The Effects of Computerized Cognitive Behavior Therapy (cCBT) on Brain Health: A Feasibility Study
Phase: NA
Conditions: HIV Infections, Depression, CBT
Sponsor: McGill University

The Effects of computerized Cognitive Behavior Therapy (cCBT) on Brain Health:  
A feasibility study 
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PROTOCOL SUMMARY 
 
 
 
Full Title 
The Effects of computerized Cognitive Behavior Therapy 
(cCBT) on Brain Health : A feasibility study 
Short title 
HIV, depression and cCBT 
Sponsor  
McGill University  
Funding 
Canadian Institute of Health Research (CIHR)  
Principal 
Investigators 
Marie-Josée Brouillette, MD, Department of Psychiatry, McGill 
University 
Gail Myhr, MD, Department of Psychiatry, McGill University 
Maxim Lewkowski, PhD, Department of Psychology, McGill University 
Associate 
investigators 
Lesley Fellows, MD 
Nancy Mayo, PhD 
Objectives 
 
 
 
Among individuals with symptoms of depression and cognitive 
difficulties, and whose depression is treated with computerized 
Cognitive Behavioral Therapy (cCBT), to what extent is reduction 
in depressive symptoms associated with reduced reports of 
cognitive difficulties.   
Secondarily, to what extent is the reduction self reported cognitive 
difficulties concordant with improvement cognitive performance.      
Study Population 
Inclusion Criteria 
 Participants in the cohort study “Understanding and Optimizing 
Brain Health in HIV Now” with at least one remaining visit 
 Able to communicate (understand and read) in English  
 Depression subscale of the HADS (HADS-D) ≥ 8  

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 Presence of self-reported cognitive difficulties (PDQ) ≥ 30  
 Score on the B-CAM > 14 
 Willing to undergo 9 sessions of cCBT as per instructions and to 
have weekly contact with a research coordinator from the central site 
(by email or phone)  
 Access to the internet 
Exclusion Criteria 
 
Current use of street drugs (excluding marijuana) 
Study Design 
Single cohort design with two repeated measures 
Sample Size 
30 participants have completed the intervention and the final evaluation  
Participant 
involvement 
Questionnaires at screening, pre- and post- intervention 
9 sessions of cCBT plus regular contacts from the central site  
 
 
 
 

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BACKGROUND  
Among people living with HIV, challenges related to brain health are emerging.  Brain health is 
a broad term referring to the inter-related factors of cognition, mood, anxiety, motivation, 
fatigue, stress and coping [1]. For example, among people with HIV, the severity of depressive 
symptoms has repeatedly been associated with the presence of self-reported cognitive 
difficulties, even in the absence of impairment on neuropsychological testing [2, 3]. There is 
uncertainty about the clinical importance of these self-reports, especially when 
neuropsychological testing is normal, as they are thought to be susceptible to patients’ biases and 
insights into their illness.  
However, there is growing evidence that these self-reports are clinically important. Among 
patients with major depressive disorder (MDD), evidence suggests that functional impairments 
is mediated by self-reported cognitive dysfunction, rather than objective cognitive dysfunction 
[4]. For example, Buist-Bouwman et al reported that more than one-quarter of the impact of 
MDD on work loss was directly attributable to self-reported cognitive difficulties and that 
cognition was a significant mediator of the association between MDD and work or role 
dysfunction [5].  
When depression is treated with antidepressant medication, some degree of improvement on 
neuropsychological tests has been documented [6, 7] . However, many studies have evaluated 
cognitive outcomes before and after treatment rather than comparing them with placebo, 
potentially biasing the results by learning effects, which limits the strength of the conclusions 
that can be drawn.  
Treatment of depression with Cognitive-Behaviour Therapy (CBT) has been shown to improve 
depressive symptoms and psychosocial functioning in patients with recurrent major depressive 
disorder [8], but there are few studies of the impact of psychotherapy on self-reported cognition 
and cognitive performance. In a group of patients with highly recurrent depression (≥4 episodes) 
over 2 years of follow-up, Conradi et al showed that those randomized to receive psycho-
education plus CBT reported the presence of cognitive symptoms significantly less of the time 
compared to those receiving psycho-education only (15% of the time or 3.6 months compared to 
47% or 11.3 months) [9]. 

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In the HIV population, a single study has examined the effect of treatment of depression on self-
reported cognitive difficulties and performance on neuropsychological tests, as part of a 
randomized controlled trial of antidepressant efficacy [10]. Following 12 weeks of antidepressant 
treatment, HIV+ individuals who reported a decrease in depressive symptoms also reported 
significantly fewer cognitive difficulties, despite an absence of improvement on 
neuropsychological testing. 
 In the context where the use of questionnaires eliciting cognitive difficulties is suggested as a 
first-line screening for HIV-Associated Neurocognitive Disorder [11], it is important to 
document the clinical factors that influence these self-reports in order to inform their clinical 
interpretation and develop interventions for individuals reporting cognitive difficulties.  
Understanding and Optimizing Brain Health Now (BHN) cohort study: Cohort participants 
(N=840) are studied prospectively over a 27-month period with visits every 9 months.  Patients 
complete questionnaires on mood (Hospital Anxiety Depression Scale-HADS), presence of 
cognitive symptoms (Patient Deficit Questionnaire-PDQ), and a computer-based evaluation of 
cognitive ability (B-CAM) [12]. 
Computerized Cognitive-Behavioral Therapy (cCBT): A number of computerized treatment 
programs have been developed to address symptoms of depression and anxiety, and several 
meta-analyses of randomized controlled trials (RCTs) have shown evidence for their 
effectiveness [13, 14]. One such program, Good Days Ahead, teaches the basic principles of 
CBT in nine therapy sessions, each typically taking 30 minutes to complete. Good Days Ahead 
has been found to be as effective as face-to-face CBT in decreasing symptoms of depression and 
anxiety [15]. Patients receiving treatment delivered by a computer can be provided with different 
levels of guidance and support: self-guidance, guidance by a technician who sends reminders, or 
guidance by a clinician [13]. A recent meta-analysis of cCBT for depression and anxiety has 
shown that the treatment delivered with no guidance or support yielded, on average, a smaller 
effect size (Cohen’s d = 0.17) than cCBT delivered with at least one hour of knowledgeable 
assistance during the course of therapy (Cohen’s d = 0.72) [15] . Offering some assistance thus 
appears to be necessary for achieving better therapy outcomes.  
STUDY OBJECTIVES 
Among individuals with symptoms of depression who report cognitive difficulties and whose 

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depression is treated with computerized Cognitive Behavioral Therapy (cCBT), to what 
extent is reduction in depressive symptoms associated with reduced reports of cognitive 
difficulties?  
Secondarily, to what extent is the reduction in self-reported cognitive difficulties concordant 
with improvement cognitive performance?     
STUDY HYPOTHESIS 
The hypothesis is that people whose depressive symptoms are reduced following treatment with 
cCBT will also report fewer cognitive difficulties than before treatment.  A second hypothesis is 
that changes in self-reported cognition will be concordant with changes in cognitive 
performance, such that people who make no improvement in self-report cognition will also show 
no improvement in cognitive performance and those who do improve on self-report will improve 
on cognitive performance.  
STUDY DESIGN 
This study is part of a larger project based upon a cohort multiple randomized controlled design 
[1]. Within a fully characterized cohort followed over time (n=840), people meeting the specific 
criteria for one or more interventions (here cCBT) are identified and a sample is randomly 
selected to receive the intervention.  When the intervention is under investigation, the remaining 
eligible persons who do not receive the intervention serve as controls.  In this study, we are not 
testing the effectiveness of cCBT as this has been demonstrated.  Rather we are focusing on 
changes in cognition in relation to depressive symptoms mediated by cCBT.  This study is an 
exploration of a hypothesis using a single cohort design with two repeated measures.  For 
exploratory studies, an N of 30 optimizes an analysis based on means under the central limit 
theorem [16] .  
POPULATION  
Individuals who report depressive symptoms and self-reports of cognitive difficulties and who 
have agreed to be contacted for sub-studies will be invited to participate.   
Inclusion criteria: 
 
Participant in the Understanding and Optimizing Brain Health in HIV Now (BHN) study 

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 
Able to communicate (understand and read) in English (Good Days Ahead software is 
only available in English) 
 
Score on the Hospital Anxiety and Depression Scale- depression subscale (HADS-D) ≥ 8  
 
Score on the Patient Deficit Questionnaire (PDQ) [17]  ≥ 30 
 
B-CAM score > 14 to ensure that they can navigate the computer program  
 
Have not had changes in medication that could potentially interfere with mood and 
cognition, and are not expected to undergo such changes for the duration of the study 
 
Have been on a stable HAART regimen for > 6 months 
 
Willing to participate in cCBT as per instructions and to have regular contacts with the 
central site  
 
Have access to the internet 
 
Have at least one remaining visit in the main cohort study 
Exclusion criteria: 
 Current use of street drugs (excluding marijuana) 
Potentially eligible participants will be identified from the BHN cohort and will be contacted by 
phone or e-mail (depending on the contact information provided by the participant) by a research 
coordinator at the central (Montreal) site who will introduce the study. Individuals who consent 
verbally will be asked to provide their email address. All participants will receive an e-mail with 
the informed consent document and will be instructed to return the e-mail to confirm consent to 
participate.  Those consenting will be asked to complete on-line questionnaires (HADS and HIV-
specific questionnaire of cognitive difficulties, the C3Q [18]) on a secure site to confirm 
eligibility and collect baseline information. Those remaining eligible will enter the intervention 
phase.  People will be contacted and screened until a maximum of 36 participants have entered 
the intervention phase. This number was chosen as sample sizes around 30 for analysis are often 
used in exploratory studies to optimize an analysis based on comparison of means under the 
central limit theorem [16], and we except some drop outs from the cCBT therapy.  
Intervention: 
Participants who are eligible will receive online access to the Good Days Ahead cCBT program. 
Good Days Ahead is a learning module based on scientifically proven, evidence-based 
techniques. The program’s content follows the teachings of the basic principles of CBT. The 

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underlying platform generates customized learning experiences for each individual user with 
content including videos, text, quizzes and interactive exercises.  The program comprises nine 
lessons of 30 minute each during which the user first learns the key concepts; then applies them 
to the program’s main character who suffers from depression; and then applies those techniques 
to their own personal challenges (http://www.empower-interactive.com/solutions/good-days-
ahead). Participants are expected to complete the nine sessions over 9-12 weeks.   
As patients complete the cCBT program, their progress will be monitored by the research 
coordinator through a secure web site, using the program’s dashboard feature that includes 
tracking of mood ratings, exercises, comprehension and completion rates. Participants will 
receive guidance during regular contacts by a trained research coordinator knowledgeable about 
the program and the basics of CBT. 
MEASUREMENT  
Three types of measures are under study: (i) depressive symptoms, (ii) self-reported cognitive 
difficulties; (ii) cognitive performance.   
(i) 
Depressive symptoms will be measured using the Hospital Anxiety and Depression Scale 
(HADS) [19] before beginning and right after cCBT completion. It comprises two 7-item scales 
designed to rate depression and anxiety. It was developed to be brief, non-threatening and to 
exclude items which might reflect somatic symptoms. It has been widely used in research [20]. A 
score on the depression subscale (HADS-D) ≥ 8 is indicative of the presence of depression. 
(ii) 
Self-reported cognitive difficulties will be measured using the C3Q collected before 
beginning and right after cCBT completion.  The C3Q is a self-report measure of cognitive 
difficulties comprised of 18 items covering multiple cognitive domains. For each item, 
individuals rate the frequency of a cognitive difficulty on a three-point scale. The items fit the 
Rasch model, producing a legitimate total score with mathematical properties ranging from 0-36 
with lower scores indicating more severe difficulties. C3Q has good content and construct 
validity and a good internal reliability (Person Separation Index 0.84) [18]. The mean score of 
C3Q among HIV+ individuals is 26.3 (SD: 8.2). 
(iii) 
Cognitive performance will be measured by the B-CAM, a computerized test of cognition 
that yields a score on a continuous metric [21].  The B-CAM is administered at the regular BHN 

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cohort visits. Two values will be used, those closest to the beginning and end of the CBT 
intervention period, usually 9 months apart.    
STATISTICAL ANALYSIS AND SAMPLE SIZE 
Basic descriptive statistics will be used to characterize the participants including values on all the 
outcomes.   
To meet the first aim of linking change in depressive symptoms (as a result of cCBT) to change 
in self-reported cognitive difficulties, an analysis based on a comparison of two means will be 
carried out.  The cCBT cohort will be classified as having changed on depressive symptoms if the 
score on the HADS-D has either fallen to below 8 or decreased by ½ SD (2 points).   The mean 
value of change on the C3Q will be compared between these two groups (depression improved vs 
no change), using an adjusted t-test based on linear regression, adjusted for covariates that differ 
between the two groups. This t-test is an estimate of between group effect size. The parameter of 
interest, however, is the within group effect size for cognitive change using the standardized 
response mean (SRM), which is the average within group change divided by the standard 
deviation of change.  The two SRMs will be compared using relative effectiveness: SRM 
(depression improved group) / SRM (depression no change group)[16].  If this ratio exceeds 1.0, 
there is supportive evidence for a greater response in the depression improved group.  This 
information on the between and within-effect sizes will be used to develop a fully powered study 
of this association.   
The extent to which changes in self-reports are concordant with changes in cognitive performance 
will be assessed using percent agreement and 95% confidence intervals (CI).  Each person will be 
classified as a responder or not based on change on the C3Q and on the B-CAM, with responder 
status defined as improvement of ½ SD. This represents a change of 4 points on the C3Q and 2.3 
points for the B-CAM. The table below shows the potential outcome patterns. If the value of c=0, 
all persons with decreased reports of cognitive difficulties also had improved cognitive 
performance with cCBT. 
 
 

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Cognitive difficulties 
C3Q 
 
 
Decreased 
no change 
Cognitive 
performance 
B-CAM 
improved 
a 
b 
no change 
c 
d 
 
To illustrate, if 12 people among the 30 were concordant on response to the two types of 
cognitive measures, the estimate of concordance would be 0.40 with a 95% CI ranging from 0.25 
to 0.58.  This exploratory analysis will allow for comparison of characteristics between people 
who were concordant to those who were not.    
POTENTIAL RISKS AND BENEFITS  
There are no foreseeable risks associated with participating in the study. The intervention offered 
through this trial (Good Days Ahead) has already been shown to have positive effects on mood. 
Therefore similar clinical benefits will be expected in the population of the current study.  
Participants will receive compensation for their time, $20 for completing the screening 
questionnaires and $80 at the completion of the study. 
ETHICS/ PROTECTION OF HUMAN SUBJECTS 
Informed consent 
All subjects will be given written information about the study and will confirm their consent to 
participate by e-mail prior to starting the study. Each subject will have sufficient opportunity to 
discuss the study and consider the information in the consent process prior to agreeing to 
participate. Subjects may withdraw consent at any time during the course of the trial. A copy of 
the consent e-mail will be retained in the subject’s study files.      
Participant Confidentiality 
All records will be kept in a secure, locked location and only research staff will have access to 
the records. Each participant will be assigned an identification code for anonymously linking 

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data. The identification information will only be accessible to the research coordinator in a 
password-protected document.  
Upon request, clinical information may be reviewed by or released to auditors, CIHR or 
regulatory agencies.  For participants who are invited to participate but refuse, the positive screen 
for the presence of depressive symptoms is communicated to the site PI as a “red flag” of 
potential significance for clinical care, according to a procedure already established in the Brain 
Health Now cohort study.   
The Good Days Ahead program is in compliance with Health Insurance Portability and 
Accountability Act (HIPAA) regulations, which ensure that personal health information remains 
private and secure. Good Days Ahead does not collect personal information such as email 
address unless the participant requests that it does so. Good Days Ahead does log the IP address 
to give an idea of which parts of the website is visited and how long the participant spends there, 
but it does not link the IP address to anything personally identifiable 
(http://www.mindstreet.com/privacy-statement).   
Record Retention 
Data and study documents will be stored securely for 7 years, after which they will be destroyed 
in keeping with the privacy and confidentiality regulations and guidelines.  
 
 

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