Internet-based Cognitive Behavioral Therapy to Reduce Depressive Symptoms After Stroke Pilot/Feasibility Study
Phase: NA
Conditions: Stroke, Depression
Sponsor: University of Pennsylvania

 
Protocol V43 13DEC27JULY2018 
Protocol Title: Internet-based Cognitive Behavioral Therapy to Reduce Depressive Symptoms 
after Stroke Pilot/Feasibility Study  
 
Short Title: Internet-based CBT for Depression after Stroke Pilot 
 
Investigators: 
Michael T. Mullen 
Laura Stein 
Scott Kasner 
 
 
Brief Description: 
 
Stroke is one of the leading causes of death and disability in the United States, with estimated 
direct and indirect costs exceeding 70 billion dollars per year.  Depression is common after 
stroke, occurring in approximately 25% of all patients.  Depression has been associated with 
lower quality of life, higher mortality, increased healthcare utilization and higher costs.  Cognitive 
behavioral therapy (CBT) interventions have been shown, in small studies, to both treat and 
prevent the development of post-stroke depression.  CBT based interventions therefore have 
the potential to improve quality of life and reduce healthcare costs after stroke.  Unfortunately, 
there are significant barriers to the widespread use of CBT in the stroke population, including 
limited access to licensed providers, high costs of treatment, and limited mobility.  Alternative 
methods for delivering CBT have the potential to improve access and reduce costs and may 
make widespread dissemination of CBT based treatment possible.  We aim to test the feasibility 
of an internet-based CBT (iCBT) program combined with a telephone/email based coaching 
servive in patients with recent stroke.  We will do this by partnering with Joyable.  Joyable is an 
existing, commercially available iCBT program.  Joyable’s  iCBT Program for Depression 
combines 42 brief online activities with a telephone/email based coaching service, which is 
designed to motivate and encourage individuals to complete the online modules.     
 
Objectives: 
 
1. Determine the feasibility of internet-based CBT in patients with recent ischemic stroke 
and depressive symptoms, by quantifying adherence to the program in a pilot population 
of 20 subjects.   
 
2. Quantify changes in depressive symptoms and quality of life in subjects pre- and post-
program participation, to provide preliminary evidence of the efficacy of internet-based 
CBT to improve outcomes after stroke. 
 
 
Primary Outcome variables 
The primary outcomes will be the number of activities in the iCBT program completed by 
participants and reduction in depressive symptoms, measured the 9-item Patient Health 
Questionnaire (PHQ-9).   
 
Secondary Outcome variables 
Secondary outcome variables will include: completion of the iCBT program, number of 
telephone/email based coaching interactions, quality of life, measured using the EuroQOL-5D 

 
Protocol V43 13DEC27JULY2018 
(EQ-5D), healthcare utilization, measured using the Stanford Health Care Utilization Survey, 
and subject satisfaction with the program. 
 
Background 
 
Depression after stroke 
Depression is common after stroke, occurring in up to one-third of all stroke patients.1  A recent 
American Heart Association (AHA) scientific statement on post-stroke depression highlighted 
the importance of this condition, noting that it was “under-recognized, under-investigated, and 
under-treated.”2   Individuals with depression after stroke have been shown to have lower 
functional status and lower quality of life than those without depression, irrespective of stroke 
severity, although the independent contribution of depression on outcomes is still not fully 
understood.  
 
Traditional Cognitive Behavioral Therapy 
Cognitive behavioral therapy (CBT) is an effective treatment for common mood 
disorders.  Studies have shown a beneficial effect of CBT for both the treatment and prevention 
of depression after stroke.3, 4  There is also evidence suggesting that CBT may provide a more 
durable and lasting treatment effect than pharmacotherapy with selective serotonin reuptake 
inhibitors.5    
 
Despite the promise of CBT, its role in routine clinical practice is limited.  There are significant 
barriers to widespread use of CBT.  First, access to experienced CBT practitioners is limited. 
6  Second, the time and travel requirements to complete a course of CBT, which may require 2-3 
visits per week for 10-12 weeks, are onerous for many patients.  This may be even more difficult 
for patients with mobility limitations, which are common after stroke.  Third, the cost of CBT may 
be prohibitive, particularly if providers do not accept insurance.6  Finally, patients may be 
resistant to in-person CBT because of stigma or fear of sharing deeply personal feelings with a 
therapist.    
 
Technology and CBT 
Technology provides an exciting alternative to traditional CBT.6-8  Internet-based CBT has the 
potential to lower costs and improve accessibility.  Internet-based CBT eliminates the 
challenges of finding a therapist and/or arranging transport to/from visits. There is also limited 
data to suggest that technology has the potential to reduce the stigma and fear associated with 
in-person therapy sessions, and subjects may actually be more likely to disclose symptoms 
when they believe they are interacting with a computer rather than a human.9     
 
Although internet-based CBT interventions may provide a lower intensity of treatment than 
traditional in-person CBT, they still have the potential to be effective.  An individual patient-data 
meta-analysis of 3876 subjects from 13 studies concluded that internet-based CBT is effective 
at treating depressive symptoms in general.10  Encouragingly Internet use is now common 
among older adults in the U.S. The Pew Research Center reported that in 2016 87% of 50-64 
year olds and 64% of adults 65 years or older use the Internet.11 The few studies of internet-
based CBT interventions among older adults have demonstrated their efficacy in reducing 
depressive symptoms among adults 50 years or older and among adults 45 years or older with 
cardiovascular disease (CVD) or risk factors for CVD.12, 13 14 Thus, an Internet-based CBT 
intervention among stroke survivors has the potential to reduce depressive symptoms.  
However, because patients with stroke have experienced a structural brain injury and may have 
residual cognitive and physical disability, dedicated study within the stroke population is 
necessary.   

 
Protocol V43 13DEC27JULY2018 
Joyable: Internet-based CBT with personalized coaching 
Joyable offers an iCBT program for Depression which is an 8-week, internet-based cognitive 
behavioral therapy (CBT) program for depression, developed alongside Robert DeRubeis PhD, 
a clinical psychologist with research expertise in the processes and outcomes of treatments for 
depression.  Joyable users complete brief interactive modules (42 total activities) on a 
smartphone or computer.  Most of these modules can be completed in 5-10 minutes and cover 
the core elements of CBT: psychoeducation, cognitive restructuring, and behavioral activation. 
In addition to its digital programs, users receive unlimited guidance and support from coaches 
via phone, text, and email. Coaches both respond to and proactively reach out to 
participants.  They are trained extensively in motivational interviewing, with the goal of driving 
participants toward completion of the CBT program. Joyable's depression program has shown 
symptom reduction of 40%, as measured by the PHQ-9, with satisfaction and completion rates 
that exceed face-to-face therapy (unpublished data, from Joyable). 
 
Joyable monitors the subjects’ mood through weekly assessments of the PHQ-9.  There are 
built-in escalation protocols, designed with Dr. Lanny Berman, the former President of the 
American Association for Suicidology. Joyable identifies safety risks both through its software 
and through extensive training of coaches. All coaches are trained with how to respond to at-risk 
clients, including providing emotional support and informing clients about appropriate resources 
to support them, including the National Suicide Prevention Lifeline and Crisis Text Line. In 
urgent cases, Joyable can also connect clients with a licensed professional by phone. 
 
Study Design 
 
Design: A pilot single arm clinical trial is proposed.  Adults (18 years or older) with ischemic 
stroke will be enrolled within 63 months of their event.  All subjects will be enrolled in Joyable’s 
iCBT program for Depression.   
 
Duration: The study will plan to enroll 20 subjects.  Each subject will be in the study for 90 
days.  The project will begin immediately after IRB approval.  The study is expected to take 
approximately 1 year to complete.   
 
Resources for human research protection: The clinical research section of the 
comprehensive stroke center at the University of Pennsylvania will conduct the study.  This 
team has extensive experience conducting both observational and interventional studies in 
stroke patients.  The clinical research team consists of four full time clinical research 
coordinators, 1 nurse practitioner, 3 vascular neurology fellows, 2 vascular neurology research 
fellows, and 7 vascular neurology attendings.  All members of the clinical research team will be 
required to complete CITI training and maintain up to date certification while the study is 
underway.  The research team will maintain training records, including copies of all pertinent 
certificates.  Prior to initiation of the study, the research team will have an in-service session to 
review the study protocol and procedures in detail.  While the study is underway, the research 
team will meet weekly to discuss the study, including enrollment, follow-up, and any other 
issues which may arise. Dr. Mullen will be primarily responsible for overseeing the study.  
 
Target Population: Adult patients hospitalized with ischemic stroke within the past 63 months.   
 
Inclusion Criteria: 
 
Age ≥18 years of age 
 
Acute ischemic stroke within the past 63 months 

 
Protocol V43 13DEC27JULY2018 
 
Regular access to the internet, sufficient to allow a minimum of interactions with the 
internet daily, either through a personal smartphone or web-based internet browser.   
 
Subject is willing and able to participate in internet-based cognitive behavioral therapy 
 
Can participate in the program in English 
 
Willingness and ability to sign informed consent by the patient 
 
Symptoms of mild to moderately depressed mood, defined as a score of 5-19 on the 
Patient Health Questionnaire-9 at the time of study enrollment. 
 
Exclusion Criteria 
 
Severely depressed patients, defined by a score of 20+ on the Patient Health 
Questionnare-9 are excluded 
 
Patients with an active bipolar disorder diagnosis are excluded 
 
Patients with personality disorder diagnoses are excluded 
 
Patients with active suicidality or past suicide attempts are excluded 
 
History of schizophrenia or schizoaffective disorder 
 
Active participation in face-to-face psychotherapy prior to stroke 
 
Patients with a history of dementia are excluded 
 
Patients with aphasia, defined as a score of 1 or greater on NIH Stroke Scale Item 9 are 
excluded. 
 
Patients without regular internet access through a computer, tablet or smartphone are 
excluded.   
 
Subjects requiring long-term inpatient nursing care are excluded.  For patients enrolled 
as inpatients, individuals being discharged to both home and acute rehab are 
eligible.  Individuals being discharged to a skilled nursing facility or hospice are 
excluded. 
 
Expected life expectancy less than 6 months or other inability to comply with study 
follow-up.  
 
Pregnant women and prisoners are excluded 
Vulnerable populations: Children, pregnant women, fetuses, neonates, and prisoners are not 
included in this research study.   
Sample Size: 20 subjects will be enrolled. 
 
Accrual:  The comprehensive stroke center at the Hospital of the University of Pennsylvania 
(HUP) is a tertiary referral center for acute ischemic stroke, with annual case volumes of 
approximately 600 strokes per year on the inpatient stroke service.  Additionally, the stroke 
team sees patients in the outpatient clinic both in follow-up from their acute hospitalization and 
in consultation to provide second opinions for patients treated elsewhere.  Due to the broad 
inclusion criteria of this study, it is expected that many of the patients seen, both inpatient and 
outpatient, will be eligible for participation in this study.  We expect that we will be able to enroll 
1-2 patients per week and will complete enrollment within 6 months.   
 
Recruitment: A stroke physician evaluates all patients with acute ischemic stroke who present 
to HUP.  All stroke team physicians will be trained investigators in this study, and they will 
screen patients for eligibility during routine clinical care.  Study physicians will also screen for 
potentially eligible subjects during outpatient clinic sessions.  All eligible subjects will be 
informed of the study, and if they are interested in participation, a study physician will obtain 
informed consent. The original signed consent form will be kept in the study binder. A copy of 

 
Protocol V43 13DEC27JULY2018 
the signed consent form will be given to the patient and another copy will be placed in the 
medical record.   
 
Procedures 
Consent: A member of the study team will approach eligible patients.  The consent form will be 
described in plain language.  The patient will be given a hard copy of the consent form for their 
reference.  Written informed consent will be obtained.  Judgements about capacity to provide 
informed consent will be made by the physicians caring for the patient and the person obtaining 
informed consent.  All patients with acute ischemic stroke received detailed neurologic 
assessments, including assessments of cognition, language function, neglect/anosognosia, and 
other domains of neurologic function.  Additionally, during the consent process the subject will 
be asked open-ended questions about the study such as: “Would you explain to me what you 
think we are asking you to do?” and “what are the possible benefits and risks to you of 
participating in this study?”  If either the clinical team feels that the patient cannot provide 
informed consent, or the patient’s responses to these open-ended questions fail to demonstrate 
sufficient comprehension to provide informed consent, in the judgment of the investigator, the 
patient will be excluded from participation.  The subject will have the ability to withdraw consent 
at any time.  
 
Study Procedures:  
 
Baseline 
After consent is obtained, the Patient Health Questionnaire-9 (PHQ-9)15 will be administered to 
the subject.  This is a simple, 9-item survey which has been validated to identify depression 
after stroke.  Patients who score between 5-19 inclusive will be enrolled in the study.  Subjects 
who score 0-4 or 20+ will receive education about post-stroke mood disorders and local 
psychiatry/psychology resources, including the contact information for regional crisis centers, 
but will not be enrolled.  Subjects who screen 20+ will have their attending physician notified so 
that appropriate referrals or treatments can be initiated by the clinical team.   
 
For patients who are enrolled, basic demographic and clinical information will be collected 
including: age, sex, race/ethnicity, past medical history (including history of hypertension, 
hyperlipidemia, coronary artery disease, chronic kidney disease, prior history of TIA/Stroke, 
prior history of anxiety, depression, or PTSD, other medical history), educational attainment, 
insurance status, marital status, number of people living in the home, medication history 
(current/prior use of an antidepressant medication), current/prior participation in psychotherapy 
or counseling for mental health problems, tobacco history (current smoker, former smoker, 
never smoker), alcohol use history (current alcohol use yes/no and if yes, number of drinks per 
week), stroke location, stroke mechanism (large vessel atherosclerosis, small vessel disease, 
cardioembolism, other, cryptogenic), discharge disposition (home, acute rehab).   
 
Additional assessments will include the NIHSS, a structured neurologic examination used to 
quantify neurologic deficits,16, 17, modified Rankin Scale,18 the Patient Health Questionnaire-9 
(PHQ-9) to assess mood,15 and the abbreviated Duke Social Support Index.19  We will also ask 
the subject a series of questions regarding availability of internet and mobile device usage, 
including how they  interact with the internet and frequency of internet use (See attached 
appendix).   
 
After baseline data collection, the subjects will be enrolled in Joyable’s iCBT program.  For 
subjects who would like to participate in the program using their smartphone, the CBT 
application will be installed on their device and they will be encouraged to complete the initial 

 
Protocol V43 13DEC27JULY2018 
evaluation and activities at the time of enrollment.  Subjects without their own devicewill be 
enrolled via a study specific tablet using the web-interface.  Subjects will be given their login 
information and information on how to access the program via the internet and install the 
program on their mobile device.  Subjects will be asked to complete the initial evaluation and 
CBT activities at the time of enrollment.   
 
Joyable is a commercially available 8-week program that consists of 5-6 online activities per 
week, for a total of 42 activities.  Most activities can be completed within approximately 5-10 
minutes.  Activities cover the core elements of CBT: psychoeducation, cognitive restructuring, 
and behavioral activation. In addition to the digital program, as a part of the Joyable product, all 
participants will be assigned a coach.  The role of the coach is to provide accountability, 
motivation, emotional support, and guidance, leading clients to get the most out of the iCBT 
program. They provide this support through a combination of phone, text, and email interactions 
determined by the client.  Joyable coaching is defined by 3 pillars: Motivational Interviewing 
(MI), Program Knowledge, and Client Experience.  All coaches are trained to competency in MI, 
an evidence-based method for structuring conversations to harness a person’s intrinsic 
motivation to change.  MI has been shown to increase engagement and improve client 
outcomes.  Coaches attend a rigorous 1-month training course, biweekly booster sessions, and 
submit tapes of client communications until they reach competency.  In addition to MI, coaches 
are trained in the iCBT program and how to support clients with obstacles that may arise and 
effectively deliver program knowledge to drive client success.  At the time of study enrollment, 
we will assist the subject in scheduling their first contact with their assigned coach.   
 
 
72 Hour Telephone Encounter 
Subjects will be contacted by the study team in person or by telephone 72+/- 24 hours after 
enrollment to troubleshoot any technical difficulties accessing the Joyable program.  
 
30 Day Telephone Encounter 
Subjects will be contacted by the study team phone or in person at 30 days +/-7 days after 
enrollment to assess technical difficulties using the Joyable program, functional status using the 
modified Rankin scale, and quality of life using the Euroqol EQ-5D.   
 
90 Day In-person Visit 
Subjects will be seen by the study team 90 days +/- 14 days after enrollment to assess their 
neurologic function using the NIHSS, mood using the PHQ-9, functional status using the 
modified Rankin Scale, Quality of life using the Euroqol EQ-5D,20, 21 healthcare utilization using 
the Stanford Health Utilization survey,22 whether any other treatment for mental health problems 
was received (including medication and psychotherapy) and perceived utility of Joyable iCBT for 
depression as well as perceived barriers to successful use of internet-based CBT.   
 
 
 
 
 
 
 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
Table 1. Study measures and timing of assessment 
  
Baseline 
72 hr 
Call 
30 day 
call 
90 day 
visit 
Demographics 
X 
Stroke information 
X 
SSRI Use 
X 
 
X 
X 
Assess for technical problems 
X 
X 
NIHSS 
X 
X 
mRS 
X 
X 
X 
EQ-5D 
X 
X 
X 
SHU 
X 
PHQ-9 
X 
X 
Semi-Quantitative assessment of perceptions about 
Internet-based CBT 
X 
NIHSS=National Institute of Health Stroke Scale, EQ-5D=Euro-Qol 5D, SHU=Stanford Health 
Utilization survey, PHQ-9=Patient Health Questionnaire 9,  
 
Analysis Plan 
 
The baseline demographic variables of the study population will be summarized using means, 
medians, and proportions as appropriate.  For each subject, we will calculate the total amount of 
time spent interacting with the Joyable program and the total number of Joyable activities that 
the patient successfully completed.  We will then calculate averages across the study 
population.  These metrics will provide important information on the average “dose” of CBT 
received.  In an exploratory analysis we will look for relationships between baseline clinical and 
demographic factors and number of activities completed. 
 
We will calculate the average PHQ-9 score at enrollment and 90 days. We will compare the 
PHQ-9 score from enrollment to day 90.  The statistical power of this test is uncertain.  In Table 
2 we present estimated study power (with α=0.05) across a range of assumptions about both 
the change in PHQ-9 over time and the standard deviation of the difference in PHQ-9 over time.  
These calculations show that although this is a small pilot study, we have >80% power to detect 
a difference in PHQ-9 of 3 or more points across a range of assumptions. The PHQ-9 will also 
be administered to subjects weekly via through the Joyable program. We will examine whether 
there are significant changes in score over time using repeated measures analysis (generalized 
estimating equations, GEE) with PHQ-9 score as the dependent variable and week as the 
independent variable. 
 
In an exploratory analysis, we will divide patients into two groups based on PHQ-9 at study 
completion (high depression symptoms, defined as median or above and low depression 

 
Protocol V43 13DEC27JULY2018 
symptoms, defined as below the median score).  Healthcare outcomes, including modified 
Rankin scale, health related quality of life, and healthcare utilization will be compared across 
groups. We hypothesize that patients with high depression symptoms will have worse functional 
outcome, lower quality of life, and higher healthcare utilization.  We will also divide patients into 
groups based on their participation in the Joyable program and compare outcomes (e.g., PHQ-9 
score, quality of life, health utilization) between subjects who showed high engagement in the 
program and those who showed low engagement.   
 
Table 2. Statistical Power for single sample paired t-test 
 
 
 
Data Confidentiality 
Internet-based files will only be made available to personnel involved in the study through the 
use of access privileges and passwords.  Paper-based records will be kept in a locked, secure 
location and only accessible to study personnel.  Prior to access to any study-related 
information, personnel will be required to sign statements agreeing to protect the security and 
confidentiality of identifiable information. Whenever feasible, identifiers will be removed from 
study-related information.   
 
No clinical information obtained by the research team will be sent to Joyable.  De-identified data 
from Joyable will be sent to the research team, which will include the number of Joyable 
activities completed by the subject, the number coaching interactions, and results of Joyable 
administered PHQ-9 and satisfaction assessments.  This data will be organized by subject 
identification number, which can be used to link to the data collected by the research team.  The 
research team will maintain a password protected file on a secured computer at the University 
of Pennsylvania which will link subject identification number to identifying information for each 
subject (name, medical record number, date of birth).  Access to this file at the University of 
Pennsylvania will be limited to the PI and the study research coordinator.  A Microsoft Excel 
document will be created which will include subject name, date of birth, and study identifier.  
This document will be uploaded to Penn+Box.  The study team at Joyable will be given access 
to the file via Penn+Box.  They will use this information to link the Joyable data elements 
described above to each subject.  Joyable will then upload a Microsoft Excel file containing this 
data and subject identifier to the study Penn+Box, where it will be downloaded by the research 
team.       
 
Patients who enroll in the study will all participating in Joyable’s iCBT Program for Depression.  
During enrollment in the study, patients will create an account with Joyable.  As a part of this 
process, subjects register with Joyable using the same process as they currently use for their 
commercially available program.  Registration requires the subject to submit the following PHI: 
name, date of birth, gender, and email address.  Access to PHI will be limited to those who need 
it.  This may include the individual coach who is assigned to each subject, coach managers who 
have access to subject data for the coaches that report to them, Joyable’s analytic team which 
1
2
3
4
5
2
61%
99%
100%
100%
100%
3
32%
85%
99%
100%
100%
4
20%
61%
92%
99%
100%
5
15%
43%
77%
95%
99%
6
12%
32%
61%
85%
96%
Difference in PHQ-9 Pre/Post Treatment
SD of the 
Difference

 
Protocol V43 13DEC27JULY2018 
has access to data for the purpose of aggregating and sharing back results to the research 
team, and a small number of engineers who can access data in order to troubleshoot bugs in 
the software.  Subject interactions with Joyable will be governed by Joyable’s existing Privacy 
Policy (see https://joyable.com/privacy) and terms of use (see https://joyable.com/terms).  
Additionally, subjects will be given the option to opt in or out of email and text based coaching 
services.  Joyable encrypts the transmission of personal information or uses Secure Socket 
Layer technology when possible.  Joyable does not encrypt the transmission of text or email 
communication.  This is made clear to the subject at the time of opt-in: 
An important note on privacy: 
Your privacy is important to us. Text messages and emails from your coach are not encrypted while in 
transit. To reduce the chance that your information is seen by the wrong recipient, we suggest you 
enable the highest security measures on your personal device (pass codes, strong passwords, 2 step 
authentication, etc). Taking these precautions will not eliminate all risks associated with communications 
sent in unencrypted text messages or email. 
By checking the box above, you are agreeing to the risks associated with unencrypted text and email and 
consent to communicating with your Joyable coach through text and email, or Skype and email if you live 
outside of the United States. 
Joyable meets or exceeds all federal requirements for protecting personal health information 
(PHI) of individuals under the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). All Joyable services operate behind a virtual private cloud with dedicated instances, 
and Joyable encrypts all PHI both in transit and at rest. Access to sensitive information is limited 
to Joyable employees directly involved with supporting any given client. Joyable participates in 
regular security assessments of both its processes and technology. 
 
Subject Confidentiality 
 
All data recorded will be kept in a spreadsheet that is managed by a member of the study team. 
This excel spreadsheet will be password protected and we will ensure that the access to this 
database is secured. Subjects will be coded using a study identification number that is detached 
from the patient's name and recorded into a separate excel spreadsheet.  All study related 
paper files will be stored in a locked cabinet and accessible only by research staff.  No 
published or presented materials will identify subjects by names, initials, or other means. The 
data set will be password protected and only accessible to the study team.  If needed for future 
research this dataset will not be used without prior IRB approval. 
 
Subject Privacy and Protected Health Information/Data Protection 
 
The following protected health information (PHI) will be collected: 
 
·    
Name 
·    
Date of birth 
·    
Medical record number 
 
This data will be recorded and secured as detailed above.   

 
Protocol V43 13DEC27JULY2018 
Joyable meets or exceeds all federal requirements for protecting personal health information 
(PHI) of individuals under the Health Insurance Portability and Accountability Act of 1996 
(HIPAA). All Joyable services operate behind a virtual private cloud with dedicated instances, 
and Joyable encrypts all PHI both in transit and at rest. Access to sensitive information is limited 
to Joyable employees directly involved with supporting any given client. Joyable participates in 
regular security assessments of both its processes and technology.   
 
References: 
 
1. 
Hackett ML, Yapa C, Parag V, Anderson CS. Frequency of depression after stroke: A systematic 
review of observational studies. Stroke; a journal of cerebral circulation. 2005;36:1330-1340 
2. 
Towfighi A, Ovbiagele B, El Husseini N, Hackett ML, Jorge RE, Kissela BM, et al. Poststroke 
depression: A scientific statement for healthcare professionals from the american heart 
association/american stroke association. Stroke; a journal of cerebral circulation. 2017;48:e30-
e43 
3. 
Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-
solving therapy for prevention of poststroke depression: A randomized controlled trial. JAMA. 
2008;299:2391-2400 
4. 
Mitchell PH, Veith RC, Becker KJ, Buzaitis A, Cain KC, Fruin M, et al. Brief psychosocial-behavioral 
intervention with antidepressant reduces poststroke depression significantly more than usual 
care with antidepressant: Living well with stroke: Randomized, controlled trial. Stroke; a journal 
of cerebral circulation. 2009;40:3073-3078 
5. 
Mikami K, Jorge RE, Moser DJ, Arndt S, Jang M, Solodkin A, et al. Increased frequency of first-
episode poststroke depression after discontinuation of escitalopram. Stroke; a journal of 
cerebral circulation. 2011;42:3281-3283 
6. 
Webb CA, Rosso IM, Rauch SL. Internet-based cognitive-behavioral therapy for depression: 
Current progress and future directions. Harv Rev Psychiatry. 2017;25:114-122 
7. 
Sztein DM, Koransky CE, Fegan L, Himelhoch S. Efficacy of cognitive behavioural therapy 
delivered over the internet for depressive symptoms: A systematic review and meta-analysis. J 
Telemed Telecare. 2017:1357633X17717402 
8. 
Hofman J, Pollitt A, Broeks M, Stewart K, van Stolk C. Review of computerised cognitive 
behavioral therapies: Products and outcomes for people with mentla health needs. Rand Health 
Q. 2016;6 
9. 
Lucas G, Gratch J, King A, Morency L-P. It's only a computer: Virtual humans increase willingness 
to disclose. Computers in Human Behavior. 2014;37:94-100 
10. 
Karyotaki E, Riper H, Twisk J, Hoogendoorn A, Kleiboer A, Mira A, et al. Efficacy of self-guided 
internet-based cognitive behavioral therapy in the treatment of depressive symptoms: A meta-
analysis of individual participant data. JAMA Psychiatry. 2017;74:351-359 
11. 
Pew Research Center. Internet/broadband fact sheet. January 2017; Accessed January 17th, 2018 
12. 
Spek V, Nyklicek I, Smits N, Cuijpers P, Riper H, Keyzer J, et al. Internet-based cognitive 
behavioural therapy for subthreshold depression in people over 50 years old: A randomized 
controlled clinical trial. Psychol Med. 2007;37:1797-1806 
13. 
Spek V, Cuijpers P, Nyklicek I, Smits N, Riper H, Keyzer J, et al. One-year follow-up results of a 
randomized controlled clinical trial on internet-based cognitive behavioural therapy for 
subthreshold depression in people over 50 years. Psychol Med. 2008;38:635-639 

 
Protocol V43 13DEC27JULY2018 
14. 
Glozier N, Christensen H, Naismith S, Cockayne N, Donkin L, Neal B, et al. Internet-delivered 
cognitive behavioural therapy for adults with mild to moderate depression and high 
cardiovascular disease risks: A randomised attention-controlled trial. PloS one. 2013;8:e59139 
15. 
de Man-van Ginkel JM, Hafsteinsdottir T, Lindeman E, Burger H, Grobbee D, Schuurmans M. An 
efficient way to detect poststroke depression by subsequent administration of a 9-item and a 2-
item patient health questionnaire. Stroke; a journal of cerebral circulation. 2012;43:854-856 
16. 
Muir KW, Weir CJ, Murray GD, Povey C, Lees KR. Comparison of neurological scales and scoring 
systems for acute stroke prognosis. Stroke; a journal of cerebral circulation. 1996;27:1817-1820 
17. 
Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine S, et al. Improved reliability of the nih 
stroke scale using video training. Ninds tpa stroke study group. Stroke; a journal of cerebral 
circulation. 1994;25:2220-2226 
18. 
Wilson JTL, Hareendran A, Hendry A, Potter J, Bone I, Muir KW. Reliability of the modified rankin 
scale across multiple raters: Benefits of a structured interview. Stroke; a journal of cerebral 
circulation. 2005;36:777-781 
19. 
Koenig HG, Westlund RE, George LK, Hughes DC, Blazer DG, Hybels C. Abbreviating the duke 
social support index for use in chronically ill elderly individuals. Psychosomatics. 1993;34:61-69 
20. 
Dorman PJ, Waddell F, Slattery J, Dennis M, Sandercock P. Is the euroqol a valid measure of 
health-related quality of life after stroke? Stroke; a journal of cerebral circulation. 1997;28:1876-
1882 
21. 
Pinto EB, Maso I, Vilela RN, Santos LC, Oliveira-Filho J. Validation of the euroqol quality of life 
questionnaire on stroke victims. Arq Neuropsiquiatr. 2011;69:320-323 
22. 
Ritter PL, Stewart AL, Kaymaz H, Sobel DS, Block DA, Lorig KR. Self-reports of health care 
utilization compared to provider records. Journal of clinical epidemiology. 2001;54:136-141 
 
 

 
Protocol V43 13DEC27JULY2018 
Appendix 
1. Screening PHQ-9 
2. Baseline CRF 
3. 72 Hour Call CRF 
4. 30 Day Call CRF 
5. 90 Day Visit CRF 
 
 
 

 
Protocol V43 13DEC27JULY2018 
1. Screening PHQ-9 
 
 
 
NOTE: SUBJECTS MUST SCORE BETWEEN 5-19, INCLUSIVE, TO BE ENROLLED 

 
Protocol V43 13DEC27JULY2018 
2.  Baseline Study CRF (FOR ENROLLED PATIENTS ONLY): 
 
1. Subject ID #:  ___ ___ ___ 
 
2. Enrolling Investigator:  ____________________ 
 
3. Age: __ __ __ 
  
4. Sex: Male 
    Female
 
 
5. Race:             (Check one)  
Caucasian 
 
 
African American 
 
Asian    
 
 
American Indian  
    or Alaskan Native 
 
Other    
 
 
 
6. Ethnicity: 
 Not Hispanic/Latino 
 
 Hispanic/Latino 
 
7. Educational attainment 
 Less than 9th grade 
 9-11th grade (includes 12th grade with no diploma) 
 High school graduate/GED or equivalent 
 Some college or AA degree 
 College graduate or above 
 Refused 
 
8. Health insurance (select all that apply) 
 Medicare 
 
 Medicaid 
 Veteran’s Health Administration 
 Private 
 Other 
 No insurance 
 
9. Symptom onset:  
 Witnessed onset  
 Last known normal 
 
        Date: __  __  /__  __ / 2 0 __  __ 
Time __ __ : __ ___   
                                month            day                 
 
hr 
hr         min         min 
  
10. Medical History/Risk Factors: 
       (Check all that apply) 
a. Hypertension 
 
 
No 
 Yes 
   
b. Diabetes      
 
 
No 
 Yes 
  
c. CAD  
  
 
 
No 
 Yes 
  
d. Atrial Fibrillation  
 
 
No 
 Yes 
 
e. CHF  
 
 
 
No 
 Yes 
   
f.  Prior TIA 
 
 
 
No 
 Yes 
 
g. Prior Stroke  
 
 
No 
 Yes 
  
h. Prior Anxiety  
 
 
No 
 Yes 
 

 
Protocol V43 13DEC27JULY2018 
i.  Prior Major Depressive Episode 
No 
 Yes 
 
j.  Prior PTSD  
 
 
 No 
 Yes 
 
l.  Other (Please List):  
 
 
  
 
11. Tobacco 
 
Never  
 
 
 Former 
  
 
Current 
     
 
12. Current Alcohol  
 
No  
 Yes 
 
 
If Yes, number of drinks per week: __ __ 
 
13. Marital Status: 
 
 
 Currently Married  
 Divorced 
 Widowed 
 Never Married  
 
14. Number of People that you currently live with: __ __  
 
15. Were you working prior to this stroke? 
 
No 
   
Part Time 
   
Full Time 
 
 
16. Prior to the stroke, were you ever on a prescription medication for anxiety, 
depression, or PTSD? 
 
No 
 Yes 
 
 
If Yes, please list: ___________________________ 
17. Prior to the stroke did you ever participate in psychotherapy or counseling with a 
therapist? 
 
No 
 Yes 
 
 
 
18. Stroke Location (check all that apply): 
 
 Right hemisphere  
 Left hemisphere  
 Posterior circulation 
 Cortical 
 Subcortical 
 
 
19. Vascular Territory of Stroke (check all that apply) 
  
 ACA  

 
Protocol V43 13DEC27JULY2018 
 MCA  
 PCA 
 ICA 
 Vertebral/Basilar 
 
20. Stroke Etiology:  
Free Text Description: ________________________ 
 
         Stroke etiology at discharge (TOAST Criteria): 
       
 
 
 
 
Large Vessel Stenosis 
 
 
Lacunar 
 
 
 
 
Cryptogenic 
 
 
 
Other: ________________ 
 
 
21. Discharge Disposition from Acute Hospitalization 
      Home  
 
 
 
 
 
      Acute Rehabilitation facility
 
 
22.  Is the subject currently on pharmacotherapy for depression? (Review current 
medications) 
 
 No 
 Yes 
 
If Yes, please list and select category from below: ___________________________ 
 
 
 SSRI 
 
 SNRI 
 
 TCA 
 
 Other 
  
 
 

 
Protocol V43 13DEC27JULY2018 
23.  Abbreviated Duke Social Support Scale 
 
 
 
  
 
 
       
 
       
Question
Number of family members within 1 hour that you can depend on or feel close 
to?
None
(1)
1-2 people
(2)
More than 2 people
(3)
Number of times in the past week in which you spent time with someone not 
living with you?
None
(1)
1-2 times
(2)
More than 2 times
(3)
Number of times in the past week that you talked with friends/relatives on the 
telephone?
0-1 times
(1)
2-5 times
(2)
More than 5 times
(3)
Number of times in the past week that you attended meetings of clubs, 
religious groups, or other groups that you belong to (other than at work)?
0-1 times
(1)
2-5 times
(2)
More than 5 times
(3)
Do family and friends understand you?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
Do you feel useful to family and friends?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
Do you know what is happening with family and friends?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
Do you feel listened to by family and friends?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
Do you feel you have a definite role in family and among friends?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
Can you talk about your deepest problem?
Hardly ever
(1)
Some of the time
(2)
Most of the time
(3)
How satisfied are you with relationships with family and friends?
Very dissatisfied
(1)
Somewhat 
dissatisfied
(2)
Satisfied
(3)
Answer

 
Protocol V43 13DEC27JULY2018 
24. NIHSS  
 
Date: __  __  /__  __ / 2 0 __  __ 
 
  
                month            day                year  
 
 
1a. Level of consciousness 
 
0   alert 
 
1   drowsy 
 
2   stuporous 
 
3   coma 
1b. LOC questions (month, age) 
 
0   both correct 
 
1   one correct 
 
2   incorrect 
1c. LOC commands (close eyes, make a fist) 
 
0   both correct 
 
1   one correct 
 
2   incorrect  
2. Best gaze 
 
0   normal 
 
1   partial gaze palsy 
 
2   forced deviation 
3. Visual fields 
 
0   no visual loss 
 
1   partial hemianopia 
 
2   complete hemianopia 
 
3   bilateral hemianopia 
4. Facial palsy 
  
0   normal 
 
1   minor 
 
2   partial 
3 complete 
5.  Motor arm 
  a. Left arm 
 
0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
  b. Right arm 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
6. Motor leg 
  a. Left leg 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z  amputation/joint fusion 
  b. Right leg 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
7.  Limb ataxia (FNF, HKS) 
 
0   absent 
  
1   present in one limb 
 
2   present in 2 limbs 
8.  Sensation (pin) 
 
0   normal 
 
1   partial loss 
 
2   severe loss 
9.  Best language 
 
0   no aphasia 
 
1   mild-mod aphasia 
 
2   severe aphasia 
 
3   mute 
 
10.  Dysarthria 
 
0   none   
 
1   mild-mod 
 
2   near to unintelligible 
 
       or worse/mute 
 
Z   intubated/barrier 
11.  Extinction and inattention 
 
0   no neglect 
 
1   partial neglect 
1. complete neglect 
 
 
 
Total Score: ___________ 

 
Protocol V43 13DEC27JULY2018 
25. Modified Rankin Scale 
 
26. Euro-QOL-5D 
Please indicate which statements best describe your own health state today. 
Mobility 
 
____I have no problems in walking about 
____I have some problems in walking about 
____I am confined to bed 
 
Self-Care 
____I have no problems with self-care 
____I have some problems washing or dressing myself 
____I am unable to wash or dress myself 
 
Usual Activities (e.g. work, study, housework, family or leisure activities) 
____I have no problems with performing my usual activities 
____I have some problems with performing my usual activities 
____I am unable to perform my usual activities 
 
Pain/Discomfort 
____I have no pain or discomfort 
____I have moderate pain or discomfort 
____I have extreme pain or discomfort 
Anxiety/Depression 
____I am not anxious or depressed 

 
Protocol V43 13DEC27JULY2018 
____I am moderately anxious or depressed 
____I am extremely anxious or depressed 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
27. Internet/Mobile Device Usage 
 
How do you access the internet?  (Select all that apply): 
 
 
 Computer 
 
 
 Tablet 
 
 
 Smart Phone 
 
What is your preferred method of internet access? (Select 1): 
 Computer 
 
 
 Tablet 
 
 
 Smart Phone 
 
Where do you typically access the internet? (Select all that apply): 
 
 
 Work 
 
 
 Home 
 
 Friend/Family member’s home 
 Public access point (i.e. Library, coffee shop, etc) 
 Other:  _______________ 
 
Where is your preferred location to access the internet? (Select 1): 
 Work 
 
 
 Home 
 
 Friend/Family member’s home 
 Public access point (i.e. Library, coffee shop, etc) 
 Other:  _______________ 
 
How often do you typically access the internet? (Select 1): 
 
 
 More than once a day 
 
 
 Once a day 
 
 
 Every couple of days 
 
 
 Once a week or less 
 
How much time per day do you typically spend on the internet? 
 
 
 <30 minutes 
 
 
 30-59 minutes 
 
 
 60-119 minutes 
 
 
 120+ minutes 
 
If you have a smartphone or tablet, do you use “Apps?”  
 
 
 No 
 
 
 Yes 
 
 
 Not Applicable - do not own a smartphone or tablet 
 
If you have a smartphone or tablet, do you ever have problems using it (e.g. 
typing, reading, using the touchscreen)? 
 No 
 
 
 Yes 
 
 
 Not Applicable - do not own a smartphone or tablet 
 
Have you ever used an “App,” website, or online platform to improve your health 
before? 

 
Protocol V43 13DEC27JULY2018 
 
 
 No 
 
 
 Yes 
 
If yes, how would you rate the experience? 
 
 
 Not helpful 
 
 
 Somewhat helpful 
 
 
 Very helpful 
 
 
 Not applicable 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
 
 
3. 72-Hour Phone Call 
 
Date: __ __ / __ __ / __ __ __ __             
                  dayday                 year                 year  
 
Does the patient have difficulty accessing  Joyable? No 0
 Yes 1
 
If yes, please specify what the problem was and how it was addressed:  
 
______________________________________________________________________
______________________________________________________________________ 
 
Name of the person who completed 48 hour follow up: 
________________________________ 
 
Signature: ________________________________ 
 
Date: __ __ / __ __ / __ __ __ __             
 month 
    day                 year  
 
 
4. 30-Day Phone Call 
 
Date: __ __ / __ __ / __ __ __ __             
                  dayday                 year                 year  
 
Does the patient have difficulty accessing  Joyable? No 0
 Yes 1
 
If yes, please specify what the problem was and how it was addressed:  
 
______________________________________________________________________
______________________________________________________________________ 
 
Name of the person who completed 48 hour follow up: 
________________________________ 
 
Signature: ________________________________ 
 
Date: __ __ / __ __ / __ __ __ __             
 month 
    day                 year  
 
1.   Is the subject currently on pharmacotherapy for depression? (Review current    
      medications) 
 
 No 
 Yes 
 
If Yes, please list and select category from below: ______________________ 

 
Protocol V43 13DEC27JULY2018 
 
 
 
 SSRI 
 
 
 SNRI 
 
 
 TCA 
 
 
 Other 
 
 
2.  Modified Rankin Scale 
 
2. Euro-QOL-5D 
Please indicate which statements best describe your own health state today. 
Mobility 
 
____I have no problems in walking about 
____I have some problems in walking about 
____I am confined to bed 
 
Self-Care 
____I have no problems with self-care 
____I have some problems washing or dressing myself 
____I am unable to wash or dress myself 
 
Usual Activities (e.g. work, study, housework, family or leisure activities) 
____I have no problems with performing my usual activities 
____I have some problems with performing my usual activities 

 
Protocol V43 13DEC27JULY2018 
____I am unable to perform my usual activities 
 
Pain/Discomfort 
____I have no pain or discomfort 
____I have moderate pain or discomfort 
____I have extreme pain or discomfort 
Anxiety/Depression 
____I am not anxious or depressed 
____I am moderately anxious or depressed 
____I am extremely anxious or depressed 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
 
 
 
5. 90 Day Visit 
 
 
Date: __  __  /__  __ / 2 0 __  __ 
 
  
                month            day                year  
 
 
 
1.  Is the subject currently on medications for depression? (Review current  
     medications) 
 
 No 
 Yes 
 
If Yes, please list and select category from below: ___________________________ 
 
 
 
 SSRI 
 
 
 SNRI 
 
 
 TCA 
 
 
 Other 
 
 
 
2. Since enrolling in this study did you participate in psychotherapy or counseling  
with a therapist OTHER THAN what was provided through Joyable? 
 
 No 
 Yes 
 
 
3. Are you currently  working? 
 No 
  
Part Time 
  
Full Time 
 
  
 
 

 
Protocol V43 13DEC27JULY2018 
 
3.  NIHSS 
 
1a. Level of consciousness 
 
0   alert 
 
1   drowsy 
 
2   stuporous 
 
3   coma 
1b. LOC questions (month, age) 
 
0   both correct 
 
1   one correct 
 
2   incorrect 
1c. LOC commands (close eyes, make a fist) 
 
0   both correct 
 
1   one correct 
 
2   incorrect  
2. Best gaze 
 
0   normal 
 
1   partial gaze palsy 
 
2   forced deviation 
3. Visual fields 
 
0   no visual loss 
 
1   partial hemianopia 
 
2   complete hemianopia 
 
3   bilateral hemianopia 
4. Facial palsy 
  
0   normal 
 
1   minor 
 
2   partial 
4 complete 
5.  Motor arm 
  a. Left arm 
 
0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
  b. Right arm 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
6. Motor leg 
  a. Left leg 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z  amputation/joint fusion 
  b. Right leg 
            0   no drift 
 
1   drift 
 
2   can't resist gravity 
 
3   no effort against gravity 
 
4   no movement 
 
Z   amputation/joint fusion 
7.  Limb ataxia (FNF, HKS) 
 
0   absent 
  
1   present in one limb 
 
2   present in 2 limbs 
8.  Sensation (pin) 
 
0   normal 
 
1   partial loss 
 
2   severe loss 
9.  Best language 
 
0   no aphasia 
 
1   mild-mod aphasia 
 
2   severe aphasia 
 
3   mute 
 
10.  Dysarthria 
 
0   none   
 
1   mild-mod 
 
2   near to unintelligible 
 
       or worse/mute 
 
Z   intubated/barrier 
11.  Extinction and inattention 
 
0   no neglect 
 
1   partial neglect 
 
complete neglect 
 
 
 
Total Score: ___________ 
 
 
 

 
Protocol V43 13DEC27JULY2018 
 
3. Modified Rankin Scale 
 
4. Euro-QOL-5D 
Please indicate which statements best describe your own health state today. 
Mobility 
 
____I have no problems in walking about 
____I have some problems in walking about 
____I am confined to bed 
 
Self-Care 
____I have no problems with self-care 
____I have some problems washing or dressing myself 
____I am unable to wash or dress myself 
 
Usual Activities (e.g. work, study, housework, family or leisure activities) 
____I have no problems with performing my usual activities 
____I have some problems with performing my usual activities 
____I am unable to perform my usual activities 
 
Pain/Discomfort 
____I have no pain or discomfort 
____I have moderate pain or discomfort 
____I have extreme pain or discomfort 
Anxiety/Depression 

 
Protocol V43 13DEC27JULY2018 
____I am not anxious or depressed 
____I am moderately anxious or depressed 
____I am extremely anxious or depressed 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
 
5. Healthcare Utilization 
Since study enrollment: 
How many times did you visit a physician? Do not include visits while 
in the hospital or to a hospital emergency room. Fill in with “0” or 
another number. 
______ 
times 
How many times did you go to a hospital emergency room? Fill in with 
“0” or another number. 
______ 
times 
How many different times did you stay in a hospital overnight or 
longer in the past 6 months? Fill in with “0” or another number. 
______ 
times 
How may total nights did you spend in the hospital? Fill in with “0” or 
another number. 
______ 
nights 
 
 
 

 
Protocol V43 13DEC27JULY2018 
6. PHQ-9 
 
 
 
 

 
Protocol V43 13DEC27JULY2018 
7. Semi-Quantitative Assessment of iCBT Program: 
 
 
 
 
 
 
 
 
Extremely Difficult
Difficult
Neutral
Easy
Extremely Easy
1
2
3
4
5
Extremely 
Dissatisfied
Dissatisified
Neutral
Satisfied
Extremely 
Satisfied
1
2
3
4
5
Extremely 
Dissatisfied
Dissatisified
Neutral
Satisfied
Extremely 
Satisfied
1
2
3
4
5
Not Helpful
Slightly Helpful
Moderately 
Helpful
Very Helpful
Extremely Helpful
1
2
3
4
5
[  ] Yes
[  ] No
Why/Why Not?
Would you recommend the program to other people 
with stroke?
Was Joyable helpful with your home and/or work life?
How satisfied were you with Joyable activities?
What did you like best about the Joyable program?
What about the Joyable program could be improved?
How satisfied were you with your Joyable coach?
Was joyable easy to use?