Mobile Cognitive Behavior Therapy Targeting Anxiety Disorders
Phase: NA
Conditions: Anxiety Disorders and Symptoms
Sponsor: Weill Medical College of Cornell University

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mobile Cognitive Behavior Therapy Targeting Anxiety Disorders 
 
Weill Cornell Medicine IRB 1803019086 
NCT05130281 
9/18/2023 
 
 

 
 
 
 
 
TITLE: Mobile Cognitive Behavior Therapy Targeting Anxiety Disorders 
 
IRB Protocol #: 1803019086 
IND/IDE # (if applicable): 
Version Date: 9/18/2023 
 
Principal Investigator: 
Faith Gunning 
Weill Cornell Medicine 
212-746-4666 
fgd2002@med.cornell.edu 
Co-Investigators: 
Arielle Linsky 
Weill Cornell Medicine  
arl2006@med.cornell.edu 
 
Monika Dargis  
Weill Cornell Medicine 
Mod9053@med.cornell.edu 
 
Jennifer Bress 
Weill Cornell Medicine  
914-997-8683 
Jeb2061@med.cornell.edu 
 
Irena Ilieva 
Weill Cornell Medicine  
212-821-0778 
Iri9005@med.cornell.edu 
 
Maddy Schier 
Weill Cornell Medicine  
(646) 289-5271 EXT. 720  
Mas4019@med.cornell.edu 
 
Francis Lee 
Weill Cornell Medicine  
212 746 5403 
fslee@med.cornell.edu 
 
 

 
 
 
Shannon Bennett  
Weill Cornell Medicine  
646 962 2820 
smb9017@med.cornell.edu 
 
Avital Falk 
Weill Cornell Medicine  
646 543 2079 
avf2003@med.cornell.edu 
 
Aliayah Himelfarb 
Weill Cornell Medicine 
alh4023@med.cornell.edu 
 
Zareen Mir 
Weill Cornell Medicine 
Zam4005@med.cornell.edu 
 
Abhishek Jaywant 
Weill Cornell Medicine 
Abj2006@med.cornell.edu 
 
Ben Giber 
Weill Cornell Medicine 
Beg4010@med.cornell.edu 
 
Breanna (Bakari) Moitt 
Weill Cornell Medicine 
Brm4021@med.cornell.edu 
 

 
 
 
Statistician: N/A 
Study Coordinator: N/A 
 
Responsible Research Nurse: N/A 
Responsible Data Manager: N/A 
 
Participating Sites: Sackler Institute, WCM. The PI is Faith Gunning. See above for contact info. 

 
 
 
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 from WCM. 

 
 
 
List of Abbreviations 
 
All abbreviations used throughout the protocol must be defined. 
 
 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center 
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
Humanitarian Use Device 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
UAP 
Unanticipated Problem 
WCM 
Weill Cornell Medicine 

 
 
Protocol Summary 
 
Please provide a brief protocol summary. 
 
Full Title: 
Mobile Cognitive Behavior Therapy Targeting Anxiety Disorders 
Short Title: 
Mobile CBT in Anxiety 
Clinical Phase: 
N/A – no drug or device involved 
Principal Investigator: 
Faith Gunning 
Sample Size: 
N = 120 
Accrual Ceiling: 
We plan to screen up to 300 subjects. 
Study Population: 
18-25 year olds who have been diagnosed with an anxiety 
disorder as per the Anxiety Disorders Interview Schedule. 
Accrual Period: 
We anticipate complete accrual of participants taking up to 1 year 
Study Design: 
Participants in this study will use an online Cognitive Behavior 
Therapy program to assist with treatment of their anxiety 
symptoms. This program is being developed by Weill Cornell 
Medicine faculty as part of the University of Pennsylvania Center 
for Health Incentives and Behavioral Economics’s established 
online platform called “Way to Health.” All participants in the 
study will be using the program; as this is a pilot study testing the 
feasibility of using an online CBT program plus non-monetary 
incentives. Participants will be told to use the program for at least 
20 minutes per day, 2 days per week, for up to 6 weeks. 
Participants will check in once a week in person or over the phone 
or a HIPAA-compliant virtual meeting platform. There will also be 
one follow up visit 6 weeks after they have stopped using the 
program. 
 
Study Duration: 
3 months 
Study Agent/ 
Intervention Description: 
There is no drug or invasive device being used; rather, we are 
simply providing an online Cognitive Behavior Therapy program 
through an existing online platform called “Way to Health” 
Primary Objective: 
The primary objective is to examine different ways of motivating 
people to make use of the online therapy program, and to assess 
whether social supports are as efficacious, or more efficacious, 
than a reward mechanism such as non-monetary incentives. We 
will randomize subjects to one of three conditions: a social 
support condition, a gain-framed condition in which participants 
can earn “points” for completing their assigned sessions, and a 

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loss-framed condition in which participants lose “points” for 
failing to complete their assigned sessions on time. We will 
compare change in anxiety from baseline to end of treatment 
between these three conditions. 
Secondary Objectives: 
A secondary objective will be to evaluate whether the three 
incentive conditions are associated with different levels of 
treatment engagement. We will measure the amount of time 
participants use the program and administer a questionnaire to 
assess participants’ subjective impressions of the program. We 
will compare these measures across the three incentive 
conditions. 
Exploratory Objectives: 
We will collect neuroimaging data from a subset of participants 
who choose to participate in MRI scans and/or 
electroencephalographic (EEG) recordings pre-intervention and 
post- intervention. We will examine these scans for neural 
changes pre- to post-intervention. We will also assess associations 
between symptom improvement and time spent on different 
modules within the program. 
Endpoints: 
We will administer several questionnaires that will assess severity 
of symptoms of anxiety in order to assess the efficacy of the 
program over time. 

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Visit 7: Subject receives questionnaires. 
Subject checks in with experimenters about 
anxiety symptoms. Optional MRI scan without 
contrast and/or EEG recording 
Visit 1: Subject is 
consented and informed 
about the mobile CBT 
program. They are 
randomized to one of 
three incentive 
conditions to engage 
with the CBT app. 
Questionnaires and 
cognitive tasks. 
Optional MRI scan 
without contrast 
and/or EEG 
recording 
 
SCHEMA 
All study assessments will be conducted either in person, over the phone, or on a HIPAA- 
compliant virtual meeting platform. Decisions about how to conduct visits will be made with 
participants, depending on safety and convenience. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Potential subject is diagnosed with an anxiety disorder 
(or experiences symptoms of anxiety). 
Potential subject is screened for this protocol. 
Visits/calls weeks 2-6: 
Subject receives 
questionnaires. Subject 
checks in with 
experimenters about 
CBT program. 
Visit 8: Subject receives questionnaires. 
Subject checks in with experimenters about 
anxiety symptoms. 

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Table of Contents 
1. 
STUDY OBJECTIVES ................................................................................................................ 6 
1.1 
Primary Objectives .......................................................................................................... 6 
1.2 
Secondary Objectives ..................................................................................................... 6 
1.3 
Exploratory Objectives .................................................................................................... 7 
2. 
BACKGROUND ....................................................................................................................... 7 
2.1 
Disease ........................................................................................................................... 7 
2.2 
Investigational Agent or Device ...................................................................................... 7 
2.3 
Rationale ......................................................................................................................... 8 
2.4 
Risk/Benefit Assessment ................................................................................................. 9 
3. 
SUBJECT SELECTION .............................................................................................................. 9 
3.1 
Study Population ............................................................................................................ 9 
3.2 
Inclusion Criteria ............................................................................................................. 9 
3.3 Exclusion Criteria ................................................................................................................. 9 
4. 
REGISTRATION PROCEDURES .............................................................................................. 10 
4.1 Patient Registration ........................................................................................................... 10 
5. 
STUDY PROCEDURES ........................................................................................................... 10 
5.1 Schedule of Evaluations .................................................................................................... 10 
5.1.1 
Screening Visit ....................................................................................................... 10 
5.1.2 
Treatment Phase ................................................................................................... 10 
5.2 
Treatment Administration ............................................................................................ 13 
5.3 
General Concomitant Medication and Supportive Care Guidelines .............................. 14 
5.4 
Duration of Therapy and Criteria for Removal from Study ........................................... 14 
5.5 
Duration of Follow Up ................................................................................................... 14 
6. 
DOSING DELAYS/DOSE MODIFICATIONS ............................................................................. 14 
7. 
PHARMACEUTICAL INFORMATION ...................................................................................... 14 
8. 
CORRELATIVE/SPECIAL STUDIES .......................................................................................... 14 
9. 
MEASUREMENT OF EFFECT ................................................................................................. 15 
10. DATA REPORTING / REGULATORY CONSIDERATIONS .......................................................... 15 
10.1 Data Collection ................................................................................................................ 15 
10.1.1 REDCap ..................................................................................................................... 15 
10.2 Regulatory Considerations .............................................................................................. 16 
11. STATISTICAL CONSIDERATIONS ........................................................................................... 16 

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11.1 Study Design/Endpoints .................................................................................................. 16 
11.2 Sample Size/Accrual Rate ................................................................................................ 17 
11.3 Stratification Factors ....................................................................................................... 17 
11.4 Analysis of Endpoints ...................................................................................................... 17 
11.4.1 Analysis of Primary Endpoints ...................................................................................... 17 
11.4.2 Analysis of Secondary Endpoints .................................................................................. 17 
11.5 Interim Analysis ............................................................................................................... 18 
11.6 Reporting and Exclusions................................................................................................. 18 
12. ADVERSE EVENT REPORTING REQUIREMENTS ...................................................................... 18 
12.1 
Adverse Event Definition ........................................................................................... 18 
12.1.1 Investigational Agent or Device Risks .................................................................... 18 
12.1.2 Adverse Event Characteristics and Related Attributions ....................................... 18 
12.2.3 Reporting of SAE to Insert Pharmaceutical Company Name .................................. 19 
12.4 AE/SAE Follow Up ............................................................................................................ 19 
13. DATA AND SAFETY MONITORING PLAN (DSMP) .................................................................. 19 
REFERENCES ................................................................................................................................ 20 

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1. 
Study Objectives 
Describe the specific aims for the study. 
 
1.1 Primary Objectives 
 
We plan to develop an online cognitive behavioral therapy program, in collaboration 
with the Center for Health Incentives and Behavioral Economics (Wharton School) that can 
be integrated into their online platform, Way to Health (https://www.waytohealth.org) that 
has been developed over the past 10 years and automates many of the research functions 
necessary for conducting randomized controlled trials of behavior interventions and 
strategic telehealth programs in areas related to primary care medicine. The platform is an 
efficient, scalable, and low cost way to test behavioral interventions. To date, the platform 
has supported NIH-funded interventions that focus on medication adherence; weight loss; 
monitoring of blood sugar, blood pressure and weight; physical activity; smoking cessation; 
sleep and patient compliance. 
One of the key features of the online platform (Way to Health) is its capacity to embed 
various incentive tools such as gamification and social support to the CBT intervention. In 
this context, these incentive components are novel to the delivery of any CBT treatment. A 
main hypothesis to be tested in this objective is whether the social support component will 
have a particular advantage to increase efficacy of CBT in this age group. This social support 
component will potentially extend the benefits of a group therapy approach, including 
connection with others, support, and encouragement. To test this hypothesis, we will 
randomize participants to one of three incentive structure conditions: a gain-framed 
incentive in which participants earn points for completing sessions, a loss-framed incentive 
in which they lose points for failing to complete sessions, and a social support incentive in 
which participants can identify a person they know to receive updates about their progress 
and support them throughout their time in the program. Participants will not be required to 
choose a person they know to receive updates about their use of the program; instead, they 
can choose to have a member of the study team serve as their social support if they are 
assigned to this condition. 
 
1.2 Secondary Objectives 
 
In addition to assessing efficacy of the three incentive strategies, a secondary objective 
is to evaluate the extent to which each strategy enhances engagement with the CBT 
intervention. Necessary to the real-world success of any technology-based health 
intervention is the frequency with which the user interacts with the technology and the 
user’s perception of how helpful and easy to use it is; even the most well-designed 
treatment will not help anyone if people never use it. We hypothesize that the social 
support incentive strategy may increase use and enjoyment of the program. We will use 
both objective data collected by the online CBT program and subjective ratings reported by 

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study participants to evaluate differences in engagement between the gain-framed, loss- 
framed, and social incentive conditions. 
 
1.3 Exploratory Objectives 
 
We will collect neuroimaging data from a subset of participants who choose to 
participate in MRI scans and/or electroencephalographic (EEG) recordings pre-intervention 
and post-intervention. We will examine these scans for neural changes along with examining 
questionnaires and interviews to assess changes in symptoms pre- and post-intervention. 
We will also assess associations between symptom improvement and time spent on different 
modules within the program. 
 
2. 
Background 
 
2.1 Disease 
 
The disease being researched is anxiety disorder, a category of psychiatric disorders 
that includes phobias, social anxiety, and panic disorders. It is characterized by 
stress that is disproportionate to the potential consequence of an event, an inability 
to stop worrying, and general restlessness. It has a one-year prevalence of 10.6% 
and a lifetime prevalence of 16.6%. In addition, it has seen a rise in prevalence in 
younger populations in recent years (Remes, 2016). 
 
2.2 Investigational Agent or Device 
 
The online CBT program will be developed with the consultation of a behavioral 
economics researcher at the University of Pennsylvania's Wharton School (Center for 
Health Incentives and Behavioral Economics; https://chibe.upenn.edu). The program 
will be integrated into their established online platform (Way to Health; 
https://www.waytohealth.org) that includes various incentive tools. Our program will 
include modules addressing, among others: psychoeducation, emotion monitoring tools, 
cognitive restructuring strategies, mindfulness practices, exposure hierarchy building 
and maintenance tools, an evolving list of weekly exposure goals, exposure exercise 
processing tool, and as-needed motivational enhancement and relapse prevention 
modules. Module content will be continually updated based on ongoing patient 
assessment. For example, the exposure hierarchy will be an interactive tool with 
evolving fear and avoidance ratings based on weekly exposure exercises accomplished 
and anxiety data collected. These data will then inform recommendations for weekly 
exposure tasks, including when to repeat exposures and when to move on to a more 
challenging task. The online CBT platform will include an interactive dashboard to 
provide the user with their program "stats" based on patient goals will be entered into 
the system; it will provide prescribed outcome measures for tracking progress toward 

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goals. Participants will be told that they must engage with the online CBT platform for at 

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least 20-25 minutes per day, 2 days per week. They are allowed to use the program 
more frequently than this if they want to. 
 
Although the proposed version of this app is new, the content and its structure 
are similar to how Cognitive Behavioral Therapy (CBT) is commonly delivered. We have a 
collaboration with University of Pennsylvania's Wharton School (Center for Health 
Incentives and Behavioral Economics; https://chibe.upenn.edu), who have an 
established online platform called Way to Health. Way to Health has been used to 
deliver interventions to thousands of patients. In 2017, the platform supported 38 
research projects and 11 clinical pilots. We are working closely with Kevin Volpp, M.D., 
Ph.D. at University of Pennsylvania who has demonstrated how incentives can increase 
adherence to mobile interventions for weight loss, physical activity, safe driving, 
smoking cessation, among others (e.g. Patel, Volpp & Asch, 2018, NEJM; Patel et al., 
2017, JAMA; Volpp et al., JAMA Internal Med). The productive team at Way to Health 
allows for quick development while maintaining a high level of rigor. All of our timeline 
goals as we have developed this project have been met by the University of 
Pennsylvania team so we are confident that we will have timely delivery of the mobile 
application. 
 
2.3 Rationale 
 
There is a growing need for anxiety treatments designed for young adults (ages 18- 
25 years of age). This age group uses mobile devices frequently, thus there is a clear 
opportunity to provide mobile treatment that is targeted for this age range. Mobile technology 
has been used to track mental health symptoms and also deliver mental-health services for 
adults with a variety of psychiatric symptoms (Dennis & O'Toole, 2014). Mobile-based 
interventions are advantageous in that they can provide momentary tailored interventions and 
collect real-time data about patient symptom severity (Burns et al. 2011). As a result, a goal of 
this work is to develop an effective mobile application for adolescents and young adults 
experiencing anxiety symptoms. The research team has an extensive background in 
understanding how adolescents and young adults may be more sensitive to certain types of 
rewards (i.e. social support), which will increase the patient's engagement with the mobile 
treatment. 
 
The mobile application will utilize a version of a traditional "gold-standard" 
behavioral therapy approach to treat anxiety disorders - cognitive behavioral therapy (CBT) 
optimized for youth. Unlike many other types of psychotherapies, the standardized nature of 
CBT makes it compatible to be delivered in a web-based format (Spence et al., 2008). In 
addition, no current version of online CBT incorporates any behavioral interventions to enhance 
engagement and adherence to the web-based treatment protocol. The underlying scientific 
query is to understand the feasibility of online delivery of CBT and assess whether web-based 
incentive tools enhance treatment motivation and engagement, and assists with maintenance 

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of treatment gains and relapse prevention. This study lays the groundwork for developing and 
optimizing methods for maximizing engagement, and thus, treatment efficacy, in young adults 
with anxiety. 
 
 
2.4 Risk/Benefit Assessment 
 
Since this is a pilot study, and we are only trying to determine the feasibility of a 
mobile CBT program, subjects will not be using the CBT program in place of existing 
therapies. All existing therapeutic programs that subjects are part of will continue as 
normal. Thus, this study presents very minimal risk to participants. They may find the 
mobile CBT program boring or uninteresting, but since it is based in CBT theory, it will not 
make anxiety symptoms worse. 
 
The optional MRI scan also presents minimal risk to participants. There will be no 
contrast used. There are no known side effects of an MRI scan. Risks include the potential 
for discomfort from MRI scanning. Some people (about one in ten) feel claustrophobic (fear 
closed spaces). Participants will be able to squeeze an emergency ball to communicate that 
they want to end the scan at any time. 
 
Risks related to the EEG recording are also minimal. Participants may complete a 
computer task during the EEG that includes unpleasant (death, mutilation) and erotic 
images. These images are drawn from a widely used stimulus set (The International 
Affective Picture System (IAPS)) that has been used in many prior EEG studies, including Dr. 
Dimitris Kiosses’s study with suicidal patients at WCM (protocol # 1603017115) as well as 
numerous studies outside of WCM (e.g. Albanese, 2019; Schupp, 2004; Weinberg, 2010; 
Sabatinelli, 2013). Risks include possible distress related to looking at emotional pictures or 
thinking about emotional situations; possible fatigue or boredom as a result of performing 
similar actions repeatedly; and possible mild skin irritation (redness) where the sensors 
contact the participant’s scalp. Skin irritation in response to EEG recording is rare and 
temporary. Participants are offered breaks between the tasks and can choose to 
discontinue the EEG recording at any time. 
 
In addition, the potential benefit of this study is that a mobile CBT program is 
created and is deemed feasible in this population. This is a potentially huge benefit, 
as mobile CBT programs could serve to enhance current CBT practices in patients 
with an anxiety disorder. 
 
 
3. 
Subject Selection 
 
3.1 Study Population 

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Subjects between 18 and 25 with a diagnosis of an anxiety disorder who meet the 
inclusion and exclusion criteria will be eligible for participation in this study. 
 
3.2 Inclusion Criteria 
 
Individuals who are between the ages of 18 and 25 and who have a primary diagnosis of 
an Anxiety Disorder, as determined by a score of 4 on the Clinical Severity Rating from the 
Anxiety Disorders Interview Schedule (ADIS), will be considered eligible to participate in this 
study. 
 
3.3 Exclusion Criteria 

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Individuals who do not meet the cutoff score on the ADIS or who have a primary 
diagnosis other than an anxiety disorder will be excluded from participating in this 
study. Additionally, participants who are currently in cognitive behavioral therapy 
outside of the app or who have changed their dose of a psychiatric medication in 
the past 12 weeks will be excluded. Participants with the intent or plan to attempt 
suicide will be excluded from this study and provided referrals for treatment. 
 
4. 
Registration Procedures 
 
4.1 Patient Registration 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure for 
Subject Registration. 
 
5. 
Study Procedures 
 
5.1 Schedule of Evaluations 
 
5.1.1 Screening Visit 
This assessment will take place either in person, over the phone, or on a HIPAA- 
compliant virtual meeting platform. Decisions about how visits will take place 
will be made with participants, depending on safety and convenience. 
 
• Anxiety Disorders Interview Schedule (ADIS) to get a Clinical Severity Rating (CSR 
must be 4 or higher to receive a primary diagnosis of Anxiety Disorder, and no 
other psychiatric conditions can have a higher CSR). 
• We will collect contact information so that we can follow up with the participant 
after the evaluation. 
• We will also collect medication and psychiatric treatment information to 
determine study eligibility. 
 
5.1.2 Treatment Phase 
All study visits will take place either in person, over the phone, or on a HIPAA-compliant 
virtual meeting platform. Decisions about how visits will take place will be made with 
participants, depending on safety and convenience. 
 
5.1.2.1 
Visit 1: Baseline 
• Participants are randomized to one of three incentive conditions (gain- 
framed points, loss-framed points, or social support). Participants in the 
social support condition will identify a person in their life who will receive 

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text message updates about their progress—or they can choose to have the 
study team receive the updates. 
• Demographic Information 
• Test of Premorbid Functioning for Wechsler Intelligence Scale for Adults 
(WAIS) unless completed within 18 months. 
• Rumination Response Scale (RRS) 
• Hamilton Rating Scale for Depression (HAM-D) 
• Hamilton Rating Scale for Anxiety (HAM-A) 
• Anxiety Sensitivity Index (ASI-3) 
• Liebowitz Social Anxiety Scale (LSAS) 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• The Temporal Experience of Pleasure Scale (TEPS) 
• Positive and Negative Affect Schedule (PANAS) 
• Emotion Regulation Questionnaire (ERQ) 
• Multidimensional Experiential Avoidance Questionnaire (MEAQ) 
• Pittsburgh Sleep Quality Index (PSQI) 
• World Health Organization Quality of Life short-form scale (WHOQOL-BREF) 
• Life Events Scale for Students (LESS) 
• Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) 
• Multidimensional Assessment of Interoceptive Awareness (MAIA) 
• Digital Working Alliance Inventory (D-WAI) 
• Medication Tracking 
• Optional MRI Tasks: Points Incentive Delay Task, Social Incentive Delay Task 
• Optional EEG  
 
5.1.2.2 
Visit 2 (+7 days from Visit 1) 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• Mobile Application Rating Scale: user version (uMARS) 
• Medication Tracking 
• Check in about how the app is working. 
 
5.1.2.3 
Visit 3 (+7 days from Visit 2) 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• Medication Tracking 
• Check in about how the app is working. 
 
5.1.2.4 
Visit 4 (+7 days from Visit 3): Midpoint 

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• Rumination Response Scale (RRS) 
• Hamilton Rating Scale for Depression (HAM-D) 
• Hamilton Rating Scale for Anxiety (HAM-A) 

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• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• The Temporal Experience of Pleasure Scale (TEPS) 
• Positive and Negative Affect Schedule (PANAS) 
• Emotion Regulation Questionnaire (ERQ) 
• Multidimensional Experiential Avoidance Questionnaire (MEAQ) 
• Pittsburgh Sleep Quality Index (PSQI) 
• World Health Organization Quality of Life short-form scale (WHOQOL-BREF) 
• Life Events Scale for Students (LESS) 
• Anxiety Sensitivity Index (ASI-3) 
• Liebowitz Social Anxiety Scale (LSAS) 
• Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) 
• Mobile Application Rating Scale: user version (uMARS) 
• Digital Working Alliance Inventory (D-WAI) 
• Medication Tracking 
 
• Check in about how the app is working. 
 
5.1.2. 5 
Visit 5 (+7 days from Visit 4) 
 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• Medication Tracking 
• Check in about how the app is working. 
 
5.1.2. 6 
Visit 6 (+7 days from Visit 5) 
 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• Medication Tracking 
• Check in about how the app is working. 
 
5.1.2.7 
Visit 7 (+7 days from Visit 6): Endpoint 
• ADIS sections for the anxiety disorder(s) the participant met criteria for at 
screening 
• Rumination Response Scale (RRS) 
• Hamilton Rating Scale for Depression (HAM-D) 
• Hamilton Rating Scale for Anxiety (HAM-A) 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• The Temporal Experience of Pleasure Scale (TEPS) 

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• Positive and Negative Affect Schedule (PANAS) 
• Emotion Regulation Questionnaire (ERQ) 
• Multidimensional Experiential Avoidance Questionnaire (MEAQ) 

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• Pittsburgh Sleep Quality Index (PSQI) 
• World Health Organization Quality of Life short-form scale (WHOQOL-BREF) 
• Life Events Scale for Students (LESS) 
• Anxiety Sensitivity Index (ASI-3) 
• Liebowitz Social Anxiety Scale (LSAS) 
• Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) 
• Mobile Application Rating Scale: user version (uMARS) 
• Digital Working Alliance Inventory (D-WAI) 
• Optional MRI Tasks: Points Incentive Delay Task, Social Incentive  Delay 
Task 
• Optional EEG  
• Medication Tracking 
• Check in about how the app is working. 
 
5.1.2.8 
Visit 8 (+42 days from Visit 7): Follow-Up 
 
• Rumination Response Scale (RRS) 
• Hamilton Rating Scale for Depression (HAM-D) 
• Hamilton Rating Scale for Anxiety (HAM-A) 
• Generalized Anxiety Disorder 7-item Scale (GAD-7) 
• Patient Health Questionnaire 9 (PHQ-9) 
• The Temporal Experience of Pleasure Scale (TEPS) 
• Positive and Negative Affect Schedule (PANAS) 
• Emotion Regulation Questionnaire (ERQ) 
• Multidimensional Experiential Avoidance Questionnaire (MEAQ) 
• Pittsburgh Sleep Quality Index (PSQI) 
• World Health Organization Quality of Life short-form scale (WHOQOL-BREF) 
• Life Events Scale for Students (LESS) 
• Anxiety Sensitivity Index (ASI-3) 
• Liebowitz Social Anxiety Scale (LSAS) 
• Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) 
• Mobile Application Rating Scale: user version (uMARS) 
• Digital Working Alliance Inventory (D-WAI) 
• Medication Tracking 
• Check in about how the app is working. 
 
5.2 Treatment Administration 
 
Treatment will be administered on an outpatient basis. 
 
Participants will be asked to engage with the mobile application at least 2 days a week 

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for 20-25 minutes per session. These sessions can be done at the participants’ 
convenience for various lengths of time. These tasks can be boring or frustrating for 

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some people, but participants are allowed to take breaks, or to make sessions shorter. 
Participants may also decide to stop participating at any time. 
 
5.3 General Concomitant Medication and Supportive Care Guidelines 
 
Participants will likely be seeking therapeutic services, medication-based as well as 
psychotherapy, outside of the research context for their anxious and depressed 
symptoms. This will be recorded by our protocol but will not interfere with their use of 
the mobile application. We do not foresee any possible risks associated with using the 
mobile application in addition to external non-CBT therapy. 
 
 
5.4 Duration of Therapy and Criteria for Removal from Study 
 
In the absence of treatment delays due to adverse event(s), treatment may continue 
for 12 weeks or until one of the following criteria applies: 
 
The study will take place for a total of 6 weeks but participants will continue to have 
access to the mobile device if they would like to after the study is complete. 
Participants are welcome to withdraw from the study at their own discretion. There 
are no general of specific changes in the patient’s condition that would render the 
patient unacceptable for further treatment in the judgement of the investigator. 
 
5.5 Duration of Follow Up 
 
Patients will be followed for 6 weeks while they are participating in the study. There 
will also be a follow up appointment 6 weeks after they finish the study. 
 
6. 
Dosing Delays/Dose Modifications 
 
Section 6 is not applicable for this study as we are not administering a drug. 
 
7. 
Pharmaceutical Information 
 
This is not applicable for this study, as we are not administering a drug. 
 
8. 
Correlative/Special Studies 
 
Section 8 is not applicable for this study as there will be no correlative/special studies 
involving specimens. 

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9. 
Measurement of Effect 
 
We will be measuring the effects of the mobile CBT program using clinical measures that 
test symptoms of anxiety and depression, namely, the Hamilton Rating Scale for Depression 
and the Hamilton Rating Scale for Anxiety. Optional fMRI scans will also be collected. The 
MRI scans will be done without contrast. 
 
 
10. 
Data Reporting / Regulatory Considerations 
 
10.1 Data Collection 
 
The data collection plan for this study is to utilize REDCap to capture treatment, 
toxicity, efficacy, and adverse event data for all enrolled patients. All data collected 
from questionnaires will be kept in the “Mobile CBT” on Weill Cornell’s secure 
REDCap system. Additional data is stored on the Weill Cornell ITS servers, Way to 
Health Servers, and on Heap Analytics Servers. 
 
10.1.1 REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management software 
system that is fully supported by the Weill-Cornell Medical Center CTSC. It is a tool 
for the creation of customized, secure data management systems that include Web- 
based data-entry forms, reporting tools, and a full array of security features 
including user and group based privileges, authentication using institution LDAP 
system, with a full audit trail of data manipulation and export procedures. REDCap is 
maintained on CTSC-owned servers that are backed up nightly and support 
encrypted (SSL-based) connections. Nationally, the software is developed, 
enhanced and supported through a multi-institutional consortium led by the 
Vanderbilt University CTSA. 
 
10.1.2 Way to Health 
 
Way to Health (W2H) is a software platform developed by the Penn Center for 
Health Incentives and Behavioral Economics (CHIBE) and is currently operated 
through a partnership between CHIBE and the Penn Medicine Center for Health Care 
Innovation. W2H is an integrated, cloud-based platform that blends behavioral 
science with scalable digital technology to improve clinical outcomes. W2H 
automates many research functions necessary for conducting randomized controlled 
trials of healthy behavior interventions. The platform facilitates online and mobile 
participant enrollment; survey administration; integrated biomedical device data 
transmissions; automated randomization in a variety of schemes; automated 

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communication with participants/patients via voice, text and email; delivery of 
financial and social incentives; utilization of gamification strategies and much more. 
For a complete list of data protections and associated policies and procedures, 
please visit https://policy.waytohealth.org. 
 
10.1.3 Heap Analytics 
 
Heap Analytics is a user behavioral analytics service that collects data on how users 
interact with websites and apps. Heap protects user privacy through automatic PII 
detection, custom install configurations, and a secure delete user API. All data sent 
to Heap is encrypted using TLS. For a full list of data protections and associated 
policies and procedures, please visit: https://heap.io/trust-center. 
 
10.2 Regulatory Considerations 
 
All protocol amendments and consent form modifications will be made by the 
Principal Investigator. 
 
 
11. 
Statistical Considerations 
 
As this study is a pilot to determine feasibility of the CBT mobile application including 
non-monetary incentives, we do not anticipate high volume data. We intend to use the 
pilot data to submit an NIH grant where we will recruit a statistician to be a part of our 
research team. 
 
11.1 Study Design/Endpoints 
 
No subjects will be forced to end participation in the study based on a lack of 
engagement with the mobile CBT program. We will be looking at whether participants 
completed the protocol as intended (i.e. usage statistics across the 6 weeks). We will gather 
the qualitative data from participants when they come for the weekly check-in visits. We 
will analyze how often participants opened the mobile app, completed the exercises and 
whether they completed the 6 week protocol, and if not, at what time point they stopped 
participating. We have no set criteria regarding what percentage must finish the protocol; 
however, if less than 25% of participants complete the protocol as intended, we will re- 
evaluate our current procedures. Such information is a critical first step before testing the 
validity of the mobile CBT platform, which will be the scope of future proposals to the NIH. 
We will also be comparing differences in efficacy and treatment engagement between three 
different incentive conditions. We will not be comparing the mobile CBT to any other type 
of treatment at this initial stage. 

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11.2 Sample Size/Accrual Rate 
 
We plan on recruiting 300 subjects over the course of a year, with the anticipation 
that 120 will participate in the study to completion. This means we hope to recruit 
approximately 25 subjects per month. 
 
11.3 Stratification Factors 
 
There are no planned patient stratification factors. 
 
11.4 Analysis of Endpoints 
 
11.4.1 Analysis of Primary Endpoints 
 
The primary purpose of the study is to compare change in anxious symptoms from 
baseline to Visit 7 (end of treatment with the mobile cognitive behavior mobile 
application) between the three incentive conditions. The primary measure of this 
endpoint will be the Hamilton Rating Scale for Anxiety (HAM-A), a 14-item questionnaire 
measure of the severity of anxiety symptoms. The items measure both psychic anxiety 
and somatic anxiety, where higher scores indicate a greater presence of symptoms and 
lower scores indicate mild to no anxiety symptoms. Secondary measures of this 
endpoint will be the Anxiety Sensitivity Index (ASI) and the Leibowitz Social Anxiety Scale 
(LSAS). The ASI is an 18-item scale containing three subscales measuring physical, 
cognitive, and social concerns regarding anxiety. Higher scores reflect greater self- 
reported concern and lower scores reflect little self-reported concern. The LSAS is a 24- 
item scale measuring fear and avoidance across social situations. Higher scores indicate 
greater fear and avoidance severity and lower scores indicate mild to no fear or 
avoidance. 
 
 
11.4.2 Analysis of Secondary Endpoints 
 
A secondary aim of the study is to compare participants’ engagement with the 
mobile app between the three incentive conditions. The primary measure of this 
endpoint is the number of sessions completed over the course of treatment. Secondary 
measures are the total time spent engaging with the app during the course of treatment 
and participants’ impressions of the program as assessed by the Mobile Application 
Rating Scale (uMARS). The uMARS is a 26-item measure of mobile application 
engagement, functionality, aesthetics, quality of information, and perceived impact. 
Higher scores indicate greater application feasibility and lower scores indicate poorer 
application feasibility. 

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11.5 Interim Analysis 
 
No planned interim analysis. 
 
11.6 Reporting and Exclusions 
 
Not applicable as we will not be using a drug or medical device. 
 
12. Adverse Event Reporting Requirements 
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The 
investigator will be required to provide appropriate information concerning any findings 
that suggest significant hazards, contraindications, side effects, or precautions pertinent to 
the safe use of the drug or device under investigation. Safety will be monitored by 
evaluation of adverse events reported by patients or observed by investigators or research 
staff, as well as by other investigations such as clinical laboratory tests, x-rays, 
electrocardiographs, etc. 
 
12.1 
Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) can be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug, and does not imply any judgment 
about causality. An adverse event can arise with any use of the drug (e.g., off-label 
use, use in combination with another drug) and with any route of administration, 
formulation, or dose, including an overdose. 
 
12.1.1 Investigational Agent or Device Risks 
 
Participants will be asked to engage with the mobile application at least 4 days a week 
for 20-25 minutes per session. These sessions can be done at the participants’ 
convenience for various lengths of time. The only potential risk is that the tasks can be 
boring or frustrating for some people, but participants are allowed to take breaks, or to 
make sessions shorter. Participants may also decide to stop participating at any time. 
 
12.1.2 Adverse Event Characteristics and Related Attributions 

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There will be no adverse events during this study as a result of the mobile CBT 
program, as patients will be continuing regular anxiety treatments. 
 
 
12.2.3 Reporting of SAE to Insert Pharmaceutical Company Name 
N/A 
12.2.4 AE/SAE Follow Up 
 
Please specify any follow up procedures for any AEs/SAEs that occur on study. Sample 
language is provided below in italics. 
 
All SAEs and AEs reported during this study will be followed until resolution or until the 
investigator confirms that the AE/SAE has stabilized and no more follow-up is required. 
This requirement indicates that follow-up may be required for some events after the 
patient discontinues participation from the study. 
 
13. 
Data and Safety Monitoring Plan (DSMP) 
 
• We will be using REDCap, a secure web application, to manage participant 
data. Only individuals listed as co-investigators on the protocol will have 
access to this database. 
• All data that is collected by the study team will be stored in the REDCap 
database. All questionnaire data collected for the study (see attachment) will 
be stored in the REDCap system. 
• Participants can discontinue engagement in the study at their own discretion. 
The only foreseeable adverse events that may cause subjects to terminate 
protocol treatment is that they may get tired or bored of the tasks they asked 
to engage in on the mobile application. 
• The researchers will report all adverse events and unanticipated problems to 
the monitoring board as soon as they occur. 
• The monitoring entity will review data/events annually with the continuing 
review for the study. 
• The researchers will terminate the protocol if they receive information from 
the monitoring board that they should do so. 
• The monitoring entity’s comments/reviews will be disseminated during the 
continuing review. 
• The study application (CBT App) environment is stored and processed on the 
Weill Cornell ITS server with analytics information sent to Heap Analytics, and 
text message communications via Way to Health. Data on IP address, phone 
carrier, and city, as well as use of the app is collected on these platforms. 

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References 
These are companies outside of Weill Cornell that will have access to 
participants’ personal information. If these data are further disclosed by them 
or their business partners, it may no longer be covered under the privacy 
protections. Text messaging does not provide a completely secure and 
confidential means of communication. Participants are made aware of the 
risks that are inherent in using text messaging. 
 
Please provide the citations for all publications referenced in the text. 
 
 
Albanese, B. J., Macatee, R. J., Stanley, I. H., Bauer, B. W., Capron, D. W., Bernat, E., ... & Schmidt, N. B. 
(2019). Differentiating suicide attempts and suicidal ideation using neural markers of emotion 
regulation. Journal of affective disorders, 257, 536-550. 
 
O. Remes, C. Brayne, R. van der Linde, L. Lafortune. A systematic review of reviews on the prevalence of 
anxiety disorders in adult populations, Brain and Behavior, 2016; 6(7), e00497, doi: 10.1002/brb3.497 
 
Schupp, H., Cuthbert, B., Bradley, M., Hillman, C., Hamm, A., & Lang, P. (2004). Brain processes in 
emotional perception: Motivated attention. Cognition and emotion, 18(5), 593-611. 
 
Weinberg, A., & Hajcak, G. (2010). Beyond good and evil: the time-course of neural activity elicited by 
specific picture content. Emotion, 10(6), 767. 
 
Weinberg, A., Perlman, G., Kotov, R., & Hajcak, G. (2016). Depression and reduced neural response to 
emotional images: Distinction from anxiety, and importance of symptom dimensions and age of onset. 
Journal of abnormal psychology, 125(1), 26. 
 
Sabatinelli, D., Keil, A., Frank, D. W., & Lang, P. J. (2013). Emotional perception: correspondence of early 
and late event-related potentials with cortical and subcortical functional MRI. Biological psychology, 92(3), 
513-519.