Cognitive Behavioral Therapy for Insomnia for Veterans With History of TBI
Phase: NA
Conditions: Insomnia, Traumatic Brain Injury
Sponsor: VA Office of Research and Development

Cognitive Behavioral Therapy for Insomnia 
for Veterans with History of TBI  
NCT02658669
September 26, 2023

Study Protocol 
Pre-study screening (15-30 minutes): Initial screening for interest and eligibility will take place in person or via 
telephone. Veterans will be given an overview of the study and, after providing verbal consent, will be screened 
with a questionnaire covering the major inclusion/exclusion criteria. Veterans who were not excluded based on 
the phone screening and who express interest in participating in the study will be invited to come to the VASDHS 
for continued evaluation of eligibility for participation in the study.  
 
Baseline-Intake (2 hours): During the intake appointment, Veterans will first provide written informed consent 
and HIPAA consent and then be screened for sleep disorders using the Duke Structured Interview for Sleep 
Disorders. At this appointment, we will further confirm/document history of mild traumatic brain injury (mTBI) by 
noting number of mTBI events, type (blast/blunt/both), and duration of LOC and PTA for each event. At this visit 
all Veterans will be assessed on a battery of self-report questionnaires selected to evaluate global areas of 
functioning including sleep, fatigue, mood, PTSD, pain, post-concussive symptoms, and quality of life (see Table 
2). We will also administer a neuropsychological assessment battery consisting of standardized measures with 
strong psychometric properties covering cognitive functions often impacted by mTBI, sleep disturbance, and/or 
depression. As part of this battery the Word Memory Test46 (WMT) will be delivered to assess validity of 
neuropsychological results. Neuropsychological data of Veterans who fail effort testing will not be included in 
subsequent moderator analyses of impact of cognitive functioning on treatment outcomes. All assessments will 
be administered by a trained research assistant. At the conclusion of this appointment, Veterans will be given a 
sleep diary to compete for 7 days to prospectively record sleep measures (e.g., “lights out,” time to fall asleep, 
time spent awake during the night, total sleep time, and “lights on”). After the baseline evaluation phase is 
completed, Veterans will be randomized into one of two treatment conditions (CBT-I or Sleep Education control). 
 
Cognitive-Behavioral Therapy for Insomnia (CBT-I: 50-minute sessions): CBT-I treatments will be randomly 
assigned and will be conducted utilizing the VA Roll-out treatment manual. The standard approach to treatment 
involves 6 weekly sessions, and addresses several important concepts, including the underlying causes of 
insomnia, sleep restriction and stimulus control techniques, relaxation training, and relapse prevention. A 
significant emphasis is placed on using a case formulation to inform the treatment, and we will do that here, 
especially as it applies to how the Veteran’s experience with mTBI informs the formulation. The session-by-
session details are presented in Table 1 below. 
 
Table 1. VA ROLL-OUT CBT-I TREATMENT PROTOCOL 
Session  
Content 
Homework 
Measures / Handouts 
1  
Comprehensive assessment  
Goal setting  
Case conceptualization  
Complete sleep diary  
Case conceptualization form  
Sleep diary  
Insomnia Severity Index (ISI) 
2  
Review sleep diary  
Provide sleep education tailored to 
patient  
Introduce Stimulus Control (SC)* and 
Sleep Restriction Therapy (SRT)** 
guidelines and rationale anchored in 
sleep regulation  
Use cognitive therapy as needed  
Emphasize most relevant components 
and add components based on case 
conceptualization  
Complete sleep diary  
Follow recommended 
times for getting into and 
out of bed  
Follow other relevant 
guidelines  
Sleep diary  
ISI 
 “A Guide to Overcoming 
Your Insomnia”  
Other relevant worksheets  
3  
Review sleep diary and adherence;  
Discuss adherence in relation to 
progress  
Modify Time in Bed (TIB) based on SRT  
Use cognitive therapy as needed  
Introduce relaxation when needed 
(unless already introduced in Session 2)  
Complete sleep diary  
Follow recommended 
times for getting into and 
out of bed  
Follow other relevant 
guidelines (including 
relaxation home practice)  
Sleep Need Questionnaire  
Sleep diary  
ISI  
Other relevant worksheets  

4 & 5  
Review sleep diary and adherence  
Discuss adherence in relation to 
progress  
Modify TIB based on SRT rules  
Use cognitive therapy as needed  
Complete sleep diary  
Follow recommended 
times for getting into and 
out of bed  
Follow other relevant 
guidelines  
Sleep Need Questionnaire  
Sleep diary  
ISI  
Other relevant worksheets  
6  
Review sleep diary and adherence  
Modify TIB based on SRT rules  
Develop continued care plan  
Develop a relapse prevention plan  
Follow continued care 
and relapse prevention 
plans  
Action Plan for Addressing 
Insomnia in the Future  
Sleep Need Questionnaire  
ISI  
 
*Sleep restriction therapy reduces nocturnal sleep disturbance primarily by restricting the time allotted for sleep 
each night so that, eventually, the time spent in bed closely matches the individual’s presumed sleep 
requirement. This treatment typically begins by calculating the individual’s average total sleep time from the 
sleep diary. An initial time-in-bed prescription is typically set at the total sleep time, however, is usually not set 
below 5 hours per night. On subsequent sessions the time in bed is titrated up or down in 20 to 30 minutes 
depending on sleep performance (sleep efficiency scores) over the past week. 
 
**Stimulus control therapy is based on the assumption that both the timing (bedtime) and sleep setting 
(bed/bedroom) are associated with repeated unsuccessful sleep attempts and, over time, become conditioned 
cues for arousal that perpetuate insomnia. As a result, the goal of this treatment is to re-associate the bed and 
bedroom with successful sleep attempts. In practice, this therapy requires instructing the patient to: (a) go to bed 
only when sleepy; (b) establish a standard wake-up time; (c) get out of bed whenever awake for long periods; 
(d) avoid reading, watching TV, eating, worrying and other sleep-incompatible behaviors in the bed/bedroom; 
and (e) refrain from daytime napping. 
 
Sleep Education Control Condition (50 minute sessions): The sleep education control condition used in this study 
is matched for number of sessions and length of sessions, however the content is modified to exclude the active 
components of standard CBT-I treatment. The sleep education control sessions focus on review of sleep diaries, 
providing information on relationship between sleep disturbance and mTBI, presentation of sleep hygiene 
education, and reviewing daily stressors that may impact sleep (see Table 2 below). 
 
Table 2. SLEEP EDUCATION CONTROL CONDITION PROTOCOL 
Session 
Content 
Homework 
Measures / Handouts 
1  
Veteran check-in 
Provide information on relationship 
between sleep disturbance and TBI 
Description of sleep management 
Complete sleep diary  
Sleep diary  
Insomnia Severity Index (ISI) 
2  
Veteran check-in 
Review sleep diary  
Present sleep hygiene education 
Complete sleep diary   
Sleep diary  
ISI 
3  
Veteran check-in 
Review sleep diary  
Present sleep hygiene education 
Complete sleep diary  
Change one aspect 
related to sleep hygiene  
Sleep diary  
ISI  
4  
Veteran check-in 
Review sleep diary  
Review stressors related to sleep 
Complete sleep diary  
Change one aspect 
related to sleep hygiene 
Sleep diary  
ISI  
5 
Veteran check-in 
Review sleep diary  
mTBI education 
Complete sleep diary  
Change one aspect 
related to sleep hygiene 
Sleep diary  
ISI 
6 
Veteran check-in 
Review sleep diary  
Review techniques learned and 
strategies used over past five weeks 
of sleep education sessions 
Complete sleep diary  
Sleep diary  
ISI 

Post-treatment Assessment: In the week following completion of the final treatment module, Veterans will be 
given a sleep diary to fill out for 7 days to prospectively assess sleep at post-treatment. At the end of the post-
treatment evaluation week Veterans will return to the VASDHS to turn in the diary and will at this time be 
administered the same battery of clinical assessments originally given during the baseline evaluation visit.  
 
1-Month Follow-up: 30 days following completion of post-treatment assessment Veterans will be contacted and 
asked to participate in a 1-week follow-up assessment of their sleep and functioning. For follow-up Veterans will 
be given a sleep diary to fill out for 7 days to prospectively assess sleep at post-treatment. At the end of the 
sleep tracking week Veterans will return to the VASDHS to turn in the diary and will at this time be administered 
the same battery of clinical assessments originally given during the baseline and post-treatment evaluation visits. 
At the conclusion of this session the Veteran will have completed participation in the study. 
 
Statistical Analysis 
 
Specific Aim 1: To determine the efficacy of CBT-I relative to a Sleep Education control in Veterans with insomnia 
following mTBI. 
 
Hypothesis 1a: Veterans treated with CBT-I will experience significant improvement in the primary outcome of 
sleep efficiency when compared to Veterans treated with Sleep Education. Sleep efficiency scores will be derived 
from the Veteran’s sleep diaries by averaging nightly sleep efficiencies for each 1-week (seven day) period of 
time. Sleep efficiency data will be collected for 1-week intervals at multiple study time points including: 1) 
baseline/pre-treatment, 2) for each week during treatment sessions 1-6, and 3) at post-treatment.  Analyses of 
this data will be conducted using a Random Regression Model, a generalized linear model described by Gibbons 
et al.64, Hedeker et al.65, and Laird et al.66. The random effects method has several advantages over more 
traditional analytic approaches such as a change score, end-point, or repeated measures ANOVA. This method 
allows the inclusion of subjects with missing data or those who were terminated early in the study, without relying 
on data imputation procedures. This method provides an estimate of the individual variability around the 
population trend, the variability of the individual intercepts (baseline values) and slopes (changes across time), 
and the correlation between them. The model will include a random intercept, a random effect for assessment 
time, and fixed effects for comparison groups and group-by-time interaction. A fully saturated treatment by time 
model will be utilized for inference. Co-variance structure will be chosen based on Akaike’s Information Criterion 
(AIC). Random group level treatment effects will also be evaluated for importance based on the model AIC. This 
allows for any group level effects to be incorporated into the model. Denominator degrees of freedom will be 
calculated using the Kenward-Roger small sample correction. Data will be analyzed from all randomized subjects 
using all available data collected at baseline, during treatment, and at post-treatment.  
 
Independent variables: Treatment group (CBT-I versus Sleep Education control) and Time (Baseline, 
Treatment Weeks 1-6, Post-treatment). 
 
Dependent variables: Insomnia severity.  
 
Hypothesis 1b: Veterans treated with CBT-I will report significant improvement on secondary outcome 
measures of depression, PTSD, and global functioning and disability when compared to Veterans treated with 
Sleep Education. Analyses of this data will be conducted using the Random Regression Model for assessments 
conducted at baseline, mid-treatment (treatment Session 3), and at post-treatment using a similar methodology 
as described for hypothesis 1a. Bonferroni adjusted alphas will be used. 
 
Independent variables: Treatment group (CBT-I versus Sleep Education control) and Time (Baseline, 
Mid-treatment [Session 3], Post-treatment). 
 
Dependent variables: Depression (PHQ-9), PTSD (PCL-S), and global functioning and disability (World 
Health Organization Disability Assessment Schedule 2 [WHODAS-2]).  
 
Specific Aim 2: Examine sleep efficiency as a mediator of distal effects of CBT-I on symptoms of comorbid 
depression and PTSD, and global functioning and disability. 
 

Hypothesis 2: Veterans demonstrating improvement in sleep efficiencies will also show improvements in 
comorbid depression, PTSD, and global functioning and disability. The dependent or outcome measures will be 
evaluated throughout the study and will be used as repeated measures for all the available time points. For this 
hypothesis, we will use the same mixed model procedure identified in Hypothesis 1a and 1b. To test for 
mediation, we will utilize the analytic strategy described by Krull and MacKinnon67,68. In this approach, four 
conditions must be met: a) a significant relationship between the independent variable (i.e., intervention 
condition) and the dependent variable, b) a significant relationship between the independent variable (i.e., 
intervention) and the proposed mediator (sleep efficiency), c) a significant relationship between the mediator 
(sleep efficiency) and the outcome measures, and d) the relationship between the independent variable 
(intervention) and outcome measures must be significantly lower after controlling for the mediator. To test for 
significant mediation, we will conduct a Sobel test69. We will also use the formula provided by MacKinnon and 
Dwyer70 to determine the percentage of the intervention condition to primary outcome path that was accounted 
for by change in the mediator. 
 
Independent variables: Treatment group (CBT-I versus Sleep Education control)  
 
Dependent variables: Depression (PHQ-9), PTSD (PCL-S), and global functioning and disability (World 
Health Organization Disability Assessment Schedule 2 [WHODAS-2]). 
 
Mediator: Sleep efficiency. 
 
Specific Aim 3: Examine the effects moderator variables on CBT-I treatment outcomes 
 
Hypothesis 3: We anticipate that several post-concussive factors such as depression, PTSD, and 
physical pain may moderate treatment outcomes whereas other factors such as global functioning and disability, 
neuropsychological functioning, and medication use will not moderate treatment outcomes. The rationale for this 
hypothesis comes from published work suggesting psychopathology and pain may play a significant role in 
maintenance of post-concussive symptoms (such as sleep disturbance) in patients with history of TBI21 thereby 
potentially impacting CBT-I treatment outcomes. Conversely, factors such as neuropsychological functioning, 
disability, and medication use have not been previously demonstrated to impact and/or moderate CBT-I 
treatment outcomes in a significant manner. These positional moderators will be explored by adding one 
outcome at a time to the Random Regression Model. 
 
Independent variable: Treatment group (CBT-I versus Sleep Education control). 
 
Dependent variable: Sleep efficiency. 
 
Moderators: Depression (PHQ-9), PTSD (PCL-S), global functioning and disability (World Health 
Organization Disability Assessment Schedule 2 [WHODAS-2]), pain (BPI), neuropsychological 
functioning, and medication use (e.g., hypnotics, SSRIs).