (as measured 
by a 0-100 therapist rating) and attention (as measured by the Symbol Digit Modalities Test) at 10 days 
compared to individuals with daily Red Light exposure. The group exposed to Bright White Light will 
also have less daytime sleepiness and fatigue (as measured by the Karolinska Sleepiness Scale (KSS) 
and the Barrow Neurological Institute Fatigue Scale (BNI-FS), a faster rate of functional recovery as 
measured by FIMTM efficiency for the rehabilitation stay and a shorter length of stay compared to those 
in the Red Light group 
 
Hypothesis 3a: Bright White Light exposure will be rated as a reasonable addition to clinical care by 
staff using Likert scale ratings.  Categorize and quantify rates of any side effects of Bright White Light 
and Red Light exposure in persons with TBI during inpatient rehabilitation.  
 
Hypothesis 3b: Bright White Light and Red Light exposure will be generally well tolerated with side 
effect profiles and rates similar to those observed in previous studies with other populations. 
 
See Appendix for Flowchart on Specific Aims of this study 
 
V. 
 Study Description 
 
We propose to recruit a prospective cohort of persons with TBI to compare effects of Bright 
White Light exposure to Red Light (RL) exposure. Light therapy treatments will be given daily in the 
morning for up to 10 days, and an Actiwatch will be worn that records movements for the entirety of the 
study. We will utilize objective assessments of sleep quality, subjective mood report, rate sleepiness and 
fatigue and complete measures of attention and participation in rehabilitation therapies to explore the 

6 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
effects of light exposure in the acute inpatient rehabilitation setting. We will also evaluate the 
anticipated device costs and staff burden involved in utilizing light therapy exposure in the inpatient 
rehabilitation clinical setting. An overview of study procedures with timeline is described in Figure 1 
below with further details in the sections that follow.   
 
Figure 1.  Overview of Study Procedures for TWILIGHT
Day 0-1
Day 2
Day 3 - 12
Day 13
Screening Procedures
 
Informed Consent 
 
Pre-Light Exposure 
Questionnaire
(Baseline Data Collection)
&
Randomization
 
Light Therapy
 
Post-Light Exposure 
Questionnaire
 
(Post-Intervention Outcome 
Assessments)
Begin Actigraphy
 
Light exposure for 30 
minutes each morning 
(white or red)
 
Sleep Log Begins
(Makley Scale)
Sleep Log Continues
(Makley Scale)
Actigraphy Continues
 
Sleep Log Continues
(Makley Scale)
Actigraphy Continues
 
 
Actigraphy & 
Light Therapy 
End
 
  
 
 
VI. 
 Screening for Eligibility:  
Although subjects will be screened for this study concurrent with screening for eligibility for 
enrollment into the Traumatic Brain Injury Model System (TBIMS) study (Traumatic Brain Injury 
Model Systems, 2013), these are independent studies and subjects will have the choice to enroll in both, 
neither, or either one. The TBI Model Systems program, sponsored by the National Institute on 
Disability and Rehabilitation Research (NIDRR), is the largest longitudinal study of TBI in the nation.  
NIDRR awards 5 year grant awards to institutions that are national leaders in medical research and 
patient care and these.  Institutions which receive this distinction are collectively termed, the TBI Model 
Systems.  As part of the TBI Model Systems, the University of Washington TBI Model Systems 
research team is recognized as providing the highest level of comprehensive specialty services from the 
point of injury through chronic care stages, including re-entry into full community life. The current grant 
cycle is for the 2012-2017 time period, and one of the areas of interest for the UW TBI Model Systems 
research team is the treatment of sleep difficulties after TBI.   
 
The screening process will begin will reviewing the medical charts for patients that are on the 
inpatient rehabilitation unit at Harborview Medical Center.  If a patient meets the inclusion criteria, 
research staff will approach the patient to determine whether the patient is cognitively capable of giving 
their consent for the study by administering the Galveston Orientation and Amnesia Test. The study will 
then be explained to the patient; or if the patient is experiencing post traumatic amnesia, the study will 
be explained to the patient’s legally authorized representative.  Consent will be obtained either from the 
patient or, if he or she is unable to provide informed consent, the patient’s legally authorized 
representative.   
 
VII. 
 Study Sample:   

7 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Study participants will be recruited from acute inpatient rehabilitation at three participating TBI 
Model Systems institutions (University of Washington, Mount Sinai, Baylor). Eligible participants will 
be within three months of sustaining a moderate to severe TBI (as defined by the TBI Model Systems 
(Traumatic Brain Injury Model Systems, 2013)), admitted to acute inpatient rehabilitation, English 
speaking, and aged 18-70 years. Exclusionary medical factors will be identified in the medical record 
and through interview during screening/baseline assessment.  In a pilot study comparing the effects of 
BWL and RL exposure in a sample of subjects with chronic TBI, Cantor et al. (Cantor, et al., 2012) 
reported an effect size of 0.63 for sleep duration. Because this pilot study involved subjects in the 
chronic phase of TBI, who were living at home rather than in an institution, and underwent a longer 
course of treatment (28 days in that study vs. 10 days in this study), we chose to take a conservative 
approach to calculating the required sample size. Based on an estimated effect size of 0.5 and 80% 
power, 128 subjects would be required to complete this study (64 per group). We anticipate recruitment 
over three years at three sites. Historical TBIMS and associated trial enrollment totals from the 
participating sites supports this study enrollment goal. 
 
VIII. Inclusion Criteria: 
1. Within three months of moderate to severe TBI  
2. Admitted to acute inpatient rehabilitation 
3. Ages 18-70 
4. English speaking 
 
VIII.  Exclusion Criteria: 
1. Complete blindness 
2. Absence of eye opening or disorders of consciousness (Rancho level of 1-3) 
3. Past medical history of retinal pathology 
4. Past medical history of light sensitivity 
5. Past medical history of narcolepsy 
6. Past medical history of bipolar disorder 
7. Past medical history of obstructive sleep apnea (OSA) 
8. Sleep disturbance defined as having a "0" rating by research staff (using all sources available).  If 
rated a "0" for no sleep disturbance, they must also NOT be receiving sleep medications in the last 
72 hours 
9. Suspected diagnosis of obstructive sleep apnea (determined by the Berlin Questionnaire) 
10. Tetraplegia with less than antigravity strength in all myotomes caudal to C6 level given the 
limitations on measuring movements with actigraphy in this population (i.e. cannot reliably detect 
upper extremity or lower extremity movement with this level of paralysis). 
11. Current medical orders indicated for night time sleep disruption (e.g. chest PT, MIE q2 hours of 
meds that disrupt sleep). *May be re-approached if the medical orders are no longer in place. 
 
IX. 
Rationale for Study Population 
 
The study population of interest is TBI in the setting of acute inpatient rehabilitation, which is 
typically moderate to severe TBI. Persons less than 18 years of age or greater than 70 years are being 
excluded from the study because of baseline sleep physiology differences seen in younger and advanced 
ages.  We wish to enroll those with sleep disturbances; those with normal sleep will not be enrolled.  We 
are excluding those who would not benefit from light exposure due to eye abnormalities or those with 
other pathology that will interfere with sleep and cannot be affected by light exposure.  Additionally, 
since actigraphy relies on limb movement for recording, those with tetraplegia would be excluded. 
 

8 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
X. 
 Data Collection and Measures 
 
Screening of subjects will need to occur to determine eligibility of subjects, including review of 
medical chart.  If patients are not eligible or are excluded based on exclusion criteria, no identifiable 
data is retained.  Once consented into the study, the exclusion criteria will be reviewed with the patient 
and/or their legal representative.  Data collection measures, areas assessed, and the timing of when this 
data is collected is shown in Table 1.    
 
 
Table 1: Data Collection Measures and Areas Assessed 
Measure 
Area to be Assessed 
Screening and 
Baseline 
(Day 0-2) 
Intervention 
 
(Days 3-12) 
Outcome  
 
(Day 13) 
Demographics  
Characteristics (age, 
education, gender) 
X 
 
 
Injury characteristics 
Cause of injury, date of 
injury, lowest GCS, 
PTA/GOAT 
X 
 
 
Medical History 
Diagnoses, medications 
at enrollment, symptoms, 
associated injuries (ICD-
9 codes), vital signs  
X 
 
 
Berlin questionnaire 
Sleep apnea 
X 
 
 
Clinician Rating: 
Delirium Rating Scale 
Revised 98 Item 1 
Sleep disturbance 
X 
 
 
Makley scale 
Sleep disturbance 
X 
X 
 
Actigraphy 
Sleep parameters 
X 
X  
 
Light Therapy Time 
Light exposure time 
 
X 
 
Medication categories 
Potential confounders 
(see data sheet) 
X 
 
X 
FIMTM Scores and 
Efficiency  
Functional score 
X 
 
X 
Hospitalization 
Acute LOS, Rehab LOS 
X 
 
X 
Symbol Digit 
Modalities Test 
Attention 
X 
 
X 
PANAS 
Mood 
X 
 
X 
Therapy participation 
Function 
X 
 
X 
Karolinska Sleepiness 
Scale 
Daytime sleepiness 
X 
 
X 
Barrow Neurological 
Institute Fatigue Scale 
Daytime fatigue 
X 
 
X 
 
A. Screening Measures: 
The following data will be used as descriptive characteristics of the subjects upon study completion.  
Initially this data will be used during the screening process to ensure appropriate patients are approached for 
participation:  
• Demographics: Age, gender, race/ethnicity, weight (kg), height (cm), BMI (calculated). 

9 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
• Injury Characteristics: Time since injury, Post-resuscitation GCS score, duration of PTA as measured 
by TBIMS procedures using the Galveston Orientation and Amnesia Test (GOAT), associated injuries 
including ICD codes. 
• Medical History:  Current diagnoses, past diagnoses, medications (at enrollment, during treatment and 
at outcome measure), vital signs. 
• Berlin Questionnaire (Netzer NC, 1999): The 10-item questionnaire consists of 3 categories related to 
the risk of having sleep apnea. Patients can be classified into High Risk or Low Risk based on their 
responses to the individual items and their overall scores in the symptom categories.  
 
 
B. Randomization Measure:  
Randomization will occur by research staff member assessing the patient for sleep disturbance, using all 
sources available, in the first item question from the Clinician Rating: Delirium Rating Scale – Revised 98 
(DelRS-R98) (Trzepacz PT, 2001). Our recent prevalence work showed that 86% of acute TBI admissions 
have sleep abnormalities using clinician ratings, specifically the DelRS-R98 (Nakase-Richardson R S. M., 
Prospective evaluation of the nature, course, and impact of acute sleep abnormality following TBI , 2013). 
Sleep disturbance questions  will be asked of the clinical staff whom were involved in caring for the patient 
during Day 1 of study participation, significant other (if available), and directly of the patient (if possible). 
The rating will be used as a sleep disturbance severity marker which will be utilized by the statistician 
during randomization to help control for sleep disturbance severity (Sjösten N, July 2009).  
 
C.  Primary Outcome Measure:   
Sleep efficiency scores derived from actigraphy data will be the primary outcome, and analysis will be 
done by Donald Fogelberg, Ph.D at the University of Washington.  An Actiwatch 2 (Philips/Respironics, 
Bend, OR) will be used for study purposes to facilitate consistent measurement across sites. We will set the 
Actiwatch to record activity data in 60-second intervals. Actigraphy data will be automatically scored with 
Actiware  software (Respironics, Philips Healthcare), which uses validated algorithms to determine whether 
an epoch of activity is “sleep” or “wake” (Cole RJ, 1992). Typically there is a lack of a consistent 
sleep/wake cycle in the study population, therefore we will be using sleep efficiency and total sleep time 
scores obtained during a set night-time interval (2200 to 0600) as the primary index of sleep function, as has 
been used in previous publications[39, 40]. We will be comparing average between group differences 
between the BWL and RL groups at baseline and after 10 days of light exposure. 
 
D. Secondary Outcome Measures: 
• Makley Scale: The Makley scale is a 4-point ordinal scale which allows staff to score sleep as follows:  
0 = asleep; 1 = drowsy/falling asleep; 2 = drowsy/waking up; 3 = awake. An hourly sleep log on each 
patient will be filled out every two hours by the unit nursing staff from 2200 to 0600 hours starting at 
baseline and through the duration of the study.[41]] 
• [42] Functional Independence Measure (FIM) is the most widely accepted functional assessment 
measure in use in the rehabilitation community. The FIMTM is an 18-item ordinal scale, used with all 
diagnoses within a rehabilitation population. It is viewed as most practical for assessment of progress 
during inpatient rehabilitation (State University of New York at Buffalo, 1997) and is assessed as part of 
normal rehabilitation care at admission and discharge from the rehabilitation unit. FIMTM efficiency is 
simply the change in FIMTM score divided by the length of rehabilitation stay and is used as marker of 
relative speed of functional change. We will evaluate for effects on both FIMTM motor and FIMTM 
cognitive scores. 
• Symbol Digit Modalities Test[43]: The SDMT is a pencil and paper test for attention that takes 
approximately five minutes to administer and is frequently used in evaluations after TBI (DeMonte, 

10 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
2009)) (Kalmar K, 2008) (Hanks R, 2008). The SDMT will be administered at enrollment and after 
intervention. The Interagency Workgroup on TBI Outcomes selected the Symbol Digit Modalities Test 
as CORE common data elements in TBI outcomes research.  
• Positive and Negative Affect Schedule: The 20-item Positive and Negative Affect Schedule (PANAS), 
developed with a sample of undergraduate students and validated with adult populations, comprises two 
mood scales, one measuring positive affect and the other measuring negative affect. Each item is rated 
on a 5-point scale ranging from 1 = very slightly or not at all to 5 = extremely to indicate the extent to 
which the respondent has felt this way in the indicated time frame. This scale is used to measure affect 
over a range of times including:  at this moment, today, the past few days, the past week, the past few 
weeks, the past year, and generally (on average). Watson et al. (Watson, 1988) reported Cronbach’s 
alpha coefficients for the various time reference periods ranging from .86 to .90 for the Positive Affect 
scale and .84 to .87 for the Negative Affect scale. For the general period, alpha was.88 for Positive 
Affect and .87 for Negative Affect. Test-retest correlations for an 8-week period ranged from .47 to .68 
for Positive Affect, .39 to .71 for Negative Affect (for the general time period, Positive Affect stability = 
.68, Negative Affect Stability = .71[44]).  
• Therapy Participation: Participation in rehabilitation therapies will be evaluated at enrollment and again 
after light therapy (day 13) by the subject’s therapist using a 0-100 scale of cooperation with therapy 
that has been previously utilized in this population.[45] 
• Karolinska Sleepiness Scale (KSS): The KSS is a well-validated, widely used single question survey 
that examines current sleepiness. 
• Barrow Neurological Institute Fatigue Scale (BNI-FS): The BNI-FS is a scale that was designed to 
examine fatigue during acute recovery from TBI. It has good internal consistency and appears to 
specifically examine a single psychometric construct of fatigue in patients with TBI (Wäljas M, 2012). 
• Clinician Feasibility Survey:  This is a likert scale survey to assess phototherapy intervention for ease of 
use, perceived relevance to rehabilitation care, and impression of effectiveness.  This survey will be 
available in paper and electronic versions.   
 
XI. 
Study Procedures:   
  
Screening and Enrollment:   
Patients’ medical records will be screened for inclusion/exclusion criteria. Informed consent will be 
obtained from the subjects after they have been determined to be cognitively capable to consent for the 
study.  A subject will be considered unable to give independent consent if they are still in PTA (as 
measured by the Galveston Orientation & Amnesia Test (GOAT), with a score <76) or their medical 
record at the time of enrollment specifies that they are unable for other reasons to independently 
consent.  If a subject is unable to consider consent independently, proxy consent will be obtained from 
the legally authorized representative (LAR).  This process is part of obtaining informed consent for the 
TBI Model System study.  In addition, clinical staff and research staff have established communication 
lines to approach patients at appropriate times that do not interfere with patient clinical care. 
 
 
Baseline and Randomization:  
Day 0-1 (2 days): After determining eligibility, the participant will be fitted with an Actiwatch 
(actigraphy) for continuous monitoring of activity levels both during the day and night (American Sleep 
Disorders Associatio, 1995). The Actiwatch will be worn continuously (with removal as needed for 
hygiene, shower or other clinical care) from enrollment to outcome measurement. Actiwatches will be 
fully charged and cleared of all previous data before being provided to a subject. Units will be set to 
record activity data in 60-second epochs. Actiwatches have sufficient built-in memory capacity and 
battery life to be used for approximately 30 days without recharging. Additionally, sleep logs that rate 
patient sleep are filled out every hour, between the hours of 2200-0600, this information is then obtained 

11 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
as completion of the Makley scale.  A complete review of symptoms and medical history will be 
obtained from the subject, LAR, and medical records.  
 
Day 2: Baseline data collection is obtained (See Appendix for Baseline Data Collection Forms).  
Measures collected include: Symbol Digit Modalities Test, Positive and Negative Affect Schedule 
(PANAS), Barrow Neurological Fatigue Scale. Clinical Staff, will be asked if there was sleep 
difficulties and therapist will be asked to rate therapy participation for that day. 
 
Day 2: Randomization. After baseline testing is completed, subjects will be randomized (50:50) using a 
2-level stratification design based on two pieces of information: 
1) Center (U. Washington-Seattle, Baylor-Dallas, Mount Sinai-New York) and  
2) Severity of Sleep Disturbance using Delirium Rating Scale-Revised 98 Item 1 
 
The rating for the Delirium Rating Scale Item 1 are:  1=Mild, 2=Moderate, 3=Severe 
 (Nakase-Richardson R S. M., Prospective evaluation of the nature, course, and impact of acute sleep abnormality following TBI , 2013) 
Using an Access Database, developed by Jason Barber at the University of Washington, centers will 
randomize the participant into either the Bright White Light Group or the Dim Red Light Group. [46]  
 
 
Light Therapy: 
Days  3-13: Each morning for 10 days, the research and/or nursing staff will set up the Litebook® 
device in the marked out area of the bedside table.  The light will be between 12 and 24 inches from the 
subject, allowing light to reach the subject’s eyes.  The subject will be in front of the device for 30 
minutes, eating or otherwise doing relaxing activities and will have the eyes open. Both BWL and RL 
will be delivered using a Litebook® (The Litebook Company Ltd; Medicine Hat, Alberta, Canada). The 
Litebook® is a small (6 inch x 5 inch x 1 inch) unit with an attached stand that is placed 12-24 inches 
from the user’s face and within 45 degrees of the visual field per manufacture guidance. Both the BWL 
and RL devices contain a data log to track the times at which the light box is turned off and on allowing 
the total time of exposure to be calculated. The cases for the BWL and RL units are visually identical. 
Research Staff will  setup the Litebook ® on the bedside/over bed table as part of the subjects’ 
morning/breakfast daily routine. The research staff will check in with nursing staff and the patient/LAR 
regarding adverse effects each day. Study medical staff will also be available for study questions or 
problems at other times and the patient’s primary medical service will also be following for their overall 
medical care per routine. Nursing staff will be trained regarding the light exposure protocol as part of 
preparation for the study and the individualized setup for each subject will be reviewed and diagrammed 
in their room on enrollment. Subjects will receive 10 morning sessions of their assigned light therapy 
(BWL vs. RL).   
 
Additional Data Collected 
1) Sleep Logs: Sleep logs will be integrated with overnight nursing rounds. Trained nursing staff 
will perform regular ratings every hour of sleep/wakefulness between 2200-0600 using the 
Makley Scale, a 4-point ordinal scale ranging from 0 (asleep) to 3 (awake). This paper sleep log 
will be collected daily by the research study staff. This is part of routine rehabilitation care and 
will not add any sleep disruption for study participants. Sleep logs will be used as one tool to 
help interpret overall actigraphy data patterns during analysis. 
2) Therapy Participation:  The physical therapist will be asked by the research staff to rate at both 
baseline days and on the final two days outcome assessment time points. 
3) Clinical Staff feedback:  phototherapy intervention will rated using a likert scale on the following 
categories: 

12 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
a. Ease of use 
b. Perceived relevance to rehabilitation care 
c. Impression of effectiveness. 
 
Post Light Therapy Outcome Assessment 
Day 13: At the conclusion of the light therapy sessions (and prior to discharge from rehabilitation),a 
blinded Outcomes Examiner will complete the post therapy outcome assessment.  This assessment will 
include the following: 
o Symbol Digit Modalities Test 
o Positive and Negative Affect Schedule (PANAS) 
o Barrow Neurological Fatigue Scale 
 
XII. 
 Data Analysis 
 
The primary outcome is the between-group difference (BWL vs. RL exposure) in average sleep 
efficiency at baseline compared to after 10 days of light treatment. ANOVA will be used to compare 
groups controlling for demographics, injury severity, and use of medications. 
 
Secondary outcomes (mood, therapy participation, attention, daytime sleepiness/fatigue) between 
groups assessed at baseline and after 10 days of light therapy will be compared using repeated measures 
ANOVA. FIMTM efficiency and inpatient rehabilitation length of stay will also be compared between 
groups using ANOVA controlling for the same variables as the primary outcome.  Descriptive analysis 
will summarize responses to the nursing burden questions including estimated staff time for the 
intervention. 
 
Initial scoring of the data will be done by each participating site with Actiware 5, a computer 
program which uses validated algorithms to determine whether an epoch of activity is “sleep” or 
“wake”. The Actiware 5 software calculates sleep/wake statistics based on night intervals and provides 
these statistics for each interval (night), as well as a mean of all intervals (nights).Using a set interval of 
sleep, the software scores each epoch (minute) as sleep or wake, based on a specific internal algorithm 
and provides analysis of data, including sleep onset latency, sleep efficiency, sleep time, wake time, % 
sleep, % wake, naps, resting and normal night time sleep. The Actigraphy software does not provide 
circadian activity rhythms analysis. The raw, de-identified actigraphy data will be transmitted in an 
encrypted zip file via email to the NDSC and stored on a secure server for further analyses. Dr. 
Fogelberg will export edited epoch-by-epoch activity data to SAS programs to perform standard 
circadian activity analysis including calculation of Amplitude, Acrophase, Mesor, and the F-statistic. 
The activity level per epoch (minute) is used to estimate circadian activity rhythms. Circadian activity 
rhythms are analyzed by fitting each subject’s activity data to a 5-parameter extended cosine model. 
 
 

13 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
 
XIII.  Data Management 
Table 2.  Performance measures. 
Performance Area 
Goal 
Review 
Schedule 
Evaluation 
Method 
Accountability* 
Pre Enrollment Activities 
Manual of Procedures 
 
 
Ready for IRB 
Glorieux, Bell, 
Hoffman 
IRB Submission 
 
 
IRB approval 
Glorieux, 
Hoffman, Dubiel 
Database  complete 
 
 
Trial data entry 
Glorieux, Barber, 
NDSC 
Actigraphic data 
handling plan complete 
 
 
Protocol 
Fogelberg 
 
Research Assistant 
trained 
 
 
Observation of 
test 
administration 
and scoring, 
physical set-up 
Glorieux, 
Zumsteg, Dubiel 
Study Binders  
 
 
 
Wasmund 
Investigator 
Communication 
 
 
 
Wasmund, 
Glorieux, 
Zumsteg, Hoffman 
Post-Enrollment Activities 
Enrollment per month 
 
 
Enrollment report 
Glorieux 
Completion of 
baseline assessments 
 
Monthly 
Review by PI, 
Data Report 
Wasmund, Site 
Coordinators 
Completion of 
intervention 
 
Monthly 
Review by PI, 
Data Report 
Wasmund, Site 
Coordinators 
Completion of outcome 
assessments 
 
Quarterly 
Review by PI, 
Data Report 
Glorieux, Site 
Coordinators 
Data Safety 
Monitoring 
100% 
Quarterly 
and as 
needed 
Review by PI, 
Quarterly report 
to Medical 
Monitor 
Olson, Hoffman, 
Zumsteg 
Data audit 
95% 
agreement 
Quarterly 
Rescoring and 
coding of 5% of 
assessments 
Glorieux 
Data Analysis/Dissemination 
Complete Data 
Analysis 
 
 
 
Hoffman,  Dubiel, 
Zumsteg, 
Fogelberg 
Complete primary 
report of study 
 
 
Submission of 
manuscript for 
review 
Hoffman et al 
Design next study 
 
 
Submission of 
Investigators 

14 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
grant proposal 
 
Identifiers 
Each study site will have specific site ID numbers; subjects will be assigned a unique number in 
consecutive order with site identification. These numbers will be assigned locally using the TWILIGHT 
Study Access Database. Study number, rather than name or medical record, will be on data collection 
forms. Consent forms with identifying information and contact forms will be filed separately from other 
study material and will be kept in a secure location (locked file or secure, password protected file on 
secure server, also with password protection). The link between study and identifying data will be 
destroyed as specified in the site’s IRB documents. 
 
Confidentiality 
Hard copies of study files will be kept in a locked cabinet or a secure location accessible only to 
individuals who have signed institutional confidentiality agreements. Study number will be on data 
collection forms (other than the locator form with contact information). Data in electronic form will be 
encrypted and stored on a University of Washington or NIDRR server only accessible by authorized 
personnel. Identified information such as name, address, medical record number or phone numbers 
needed to initially identify participants or their LAR will be kept in separate files from the study data.  
 
Only study personnel as well as representatives of the human protection offices, and representatives of 
the funding agency will have access to study records. The study will not intentionally collect any data 
that would need to be shared with state or local authorities. If the participant responds to assessment 
items or volunteers information about an intent to harm themselves or others (such as in review of 
systems questions), a standard IRB approved protocol (identical to the TBI Model System protocol) will 
be executed to manage such disclosures to ensure participant or others’ safety and the subject’s inpatient 
rehabilitation resident or attending physician will be informed verbally immediately.  
 
Disposition of data 
At each study site hard copy data will be stored in locked file cabinets or a secure location while the 
study is ongoing. When the study is complete, the data will be sent to a secure institutional records 
management location at each site similar to those used to store archived medical records as required by 
local and other regulations as applicable to each site. Washington State law requires clinical trial data be 
retained for 25 years. Electronic data will be entered into a database developed by the National Data and 
Statistical Center using an ACCESS database that will be kept behind secure firewall on servers 
accessible to site data managers with password-protected access. At the end of the study, each 
investigator will get a copy of the de-identified data. At the end of the study, all local copies of the 
contact information files will be destroyed. 
 
ACG data: De-identified actigraphic data will be transmitted in an encrypted ZIP file via UW secure 
and government email to the NDSC and stored on a secure, password-protected server accessible only to 
site data managers and PIs. 
 
Demographic, Injury Characterization, Traumatic Brain Injury Model System (TBIMS) 
Outcomes: Data will be recorded on paper or directly into database developed by the National Data and 
Statistical Center at Craig Hospital using an ACCESS database that will be kept behind secure firewall 
on servers accessible to site data managers with password-protected access. Hard copies of the data will 
be stored in locked file cabinets or a secure location while the study is ongoing. Only de-identified data 
is released from the NDSC. 

15 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
Paper and Pencil Tests, Cognitive Tests, Interviews: Data will be recorded on paper. All subjective 
questionnaires and cognitive testing scores will be entered into the secure database developed by the 
TBIMS NDSC at Craig Hospital using an ACCESS database that will be kept behind secure firewall on 
servers accessible to site data managers with password-protected access. Hard copies of the data will be 
stored in locked file cabinets or a secure location while the study is ongoing.    
 
Sharing study results 
Treatment conducted as part of this study may be of benefit to an individual participant (e.g. progress on 
cognitive testing over time). The main sharing of study results, however, will be with the general public 
and medical community which may benefit from our study outcome. We plan to report our findings in 
published material and at medical conferences. Data sharing will follow the TBIMS protocol. 
 
XIV. Safety and Adverse Events 
Each subject will be followed medically daily by their rehabilitation resident and attending physicians 
and have 24 hour monitoring by rehabilitation nursing. The research assistant at each site will check in 
with the patient/LAR and nursing staff daily Monday through Friday to elicit any concerns.  Jared 
Olson, M.D. a physiatrist in the University of Washington’s Department of Rehabilitation Medicine has 
expertise in TBI treatment and research procedures and has agreed to be the Data Safety Monitor 
(DSM).  He will receive a quarterly summary of all Adverse Events for review and will be contacted by 
the study team within 24 hours of any Serious Adverse Event to review with the study physician.  Any 
serious adverse event will be reported to the Human Subjects Division as well immediately.  At 
quarterly intervals after subject enrollment begins, the DSM will review and evaluate the studies’ 
clinical efficacy and safety data.   The DSM will monitor study progress, examine adverse events (AEs) 
and serious adverse events (SAEs), and recommend the continuation without change, suspension, or 
termination of a study. 
 
XV. 
 Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria: 
•   Unexpected in nature, severity, or frequency (i.e. not described in study-related documents 
such as the IRB-approved protocol or consent form, the investigators brochure, etc) 
•   Related or possibly related to participation in the research (i.e. possibly related means there is 
a reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
•   Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.   
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality results 
in study withdrawal,  is associated with a serious adverse event, is associated with clinical signs or 
symptoms, or is considered by the investigator to be of clinical significance. 
 
Serious Adverse Event 

16 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is: fatal, 
life-threatening, prolongs hospital stay, results in persistent or significant disability or incapacity, a 
congenital anomaly or birth defect, or an important medical event.  
All adverse events that do not meet any of the criteria for serious should be regarded as non- serious 
adverse event. 
 
Important medical events are those that may not be immediately life threatening, but are clearly of 
major clinical significance.   They may jeopardize the subject, and may require intervention to prevent 
one of the other serious outcomes noted above.   
 
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as the period from 
the initiation of any study procedures to the end of the study treatment follow-up. For this study, the 
study treatment follow-up is defined as 2 days following the last study treatment (Day 15). 
 
Hospitalization 
Subjects will be hospitalized patients receiving care for their recent traumatic brain injury.  Therefore, 
hospitalization is a requirement to be a part of this study, and will not be included as an adverse event 
for this study. 
 
XVI. Recording of Adverse Events 
At each contact with the subject, the study staff must seek information on adverse events by specific 
questioning.   Information on all adverse events should be recorded immediately in the source document, 
and also in the appropriate adverse event module of the case report form (CRF).  All clearly related 
signs, symptoms, and abnormal diagnostic procedures results should recorded in the source document, 
though should be grouped under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of each 
event should be followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause.   Serious adverse events that are still ongoing at the end of the 
study period must be followed up to determine the final outcome. Any serious adverse event that occurs 
after the study period and is considered to be possibly related to the study treatment or study 
participation should be recorded and reported immediately. 
Minimum information required for each AE includes type of event, duration (start and end dates), 
severity, seriousness, causality to study, action taken, and outcome. 
 
Evaluating Adverse Events 
Assessment should include the intensity (severity) of the event and the relationship to Study 
Intervention(s). 
Severity of AEs will be graded by the Investigator using the following criteria as guidelines: 
1)  Mild: Nuisance, barely noticeable. 
2)  Moderate: Uncomfortable, troublesome symptoms not significantly interfering with daily activities 
or sleep. 
3)  Severe: Symptoms significantly interfere with daily activities or sleep. 
 
The relationship of the AE to the study treatment should be specified by the Investigator, using the 
following definitions: 
1)  Not Related: Concomitant illness, accident or event with no reasonable association with treatment. 

17 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
2)  Unlikely: The reaction has little or no temporal sequence from administration of the study treatment, 
and/or a more likely alternative etiology exists. 
3)  Possibly Related: The reaction follows a reasonably temporal sequence from administration of the 
treatment and follows a known response pattern to the suspected treatment; the reaction could have been 
produced by the study treatment or could have been produced by the subject’s clinical state or by other 
modes of therapy administered to the subject. 
4)  Probably Related: The reaction follows a reasonable temporal sequence from administration of study 
treatment; is confirmed by discontinuation of the study treatment or by rechallenge; and cannot be 
reasonably explained by the known characteristics of the subject’s clinical state. 
5)  Definitely Related: The reaction follows a reasonable temporal sequence from administration of 
study treatment; that follows a known or expected response pattern to the study treatment; and that is 
confirmed by improvement on stopping or reducing the dosage of the study treatment, and reappearance 
of the reaction on repeated exposure. 
 
Notifying the Principal Investigator 
Any study-related unanticipated problem posing risk of harm to subjects or others that are not Adverse 
Events should be reported on the “Unanticipated Problems Form”.  Any type of serious adverse event, 
must be reported to the site Principal Investigator or designee within 1 business day of the event.   
Within the following 48 hours, the investigators must provide further information on the serious adverse 
event or the unanticipated problem in the form of a written narrative.   This should include a copy of the 
completed Serious Adverse Event form, and any other diagnostic information that will assist the 
understanding of the event.  
   
Notifying the Local IRB 
At the University of Washington, Dr. Jeanne Hoffman or Dr. Jennifer Zumsteg will be responsible for 
safety reporting to the IRB and complying with their reporting requirements.   The other sites for this 
project will have an investigator who is responsible for safety reporting to their local IRBs. Copies of 
each report and documentation of IRB notification and receipt will be kept in the locked secured study 
file.  
 
Notifying the Data Safety Monitor 
Unanticipated  problems  posing  risks  to  subjects  or  others  and  serious  adverse  events associated 
with the research will be forwarded to the Data Safety Monitor of the study at the University of 
Washington, within 24 hours. 
Stopping Rules 
There are no planned interim or futility analyses. The Data Safety Monitor may recommend stopping for 
safety based on overall study review. 
 
Independent Data Safety Monitor 
The Data Safety Monitor is required to review all unanticipated problems involving risk to volunteers or 
others, serious adverse events and all volunteer deaths associated with the protocol and provide an 
unbiased written report. At a minimum the Data Safety Monitor should comment on the outcomes of the 
event or problem and in the case of a serious adverse event or death comment on the relationship to 
participation in the study.  The Data Safety Monitor should also indicate whether he concurs with the 
details of the report provided by the study investigator. 
 
XVII.  Ethical Considerations/Protection of Human Subjects 
Ethical Conduct of the Study 

18 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
This study is to be conducted according to US and international standards of Good Clinical Practice 
(FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable 
government regulations and Institutional research policies and procedures. 
 
Institutional Review Board (IRB) 
This protocol and any amendments will be submitted to a properly constituted Institutional Review 
Board (IRB), in agreement with local legal prescriptions, for formal approval of the study conduct.  The 
decision of the IRB concerning the conduct of the study will be made in writing to the investigator.  
 
Subject Information and Informed Consent 
This study will be conducted in compliance with Title 45 Part 46 of the CFR pertaining to informed 
consent.  At the first visit, subjects will give their written consent to participate in the study after having 
been informed about the nature and purpose of the study, participation/termination conditions, risks, and 
potential benefits.  Informed consent is a process that is initiated prior to the individual’s or proxy’s 
agreeing to participate in the study and continuing throughout the individual’s study participation. 
Extensive discussion of risks and possible benefits of this therapy will be provided to the participants 
and their families. Consent forms describing in detail the Study Agent(s)/Intervention(s) study 
procedures and risks are given to the participant/proxy and written documentation of informed consent is 
required prior to starting study agent/intervention. Consent forms will be IRB approved and the 
participant/proxy will be asked to read and review the document. Upon reviewing the document, the 
investigator will explain the research study to the participant/proxy and answer any questions that may 
arise.  The participants/proxies should have sufficient opportunity to discuss the study and process the 
information in the consent process prior to agreeing to participate.  The participants/proxies may 
withdraw consent at any time throughout the course of the study.  A copy of the informed consent 
document will be given to the participants/proxies for their records. The rights and welfare of the 
participants will be protected by emphasizing to them that the quality of their medical care will not be 
adversely affected if they decline to participate in this study. 
 
Sample Characteristics that Raise Special Concerns 
Participants may not be sufficiently able to independently provide informed consent.  We will have 
proxy consent forms for the subject and the Legally Authorized Representative (LAR) in this case. 
Decision making capacity assessment is described in the above study procedure narrative. We do not 
anticipate re-consenting subjects as the study duration is only 10 days of intervention. 
 
XVIII.  Potential Risks, Potential Benefits, Intent to Benefit, and Risk/Benefit Ratio 
Potential risks 
 
Subjects may experience an adverse reaction to the active or comparison treatment; significant 
adverse reactions are unlikely given literature on these light therapy interventions in a variety of 
populations.  The intervention involves exposure to light, which can be bright and which some 
participants may find bothersome. Side effects of the bright white light are generally mild and subside 
but can include hypomania, irritability, headache, nausea, eye strain or vision changes and sleep changes 
(Chang AM, 2012).  Other side effects are not anticipated given the study target population and the 
study team’s experience with sleep changes after TBI and light therapy. Other study procedures 
including the questions about cognition such as memory may be uncomfortable either physically or 
emotionally and will be approached respectfully and confidentially. The placement of the Actiwatch on 
the wrist will result in contact with the skin, and like any watch, could result in contact dermatitis.  
Contact Dermatitis is readily treated with skin lotion and may involve repositioning the device.  Prior 
studies have not reported this as a problem.  

19 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
As with any study, there is also a remote chance that an outside party may discover a 
participant’s identity and participation in the study. Risk of physical harm or injury is unlikely given the 
mild nature of reported side effects in the literature regarding light exposure and the non-invasive nature 
of actigraphy. No risk to study personnel is anticipated. 
 
 
Alternative common treatments for insomnia include sedative drugs / sleep medications, 
behavioral interventions and environmental modifications. These other interventions will be recorded 
and will not be blocked during this study.   
 
Protection Against Risk 
1. We will have a Data Safety Monitor who is independent of the study to review regular reports of any 
reported related or unrelated adverse events as noted above.  All serious adverse events will be 
reported within 24 hours to him as well as to the IRB, Dr. Hoffman and site PIs. Our DSM will be 
able to halt recruitment until any adverse events are thoroughly explored.  A summary of all adverse 
events will be generated quarterly. 
 
2. Subjects will be interviewed in private settings, will be counseled that they may refuse to answer any 
question, and will be reassured that the information they provide is confidential. 
 
3. We will take all the usual steps to protect the confidentiality of personal information, including but 
not limited to dissociating identifying information from research data; using unique alpha-number 
coding systems that permit linkages to identifying data only via files that are stored separately; 
storage of data on password protected servers or computers; storage of paper data forms in locked 
files within locked rooms with access limited to approved research staff. All investigators and 
research staff are required to undergo HIPAA training and to sign a confidentiality agreement under 
the authority of the Human Subjects Division of the University of Washington and participating 
sites. 
 
Risk Management 
Loss of Confidentiality: All of the paper-based assessments will be kept in locked file cabinets at the 
study site. All data will be identified by a subject number. The link between participant identities and 
subject number will be kept separately from the study data. All personnel will receive HIPAA training 
as required by the University of Washington’s Human Subjects Division. 
 
XIX. Importance of Knowledge to be Gained 
 
At the completion of this study, we will have evidence on whether Bright White Light Therapy 
improves sleep after TBI. If this study is successful, we will have an immediately available, effective, 
non-invasive way of improving sleep for patients who have experienced a TBI that will enhance not 
only sleep timing but also thinking abilities and possibly long-term recovery after TBI. 
 
 

20 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
XX. 
 Study Finances 
Funding Source 
This study is financed through TBI Model System Grant for the 2012-2017 Grant Cycle.  This a module 
multi-site project that will be conducted at three locations.  All participating sites have received funding 
from the National Institute on Disability and Rehabilitation Research. 
 
Subject Stipends or Payments 
There is no compensation planned for subjects who choose to participate in this study. 
 
XXI. Overall Project Evaluation 
 
Overall study data completeness, timeliness, and quality will be monitored by the study investigators. 
Automated data reports will be generated monthly, displaying information relevant to the milestones described 
in the previous section. For example, cumulative subject accrual rates, subject retention rates, inter-rater 
reliability, and data accuracy reports will be generated routinely to monitor progress toward goals. Progress 
toward study milestone will be discussed at the project meetings.  Quarterly reports will be filed with the 
NIDRR project officer.  Quarterly safety reports will be submitted to Dr. Olson. Annual reports will be filed 
with the TBIMS Annual Reports. 
 
Investigators and key study personnel will meet by telephone bi-weekly prior to the initiation of the 
intervention to discuss progress. Investigators will meet twice yearly at the TBIMS Project Directors meeting. 
Site teams will meet weekly during the intervention period to discuss progress and barriers. 
If problems arise or tasks are not progressing as planned, Dr. Hoffman will work with the research team to 
devise an action plan.  Plans will be put in writing with a timeline to correct the problem.  Ms. Glorieux will 
track and follow-up on these plans. Any significant problems that would affect overall project outcomes will be 
reviewed with the NIDRR project officer to obtain additional assistance in developing an action plan.   
 
Table 3: Timeline of Research Activities 
 
 
 
 
 
 

21 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Figure 2. Project Staff Flow Chart 
 
 
 
 
 

22 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
List of Acronyms and Abbreviations 
 
• ACG = Actigraphy 
• AE= adverse event 
• BMI = body mass index 
• BNI-FS = Barrow Neurological Institute Fatigue Scale 
• BWL = Bright white light (experimental treatment condition in this study) 
• DSM = Data safety monitor 
• GCS = Glasgow Coma Scale 
• GOAT = Galveston Orientation and Amnesia Test 
• KSS = Karolinska Sleepiness Scale 
• LAR = Legally authorized representative 
• NDSC = National Data and Statistical Center for the Traumatic Brain Injury Model S 
• NIDRR = National Institute on Disability and Rehabilitation Research 
• PANAS = Positive and Negative Affective Schedule 
• PTA = Post-traumatic amnesia 
• RL = Dim red light (comparison treatment condition in this study) 
• SAE = Serious adverse event 
• SDMT = Symbol Digit Modalities Test 
• TBI = Traumatic brain injury 
• TBIMS = Traumatic brain injury Model System 
 
 
 
 
 
 
 
 
 
 
 
 

23 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
Works Cited 
 
1. 
Orff, H.J., L. Ayalon, and S.P. Drummond, Traumatic brain injury and sleep disturbance: a review of 
current research, in J Head Trauma Rehabil. 2009: United States. p. 155-65. 
2. 
Mathias JL, A.P., Prevalence of sleep disturbances, disorders, and problems following traumatic brain 
injury: A meta analysis. . Sleep Med, 2012;13: p. 898-905. 
3. 
Ouellet, M.C., J. Savard, and C.M. Morin, Insomnia following traumatic brain injury: a review. 
Neurorehabil Neural Repair, 2004. 18(4): p. 187-98. 
4. 
Ouellet, M.C., S. Beaulieu-Bonneau, and C.M. Morin, Insomnia in patients with traumatic brain injury: 
frequency, characteristics, and risk factors. J Head Trauma Rehabil, 2006. 21(3): p. 199-212. 
5. 
Verma, A., V. Anand, and N.P. Verma, Sleep disorders in chronic traumatic brain injury. J Clin Sleep 
Med, 2007. 3(4): p. 357-62. 
6. 
Ayalon, L., et al., Circadian rhythm sleep disorders following mild traumatic brain injury. Neurology, 
2007. 68(14): p. 1136-40. 
7. 
Makley, M.J., et al., Prevalence of sleep disturbance in closed head injury patients in a rehabilitation 
unit, in Neurorehabil Neural Repair. 2008: United States. p. 341-7. 
8. 
Ohayon, M.M. and C.F. Reynolds, 3rd, Epidemiological and clinical relevance of insomnia diagnosis 
algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD), in 
Sleep Med. 2009: Netherlands. p. 952-60. 
9. 
Larson, E.B. and F.S. Zollman, The effect of sleep medications on cognitive recovery from traumatic 
brain injury. J Head Trauma Rehabil, 2010. 25(1): p. 61-7. 
10. 
Flanagan, S.R., B. Greenwald, and S. Wieber, Pharmacological treatment of insomnia for individuals 
with brain injury, in J Head Trauma Rehabil. 2007: United States. p. 67-70. 
11. 
Carter, K.A., C.J. Lettieri, and J.M. Pena, An unusual cause of insomnia following IED-induced 
traumatic brain injury. J Clin Sleep Med, 2010. 6(2): p. 205-6. 
12. 
Chesson, A.L., Jr., et al., Practice parameters for the use of light therapy in the treatment of sleep 
disorders. Standards of Practice Committee, American Academy of Sleep Medicine. Sleep, 1999. 22(5): 
p. 641-60. 
13. 
Englander, J., et al., Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, 
depression and other factors. Brain Inj, 2010. 24(12): p. 1379-88. 
14. 
Banks, S. and D.F. Dinges, Behavioral and physiological consequences of sleep restriction. J Clin Sleep 
Med, 2007. 3(5): p. 519-28. 
15. 
Mishima, K., et al., Morning bright light therapy for sleep and behavior disorders in elderly patients 
with dementia. Acta Psychiatr Scand, 1994. 89(1): p. 1-7. 
16. 
Riemersma-van der Lek, R.F., et al., Effect of bright light and melatonin on cognitive and noncognitive 
function in elderly residents of group care facilities: a randomized controlled trial. JAMA, 2008. 
299(22): p. 2642-55. 
17. 
Fogelberg, D.J., et al., Association of sleep and co-occurring psychological conditions at 1 year after 
traumatic brain injury. Arch Phys Med Rehabil, 2012. 93(8): p. 1313-8. 
18. 
Reeves, G.M., et al., Improvement in depression scores after 1 hour of light therapy treatment in 
patients with seasonal affective disorder, in J Nerv Ment Dis. 2012: United States. p. 51-5. 
19. 
Chang, A.M., et al., Human responses to bright light of different durations, in J Physiol. 2012: England. 
p. 3103-12. 
20. 
Riemersma-van der Lek, R.F., et al., Effect of bright light and melatonin on cognitive and noncognitive 
function in elderly residents of group care facilities: a randomized controlled trial, in JAMA. 2008: 
United States. p. 2642-55. 
21. 
Terman, M. and J.S. Terman, Light therapy for seasonal and nonseasonal depression: efficacy, protocol, 
safety, and side effects. CNS Spectr, 2005. 10(8): p. 647-63; quiz 672. 

24 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
22. 
Wirz-Justice, A. and M. Terman, Chronotherapeutics (light and wake therapy) as a class of 
interventions for affective disorders, in Handb Clin Neurol. 2012: Netherlands. p. 697-713. 
23. 
Morgenthaler, T.I., et al., Practice parameters for the clinical evaluation and treatment of circadian 
rhythm sleep disorders. An American Academy of Sleep Medicine report. Sleep, 2007. 30(11): p. 1445-
59. 
24. 
Zollman, F.S., C. Cyborski, and S.A. Duraski, Actigraphy for assessment of sleep in traumatic brain 
injury: case series, review of the literature and proposed criteria for use. Brain Inj, 2010. 24(5): p. 748-
54. 
25. 
Ayalon, L., et al., Circadian rhythm sleep disorders following mild traumatic brain injury, in Neurology. 
2007: United States. p. 1136-40. 
26. 
Fogelberg, D.J., et al., Association of sleep and co-occurring psychological conditions at 1 year after 
traumatic brain injury, in Arch Phys Med Rehabil. 2012, 2012 American Congress of Rehabilitation 
Medicine. Published by Elsevier Inc: United States. p. 1313-8. 
27. 
Watson, N.F., et al., Hypersomnia following traumatic brain injury. J Clin Sleep Med, 2007. 3(4): p. 
363-8. 
28. 
Gumber, S., et al., Treatment of post TBI fatigue with light exposure, in American Psychological 
Association, Division of Rehabilitation Psychology 15th Annual Congress. 2013: Jacksonville, FL. 
29. 
Wood, R.L., et al., Clinical and cost effectiveness of post-acute neurobehavioural rehabilitation. Brain 
Inj, 1999. 13(2): p. 69-88. 
30. 
Whitmore, R.G., et al., Is aggressive treatment of traumatic brain injury cost-effective? J Neurosurg, 
2012. 116(5): p. 1106-13. 
31. 
Jason M. Sutherland, P.D., Elliott S. Fisher, M.D., M.P.H., and Jonathan S. Skinner, Ph.D., Getting Past 
Denial — The High Cost of Health Care in the United States. NEJM, 2009. 361(13): p. 1227-1230. 
32. 
Cuthbert JP, C.J., Whiteneck GG, Harrison-Felix C, Graham JE, Bell JM et al., Extension of the 
representativeness of the Traumatic Brain Injury Model Systems National  Database: 2001 to 2010. . J 
Head Trauma Rehabil. United States, 2012: p. E15-27. 
33. 
Lakshmanan, R., Loo, J. A., Drake, T., Leblanc, J., et al., Metabolic crisis after traumatic brain injury is 
associated with a novel microdialysis proteome. . Neurocrit Care 2010: p. 12, 324-336. 
34. 
Zollman FS, L.E., Wasek-Throm LK, Cyborski CM, Bode RK., Acupuncture for treatment of insomnia 
in patients with traumatic brain injury: a pilot intervention study. . J Head Trauma Rehabi, Mar-Apr 
2012: p. 27(2):135-42. 
35. 
Cuthbert, J.P., et al., Extension of the representativeness of the Traumatic Brain Injury Model Systems 
National Database: 2001 to 2010, in J Head Trauma Rehabil. 2012: United States. p. E15-27. 
36. 
Netzer, N.C., et al., Using the Berlin Questionnaire to identify patients at risk for the sleep apnea 
syndrome, in Ann Intern Med. 1999: United States. p. 485-91. 
37. 
Trzepacz PT, M.D., Torres R, Kanary K, Norton J, Jimerson N., Validation of the Delirium Rating Scale 
– Revised:  Comparison with the Delirium Rating Scale and the Cognitive Test for Delirium. J 
Neuropsychiatr Clin Neuroscience, 2001: p. 13:229-42. 
38. 
Makley MJ, E.J., Drubach DA, Kreuz AJ, Celnik PA, Tarwater PM, Prevalence of  sleep disturbance in 
closed head injury patients in a rehabilitation uni. Neurorehabil Neural  Repair., 2008: p. 341-7. 
39. 
Guide for the Uniform Data Set for Medical Rehabilitation (including the FIM(TM) instrument. 1997: 
Buffalo, NY 14214-3007, Buffalo, NY 14214-3007. 
40. 
Shum D, M.K., Bain J., Construct validity of eight tests of attention: Comparison of normal and closed 
head injured samples. Clinical Neuropsychologist 1990: p. 4(2):151-62. 
41. 
Watson, D., Clark, L. A., & Tellegen, A., Development and validation of brief measures of positive and 
negative affect:  The PANAS scales.  . Journal of Personality and Social Psychology, 1988: p. 54 (6), 
1063-1070. 
42. 
Silva, M.A., et al., Posttraumatic confusion predicts patient cooperation during traumatic brain injury 
rehabilitation. Am J Phys Med Rehabil, 2012. 91(10): p. 890-3. 

25 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
43. 
Forbes, D., et al., Light therapy for managing cognitive, sleep, functional, behavioural, or psychiatric 
disturbances in dementia. Cochrane Database Syst Rev, 2009(4): p. CD003946. 
 
 
 

26 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
I. 
References 
Genetic influences on outcome following traumatic brain injury. (2007). Neurochem Res, 32, 905-915. 
Abdullah, L. C. (2011). Proteomic CNS Profile of Delayed Cognitive Impairment in Mice Exposed to Gulf War 
Agents. Neuromolecular Med, 13, 275-288 . 
Abdullah, L. E. (2012). Lipidomic Profiling of Phosphocholine Containing Brain Lipids in Mice with 
Sensorimotor Deficits and Anxiety-Like Features After Exposure to Gulf War Agents. Neuromolecular 
Med. 
Abdullah, L. L. (2009). Serum Abeta levels as predictors of conversion to mild cognitive impairment/Alzheimer 
disease in an ADAPT subcohort . Mol Med , 15, 432-437. 
Abdullah, L. L.-g. (2009). High serum Abeta and vascular risk factors in first-degree relatives of Alzheimer's 
disease patients. Mol Med , 15, 95-100. 
Abdullah, L. R. (2009). Proteomic Analysis of Human Neuronal Cells Treated with the Gulf War Agent 
Pyridostigmine Bromide. J Proteomics Bioinform , 2, 439-444. 
Ait-ghezala, G. A. (2008). Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma 
in Alzheimer's disease. Cytokine , 44, 283-287. 
Ait-Ghezala, G. M. (2005). Genomic regulation after CD40 stimulation in microglia: relevance to Alzheimer's 
disease. Brain Res Mol Brain Res, 140, 73-85. 
Akerstedt T, G. M. (1990). Subjective and objective sleepiness in the active individual. International Journal of 
Neuroscience , 52: 29–37. 
Alger SE, L. H. (2012 Jun 23). Slow wave sleep during a daytime nap is necessary for protection from 
subsequent interference and long-term retention. . Neurobiol Learn Mem. 
American Sleep Disorders Associatio. (1995). Practice parameters for the use of actigraphy in the clinical 
assessment of sleep disorders. Sleep, 18:285-7. 
Ayalon L, B. K. (2007). Circadian rhythm sleep disorders following mild traumatic brain injury. Neurology, 
1136-40. 
Banks S, D. D. (2007). Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med, 
3(5):519-28. 
Bennett, C. C. (1995). Evidence that the APOE locus influences rate of disease progression in late onset familial 
Alzheimer's Disease but is not causative. Am J Med Genet , 60, 1-6. 
Berson DM, D. F. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science, 
295(5557):1070-1073. 
Borgaro SR, G. S. (2004). Fatigue after brain injury: initial reliability study of the BNI Fatigue Scale. Brain Inj , 
18:685-90. 
Cantor, J. B., Cicerone, K., Dijkers, M. P., Gordon, W., Hammond, F. M., Kolakowsky-Hayner, S. A., . . . 
Spielman, L. (2012). Insomnia, fatigue, and sleepiness in the first 2 years after traumatic brain injury: an 
NIDRR TBI model system module study. The Journal of head trauma rehabilitation, 27(6):E1-14. 
Carter KA, L. C. (2010). An unusual cause of insomnia following IED-induced traumatic brain injury. J Clin 
Sleep Med, 6(2):205-6. 
Castriotta RJ, A. S. (2009). Treatment of sleep disorders after traumatic brain injury. J Clin Sleep Med, 5:137-
44. 
Castriotta RJ, W. M. (June 15, 2007). Prevalence and consequences of sleep disorders in traumatic brain injury. 
J CLin Sleep Med, 349-56. 
Chang AM, S. N. (2012). Human responses to bright light of different durations. J Physiol, 590(Pt 13):3103-12. 
Chesson AL, J. L.-D. (1999). Practice parameters for the use of light therapy in the treatment of sleep disorders. 
Standards of Practice Committee, American Academy of Sleep Medicine. Sleep, 2. 
Chuang, P. C. (2010). Neuroglobin genetic polymorphisms and their relationship to functional outcomes after 
traumatic brain injury. . J Neurotrauma, 27, 999-1006. 
Cole RJ, K. D. (1992). Automatic sleep/wake identification from wrist activity. Sleep, 15 (5):461–469. 

27 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Crawford, F. A. (2000). Gender-specific association of the angiotensin converting enzyme gene with 
Alzheimer's diseas. Neurosci Lett , 280, 215-219 . 
Crawford, F. C. (2000). A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's 
disease. Neurology , 55, 763-768. 
Crawford, F. C. (2000). The genetic association between Cathepsin D and Alzheimer's disease. Neurosci Lett , 
289, 61-65. 
Crawford, F. C. (2006). Cocaine induced inflammatory response in human neuronal progenitor cells. J 
Neurochem, 97, 662-674. 
Crawford, F. C. (2012). Identification of plasma biomarkers of TBI outcome using proteomic approaches in an 
APOE mouse model. . J Neurotrauma, 29, 246-260. 
Crawford, F. F. (1999). No genetic association between polymorphisms in the Tau gene and Alzheimer's 
disease in clinic or population based samples. Neurosci Lett , 266, 193-196. 
Crawford, F. T. (1999). The alpha-2 macroglobulin gene is not associated with Alzheimer's disease in a case-
control sample. Neurosci Lett, 270, 133-136. 
Crawford, F. V. (2002). APOE genotypeinfluences acquisition and recall following traumatic brain injury. . 
Neurology, 58, 1115-1118. 
Crawford, F. W. (2009). Apolipoprotein E-genotype dependent hippocampal and cortical responses to traumatic 
brain injury. . Neuroscience , 159, 1349-1362. 
Cuthbert JP, C. J.-F. (2012). Extension of the representativeness of the Traumatic Brain Injury Model Systems 
National Database: 2001 to 2010. . J Head Trauma Rehabil. United States, E15-27. 
Dardiotis, E. F. (2010). Genetic association studies in patients with traumatic brain injury. Neurosurg Focus, 28. 
Dash MB, C. C. (2009). Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep 
and waking states. J. Neuroscience, 29:620-9. 
DeMonte, V. G. (2009)). Improved sensitivity of the rapid screen of mild traumatic brain injury. J Clin Exp 
Neuropsychology, 6, 1-11. 
Diaz-Arrastia, R. &. (2006). Genetic factors in outcome after traumatic brain injury: what the human genome 
project can teach us about brain trauma. J Head Trauma Rehabil , 361-374. 
Diekelmann S, W. I. (2009). The whats and whens of sleep-dependent memory consolidation. Sleep Med Rev, 
13:309-21. 
DM, B. (2007). Phototransduction in ganglion-cell photoreceptors. Pflugers Arch, 454(5):849-855. 
Englander J, B. T. (2010). Fatigue after traumatic brain injury: Association with neuroendocrine, sleep, 
depression and other factors. Brain Inj, 24(12):1379-88. 
Ferguson, S. M. (2010). Apolipoprotein E genotype and oxidative stress response to traumatic brain injury. 
Neuroscience, 168, 811-819. 
Flanagan SR, G. B. (2007). Pharmacological treatment of insomnia for individuals with brain injury. J Head 
Trauma Rehabil, 67-70. 
Fogelberg DJ, H. J. (2012). Association of sleep and co-occurring psychological conditions at 1 year after 
traumatic brain injury. Fogelberg DJ, Hoffman JM, Dikmen S, Temkin NR, Bell KR. Association of sleep 
and co-occurring psychological conditions at 1 year after traumatic brain injury. Arch Phys Med 
Rehabil., 1313-8. 
Forbes D, C. I. (2011). Light therapy for managing cognitive, sleep, functional, behavioural, or psychiatric 
disturbances in dementia (Cochrane Database Syst Rev 2009). Sleep, 34:111-9. 
Freeman, T. R. (2005). Neuropsychiatric associations of apolipoprotein E alleles in subjects with combat-
related posttraumatic stress disorder. . J Neuropsychiatry Clin Neurosci, 17, 541-543. 
Friedman L, S. A.-I. (May 2012). Brief morning light treatment for sleep/wake disturbances in older memory-
impaired individuals and their caregivers. Sleep Med, 13(5):546-9. 
Gao, W.-M. C. (2007). A gel-based proteomic comparison of human cerebrospinal fluid between inflicted and 
non-inflicted pediatric traumatic brain injury. J Neurotrauma, 24, 43-53. 

28 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Genét, G. F. (2013). Trauma-induced coagulopathy: standard coagulation tests, biomarkers of coagulopathy, 
and endothelial damage in patients with traumatic brain injury. J Neurotrauma , 30, 301-306. 
Gong, D. H. (2012). Prognostic relevance of circulating endothelial progenitor cells for severe traumatic brain 
injury. Brain Inj , 26, 291-297. 
Gumber S, S. A. (2013). Treatment of post TBI fatigue with light exposure. Jacksonville, FL, United States: 
American Psychological Association, Division of Rehabilitation Psychology 15th Annual Congress. 
Hanks R, M. S.-R. (2008). The predictive validity of a brief neuropsychological battery for persons with 
traumatic brain injury. Arch Phys Med Rehabil , 89:950-7. 
Haqqani, A. H. (2007). Biomarkers and diagnosis; protein biomarkers in serum of pediatric patients with severe 
traumatic brain injury identified by ICAT-LC-MS/MS. J Neurotrauma , 24, 54-74. 
Hendoui, N. B. (2013). Reliability of calcium-binding protein S100B measurement toward optimization of 
hyperosmolal therapy in traumatic brain injury. Eur Rev Med Pharmacol Sci , 17, 477-485. 
Ho, L. Z.-O. (2012). Elevated plasma MCP-1 concentration following traumatic brain injury as a potential 
"predisposition" factor associated with an increased risk for subsequent development of Alzheimer's 
disease. . J Alzheimers Dis, 31, 301-313. 
Irizarry, M. (2004). Biomarkers of Alzheimer disease in plasma. NeuroRx 1, 226-234. 
Jennum P, K. J. (July 2011). Health, social and economical consequences of sleep-disordered breathing: a 
controlled national study. . Thorax, 66(7):560-6. 
Jha A, W. A.-F. (Jan-Feb 2008). A randomized trial of modafinil for the treatment of fatigue and excessive 
daytime sleepiness in individuals with chronic traumatic brain injury. . J Head Trauma Rehabil, 23 
(1):52-63. 
JJ, G. (August 2008). Treatment of circadian rhythm sleep disorders with light. Ann Acad Med Singapore, 
37(8):669-76. 
Kalmar K, N. T.-R. (2008). Feasibility and utility of a brief neuropsychological test battery for use during acute 
inpatient rehabilitation after TBI. Arch Phys Med Rehabil, 89:94. 
Kayihan, G. C. (2010). Gulf War agents trigger discrete transcriptional changes in human neuronal cells. 
Toxicological & Environmental Chemistry, 92, 1783-1799 . 
Krueger, F. P. (2011). The role of the Met66 brain-derived neurotrophic factor allele in the recovery of 
executive functioning after combat-related traumatic brain injury. J Neurosci, 31, 598-606. 
Lakhan, S. E. (2009). Schizophrenia genomics and proteomics: are we any closer to biomarker discovery? . 
Behav Brain Funct , 5, 2. 
Lakshmanan, R. L. (2010). Metabolic crisis after traumatic brain injury is associated with a novel microdialysis 
proteome. . Neurocrit Care , 12, 324-336. 
Larson EB, Z. F. (2010). The effect of sleep medications on cognitive recovery from traumatic brain injury. J 
Head Trauma Rehabil, 25(1):61-7. 
Lim J, D. D. (2008). Sleep deprivation and vigilant attention. Ann N Y Acad Sci, 1129:305-22. 
Lista, S. F. (2013). Blood and plasma-based proteomic biomarker research in Alzheimer's disease. Prog 
Neurobiol , 101-102, 1-17. 
Lockley SW, G. J. (2006). Circadian photoreception: Spotlight on the brain. Curr Biol, 16(18):R795-7. 
Longordo F, K. C. (2009). Consequences of sleep deprivation on neurotransmitter receptor expression and 
function. . European Journal of Neuroscience , 29:1810-9. 
Luis, C. A. (2009). Serum beta-amyloid correlates with neuropsychological impairment. Neuropsychol Dev 
Cogn B Aging Neuropsychol Cogn, 16, 203-218. 
Luis, C. A.-G. (2011). Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-
Amyloid. Int J Alzheimers Dis. 
Makley MJ, E. J. (2008). Prevalence of sleep disturbance in closed head injury patients in a rehabilitation uni. 
Neurorehabil Neural Repair., 341-7. 
Makley MJ, J.-G. L. (2009). Return of memory and sleep efficiency following moderate to severe closed head 
injury. Neurorehabil Neural Repair, 23 (4):320-6. 

29 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Marshall L, H. H. (2006). Boosting slow oscillations during sleep potentiates memory. Nature , 444:610-613. 
Martins-de-Souza, D. M. (2010). Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis 
dysfunction and potential biomarkers candidates for schizophrenia. J Psychiatr Res, 44, 1176-1189. 
Mathias JL, A. P. (2012;13). Prevalence of sleep disturbances, disorders, and problems following traumatic 
brain injury: A meta analysis. . Sleep Med, 898-905. 
McDermott CM, L. G. (2003). Sleep deprivation causes behavioral, synaptic, and membrane excitability 
alterations in hippocampual neurons. J. Neuroscience, 23:9687-95. 
Melyan Z, T. E. (2005). Addition of human melanopsin renders mammalian cells photoresponsive. Nature, 
433(7027):741-745. 
Mishima K, O. M. (1994). Morning bright light therapy for sleep and behavior disorders in elderly patients with 
dementia. Acta Psychiatr Scand, 89(1):1-7. 
Morgenthaler TI, L.-C. T. (2007, Nov 30). An American Academy of Sleep Medicine Report: Practice 
parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders. Sleep, 30(11), 
1445-59. 
Nakase-Richardson R, K. T. (2012). The role of sleep in maximizing rehabilitation outcome: Experience of 
three VHA programs. Recorded symposium. 2012 American Psychological Association Annual 
Conference. 
Nakase-Richardson R, S. D. ( (under review)). Does White Light Exposure Differ Among Acute 
Neurorehabilitation Admissions? 
Nakase-Richardson R, S. D. ((Under Review)). Feasibility of Polysomnography Objective Sleep Assessment in 
the Acute Moderate to Severe Traumatic Brain Injury Patient. 
Nakase-Richardson R, S. M. (2013). Prospective evaluation of the nature, course, and impact of acute sleep 
abnormality following TBI. Archives of Physical Medicine and Rehabilitation, 875-82. 
Nakase-Richardson R, S. M. (2013). Prospective evaluation of the nature, course, and impact of acute sleep 
abnormality following TBI . Archives of Physical Medicine and Rehabilitation 2013;, 94 (5): 875-82. 
National Data and Statistical Center. (2013, August 1). VA Polytrauma Center Database Syllabus. Retrieved 
from Traumatic Brain Injury Model Systems National Database: www.tbindscva.org/Syllabus.aspx 
Neikrug AB, R. M.-I. (2012). Bright light therapy protects women from circadian rhythm desynchronization 
during chemotherapy for breast cancer. Behav Sleep Med, 10(3):202-16. 
Netzer NC, S. R. (1999). Using the Berlin Questionnaire to identify patients at risk for the sleep apnea 
syndrome. Ann Intern Med, 485-491. 
Ohayon MM, R. C. (2009). 3rd. Epidemiological and clinical relevance of insomnia diagnosis algorithms 
according to the DSM-IV and the International Classification of Sleep Disorders (ICSD). Sleep Med. , 
952-60. 
Okonkwo, D. O. (2013). GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from 
the prospective TRACK-TBI Study. J Neurotrauma. 
Orff HG, A. L. (2009). Traumatic brain injury and sleep disturbance: a review of current research. J Head 
Trauma Rehabilitation, 155-65. 
Ouellet MC, M. C. (2007). Efficacy of cognitive-behavioral therapy for insomnia associated with traumatic 
brain injury: a single-case experimental design. Arch Phys Med Rehabil, 1581-92. 
Ouellet MC, S. J. (2004). Insomnia following traumatic brain injury: a review. Neurorehabilitation Neural 
Repair, 18 (4): 187-98. 
Pineda, J. L. (2007). Clinical significance of alphaII-spectrin breakdown products in cerebrospinal fluid after 
severe traumatic brain injury. J Neurotrauma, 24, 354-366. 
Ponsford JL, Z. P.-N. (May-Jun 2012). Fatigue and sleep disturbance following traumatic brain injury--their 
nature, causes, and potential treatments. J Head Trauma Rehabil, 27(3):224-33. 
R., N.-R. (2012). Sleep disturbance during acute inpatient rehabilitation. Recorded symposium: Wrestling with 
Hypnos: Sleep, Wake, and Fatigue After TBI. 2012 American Congress of Rehabilitation Medicine 
Annual Conference. 

30 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
RD., L. (Jan 2005). What is the optimal implementation of bright light therapy for seasonal affective disorder 
(SAD)? J Psychiatry Neurosci, 30(1):72. 
Reeves GM, N. G. (2012). Improvement in depression scores after 1 hour of light therapy treatment in patients 
with seasonal affective disorder. J Nerv Ment Dis., 51-55. 
Revell VL, B. H. (Jan 2006). Advancing human circadian rhythms with afternoon melatonin and morning 
intermittent bright light. J Clin Endocrinol Met, 91(1):54-9. 
Riemersma-van der Lek RF, S. D. (2008). Effect of bright light and melatonin on cognitive and noncognitive 
function in elderly residents of group care facilities: a randomized controlled trial. JAMA, 2642-55. 
Roses, A. &. (1997). ApoE, Alzheimer's disease, and recovery from brain stress. Ann N Y Acad Sci , 826, 200-
212. 
Schneider Soares, F. M. (2012). Interleukin-10 is an independent biomarker of severe traumatic brain injury 
prognosis. Neuroimmunomodulation, 19, 377-385. 
Services, S. A. (1982). Symbol digit modalities test: Manual. Los Angeles: Western Psychological. 
Sheinerman, K. S. (2012). Plasma microRNA biomarkers for detection of mild cognitive impairment. Aging, 4, 
590-605. 
Sherer M, Y. S.-R. (2009). Patterns of recovery of posttraumatic confusional state in neurorehabilitataion 
admissions after traumatic brain injury . Arch Phys Med Rehabil, 90(10):1749-54. 
Shum D, M. K. (1990). Construct validity of eight tests of attention: Comparison of normal and closed head 
injured samples. Clinical Neuropsychologist , 4(2):151-62. 
Silva, M., Nakase-Richardson, R., M, S., SD, B., CC, E., & SA, Y. (2012). Posttraumatic confusion predicts 
patient cooperation during traumatic brain injury rehabilitation. Am J Phys Med Rehabil, 91 (10):890-3. 
Sjösten N, K. M. (July 2009). Obstructive sleep apnoea syndrome as a predictor of work disability. Respir Med, 
103(7):1047-55. 
Smith MR, R. V. (Mar 2009). Phase advancing the human circadian clock with blue-enriched polychromatic 
light. Sleep Med, 10(3):287-94. 
State University of New York at Buffalo. (1997). Guide for the Uniform Data Set for Medical Rehabilitation 
(including the FIM(TM) instrument. Buffalo, NY , United States. 
Terman M, T. J. (2005). Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and 
side effects. CNS Spectr , 10(8):647-63. 
Traumatic Brain Injury Model Systems. (2013, August 1). Identification of Subjects. Retrieved from National 
Data and Statistical Center: www.tbindsc.org/SOP.aspx 
Trzepacz PT, M. D. (2001). Validation of the Delirium Rating Scale – Revised: Comparison with the Delirium 
Rating Scale and the Cognitive Test for Delirium. J Neuropsychiatr Clin Neuroscience, 13:229-42. 
Turner PL, M. M. (2008). Circadian photoreception: Ageing and the eye's important role in systemic health. Br 
J Ophthalmol, 92(11):1439-1444. 
Verma A, A. V. (2007). Sleep disorders in chronic traumatic brain injury. J Clin Sleep Med, 3(4):357-62. 
Viant, M. R. (2005). An NMR metabolomic investigation of early metabolic disturbances following traumatic 
brain injury in a mammalian model. NMR Biomed, 18, 507-516. 
Walder, B. R. (2013). The prognostic significance of the serum biomarker H-FABP in comparison with S100b 
in severe traumatic brain injury. J Neurotrauma. 
Wäljas M, I. G. (2012). Reliability, validity and clinical usefulness of the BNI fatigue scale in mild traumatic 
brain injury. Brain Inj, 26:972-8. 
Walker, M. (2009). The role of sleep in cognition and emotion. Ann New York Acad Science, 1156:168-97. 
Waters, R. &. (2005). Genetic influences on outcome following acute neurological insults. . Curr Opin Crit 
Care, 11, 105-110. 
Watson NF, D. S. (2007). Hypersomnia following traumatic brain injury. J Clin Sleep Med, 3(4):363-8. 
Watson, D. L. (1988). Development and validation of brief measures of positive and negative affect: The 
PANAS scales. . Journal of Personality and Social Psychology, 54 (6), 1063-1070. 

31 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Webster JB, B. K. (March 2001). Sleep apnea in adults with traumatic brain injury: a preliminary investigation. 
Arch Phys Med Rehabilitation, 316-21. 
Whitmore RG, T. J. (2012). Is aggressive treatment of traumatic brain injury cost-effective? . J Neurosurg , 
116(5):1106-13. 
Wilde MC, C. R. (2007). Cognitive impairment in patients with traumatic brain injury and obstructive sleep 
apnea. Arch Phys Med Rehabil, 88: 1284-8. 
Wirz-Justice A, T. M. (2012). Chronotherapeutics (light and wake therapy) as a class of interventions for 
affective disorders. Handb Clin Neurol, 697-713. 
Wood RL, M. J. (1999). Clinical and cost effectiveness of postacute neurobehavioural rehabilitation. Brain Inj , 
13(2):69-88. 
Yordoova J, K. V. (2012). Increased alpha (8-12 Hz) activity during slow wave sleep as a marker for the 
transition from implicit knowledge to explicit insight. . J Cogn Neurosci, 24:119-32. 
Zeitzer JM, D. D. (2000). Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase 
resetting and suppression. J Physiol, 526 Pt 3:695-702. 
Zhao, W. H. (2013). Decreased level of olfactory receptors in blood cells following traumatic brain injury and 
potential association with tauopathy. J Alzheimers Dis , 34, 417-429. 
Zhou W, X. D. (Apr 25 2008). Meta-analysis of APOE4 allele and outcome after traumatic brain injury. J 
Neurotrauma, (4):279-90. 
Zollman FS, C. C. (2010). Actigraphy for assessment of sleep in traumatic brain injury: case series, review of 
the literature and proposed criteria for use. Brain Inj, 24 (5):748-54. 
Zollman FS, L. E.-T. (Mar-Apr 2012). Acupuncture for treatment of insomnia in patients with traumatic brain 
injury: a pilot intervention study. J Head Trauma Rehabi, 27(2):135-42. 
Zunzunegui C, G. B. (2011). Sleep disturbance impairs stroke recovery in the rat. . Sleep, 34(9):1261-9. 
 
 
 

32 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Appendix 
 
• Inclusion/Exclusion Checklist 
• Makley Sleep Scale Form 
• Berlin Questionnaire 
• Del-R-98, Question 1 Form 
• Functional Independence Measure (FIM)™ 
• PANAS 
• Karolinska Sleepiness Scale 
• Barrow Neurological Institute Fatigue Scale 
• Quarterly Staff Survey (a.k.a. Clinician Feasibility Survey) 
• Overview of Study Figure 
 
 
 
 

33 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
 
TWILIGHT Study Inclusion and Exclusion Checklist 
 
Inclusion Criteria 
Must meet all of the criteria below 
 
 Have experienced a moderate to severe TBI.  Defined by any of the following:  
1) Loss of Consciousness greater than 30 minutes.  
2) Emergency Room admission with a Glasgow Coma Scale of 12 or below.   
3) Intracranial abnormalities on imaging.   
4) Post-traumatic amnesia that lasts more than 24 hours. 
 
 Admitted to acute inpatient rehabilitation unit at Harborview Medical Center within 3 months of their Traumatic 
Brain Injury. 
 
 Able to communicate in English.   
 
 Between the ages of 18 and 70 years old   
 
 
Exclusion Criteria 
Unable to enroll if any of the following are true 
 
 Complete blindness   
 
 Absence of eye opening or disorders of consciousness (Rancho level 1-3) 
 
 Does not have sleep disturbance (rating of “0” on item one of the DelRS-R98. If has a rating of “0”, but if taking 
sleep medication in the last 72 hours, then include) 
 
 Tetraplegia with less than antigravity strength in all myotomes caudal to C6 level given the limitations on 
measuring movements with actigraphy in this population (i.e. cannot reliably detect upper extremity or lower 
extremity movement with this level of paralysis). 
 
 Past medical history of retinal pathology   
 
 Past medical history of light sensitivity   
 
 Past medical history of narcolepsy   
 
 Past medical history of bipolar disorder   
 
 Past medical history of obstructive sleep apnea   
 
 Suspected sleep apnea. (Determined by administering the Berlin questionnaire) 
 
 Current medical orders indicated for night time sleep disruption (e.g. chest PT, MIE q2 hours of meds that disrupt 
sleep)".  For these subjects, may re-approached if the medical orders are no longer in place.   
 
 

34 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
TWILIGHT STUDY 
 
 
 
 
☐ Was watch verified as on?        Staff Initials _____ 
 
 
Makley Sleep Scale Form 
Clinician rating 
Time 
Rounding 
Initials 
Sleep Rating Given Observation in the Last Hour 
(circle) 
2200 
 
0 
1 
2 
3 
2300 
 
0 
1 
2 
3 
0000 
 
0 
1 
2 
3 
0100 
 
0 
1 
2 
3 
0200 
 
0 
1 
2 
3 
0300 
 
0 
1 
2 
3 
0400 
 
0 
1 
2 
3 
0500 
 
0 
1 
2 
3 
0600 
 
0 
1 
2 
3 
Ratings: 
 
Asleep 
Drowsy/falling 
asleep 
Drowsy/waking 
up 
awake 
 
Where there any adverse events or effects? 
☐Yes  ☐ No   
 Source:__________________ 
 
If yes, please 
explain___________________________________________________________________________________ 
 
 
Date:     ________________ 

35 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Makley Sleep Log guidelines and FAQ’s 
Data collection 
1. The sleep log can by collected by nurses or MA staff 
2. Clinical staff will do data collection rounding on an hourly basis and rate the patient accordingly with a 0,1,2 or 3 
3. The rating for each hour is the clinical staffs best assessment of observed sleep/non-sleep state based on how 
they were found, not what was being done clinically, if anything 
4. Hourly ratings may be collected on paper or electronically 
5. Sleep log for the first night, along with any and all information about the participant’s sleep over the last 3 nights 
will be used to randomize. Information about the participant’s sleep will be asked of any family or friends’ 
present, clinical staff, medical chart review, and nursing notes. Please look to see if the participant has or is on 
any sleep medications in the past 72 hours. 
6. Once the research staff has all information, they will rate the participant using the DelRS-98 item #1 to score 
their severity of sleep 
7.  Data may need to be used to reconcile actigraphy data if there are questions 
8. Research staff should collect the sleep logs on a daily basis and place a copy in the participants file (de-
identified) 
 
FAQ’s 
1. Clinically what's the difference between 1 (falling asleep) and 2 (waking up) in the setting of night time 
rounds? Can we tell? Answer: Make your best clinically assessment. If patient is fully asleep then score 
= 0, if patient is fully awake then score = 3. 
2. What do we do with missing hours on a sleep log? Answer: note it as missing data; follow-up with staff 
training/study education. 
3. What do we do when a sleep log is entirely missing? Answer: keep looking to see if it can be found; 
include notation in case notes; follow-up with staff training/study education. 
4. Staff says a patient slept fine but family notes the patient was restless overnight, what data do we take 
for rating of sleep disturbance in the study?  Answer: Clinically we know that patients/subjects will be 
observed at different time points and that the type and quality of observations will be variable. 
Research staff should collect all available data and make their best summary of presence/absence of 
ANY sleep changes and if present the rating of severity (using the Del-RS-R 98 item 1) considering that 
this type of data is generally additive to describe what's happened overnight and not necessarily 
either/or. To score a subject as having no sleep disturbance there should be no clinical data that says 
the patient didn't sleep perfectly well (i.e. patient/caregiver/family report is all that sleep was fine, no 
medications given). 
 
 

36 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
BERLIN QUESTIONNAIRE  
Height (m) ________ Weight (kg)________ Age______ Male / Female  
Please choose the correct response to each question.  
 
CATEGORY 1  
1. Do you snore?  
a. Yes  
 
 
 
b. No   
 
 
c.  Don’t know  
If you snore:  
 
2. Your snoring is:  
a. Slightly louder than breathing  
b. As loud as talking  
c. Louder than talking  
d. Very loud – can be heard in adjacent rooms  
3. How often do you snore  
a. Nearly every day  
b. 3-4 times a week  
c. 1-2 times a week  
d. 1-2 times a month  
e. Never or nearly never  
4. Has your snoring ever bothered other people?  
a. Yes  
b. No  
c. Don’t Know  
5. Has anyone noticed that you quit breathing during your sleep?  
a. Nearly every day  
b. 3-4 times a week  
c. 1-2 times a week  
d. 1-2 times a month  
e. Never or nearly never  
CATEGORY 2  
6. How often do you feel tired or fatigued after your sleep?  
a. Nearly every day  
b. 3-4 times a week  
c. 1-2 times a week  
d. 1-2 times a month  
e. Never or nearly never  
7. During your waking time, do you feel tired, fatigued or not up to par?  
a. Nearly every day  
b. 3-4 times a week  
c. 1-2 times a week  
d. 1-2 times a month  
e. Never or nearly never  
 
8. Have you ever nodded off or fallen asleep while driving a vehicle?  

37 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
a. Yes  
b. No  
 
If yes:  
9. How often does this occur?  
a. Nearly every day  
b. 3-4 times a week  
c. 1-2 times a week  
d. 1-2 times a month  
e. Never or nearly never  
 
CATEGORY 3  
10. Do you have high blood pressure?  
a. Yes  
b. No  
c. Don’t know 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

38 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
Rating Sleep-Wake cycle disturbance: 
Question 1 is utilized in this study 
 

39 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
FIM- 
Functional 
Independence 
Measure
 
 
 
 

40 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
 
 
 
 
 
 
 
 

41 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
BASELINE 
Pt. not able to report ☐ 
Sleepiness Scale: (Karolinska Sleepiness Scale) 
Here are some descriptors about how alert or sleepy you might be feeling right now.  Which one corresponds to 
the statement describing how you feel at this moment? 
i. 
Extremely alert 
ii. 
Very alert 
iii. 
Alert 
iv. 
Rather Alert 
v. 
Neither alert nor sleepy 
vi. 
Some signs of sleepiness 
vii. 
Sleepy, but no difficulty remaining awake 
viii. 
Sleepy, some effort to keep alert 
Pre Light Treatment  
 
 
 
Date:  
___________  
 
Score:  ___________________ 
 
 

42 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
BASELINE 
Barrow Neurological Institute Fatigue Scale 
Pt. not able to report ☐ 
Please rate the extent to which each of the items below has been a problem for you since your injury.  
You should choose only ONE number from 0-7 on the scale below when making your response.  
0 
1 
2 
3 
4 
5 
6 
7 
Rarely a 
problem 
Occasional problem 
but not frequent 
 
A Frequent 
Problem 
A problem most of 
the time 
 
1. How difficult is it for me to maintain my energy throughout the day?  
 
______ 
2. How difficult is it for me to participate in activities because of fatigue? 
 
______ 
3. How difficult is it for me to stay awake during the day? 
 
 
 
______ 
4. How difficult is it for me to complete a task without becoming tired?  
 
______ 
5. How difficult is it for me to stay alert during activities? 
 
 
 
______ 
6. How difficult is it for me to build my energy level once I wake up in the morning? 
______ 
7. How difficult is it for me to stay out of my bed during the day? 
 
 
______ 
8. How difficult is it for me to stay alert when I am not involved in something?  
______ 
9. How difficult is it for me to attend to something without becoming sleepy? 
 
______ 
10. How difficult is it for me to last the day without taking a nap? 
 
 
______  
 
 
 
 
 
 
11. Please circle your OVERALL level of fatigue since your injury: 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
problem 
 
 
 
 
 
 
 
 
 
Severe 
Problem 
 
 
 
 
 
 
 
 
 
 
 
 
 

43 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
 
 
Quarterly Staff Survey 
If you have been involved in the care of a patient enrolled in the TWILIGHT Study in the past three months please 
answer the questions below.  
Date:______________ 
Please check one: 
 
 
 
 
 
 
 
 Rehabilitation Nurse 
 Rehabilitation Therapist (PT, OT, SLP, TR) 
 Other 
Please indicate whether you agree or disagree with the following statements: 
Q1:  It was easy to integrate light therapy into patient care. 
1 
2 
3 
4 
5 
Strongly Disagree 
Disagree 
Neither agree or 
disagree 
Agree 
Strongly Agree 
 
Q2:  Light therapy did not increase my work load. 
1 
2 
3 
4 
5 
Strongly Disagree 
Disagree 
Neither agree or 
disagree 
Agree 
Strongly Agree 
 
Q3:  Light therapy should be offered as a routine treatment option in in-patient rehabilitation. 
1 
2 
3 
4 
5 
Strongly Disagree 
Disagree 
Neither agree or 
disagree 
Agree 
Strongly Agree 
 
Comments? 
 
 
 

44 
Manual of Procedures: TWILIGHT Study  
 
Rev: 9/2/2014 
 
TWILIGHT Study: Treatment with Light Therapy  
Effect of light exposure during acute rehabilitation on sleep after traumatic brain injury 
 
Overview for Study Participants