Cranial Electrotherapy Stimulation for the Treatment of Major Depressive Disorder in Adults
Phase: NA
Conditions: Major Depressive Disorder
Sponsor: Fisher Wallace Laboratories

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Protocol Title  
Cranial Electrotherapy Stimulation for the Treatment  of 
Major Depressive Disorder in Adults (CES-MDD)  
  
Sponsor  
FISHER WALLACE LABORATORIES, INC.  
630 FLUSHING AVENUE  
SUITE #104  
BROOKLYN, NEW YORK 11206  
  
Protocol Number:  
FW-200-05  
Version Number:  
5.0  
Version Date:  
  
07-Jun-2022  
  
Confidentiality Statement  
This document is confidential and may not be disclosed without prior written consent of Fisher Wallace  
Laboratories, Inc.  This study will be performed in accordance with all stipulations of the protocol and in 
compliance with all applicable Fisher Wallace Laboratories Inc. Policies and Procedures.  
This study will be conducted in accordance with the ethical principles that originate from the Declaration of Helsinki 
and the Belmont Report. Study conduct will comply with applicable US FDA, state, and local Regulations.  
  
  
  
   
 

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PROTOCOL APPROVAL PAGE  
  
Protocol Title:  Cranial Electrotherapy Stimulation for the Treatment of Major Depressive Disorder in 
Adults (CES-MDD)  
  
Protocol Number: FW-200-05  
  
  
Date:  07-Jun-2022  
  
  
  
We the undersigned have read and approve the clinical investigational plan specified above and agree on its 
content:   
  
  
 
  
  
 
  
29-Nov-2022 | 14:13 PS
  
 
Kelly Roman, CEO, Fisher Wallace Laboratories, Inc.  
 
Date  
  
 
  
  
  
29-Nov-2022 | 06:33 EST
______________________________________________  
Kyle Lapidus, MD, PhD, Principal Investigator  
  
 
Date  
  
  
  

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INVESTIGATOR STATEMENT OF COMPLIANCE  
  
I have read this protocol and agree to conduct and/or supervise the study in accordance with the relevant, 
current protocol, in accordance with accepted good clinical practice principles, and will only make changes 
in a protocol after notifying Fisher Wallace Laboratories, Inc. and receiving written authorization from 
Fisher Wallace Laboratories, Inc.  
I agree to obtaining the written and dated approval of an Institutional Review Board (IRB) prior to initiation 
of the study and will promptly file all required reports with the IRB.   
I agree to ensure that all associates, colleagues, and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments.  
I agree to maintain adequate and accurate records and to make those records available for inspection to both 
Fisher Wallace Laboratories, Inc. and regulatory authorities, and to assist Fisher Wallace Laboratories in 
resolving any questions regarding study data  
I agree to disclose to Fisher Wallace Laboratories, Inc. accurate financial information as required by FDA 
regulations (21 CFR 54).  
I agree to maintain the confidentiality of this study, all study related documents and data; and will not 
disclose any content without prior written consent; provided, however, that I may submit the results of the 
study for publication upon giving Fisher Wallace Laboratories 30 days in which to review the manuscript 
for confidential information and to protect and perfect any intellectual property rights.  
  
The signature below attests that I have read and understand the contents of this protocol (or revisions 
to the protocol) and will adhere to the study protocol requirements as presented including all 
statements regarding confidentiality, and according to local legal and regulatory requirements and 
applicable U.S. Federal Regulations.  
  
  
Investigator Signature:  
 
  
  
  
   
 
  
 
 
 

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PROTOCOL REVISION HISTORY   
Version  Date  
Description of Change  
Brief Rationale  
1.0  
29-Mar-22  
Not Applicable  
Initial Version  
2.0  
19-Apr-22  
Exclusion Criteria Modification  
Addition of Exclusion Criteria to  
Exclude Employees, Family 
Members or Personal Associate of 
the Sponsor   
3.0  
16-May-22  Exclusion Criteria Modification  
Concomitant Medication  
Clarification and Hospitalization  
Language Clarification  
4.0  
19-May-22  Revision to Baseline  
Instrument Inclusion Criteria  
Participants are not excluded due to 
PHQ-9 & QIDS-SR baseline scores 
outside of moderate range  
5.0  
08-Jun-22  
Modification to the study target 
population   
Allow enrollment of patients with 
severe depression and  
corresponding higher baseline BDIII 
scores  
  
  
  
 
 
 
 
 
 
 
 
  
  
  
  

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LIST OF ABBREVIATIONS/ACRONYMS  
    
TERM  
DEFINITION  
ADE  
Adverse Device Effect  
AE  
Adverse Event  
BDI-II  
Beck Depression Inventory Second Edition  
CDC  
Centers for Disease Control and Prevention  
CES  
Cranial Electrotherapy Stimulation  
CMOS  
Complementary Metal Oxide Semiconductor  
CRO  
Contract Research Organization  
DBS  
Deep Brain Stimulation   
DD  
Device Deficiency  
DMP  
Data Management Plan  
ECT  
Electroconvulsive Therapy   
ePRO  
Electronic Patient Reported Outcomes  
FDA  
Food and Drug Administration  
GCP  
Good Clinical Practice  
ICH  
International Conference on Harmonization  
ISO  
International Organization for Standardization  
IRB  
Institutional Review Board  
JBI  
James Blinding Index  
LED  
Light Emitting Diode  
MDD  
Major Depressive Disorder  
MINI  
Mini-International Neuropsychiatric Interview   
PHQ-9  
Patient Health Questionnaire-9  
PI  
Principal Investigator  
QIDS-SR  
Quick Inventory of Depressive Symptomatology Self-Report  

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RCT  
Randomized Controlled Trial  
SADE  
Serious Adverse Device Effect  
SAE  
Serious Adverse Event  
SAFTEE  
Systematic Assessment for Treatment of Emergent Events   
SOP  
Standard Operating Procedure  
TMF  
Trial Master File  
TMS  
Transcranial Magnetic Stimulation   
UADE  
Unanticipated Serious Adverse Device Effect  
VNS  
Vagus Nerve Stimulation  
  
  
  
  
 

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     TABLE OF CONTENTS  
INVESTIGATOR STATEMENT OF COMPLIANCE 
3 
LIST OF ABBREVIATIONS/ACRONYMS 
5 
1  General 
12 
1.1  Sponsor Information 
12 
1.2  Principal Investigator, Coordinating Investigators and Investigation Site(s) Contact Information 
12 
1.2.1  List of Investigative Sites and Roles of Parties 
12 
1.2.2  List of External Organizations 
12 
1.3  Overview of Clinical Investigation 
13 
2  Introduction 
16 
2.1  Background 
16 
2.2  Study Rationale 
18 
3  Investigational Device 
18 
3.1  Intended Use 
18 
3.2  Populations and Indications for which the Investigational Device is Intended 
18 
3.3  Description of the Investigational Device 
18 
3.3.1  Accessories 
22 
3.3.2  Conditions of Use 
22 
3.3.3  Cleaning the Device 
22 
3.3.4  Signal Forms 
22 
3.3.5  Voltage and Current Output 
23 
3.3.6  Electronics/Controller 
23 
3.3.7  Software 
24 
3.4  Manufacturer of the Investigational Device 
24 
3.5  Model Name and Number including Software Version and Accessories 
24 
3.6  Device Traceability During and after the Clinical Investigation 
24 
3.7  Device Materials in Contact with Tissues or Body Fluids 
25 
3.8  Summary of Training and Experience Needed to Use the Investigational Device 
25 
4  Justification for the Design of the Clinical Investigation 
25 
4.1  Summary of Non-Clinical/Preclinical Studies 
25 
4.2  Summary of Clinical Studies 
26 

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5  Benefits and Risks of the Investigational Device, Clinical Procedure and Clinical Investigation 
33 
5.1  Anticipated Clinical Benefit 
33 
5.2  Potential Anticipated Adverse Events 
33 
5.3  Steps to Control or Mitigate the Risks 
34 
5.4  Residual Risks Associated with the Investigational Device 
34 
5.5  Other Complications and Risks in Clinical Use 
34 
5.6  Risk-to-Benefit Rationale 
34 
6  Objectives and Hypothesis of the Clinical Investigation 
35 
6.1  Rationale for Study Endpoints Selection and Measurement 
35 
6.2  Primary Objective 
35 
6.2.1  Primary Endpoint 
35 
6.3  Secondary Endpoints 
36 
6.4  Safety Endpoints 
36 
6.5  Observational Data Collection 
36 
7  Design of the Clinical Investigations 
36 
7.1  General 
36 
7.1.1  Study Procedures and Evaluations 
36 
7.1.2  Measures to Minimize or Avoid Bias 
38 
7.2  Subjects 
38 
7.2.1  Inclusion Criteria for Subject Selection 
38 
7.2.2  Exclusion Criteria for Subject Selection 
39 
7.2.3  Point of Enrollment 
40 
7.2.4  Total Expected Duration of the Clinical Investigation 
40 
7.2.5  Number of Subjects Required in the Clinical Investigation 
40 
7.2.6  Expected Duration of Subject Participation 
40 
7.3  Study Visits 
40 
7.3.1  Schedule of Assessments 
41 
7.3.2  Prescreening 
45 
7.3.2.1  Demographics 
45 
7.3.2.2  BDI-II 
45 
7.3.2.3  PHQ-9 
45 

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7.3.2.4  Mini International Neuropsychiatric Interview (M.I.N.I.) 
45 
7.3.3  Consent and Initial Eligibility 
46 
7.3.3.1  Informed Consent 
46 
7.3.6  Subject Identification and Randomization 
48 
7.3.6.1  Device Shipment 
48 
7.3.7  Subject Training 
48 
7.3.7.1  James Blinding Index 
49 
7.3.8  Period 1: Week 1 Device Usage 
49 
7.3.9  Period 1: Week 1 Evaluation 
49 
7.3.10  Period 2: Week 2 Device Usage 
49 
7.3.11  Period 2: Week 2 Evaluation 
49 
7.3.12  Period 3: Weeks 3-4 Device Usage 
50 
7.3.13  End of Therapy: Week 4 Evaluation 
50 
7.3.14  Unscheduled Visits 
50 
7.3.15  Criteria and Procedures for Subject Withdrawal or Discontinuation 
50 
7.3.15.2  Subject Replacement 
51 
7.3.15.3  Lost to Follow-Up 
52 
7.4  MONITORING 
52 
7.4.1  Source Data and Documentation 
52 
7.4.2  Audits and Inspections 
52 
8  Statistical Design and Analysis 
52 
8.1  Analysis Population 
53 
8.2  Descriptive Statistics 
53 
8.3  Analytical Procedures 
53 
8.4  Significance Level and Power of the Primary Endpoint and Overall Statistical Testing Strategy 
53 
8.5  Sample Size Calculation and Justification 
54 
9  Data Management 
54 
9.1  Procedures For Data Management 
54 
9.1.1  Electronic Patient Reported Outcomes 
54 
9.1.2  Data Queries 
55 
9.1.3  Confidentiality 
55 

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9.2  Procedures For Verification And Validation Of EPRO System 
55 
9.3  Procedures For Data Retention 
55 
9.4  Specified Retention Period 
55 
9.5  Clinical Quality Assurance 
55 
10  Amendments to the Protocol 
55 
11  Deviations from the Protocol 
56 
11.1  Investigator Deviations from Protocol 
56 
11.2  Procedures for Deviation Recording, Reporting and Analyzing 
56 
11.3  Corrective and preventive actions and principal investigator disqualification criteria 
56 
12  Device Accountability 
56 
12.1  Investigational Device Disposition 
56 
12.2  Clinical Supplies Accountability 
56 
12.3  Investigational Device Accountability Record 
57 
13  Regulatory Compliance 
57 
13.1  Statements Of Compliance 
57 
13.2  Institutional Review Board 
58 
13.3  Provision Of Investigational Device 
58 
13.4  Principal Investigator’s Study Reporting Responsibilities 
58 
14  Informed Consent Process 
58 
14.1  General Informed Consent Process 
58 
15  Adverse Events, Adverse Device Effects and Device Deficiencies 
59 
15.1  Definitions 
59 
15.2  Reporting 
60 
15.2.1  Investigator Responsibilities 
60 
15.2.2  Sponsor Responsibilities 
61 
15.3  Anticipated Potential Adverse Events 
62 
15.4  Emergency Contact Details 
62 
16  Vulnerable Populations 
62 
17  Suspension or Premature Termination of the Clinical Investigation 
62 
17.1  Criteria For Suspension OR Premature Termination 
62 
17.2  Subject Follow-Up In The Case Of Study Termination 
63 

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18  Publication Policy 
63 
18.1  Clinical Trial Registration 
63 
19  Bibliography 
64 
20  Appendices 
65 
20.1  Appendix 1:  Device Component Names, Model Numbers and Versions 
65 

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1  GENERAL  
1.1  SPONSOR INFORMATION  
The sponsor of this study is:  
Fisher Wallace Laboratories, Inc.  
630 Flushing Avenue, Suite #104  
Brooklyn New York, New York 11206  
1.2  PRINCIPAL INVESTIGATOR, COORDINATING INVESTIGATORS AND INVESTIGATION SITE(S) CONTACT 
INFORMATION  
The Principal Investigator (PI) for this study is:    
Kyle Lapidus, MD, PhD  
300 West 72 Street #1D New 
York, NY 10023 
kylelapidus@gmail.com  
(917) 969-3445  
1.2.1 List of Investigative Sites and Roles of Parties  
The FW-200-05 trial is a decentralized clinical investigation due to the COVID-19 pandemic. As Principal 
Investigator, Dr. Kyle Lapidus will oversee the study conduct and the safety of the subjects. Climb will 
establish and maintain the electronic patient reported outcomes (ePRO)/electronic data capture platform, 
provide clinicians to qualify subjects for study participation, and provide investigative staff for non-clinical 
subject assistance including subject training on device handling. Climb will also support Fisher Wallace 
Laboratories, Inc. (Sponsor) with coordinating the shipping of investigational devices to subjects. NAMSA 
(CRO) will be responsible for supporting the Sponsor with study management activities.    
1.2.2 List of External Organizations  
Climb  
1808 Wedemeyer St. Suite 326  
San Francisco, CA 94129  
(415) 484-8997  

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www.climb.care  
  
NAMSA  
400 Hwy 169 S, Suite 500  
Minneapolis, MN 55426 
(763) 287-3830 
www.namsa.com  
  
1.3  OVERVIEW OF CLINICAL INVESTIGATION  
Full Title  
Cranial Electrotherapy Stimulation for the Treatment of Major Depressive 
Disorder in Adults  
Short Title  
CES-MDD  
Protocol Number  
FW-200-05  
Protocol Version  
Version 5.0  
Study Sponsor  
Fisher Wallace Laboratories, LLC. 630 
Flushing Avenue, Suite #104  
Brooklyn New York, New York 11206  
Study Purpose  
This prospective, fully remote, randomized, controlled, triple-blind 
(subject, Principal Investigator, Sponsor) pivotal study is designed to 
evaluate the safety and efficacy of the Fisher Wallace Stimulator FW200 
to deliver Cranial Electrotherapy Stimulation (CES) for the treatment of 
moderate to severe Major Depressive Disorder (MDD) in adults.  
  
Investigational Product  
Fisher Wallace Stimulator® FW-200  
  
Study Objective  
  
To demonstrate the safety and effectiveness of FW-200 CES 
selfadministered for the treatment of moderate to severe MDD in adults  

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Study Endpoints  
Primary:   
● 
Change in the Beck Depression Inventory Second Edition (BDIII) 
at week two compared to baseline. Secondary:  
● 
Change in the BDI-II at weeks one and four compared to 
baseline.  
● 
Change in the Patient Health Questionnaire-9 (PHQ-9) and 
Quick Inventory of Depressive Symptomatology Self-Report 
(QIDS-SR) at weeks one, two, and four compared to baseline.  
● 
BDI-II responder rate at four weeks.  
Safety:  
● 
Determine the rate of device related adverse events.  
Study Design  
Remote, decentralized, randomized, controlled, triple blind (subject, 
Principal Investigator, Sponsor), pivotal investigation  
  
Inclusion Criteria  
1.  
Age 21-65 years and a resident of the United States of America 
2.  
Meets DSM-5 diagnostic criteria for moderate to severe Major  
 
Depressive Disorder   
3. 
Baseline BDI-II score between 20 and 63, inclusive (in Moderate 
to Severe range)  
4. 
Able to receive packages to their home via UPS/Fedex/USPS or 
other delivery service  
5. 
Willing and able to send and receive study related text messages 
on an internet capable mobile device throughout the duration of the study  
6. 
Owns and uses a personal, verifiable email address  
7. 
Able to commit to two (2) 20-minute treatment sessions per day 
for 4 weeks, one treatment upon waking for the day and one treatment 
before going to bed  
8. 
Willing to abstain from use of recreational drugs, hypnotics, 
steroids, and/or marijuana products through study completion   
9. 
Willingness to not initiate treatment for a mental health issue 
during the course of the study  
10. 
Fluent in English  
11. 
Sexually active females of childbearing potential willing to 
commit to practicing at least one or more of the following methods of 
contraception during the study: intrauterine device (IUD), barrier method 
in combination with a spermicide, oral/hormonal contraception, or 
abstinence   
12. 
In the opinion of the investigator, able to comply with study 
requirements and complete the study  

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Exclusion Criteria  
1. 
History of suicide attempt or active suicidal ideation with plan or 
intent in the past 30 days.   
2. 
In the opinion of the investigator, considered high risk of suicide 
3.  
Previous hospitalization or institutionalization for mental health 
condition within one year of study entry.   
4. 
Underwent electronic brain stimulation or neuromodulation within 
the past one year, including CES, transcranial magnetic stimulation, 
electroconvulsive therapy, and deep brain stimulation  
5. 
Modification of prescription medications that affect the nervous 
system including those for mental health issues within 30 days of study 
entry. A patient who has been on a stable dose of prescription 
medications that affect the nervous system or being used for a mental 
health issue for at least 30 days prior to study entry and are not expected 
to modify their medication while on the trial are allowed to participate.  
6. 
Use of recreational drugs, hypnotics, steroids, and/or marijuana 
products in the past 30 days  
7. 
History of alcohol use disorder or other substance use disorder in 
the past 12 months  
8. 
Females currently pregnant or planning to conceive during study 
participation, or unwilling to comply with birth control requirements  
9. 
Known history of heart disease   
10. 
Known history of trigeminal neuralgia  
11. 
Implanted with an electronic device such as a defibrillator, deep 
brain stimulator, or pacemaker   
12. 
Unstable medical condition including any condition requiring 
hospitalization or change in treatment in the prior 30 days   
 
13. 
Legally blind and/or deaf and without in-home care service to 
assist with study participation  
14. 
Meets M.I.N.I. assessment criteria for, or has been diagnosed 
with, any of the following: Bipolar I disorder, bipolar II disorder, other 
specified bipolar and related disorder, panic disorder, agoraphobia, social 
anxiety disorder (social phobia), obsessive-compulsive disorder, 
posttraumatic stress disorder, alcohol use disorder in the past 12 months, 
substance use disorder (non-alcohol) in the past 12 months, any 
psychotic disorder (e.g., schizophrenia, schizoaffective disorder), major 
depressive disorder with psychotic features, anorexia nervosa, bulimia 
nervosa, binge-eating disorder, generalized anxiety disorder, any 
cognitive or developmental disorder (e.g., autism, Down’s Syndrome), 
any personality disorder or psychiatric disorder that may interfere with 
study participation  
15. 
Current participation in another investigational study or 
participated in an investigational study within the past 30 days  
16. 
In the opinion of the investigator, may not be able to comply with 
study requirements  
17. 
Any employee, family member, or personal associate of the  
Sponsor or their designees conducting the study  

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Target Population/ Sample 
Size  
Adults ages 21-65 years. A total of 250 evaluable subjects  
(approximately 1:1 allocation) will be included in this study.  Subject will 
be located in the United States and have a diagnosis of moderate to 
severe Major Depressive Disorder.   
Number of Site(s)  
One investigative site in the US with subject activities conducted via a 
decentralized/remote method.   
Study Duration  
Estimated subject participation time is approximately 6 weeks: 2-week 
lead-in period followed by 4 weeks of treatment.  
Statistical Methods  
Continuous data will be summarized with mean, standard deviation, 
median, minimum, maximum, and number of evaluable observations. 
Categorical variables will be summarized with frequency counts and 
percentages. Confidence intervals may be presented, where appropriate, 
using the t-distribution for continuous data and ClopperPearson Exact 
method for categorical variables.   
The primary endpoint is the change in BDI-II at week 2 compared to 
baseline. Analysis will be based on a linear model for change, adjusted 
for each subject’s baseline value, comparing the randomized groups.  
  
 
2  INTRODUCTION  
2.1  BACKGROUND  
Mental health treatment was the greatest healthcare cost in the U.S. prior to the pandemic, more than cancer, 
heart disease, or diabetes. Mental health care costs have further increased in the past two years. According to 
the Centers for Disease Control and Prevention (CDC), the rate of clinical depression among US adults has 
more than tripled since the COVID-19 pandemic began (Czeisler et al., 2020). The U.S. is in the midst of an 
unprecedented mental health crisis, and the American public requires treatment options that are effective, 
safe, and efficiently delivered to patients. There was a large, unmet clinical need for treatment of depression 
before COVID-19, and there will continue to be such a need after the pandemic is brought under control.   
There are significant gaps in the delivery of care to patients suffering from depression. In the U.S., the 
majority of patients with depression who are treated with antidepressant medication receive their 
prescription not from a board-certified psychiatrist, but from their primary care physician. These clinicians 
are usually not responsible for making psychiatric diagnoses, and do not formally monitor side effects or 
evaluate response (Mann, 2011). Cognitive behavioral therapy and other forms of in-person psychotherapy 

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are expensive and require a high level of sustained patient engagement in order to be effective. Inadequate 
access to mental health resources has long been an issue for many segments of the U.S. population. This 
reality of the U.S. mental healthcare system means that Cranial Electrotherapy Stimulation (CES), as a low 
risk, home-based intervention, provides a potentially clinically important benefit for treating patients with 
depression.   
Beginning approximately twenty years ago, new, effective forms of neuromodulation became available, 
some of which the FDA has reviewed for clinical use, including transcranial magnetic stimulation (TMS), 
deep brain stimulation (DBS), and vagus nerve stimulation (VNS). In the case of CES, which was already 
commercially available with long track records of safety, a number of pilot studies and a substantial amount 
of anecdotal evidence supported safety and effectiveness. The development of new neuromodulatory 
treatments greatly increased interest in the clinical potential of all forms of neurostimulation to treat 
depression. Scientific and clinical interest also re-focused on older methods of therapy, such as 
electroconvulsive therapy (ECT), which, like CES, delivers alternating current, albeit ECT delivers an 
exponentially higher dose of electrical stimulation designed to cause a seizure and thus requires anesthesia 
to administer. The Fisher Wallace Stimulator delivers a low dose of pulsed alternating current which is 
comfortable and safe to self-administer and is intended to be used by the patient twice a day to treat 
depression.   
In recent years, animal and clinical research on CES for alleviating depression has increased, and it has been 
found that higher frequencies can overcome the impedance of the human skull (Mindes, 2015). 
Neurophysiological effects have been studied using concurrent brain magnetic resonance imaging  
(Ghobadi-Azbari, 2020) and electroencephalography (EEG) (Merlet, 2013; Miniussi, 2012). Computational 
modeling (Datta, 2013 a, b; Khadka, 2020) of stimulation effects using models of electrical behavior in 
tissues of the head, skull and brain provides additional data suggesting that stimulation may have beneficial 
impact.   
CES is a low-cost, non-invasive, wearable form of low intensity neural stimulation that has been used 
clinically for over 100 years (Mindes, 2015). This body of evidence from use of CES, and comparison with 
other neuromodulation methods, indicate that CES is a safe form of neural stimulation that causes minimal 
side effects. This large body of evidence also suggested possible benefits of regular CES for a range of 
neuropsychiatric indications, including depression.  
The Fisher Wallace Stimulator was cleared by the FDA for the treatment of depression, anxiety and 
insomnia in 1990 and has been on the market for 32 years - under the brand Liss Cranial Stimulator from 
1990-2007, and under the brand Fisher Wallace Stimulator from 2007 to the present. Over 100 published 
scientific articles analyzing the safety and effectiveness of CES are available on PubMed.gov. Uncontrolled 
and controlled clinical studies as well as many mechanistic studies have been performed in the US, with 
better quality research being generated over the past decade. These studies investigated and evaluated the 
effectiveness and safety of CES devices in various patient populations, as well as possible biological 
mechanisms of action.   

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2.2  STUDY RATIONALE  
While the precise mechanism of action for CES is not yet known, there is substantial research and decades 
of use showing that CES does have physiological effects on the brain, and that those effects are consistent 
with CES alleviating depression.  This study will leverage the opportunities and efficiencies of the telehealth 
environment to investigate the benefits of CES for adults with moderate to severe MDD. In doing so, the 
study will more accurately represent the real-world experience of patients using CES, as CES devices are 
typically prescribed for home use, and more psychiatric care is being provided via telemedicine.  
This prospective, fully remote, randomized, controlled, triple-blind study is designed to evaluate the safety 
and efficacy of FW-200 self-administered Cranial Electrotherapy Stimulation (CES) in adults with moderate 
to severe Major Depressive Disorder (MDD).  
3  INVESTIGATIONAL DEVICE  
3.1  INTENDED USE  
The Fisher Wallace Stimulator FW-200 is a non-invasive medical device intended to treat adult patients with 
moderate to severe Major Depressive Disorder (MDD). The FW-200 is a prescription device for use at home 
by the patient without a medical professional, though the device may also be used in a professional health 
care setting or extended care facility.   
3.2  
POPULATIONS AND INDICATIONS FOR WHICH THE INVESTIGATIONAL DEVICE IS INTENDED  
  
The indicated use is Cranial Electrotherapy Stimulation in adults (ages 21-65 years) for 20 minutes twice 
daily, upon waking for the day and at bedtime, to reduce symptoms of moderate to severe MDD.  
3.3  DESCRIPTION OF THE INVESTIGATIONAL DEVICE  
The FW-200 is a fixed output version of the commercially available FW-100 which has variable output. 
Whereas the commercially available FW-100 is able to deliver output at four different Levels, 1-4, the 
FW200 only outputs at Level 2.   
The FW-200 device consists of the following components (also refer to figures below):  
● CES device controller  
● Electrode receptacle with sponge  
● Electrode lead wires (red and black)  
● Sponges 4-pack  
● Velcro headband  
● Carry case  
● User guide  
● AA batteries  

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Figure 1: FW-200 CES Device  
  
Figure 2: Headset Electrode Wires and Applicator Sponges  

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Figure 3: Velcro Headband   
Figure 4: FW carry case  
Figure 5: Sponges 4-pack   
Figure 6 demonstrates the functional principle of the FW-200 device. The controller contains a dial for users 
to turn the device on and off. An LED panel on the controller displays the output level of the device and 
confirms the device is on. Figure 8 displays images of patients wearing and handling the FW-200 device 
components. The controller is connected to two sponges that are secured to the patient’s head with a 
headband.   
  
Figure 6: Functional Block Diagram  
  

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Figure 7: Wearing and Handling of the FW-200  
  
As described in the User Guide, the patient’s scalp and hair must be clean before electrode application to 
minimize the risk of irritation caused by placement of the electrodes. The sponge electrodes, as well as the 
scalp and hair beneath the electrodes, must be wet for electrode conductivity to occur. New headsets are 
provided with pre-installed sponges in the white plastic sponge receptacles. The sponges provided are 
dehydrated and will expand when wet.  
After snapping the white sponge receptacles to the wires and inserting the other ends of the wires into the 
top of the device, patients must saturate the sponges with water. The electrode sponges should be replaced 
every two weeks, or if they become stained or appear degraded in any way.  
The patient places the headband on the head so that it sits above the eyebrows. The wet electrodes, in the 
receptacles with attached wires, are placed beneath the headband, above the sideburns. The bottom of the 
electrode should be in line with the top of the ear. The physiological location of electrode placement is the 
squamous temporal bone above the very posterior part of the zygomatic arch.    
Once the wet sponge electrodes are placed securely beneath the headband, with wires connected, the device 
is turned on by rotating the dial. The dial is rotated counterclockwise to go from the OFF to ON position 
(there is a click when the dial is rotated to ON). The green ON light should illuminate and the first and 
second (Level #2) yellow indicator lights should also flashes yellow, indicating Level #2 output. If the green 
ON light does not illuminate, the user should replace the batteries. If the yellow indicator lights do not 
illuminate, the user should press the electrodes against his/her head to expel more water, or rewet the 
sponges or tighten the headband.  

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Depending on skin sensitivity, patients may or may not feel a sensation of stimulation (prickly sensation, 
warmth) when the device is used on the head at Level #2. Although the dial does show four levels, all 
settings will administer Level #2 stimulation to the study subject.  
Study subjects will use the device twice daily: once for 20 minutes after waking up for the day and once 
again for 20 minutes before going to bed.  
3.3.1 ACCESSORIES  
The FW-200 is provided as a complete kit. For any device replacement needs (lead wires, sponge 
receptacles, sponge pack or headband), a new complete kit will be shipped.   
3.3.2 CONDITIONS OF USE  
Users will be provided instructions regarding the conditions of this use.  The environment where the system 
is used should be one that has the following operating conditions:  
● Temperature range: 41 to 95℉ (5 to 40℃)  
● Relative humidity range: 10% to 93%, non-condensing  
  
Do not allow water to enter the device. The Fisher Wallace Stimulator® should not be exposed to 
environmental conditions where the system may get wet. Operation in close proximity (e.g., within 1m) to a 
shortwave or microwave therapy equipment may reduce the output performance of the device.  
Keep the device out of reach of children. Electronic monitoring equipment such as ECG monitors and ECG 
alarms may not operate properly when CES stimulation is in use. High frequency surgical equipment may 
not be used when CES stimulation is in use. This device is not suitable for use with oxygen or in the 
presence of a flammable anesthetic mixture with air or oxygen, or with nitrous oxide.  
3.3.3 CLEANING THE DEVICE  
The device and headset require cleaning for reuse. Reference the User Guide for the cleaning instructions. 
Investigative staff and subjects will be trained on the cleaning process during device handling training.  
3.3.4 SIGNAL FORMS  
Both the monopolar waveforms in the FW-200 will make use of three frequencies: 1) 15 kHz; 2) 15 Hz; and 
3) 500 Hz. The 15 kHz frequency refers to the carrier frequency. The 500Hz frequency controls the on and 
off times of the carrier. The 15Hz frequency controls the polarity reversal of the combined 15kHz and 
500Hz signals. The voltage amplitude of the output signal is the same for both polarities. The combined 
voltage amplitude will be twice the monopolar form.  

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3.3.5 VOLTAGE AND CURRENT OUTPUT   
The FW-200 has been designed to provide a constant current. This is done with a fixed voltage and a 
resistive feedback circuit called the Constant Current Controller. Users should be receiving approximately 2 
mA peak-to-peak (in the monopolar scheme) and 4 mA peak-to-peak (in the bipolar scheme).  
Voltage and current are directly related to each other by the resistance of the load (in this case the human 
head). Therefore, a constant current controller was needed to address the variability in the resistance of the 
human head. The constant current controller adjusts its own resistance so that the human head plus the 
controller will produce a fixed current for the Output voltage. At a resistance of 100 Ohms, the voltage 
output is approximately 400 mV. At 200 Ohms, the voltage output is double, approximately 800 mV.  
The average current output relates to the modulation of the signal. If the voltage was applied constantly, the 
average current would be 2mA because it is being modulated the average current is reduced by each duty 
cycle: 50% due to the 15kHz on/off carrier modulation; 50% due to the 500Hz on/off modulation of the 
carrier and 75% due the off time between the 15Hz polarity reversal.   
That provides an average current of 0.375 mA.  
3.3.6 ELECTRONICS/CONTROLLER  
Figure 9 below is a block diagram of the electronics system. It demonstrates the key connections between 
the major systems that make up the Printed Circuit Board Assembly (PCBA). The batteries provide power 
for the entire system operation.  The microcontroller (MCU) takes input from the Dip Switch and a Rotary 
switch. In turn, it controls the light emitting diodes (LEDs) and the complementary metal oxide 
semiconductor (CMOS) Analog Switch. The MCU will also power the LEDs to visually affirm that the 
device is on. The Voltage Regulator takes power from the Batteries and increases the voltage for the output 
circuitry. The Microcontroller produces the three frequencies and modulates the Output using the CMOS 
Analog Switch. The Analog Switch is able to both turn on and off the voltage as well as swap the Output’s 
polarity. The Constant Current Controller maintains current through the Output by the use of a resistive 
feedback circuit. This circuit varies its own resistance so that 2mA is maintained even if there are 
differences at the output.  The Microcontroller will drive the Buzzer to indicate the end of the session.   

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Figure 9: Electronics Block Diagram  
  
3.3.7 SOFTWARE  
The FW-200 contains firmware. All functions of the device are controlled by integrated circuits.    
3.4  MANUFACTURER OF THE INVESTIGATIONAL DEVICE  
The FW-200 is manufactured by Fisher Wallace Laboratories, Inc. via its contract manufacturer.   
3.5  MODEL NAME AND NUMBER INCLUDING SOFTWARE VERSION AND ACCESSORIES  
The names, model numbers and versions of the components of the FW-200 to be used in this study are 
provided in Appendix 1.  
3.6  DEVICE TRACEABILITY DURING AND AFTER THE CLINICAL INVESTIGATION  
The FW-200 and the accessory components are identifiable by lot number, equipment number, or serial 
number. These component lot numbers and reference numbers will be tracked by the Sponsor using a device 
accountability log. Return of investigational products will be reconciled against clinical study shipping logs.  
The Sponsor or designee shall keep records documenting the receipt, use, and return of the investigational 
devices. Dispositions of all investigational devices will be maintained in the ePRO.  
The FW-200 devices and accessories will remain within the expiry date for the duration of the clinical study. 
FW-200 devices and accessories will be replaced in study site inventory and returned to the Sponsor prior to 
their expiry date. Replacement FW-200 devices will be provided as necessary.  

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3.7  DEVICE MATERIALS IN CONTACT WITH TISSUES OR BODY FLUIDS  
The FW-200 materials that will be in direct contact with tissues are listed Appendix 1.  
3.8  SUMMARY OF TRAINING AND EXPERIENCE NEEDED TO USE THE INVESTIGATIONAL DEVICE  
The FW-200 components are intended for use at home by study subjects.   
Prior to the subject receiving the study device, a member of the investigative team will verify that the 
subject has completed a self-paced video training detailing the device components, how to use them, and 
how to clean them for personal reuse. Additionally, investigational staff will conduct a live demonstration 
via video conference of the device including a review of the User Guide with the subject. The subject will 
be required to confirm his/her understanding of device usage and cleaning process prior to using the FW200 
independently. The investigational team will be available to answer device-related questions upon request 
from a subject. Subject training completion will be documented in the ePRO.  
4  JUSTIFICATION FOR THE DESIGN OF THE CLINICAL INVESTIGATION  
4.1  SUMMARY OF NON-CLINICAL/PRECLINICAL STUDIES  
  
The following testing has been completed:   
Non-Clinical Section  Description/Test Results  
Electrical Safety and  
Electromagnetic  
Compatibility  
Electrical safety and EMC testing demonstrated compliance with IEC  
60601-2- 10:2012, AMD1:2012; IEC 60601-1:2015,  
AMD1:2012; IEC 60601-1-11:2015, AMD1:2012; BS EN 60601-1:2006 + 
A12:2014, and IEC/EN 60529:2013.  
Software  
Software documentation and verification and validation testing was 
completed for the FW-200 software, which has Moderate Level of Concern.  
Sterilization and 
Shelf-Life  
 
 
 
 
The Fisher Wallace Stimulator, Model FW-200 is not provided sterile. 
Accelerated shelf-life testing has been completed and has validated a 
5year shelf-life for the FW-200 as of 3/8/2022. Reference report  
#EMTS290227 via EMTS Lab Inc. Fisher Wallace plans to conduct a 
realtime shelf-life study to validate a 5-year shelf life.  

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Bench Performance 
Testing  
Bench performance testing was conducted as recommended in FDA’s 
Special Controls for CES devices, including:  
● 
Waveform  
● 
Output mode  
● 
Pulse duration  
● 
Frequency  
● 
Train delivery  
● 
Maximum charge and energy  
   
Stress/wear testing was conducted to verify that the device thumbwheel 
and headband withstand use throughout the expected use life of the 
device.   
  
Passing results were achieved.  
  
4.2  SUMMARY OF CLINICAL STUDIES  
To examine the safety and effectiveness of the Fisher Wallace Stimulator, Model FW- 200, for treatment of 
major depressive disorder (MDD), a double-blind randomized controlled trial (RCT) was performed in a 
fully remote fashion during the COVID-19 pandemic. Subjects with either mild, moderate, or severe major 
depressive disorder were enrolled in the study. Throughout the treatment period, participants administered 
twice daily 20-minute treatments with either the active device or a sham device treatment. Participants were 
randomized into immediate or delayed treatment arms. In the immediate treatment arm, participants 
administered active treatment (20 minutes of clinical stimulation per treatment session) for 8 weeks. 
Participants in the delayed treatment arm received sham stimulation (two seconds of clinical stimulation and 
19 minutes and 58 seconds of zero stimulation per treatment session) for 4 weeks, before being unblinded. 
At that point, participants were crossed over to active treatment for the following 4 weeks.  
Participants completed reports of compliance with treatment, as well as assessments of symptoms and side 
effects throughout the study, particularly at weeks 2, 4, and 8. Physician assessments were performed 
prerandomization and at 4 weeks.  
The primary outcome measure was change in Beck Depression Inventory Second Edition (BDI-II) score 
from baseline to week 4 in immediate versus delayed treatment arms. The BDI-II is a widely used 
selfreported instrument to assess the severity of depression in adolescents and adults from different cultural 
groups and populations (Beck Depression Inventory-Second Edition | The National Child Traumatic Stress 

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Network, n.d.). Secondary outcome measures included: change in Hamilton Depression Rating Scale from 
baseline to week 4, change in BDI-II from baseline to week 2, change in BDI-II from week 4 to 8, change in 
Patient Health Questionnaire-8 from baseline to week 2 and week 4, as well as safety and tolerability as 
measured by Systematic Assessment for Treatment of Emergent Events (SAFTEE).  
This study enrolled 275 participants with 137 participants in the Immediate Treatment arm and 138 
participants in the Delayed Treatment arm. Of these, 83 participants in the Immediate Treatment arm and 78 
participants receiving delayed treatment completed 4-week assessments.  
Table 1 provides the percentages of side effects experienced by subjects in both treatment arms at Week 4. 
Table 2 displays the percentages of patient-reported side effects at Week 8. There were no reported serious 
adverse events. Overall, more adverse events were reported in the Delayed Treatment arm than the 
Immediate Treatment arm. Minor symptoms reported were similar in both groups with 13/34 symptoms on 
SAFTEE reported more frequently in the Immediate Treatment group and 21/34 symptoms reported more 
frequently by individuals in the Delayed Treatment arm.  
  
Table 1: Side Effects Reported by Subjects at Week 4  
 
   
Immediate 
Treatment  
Delayed 
Treatment  
Total  
Have you felt weak?  
14.0% (8/57)  
15.1% (8/53)  
14.5% (16/110)  
Have you felt drugged or like a zombie?   
3.5% (2/57)  
5.7% (3/53)  
4.5% (5/110)  
Have you been sweating more than usual?   
5.3% (3/57)  
7.5% (4/53)  
6.4% (7/110)  
Have you felt tired during the day?   
54.4% (31/57)  
66.0% (35/53)  60.0% (66/110)  
Have you had difficulty staying awake during the day?  22.8% (13/57)  
30.2% (16/53)  26.4% (29/110)  
Have you had difficulties waking up fresh in the 
morning?   
56.1% (32/57)  
62.3% (33/53)  59.1% (65/110)  

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Have you gained weight?   
21.1% (12/57)  
18.9% (10/53)  20.0% (22/110)  
Do you think some foods taste different/odd?   
7.0% (4/57)  
11.3% (6/53)  
9.1% (10/110)  
Have you felt more hungry than usual?   
14.0% (8/57)  
17.0% (9/53)  
15.5% (17/110)  
Have you been more thirsty than usual?   
24.6% (14/57)  
22.6% (12/53)  23.6% (26/110)  
Have your stools been hard or difficult to pass?   
15.8% (9/57)  
20.8% (11/53)  
18.2% (20/110)  
Have you needed to go to the toilet often?   
24.6% (14/57)  
17.0% (9/53)  
20.9% (23/110)  
Has your skin been more sensitive to the sun?   
0.0% (0/57)  
0.0% (0/53)  
0.0% (0/110)  
Have you noticed any areas of darker skin?   
0.0% (0/57)  
3.8% (2/53)  
1.8% (2/110)  
Are you experiencing any skin irritation where you 
place the Fisher Wallace device?  
7.0% (4/57)  
3.8% (2/53)  
5.5% (6/110)  
Do you have diabetes?   
3.5% (2/57)  
5.7% (3/53)  
4.5% (5/110)  
Have you been told that your blood sugar levels are 
high?   
8.8% (5/57)  
15.1% (8/53)  
11.8% (13/110)  
Have you noticed a change in your blood sugar 
levels?   
0.0% (0/57)  
0.0% (0/53)  
0.0% (0/110)  
Has your vision been blurry?   
8.8% (5/57)  
15.1% (8/53)  
11.8% (13/110)  
Have your eyes felt dry and gritty?   
15.8% (9/57)  
24.5% (13/53)  20.0% (22/110)  

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Are you experiencing any unusual eyestrain or 
headaches?  
22.8% (13/57)  
17.0% (9/53)  
20.0% (22/110)  
Have you found that your words dont come out 
clearly?   
7.0% (4/57)  
3.8% (2/53)  
5.5% (6/110)  
Have you found it difficult to swallow?   
1.8% (1/57)  
1.9% (1/53)  
1.8% (2/110)  
Have you felt anxious?   
49.1% (28/57)  
34.0% (18/53)  41.8% (46/110)  
Have you felt agitated?   
33.3% (19/57)  
26.4% (14/53)  30.0% (33/110)  
Have you lost interest in enjoyable things?   
42.1% (24/57)  
34.0% (18/53)  38.2% (42/110)  
Have you experienced fits/jerks?   
1.8% (1/57)  
1.9% (1/53)  
1.8% (2/110)  
Have your arms or legs been shaky?   
3.5% (2/57)  
11.3% (6/53)  
7.3% (8/110)  
Have you had restless legs?   
8.8% (5/57)  
22.6% (12/53)  15.5% (17/110)  
Have you been less interested in sex?   
17.5% (10/57)  
24.5% (13/53)  20.9% (23/110)  
Have you found it difficult to enjoy sex?   
15.8% (9/57)  
13.2% (7/53)  
14.5% (16/110)  
Have you been unable to reach orgasm?   
24.6% (14/57)  
18.9% (10/53)  21.8% (24/110)  
Have the areas around your nipple been sore and/or 
swollen?   
3.5% (2/57)  
0.0% (0/53)  
1.8% (2/110)  
Have you experienced any side effect at all including 
but not limited to those you've already answered?  
19.3% (11/57)  
7.5% (4/53)  
13.6% (15/110)  

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Each row of the table includes only those subjects with a response of Yes or No.  
 
  
  
Table 2: Side Effects Reported by Subjects at Week 8  
   
Immediate 
Treatment  
Delayed 
Treatment  
Total  
Have you felt weak?  
18.0% (11/61)  
11.7% (7/60)  
14.9% (18/121)  
Have you felt drugged or like a zombie?   
8.2% (5/61)  
3.3% (2/60)  
5.8% (7/121)  
Have you been sweating more than usual?   
6.6% (4/61)  
10.0% (6/60)  
8.3% (10/121)  
Have you felt tired during the day?   
63.9% (39/61)  
63.3% (38/60)  
63.6% (77/121)  
Have you had difficulty staying awake during the day?   
21.3% (13/61)  
28.3% (17/60)  
24.8% (30/121)  
Have you had difficulties waking up fresh in the 
morning?   
65.6% (40/61)  
61.7% (37/60)  
63.6% (77/121)  
Have you gained weight?   
26.2% (16/61)  
20.0% (12/60)  
23.1% (28/121)  
Do you think some foods taste different/odd?   
0.0% (0/61)  
15.0% (9/60)  
7.4% (9/121)  
Have you felt more hungry than usual?   
18.0% (11/61)  
13.3% (8/60)  
15.7% (19/121)  

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Have you been more thirsty than usual?   
18.0% (11/61)  
20.0% (12/60)  
19.0% (23/121)  
Have your stools been hard or difficult to pass?   
26.2% (16/61)  
25.0% (15/60)  
25.6% (31/121)  
Have you needed to go to the toilet often?   
18.0% (11/61)  
10.0% (6/60)  
14.0% (17/121)  
Has your skin been more sensitive to the sun?   
0.0% (0/61)  
3.3% (2/60)  
1.7% (2/121)  
Have you noticed any areas of darker skin?   
3.3% (2/61)  
5.0% (3/60)  
4.1% (5/121)  
Are you experiencing any skin irritation where you 
place the Fisher Wallace device?  
4.9% (3/61)  
1.7% (1/60)  
3.3% (4/121)  
Do you have diabetes?   
1.6% (1/61)  
6.7% (4/60)  
4.1% (5/121)  
Have you been told that your blood sugar levels are 
high?   
6.6% (4/61)  
3.3% (2/60)  
5.0% (6/121)  
Have you noticed a change in your blood sugar levels?  
1.6% (1/61)  
0.0% (0/60)  
0.8% (1/121)  
Has your vision been blurry?   
13.1% (8/61)  
18.3% (11/60)  
15.7% (19/121)  
Have your eyes felt dry and gritty?   
26.2% (16/61)  
20.0% (12/60)  
23.1% (28/121)  
Are you experiencing any unusual eyestrain or 
headaches?  
16.4% (10/61)  
21.7% (13/60)  
19.0% (23/121)  

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Have you found that your words dont come out clearly?   8.2% (5/61)  
5.0% (3/60)  
6.6% (8/121)  
Have you found it difficult to swallow?   
0.0% (0/61)  
1.7% (1/60)  
0.8% (1/121)  
Have you felt anxious?   
37.7% (23/61)  
33.3% (20/60)  
35.5% (43/121)  
Have you felt agitated?   
29.5% (18/61)  
26.7% (16/60)  
28.1% (34/121)  
Have you lost interest in enjoyable things?   
37.7% (23/61)  
31.7% (19/60)  
34.7% (42/121)  
Have you experienced fits/jerks?   
3.3% (2/61)  
1.7% (1/60)  
2.5% (3/121)  
Have your arms or legs been shaky?   
1.6% (1/61)  
1.7% (1/60)  
1.7% (2/121)  
Have you had restless legs?   
8.2% (5/61)  
11.7% (7/60)  
9.9% (12/121)  
Have you been less interested in sex?   
19.7% (12/61)  
21.7% (13/60)  
20.7% (25/121)  
Have you found it difficult to enjoy sex?   
14.8% (9/61)  
13.3% (8/60)  
14.0% (17/121)  
Have you been unable to reach orgasm?   
9.8% (6/61)  
15.0% (9/60)  
12.4% (15/121)  
Have the areas around your nipple been sore and/or 
swollen?   
0.0% (0/61)  
3.3% (2/60)  
1.7% (2/121)  
Have you experienced any side effect at all including 
but not limited to those you've already answered?  
18.0% (11/61)  
8.3% (5/60)  
13.2% (16/121)  
Each row of the table includes only those subjects with a response of Yes or No.  
  

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Subjects in the Immediate Treatment arm experienced a decrease of 10.4 points in BDI-II scores. This 
decrease of greater than ten points is indicative of antidepressant effectiveness.  
More than 40% of the patients had a decrease of 50% in BDI-II or more. Due to high levels of placebo 
response, the between group difference in BDI-II change was -0.8 (p = 0.496). Significantly, and despite the 
fairly large drop in BDI-II during the first four weeks in the sham arm, the switch to active treatment was 
associated with additional improvement (BDI-II decrease from week 4 to 8 of 3.6 points) beyond what they 
had experienced during the first four weeks, while the Immediate Treatment arm only showed minimal 
additional improvement in this period (BDI-II decrease of 0.6 points, p < 0.01), representing an 
improvement of more than 15% from BDI-II scores from the end of the sham period. Thus, the data 
demonstrate the effectiveness of the FW-200 in treating depression.  
5  
BENEFITS AND RISKS OF THE INVESTIGATIONAL DEVICE, CLINICAL 
PROCEDURE AND CLINICAL INVESTIGATION  
5.1  ANTICIPATED CLINICAL BENEFIT  
Participation in this study may treat moderate to severe Major Depressive Disorder in adults (ages 21-65).  
Knowledge gained from this study may enable future patients to benefit from CES.  
5.2  POTENTIAL ANTICIPATED ADVERSE EVENTS  
Potential anticipated adverse events are those that may occur in association with a CES treatment, including 
those AEs listed below that are known risks from clinical experience/use of the FW-200 and similar CES 
devices (Federal Register :: Neurological Devices; Reclassification of Cranial Electrotherapy Stimulator 
Devices Intended To Treat Anxiety and/or Insomnia; Effective Date of Requirement for Premarket Approval 
for Cranial Electrotherapy Stimulator Devices Intended To Treat Depression, n.d.).   
Risks associated with CES and CES devices include:  
● Skin irritation  
● Headaches  
● Dizziness  
● Electrical shocks and burns  
The FW-200 is contraindicated for patients with the following:   
● Demand or sensing type pacemakers, or any other form of implanted electronics  
● Known heart disease  
● A poor reaction to the idea of electrical stimulation of any kind  
● Skin irritation around either electrode site  
● The device should not be used around the Carotid sinus  

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As stated in the CES-MDD User Guide section, the FW-200 should not be used on the throat, neck or eyes. 
Subjects should avoid using the device near areas of the body where there is embedded shrapnel or metal 
plates. There is no danger to subjects using the device who have had dental fillings.   
Subjects may experience skin irritation at the site of sponge electrode placement, especially if the sponges 
deteriorate or if contact is made between the skin and the metal part of the sponge receptacle, or if the 
sponges are not thoroughly wet before each use. Please refer to the CES-MDD User Guide for more 
information.   
5.3  STEPS TO CONTROL OR MITIGATE THE RISKS  
A Risk Management Program has been established by Fisher Wallace Laboratories. Risks associated with 
the FW-200 have been minimized by the design, labeling, and or training. An experienced investigator and 
site staff as well as licensed psychiatric care providers have been chosen to conduct this study.  They have 
been trained on the study protocol as well as the investigational device.  They are familiar with the disease 
state, moderate to severe MDD, and have appropriate experience to evaluate and navigate changing care 
needs for the subjects, if applicable.  Adverse events will also be monitored throughout the study by the 
Principal Investigator and/or designee using the ePRO.     
5.4  RESIDUAL RISKS ASSOCIATED WITH THE INVESTIGATIONAL DEVICE  
Residual risk is defined as the risk remaining after protective measures have been taken. The residual risk 
was reviewed by the Sponsor and deemed acceptable or acceptable with continuous monitoring.   
5.5  OTHER COMPLICATIONS AND RISKS IN CLINICAL USE  
There are no additional risks or complications known during clinical use beyond those already listed in this 
protocol.    
5.6  RISK-TO-BENEFIT RATIONALE  
It is expected that subjects enrolled in this study will not be exposed to risks beyond those normally 
associated with CES devices. CES devices have been extensively studied and the risks have been shown to 
be low. There was a low rate of adverse events in prior research with the FW-200.  
The FW-200 may reduce the risk of moderate to severe MDD in adults. A prior study of the FW-200 in 
adults with mild, moderate, and severe MDD demonstrated very low risk of the device itself, in addition to a 
trend towards improvement in MDD symptoms by week 2 of device usage.    
Based upon review of the risk measures taken with the device and the results of prior studies with the 
FW200, as well as the risk mitigation measures in the protocol, and consideration of the potential benefits to 
study subjects or future patients, the risk/benefit profile for the FW-200 is considered acceptable and 
justifies conducting this study.   

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6  OBJECTIVES AND HYPOTHESIS OF THE CLINICAL INVESTIGATION  
6.1  RATIONALE FOR STUDY ENDPOINTS SELECTION AND MEASUREMENT  
  
The primary endpoint is the change in the Beck Depression Inventory Second Edition (BDI-II) at week two 
of study therapy compared to baseline. A two-week time point for the primary endpoint offers the ability to 
detect an acute change in patient status with use of the FW-200, which may be an advantage over other 
therapies. For example, pharmacological treatment can require titration to a full therapeutic dose, which 
may depend on individual patient characteristics, including the patient’s age, treatment setting, 
comorbidities, concomitant pharmacotherapy, or specific medication side effects, all which may lead to a 
lengthy titration process. Psychotherapy approaches require a similar tailored approach. Guidelines note that 
for both pharmacological and psychotherapy approaches may require 4 to 8 weeks of treatment (Gelenberg, 
2010).  
Secondary endpoints include: Change in BDI-II scores at one and four weeks compared to baseline, change 
in PHQ-9 and QIDS-SR scores at one week, two weeks, and four weeks compared to baseline, and BDI-II 
responder rate (i.e., % of subjects with a 50% or better improvement in score from baseline) at four weeks. 
The PHQ-9 is a validated tool for assessing depression severity and response to treatment (Nida, n.d.) The 
QIDS-SR has been demonstrated to be a valid measure of depression symptom severity in both research and 
clinical settings (Rush et al., 2003). The secondary endpoints of BDI-II at one and four weeks plus the BDIII 
responder rate at four weeks aim to provide additional evidence of effectiveness over additional time points.   
Safety of the FW-200 will be assessed with standard adverse event data collection over the course of the 
study, comparing sham-assigned subject data to active treatment subject data. Adverse events for both sham 
and active device subjects will be MedDRA coded and analyzed for trends.  
During this trial, the subject, Principal Investigator, and Sponsor will be blind to the study treatment 
assignment. The James Blinding Index will be used to assess blinding after the subject completes training on 
device usage.  
  
Only subjects with moderate to severe MDD will be enrolled in the trial.  This triple blind, sham controlled 
study intends to collect data to demonstrate that the FW-200 device delivers CES that improves symptoms 
of moderate to severe MDD in adults.   
6.2  PRIMARY OBJECTIVE  
To demonstrate the safety and effectiveness of FW-200 CES self-administered for the treatment of moderate 
to severe MDD in adults.  
  
6.2.1 PRIMARY ENDPOINT  
This study’s primary endpoint is the change in BDI-II score at two weeks compared to baseline.  

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6.3  SECONDARY ENDPOINTS  
  
This study’s secondary endpoints include:   
● Change in BDI-II score at one and four weeks compared to baseline.  
● Change in PHQ-9 and QIDS-SR scores at one week, two weeks, and four weeks compared to 
baseline.  
● BDI-II responder rate (i.e., % of subjects with a 50% or better improvement in score from baseline) 
at four weeks   
6.4  SAFETY ENDPOINTS  
The safety endpoint is to determine the rate of device and procedure related adverse events.  
6.5  
OBSERVATIONAL DATA COLLECTION   
An evaluation of subject James Blinding Index (JBI) responses versus treatment allocation after initial 
device training will be performed.  
7  DESIGN OF THE CLINICAL INVESTIGATIONS  
7.1  GENERAL  
This prospective, fully remote, randomized, controlled, triple-blind (subject, Principal Investigator, Sponsor) 
pivotal study is designed to evaluate the safety and efficacy of the Fisher Wallace Stimulator FW-200 to 
deliver Cranial Electrotherapy Stimulation (CES), self-administered, for the treatment of moderate to severe 
Major Depressive Disorder (MDD) in adults over 4 weeks.  
  
7.1.1 Study Procedures and Evaluations  
Potential subjects will complete an online pre-screening process to assess whether they are potentially 
qualified to participate in this study. Pre-screening questions will include inclusion/exclusion criteria, 
demographics, medical history, and concomitant medications. Candidate subjects will also take the BDI-II 
and PHQ-9 assessments. Select questions from the Mini International Neuropsychiatric Interview (M.I.N.I.) 
will also be required. The ePRO will be programmed to determine if the candidate’s answers meet eligibility 
criteria for the study. If not, the candidate will be notified via email or SMS text that they are not suitable for 
study participation. If the candidate meets pre-screening eligibility, the ePRO will notify the candidate via 
email or SMS text that a member of the investigational staff will be in contact to further discuss study 
requirements and eligibility.  
Investigative staff will speak with pre-screened potential subjects by telephone to describe study 
expectations and perform the informed consent process. Investigative staff will also ask the candidate to 
confirm that data provided during the pre-screening process is accurate and is allowed to be used for study 
evaluation purposes. If the candidate subject does not consent to study participation or the use of their 
prescreening data, the candidate will be deemed a pre-screen failure. If the candidate subject signs the 

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informed consent form and allows the use of their pre-screening data, the candidate will advance to study 
enrollment.   
From the point of enrollment, subjects in screening will begin a 14-day minimum lead-in period. At the 
conclusion of the lead-in period, screened subjects will retake the BDI-II and PHQ-9 assessments, and 
additionally take the QIDS-SR assessment to establish baseline data. A BDI-II score between 20 and 63, 
inclusive, will serve to indicate that a subject’s moderate to severe MDD has been stable during the lead-in 
period.  
If the BDI-II score is not within the range, the subject’s MDD will be considered insufficiently stable for 
study entry. The subject will be notified that they are no longer eligible for study participation and they will 
be considered a screen failure.  
If the screened subject’s data is within the acceptable range for the BDI-II, the subject will advance to 
scheduling a meeting with a clinician from the investigative team. Via teleconference, the clinician will 
administer the M.I.N.I. assessment and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) 
evaluation.   
If the clinician identifies that the subject’s results do not meet both M.I.N.I. and DSM-5 criteria for 
moderate to severe MDD, the subject will be notified that they are no longer eligible for study participation. 
Additionally, during the live interview, the clinician may deem the subject a screen failure should they no 
longer meet all inclusion criteria or meet any exclusion criteria.   
If the clinician diagnoses the subject with moderate to severe MDD based on the results of the M.I.N.I. and 
DSM-5 assessments, and determines that the subject meets all other eligibility criteria, the subject will be 
prescribed study treatment by the clinician and be randomized to a study treatment arm (sham device or 
active treatment device). Only eligible subjects will be enrolled in the study, randomized to a treatment arm, 
and receive an investigational device shipped directly to them by an unblinded Sponsor designee.    
Prior to starting self-administered therapy with the FW-200 sham or active device, subjects will review an 
online device training video and undergo a live device and ePRO training with investigative staff. The day 
after successfully completing live training with investigative staff, subjects will begin self-administered 
therapy twice per day, one 20-minute session after waking for the day and one 20-minute session before 
going to bed. Each day of study therapy, subjects will confirm in ePRO that they completed both treatment 
sessions for the day. Subjects will also be asked if there have been any changes to their medications or 
health status within the past 24 hours. This will be captured as free text to allow subjects to describe any 
positive or negative (adverse events) experiences during study therapy.  
At the following time points, subjects will retake the BDI-II, PHQ-9, and QIDS-SR assessments:   
● Week 1 (Day 7 of therapy)  
● Week 2 (Day 14 of therapy)  
● Week 4 (Day 28 of therapy)   
For the Week 1 and Week 2 evaluations, subjects will have 2 additional days to complete the assessments. 
For the Week 4 evaluation, subjects will have 5 additional days to complete the assessments. Should a 

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subject complete one of these assessments outside the allowed time window, this instance will be 
documented as a minor protocol deviation. Subjects will not be withdrawn from the study for minor 
protocol deviations.   
Subject participation in the study concludes after completion of the Week 4 evaluation. At that time, subjects 
will be contacted to return the investigational device and log in ePRO any adverse experiences or 
medication changes within the past 24 hours.     
7.1.2 Measures to Minimize or Avoid Bias  
The Principal Investigator is an expert user of the study device and will serve as a trainer on device handling 
for investigative staff. All investigative staff will be trained on the use of the device, this protocol, use of the  
ePRO, and Good Clinical Practices (GCP).  Additional training may be provided to the Principal 
Investigator or investigative staff by Climb, NAMSA, or the Sponsor as needed.   
This study is prospective, randomized, sham controlled study, triple blinded for the subject, Principal 
Investigator, and Sponsor. Randomization provides a level of protection against bias as it tends to balance all 
confounders, both measured and unmeasured. Pre-specified endpoints and analysis plans, with a statistically 
powered sample size further minimize the potential for bias. The planned two-week lead-in period to 
establish a stable baseline should minimize bias due to regression to the mean.   
7.2  SUBJECTS  
7.2.1 Inclusion Criteria for Subject Selection  
Subjects will need to meet all the following inclusion criteria:    
1. Age 21-65 years and a resident of the United States of America  
2. Meets DSM-5 diagnostic criteria for moderate to severe Major Depressive Disorder   
3. Baseline BDI-II score between 20 and 63, inclusive (in moderate to severe range)  
4. Able to receive packages to their home via UPS/FedEx/USPS or other delivery service  
5. Willing and able to send and receive study related text messages on an internet capable mobile 
device throughout the duration of the study   
6. Owns and uses a personal, verifiable email address  
7. Able to commit to two (2) 20-minute treatment sessions per day for 4 weeks, one treatment upon 
waking for the day and one treatment before going to bed  
8. Willing to abstain from use of recreational drugs, hypnotics, steroids, and/or marijuana products 
through study completion   
9. Willingness to not initiate treatment for a mental health issue during the course of the study 10. 
Fluent in English  

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11. Sexually active females of childbearing potential willing to commit to practicing at least one or more 
of the following methods of contraception during the study: intrauterine device (IUD), barrier 
method in combination with a spermicide, oral/hormonal contraception, or abstinence   
12. In the opinion of the investigator, able to comply with study requirements and complete the study  
  
7.2.2 Exclusion Criteria for Subject Selection  
Subjects will not meet any of the following exclusion criteria:  
1. History of suicide attempt or active suicidal ideation with plan or intent in the past 30 days   
2. In the opinion of the investigator, considered high risk of suicide  
3. Previous hospitalization or institutionalization for mental health condition within one year of study 
entry  
4. Underwent electronic brain stimulation or neuromodulation within the past one year, including CES, 
transcranial magnetic stimulation, electroconvulsive therapy, and deep brain stimulation  
5. Modification of prescription medications that affect the nervous system including those for mental 
health issues within 30 days of study entry. A patient who has been on a stable dose of prescription 
medications that affect the nervous system or being used for a mental health issue for at least 30 days 
prior to study entry and are not expected to modify their medication while on the trial are allowed to 
participate.  
6. Use of recreational drugs, hypnotics, steroids, and/or marijuana products in the past 30 days  
7. History of alcohol use disorder or other substance use disorder in the past 12 months  
8. Females currently pregnant or planning to conceive during study participation, or unwilling to 
comply with birth control requirements  
9. Known history of heart disease   
10. Known history of trigeminal neuralgia  
11. Implanted with an electronic device such as a defibrillator, deep brain stimulator, or pacemaker   
12. Unstable medical condition defined as any condition requiring hospitalization or change in treatment 
in the prior 30 days   
13. Legally blind and/or deaf and without in-home care service to assist with study participation  
14. Meets M.I.N.I. assessment criteria for, or has been diagnosed with, any of the following: Bipolar I 
disorder, bipolar II disorder, other specified bipolar and related disorder, panic disorder, agoraphobia, 
social anxiety disorder (social phobia), obsessive-compulsive disorder, posttraumatic stress disorder, 
alcohol use disorder in the past 12 months, substance use disorder (non-alcohol) in the past 12 

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months, any psychotic disorder (e.g., schizophrenia, schizoaffective disorder), major depressive 
disorder with psychotic features, anorexia nervosa, bulimia nervosa, binge-eating disorder, 
generalized anxiety disorder, any cognitive or developmental disorder (e.g., autism, Down’s 
Syndrome), any personality disorder or psychiatric disorder that may interfere with study 
participation  
15. Current participation in another investigational study or participated in an investigational study 
within the past 30 days  
16. In the opinion of the investigator, may not be able to comply with study requirements and complete 
the study  
17. Any employee, family member, or personal associate of the Sponsor or their designees conducting 
the study  
7.2.3 Point of Enrollment   
A subject is considered enrolled in this study after they have signed the informed consent form and 
consented to allow the use of their data collected during the pre-screening process for study evaluations.  
If either of these conditions are not met, the subject will be considered a screen failure if the ICF has been 
signed, or a pre-screen failure if the ICF has not yet been signed.    
7.2.4 Total Expected Duration of the Clinical Investigation  
The total duration of the study enrollment period is anticipated to be three months.  
7.2.5 Number of Subjects Required in the Clinical Investigation  
A total of 250 evaluable subjects (in a 1:1 allocation ratio of treatment and control) are initially planned for 
this study. The subjects will be recruited through the use of digital advertising that Climb and its affiliates 
will singularly manage.  
7.2.6 Expected Duration of Subject Participation  
The expected duration of subject participation is approximately 6 weeks. There is a 2 week lead-in process 
followed by 4 weeks of study treatment.  
7.3  STUDY VISITS 

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7.3.1 Schedule of Assessments  
  
Assessments 
and Device  
Activities   
Recruitment  
 
 
Enrolment  
 
Period 1  
Period 1 
Eval  
Period 2  
Period 2 
Eval  
Period 3  
EOT  
Unschedu 
led  
Activity   
Pre- 
Screening  
Consent and  
Eligibilityc  
Screening  
Lead-In  
Start  
Screening  
Lead-In  
Complete /  
Baseline  
 
Diagnosis   
/  
Randomi 
zation  
Subject 
Trainingc  
Week 1  
Device  
Usage  
 
 
Week 2 
Eval  
Weeks 3- 
4 Device  
Usage  
Week  
4 Eval  
Safety /  
Unsche 
duled  
Clinical  
Interview /  
Reevaluationc  
Week 1 
Eval  
Week 2  
Device  
Usage  
Timeline /  
Window  
(Days)  
Prior to  
Informed  
Consent  
After Initial 
Pre-Screen 
and before 
Lead-In   
Start of  
Lead-In,  
Minimum 
14 Days 
before 
baseline  
Minimum  
14 Days to 
complete 
Lead-In   
 
Prior to  
Day 0  
Prior to  
Day 0  
Day 0 +7  
[first day 
of use 
and 
continui 
ng for 7 
days]d  
 
 
Day 14 + 2 
days  
Day 15 – 
28  
Day 28 
+5 days   
N/A  
Prior to Day 0  
Day 7 + 
2 days  
Days 814 
Inclusion /  
Exclusion 
criteriaa  
X  
  
X  
  
  
  
  
  
  
  
  
  
  
  
Demographics  
X  
  
X  
  
  
  
  
  
  
  
  
  
  
  
Beck  
Depression  
Inventory-II  
(BDI-II)  
X  
  
X  
X  
  
  
  
  
X  
  
X  
  
X  
X  

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Personal  
Health  
Questionnaire  
Depression  
Scale (PHQ-9)  
X  
  
X  
X  
  
  
  
  
X  
  
X  
  
X  
X  
Mini- 
International 
Neuropsychiat 
ric Interview  
X  
  
X  
  
Xe  
  
  
  
  
  
  
  
  
  
(MINI) 
questions  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
Medications  
X  
  
X  
  
  
  
  
  
  
  
X  
  
X  
  
Medical 
History  
X  
  
X  
  
  
  
  
  
  
  
  
   
   
  
Informed 
Consent  
  
X  
  
  
  
  
  
  
  
  
  
  
  
  
Eligibility 
Evaluationb  
   
X  
  
  
X  
  
  
  
  
  
  
  
  
  
Quick  
Inventory of  
Depressive  
Symptomatolo 
gy-Self Report 
(QIDS-SR)  
  
  
  
X  
  
  
  
  
X  
  
X  
  
X  
X  

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DSM-5  
Interview  
   
  
  
  
X  
  
  
  
  
  
  
  
  
  
DSM-5  
Diagnosis  
   
  
  
   
  
X  
  
  
  
  
  
  
  
  
Randomizatio 
n  
   
  
  
   
  
 X  
  
   
  
  
   
   
   
   
Device 
Training  
   
  
  
   
  
   
X  
   
  
  
   
   
   
   
Device  
Usage/Diary  
   
  
  
   
  
   
   
X  
  
X  
   
X  
   
   
Device Return  
   
  
  
   
  
   
   
   
  
  
   
   
X  
X   
(if  
applicable 
)  
Adverse 
Events  
   
  
  
   
  
   
   
X  
X  
X  
X  
X  
X  
X  
 
 

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a 
Inclusion/Exclusion Criteria during Pre-Screening within the Recruitment Phase includes the potential subject’s ability to meet 
inclusion or exclusion criteria that do not require assessment by a clinician from the investigative staff.  
b 
Eligibility Evaluation occurs after informed consent is signed. This includes review of all potential subject data received to 
determine if inclusion criteria are met and no exclusion criteria are met. c Study Activity that requires telephone contact with the candidate 
subject/subject. d Day 0 is defined as the first day of the subject’s self-administered treatment. e Complete M.I.N.I. interview conducted by 
the clinician with the subject.  

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7.3.2 Prescreening  
Potential subjects will be directed to a website (https://trials.climb.care/participate). The website will 
provide potential subjects with information regarding the study and expectations.  They will also be 
presented with an information privacy policy which they must confirm they agree with prior to submitting 
responses for investigative staff review.      
Interested participants will complete the following pre-screening assessments in ePRO:   
● Eligibility questions pertaining to Inclusion/Exclusion criteria (includes medical history and 
concomitant medications)  
● Demographics  
● BDI-II  
● PHQ-9  
● Questions from M.I.N.I.  
The website will inform the potential subject if they are a potential candidate for the study based on their 
initial answers.   
7.3.2.1 Demographics  
The candidate subject will provide the following demographic information: self-identified gender, biological 
sex, age, race, and ethnicity.   
7.3.2.2 BDI-II  
To assess severity of depression, the potential subject will answer this 21-question multiple-choice selfreport 
inventory. The candidate subject’s BDI-II score must be within the range of 20-63 indicating moderate to 
severe MDD.    
7.3.2.3 PHQ-9  
The candidate subject will answer this questionnaire, a 9-item scale covering the DSM criteria for major 
depressive disorder, with a diagnostic algorithm and score based assessment of presence and severity of 
depression.  
7.3.2.4 Mini International Neuropsychiatric Interview (M.I.N.I.)  
The candidate subject will self-report their answers to select questions from the M.I.N.I using ePRO.  The 
M.I.N.I. is an assessment tool for the major psychiatric disorders in DSM-5 (Sheehan et al., 2010).  If any 
answers indicate that the subject may be experiencing a condition that meets any exclusion criteria, the 
candidate will not advance further in the pre-screening process.   
  

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7.3.3 Consent and Initial Eligibility  
Potential subjects who successfully complete the automated pre-screening process will be contacted by 
investigative staff to schedule a telephone or video conference. During this meeting, the investigative staff 
will review the purpose of the study, the daily requirements of study participation, answer any preliminary 
questions from the candidate, and confirm that the data provided during pre-screening is still accurate. 
Should the subject indicate that data reported during pre-screening requires revision/correction, the 
investigative staff will review the change(s) and determine if the candidate is still potentially eligible for 
study entry. If not, the investigative staff will inform the candidate that they are no longer able to be 
considered for the study. If the change does not cause the candidate to fail pre-screening, the investigative 
staff will make the change in ePRO and enter a reason for change in ePRO as well. The ePRO includes an 
audit history to display changes to reported data, the author of the change, and the date/time when the 
change was saved.   
If the candidate agrees to learn more about the study, the study staff member will perform the informed 
consent process. Investigative staff will also ask the candidate to confirm that the data collected during the 
pre-screening process can be used for study screening and evaluation purposes. If the candidate subject does 
not consent to study participation or to the use of their pre-screening data, the candidate will be deemed a 
pre-screen failure. All pre-screening data for that candidate will not be saved in ePRO for the study. If the 
candidate subject signs the informed consent form and allows the use of their pre-screening data for the 
study, the candidate will advance to study enrollment.   
7.3.3.1 Informed Consent  
The investigative team will introduce the potential participant to the clinical investigation by explaining the 
protocol including the study objectives, procedures, and participation requirements.   
If the potential participant is interested in participating, the study staff will review the informed consent 
form. This will include describing the clinical investigation, potential discomforts, risks, and benefits of 
participation. The potential subject will have sufficient time to decide whether they wish to participate in 
this clinical investigation.   
Any queries that the potential participant may have regarding this clinical investigation will be addressed 
appropriately by the investigative team.  Potential subjects will be instructed that they are free to obtain 
further information from the Principal Investigator and investigative team at any time and that they are free 
to withdraw their consent and to discontinue their participation in the clinical investigation at any time 
without prejudice.  
If the potential participant is willing to participate in the clinical investigation, he/she must read, understand 
and sign the informed consent form. The informed consent form will be sent to the potential subject 
electronically via a validated signature program such as DocuSign. The potential subject will be asked to 
complete the electronic signature of the form. The Principal Investigator or designee who conducted the 
informed consent discussion will also sign. A copy of the signed consent will be provided to the subject 
electronically.    

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Written or electronic informed consent from the subject must be obtained before any clinical investigation 
related procedures are performed.  
7.3.4 Screening Lead-In and Baseline  
Upon signing the informed consent form, subjects will begin the screening lead-in period of 14-days 
minimum. No data will be collected from the subject during this time; however, the data collected during 
pre-screening will be saved in ePRO as study eligibility data.  
After 14 days of lead-in time, subjects will be prompted to retake the BDI-II and PHQ-9 assessments in 
ePRO. Subjects will also take a QIDS-SR assessment in ePRO. A subject must have a BDI-II score between 
20 and 63, indicating moderate to severe MDD, at both initial pre-screening and baseline to participate in 
the study.   
If the BDI-II assessment score is not within the moderate to severe MDD range, the subject’s health will be 
considered insufficiently stable for study entry. The subject will be notified that they are no longer eligible 
for study participation and they will be considered a screen failure.  
If the screened subject’s data is within the moderate to severe MDD range for the BDI-II assessment, the 
subject will advance to scheduling a meeting with a clinician from the investigative team.  
7.3.5 Clinical Interview and Eligibility Reevaluation  
Subjects with baseline BDI-II scores within the range of moderate to severe MDD will be contacted to 
schedule a meeting with a clinician from the investigative staff.  
During this teleconference or video conference with the subject, the clinician will conduct the M.I.N.I. and 
DSM-5 assessments to evaluate the subject for moderate to severe MDD. If the clinician determines that the 
subject cannot be diagnosed with moderate to severe MDD, the subject will be deemed a screen failure and 
discontinued from study participation. Subjects who have or appear to have any of the following diagnoses 
or conditions will also be excluded from further study participation and documented as a screen failure:   
● Bipolar I disorder  
● Bipolar II disorder  
● Other specified bipolar and related disorder  
● Panic disorder  
● Agoraphobia  
● Social anxiety disorder (social phobia)  
● Obsessive-compulsive disorder  
● Posttraumatic stress disorder  
● Alcohol use disorder in the past 12 months  
● Substance use disorder (non-alcohol) in the past 12 months  
● Any psychotic disorder (e.g., schizophrenia, schizoaffective disorder)  
● Major depressive disorder with psychotic features  
● Anorexia nervosa  

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● Bulimia nervosa  
● Binge-eating disorder  
● Generalized anxiety disorder  
● Any cognitive or developmental disorder (e.g., autism, Down’s Syndrome)  
● Any personality disorder or psychiatric disorder that may interfere with study participation  
Subjects who meet moderate to severe MDD criteria per the M.I.N.I. and DSM-5 assessment will be 
diagnosed as having moderate to severe MDD by the clinician.  
After confirming a diagnosis of moderate to severe MDD for the subject, the clinician will review the 
subject’s reported information in ePRO to ensure the subject continues to meet study eligibility criteria. Any 
subject who fails to fulfill any element of the inclusion and exclusion criteria will be considered a screen 
failure.  
Subjects who meet all study eligibility criteria and receive a diagnosis of moderate to severe MDD from the 
clinician will advance to receiving a prescription for an investigational device to be used during the study.   
7.3.6 Subject Identification and Randomization   
Once eligibility is confirmed by the clinician and a prescription is written for the investigational device, the 
subject will be assigned a unique identification (ID) number by Climb. The subject ID number will consist 
of 01 for the first subject, 02 for the second subject, and so on.  This number will be used to identify the 
subject during their participation in the study. Climb will maintain a log of all subjects enrolled in the 
clinical study including their names, their study ID number, and contact information.   
The subject will also be randomized (approximately 1:1) to either the treatment group (active device) or the 
control (sham device).  Climb will create and maintain the randomization table and assign subjects to each 
group. The randomization data will be restricted to unblinded investigative staff members only until the 
conclusion of the study. The unblinded team will be responsible for maintaining the randomization table.  
7.3.6.1 Device Shipment  
An unblinded investigative staff member who is not associated with any other function of the study will 
receive the subject’s randomization allocation and contact/shipping address information. The study device 
type, either sham or active treatment, assigned to the subject through the randomization process will be 
directly shipped to the location requested by the subject by a third party vendor in collaboration with the 
unblinded investigative staff member.   
7.3.7 Subject Training  
The subject will be advised to not use the investigational device until after receiving live training. Prior to 
the live training, the subject will be asked to complete online device training using pre-recorded videos.   
Once the subject receives the investigational device, they must participate in a live training with 
investigative staff to further learn how to correctly place and use the device, clean the device components 
that will be reused, and complete data collection in ePRO. The trainer will explain that the device is locked 

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at Level 2 and that the subject may or may not feel a sensation of stimulation, regardless of whether the 
device is a placebo or active device.    
The subject will confirm in ePRO that their training was completed. The trainer will also record in ePRO 
that training was completed. The subject will continue to have access to the pre-recorded instructional video 
and usage manual during the study as needed for additional reference and may contact the investigative staff 
for device handling support during the study.   
7.3.7.1 James Blinding Index  
After participating in the live device training session with investigative staff, the subject will be asked in 
ePRO which type of investigational device they believe they received (active device or control). The subject 
will select from 5 options to indicate if they strongly believe they have an active device, somewhat believe 
they have an active device, do not know, somewhat believe they have a sham device, or strongly believe 
they have a sham device. The subject’s response will be analyzed using the James Blinding Index.   
7.3.8 Period 1: Week 1 Device Usage  
Subjects will begin using the investigational device the day after the live training session with investigative 
staff. Subject will use the device as instructed, for 20 minutes after waking for the day and for 20 minutes 
prior to going to bed. Each day of study therapy, subjects will report in ePRO whether or not they used the 
study device as instructed and if there had been a change to their health status or medications over the 
previous 24 hours.     
7.3.9 Period 1: Week 1 Evaluation  
After completion of at least 1 week (7 days plus up to 2 additional days) of device usage, subjects will be 
requested to complete the following in ePRO:  
● BDI-II  
● PHQ-9  
● QIDS-SR  
● Any Adverse Events  
● Any changes to their reported concomitant medications  
7.3.10 Period 2: Week 2 Device Usage  
Subjects will continue daily use of the device and report in ePRO whether or not they used the study device 
as instructed and if there had been a change to their health status or medications over the previous 24 hours.   
7.3.11 Period 2: Week 2 Evaluation   
After completing Week 2 (7 days plus up to 2 additional days) of device usage, subjects will be requested to 
complete the following in ePRO:  

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● BDI-II  
● PHQ-9  
● QIDS-SR  
● Any Adverse Events  
● Any changes to their reported concomitant medications  
7.3.12 Period 3: Weeks 3-4 Device Usage   
Subjects will continue daily use of the device and report in ePRO whether or not they used the study device 
as instructed and if there had been a change to their health status or medications over the previous 24 hours.   
7.3.13 End of Therapy: Week 4 Evaluation   
After completion of at least 4 weeks (28 days plus up to 5 additional days) of device usage, subjects will be 
requested to detail or answer the following in ePRO:  
● BDI-II  
● PHQ-9  
● QIDS-SR  
● Any Adverse Events  
● Any changes to their reported concomitant medications  
At End of Therapy, subjects will be contacted to return the study device to the unblinded Sponsor 
representative. Investigative staff will verify all subject data has been completed and exit the subject from 
the study.   
7.3.14 Unscheduled Visits  
Should a subject be withdrawn early from the study, investigative staff will ask the subject to report the 
adverse event in ePRO (if applicable), and complete the following assessments:   
● BDI-II   
● PHQ-9  
● QIDS-SR  
The investigative staff will also assist the subject in returning the investigational device.   
7.3.15 Criteria and Procedures for Subject Withdrawal or Discontinuation  
7.3.15.1 Subject Withdrawal and Discontinuation  
During the course of this clinical investigation, subjects will be or may elect to withdraw from further 
treatment.   

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All subjects discontinued from the clinical investigation due to an unexpected adverse device effect, directly 
related to the clinical investigation, will be followed by investigative staff to the best of their ability until the 
effect resolves, or reaches a stable condition, in case of the undesirable event of an occurred permanent 
impairment. Investigative staff will document in ePRO the date and reason(s) for subject withdrawal. All 
subjects who discontinue treatment for any reason shall be contacted by investigative staff in an effort to 
follow the subject for safety.  
Subjects have the right to withdraw from the study at any time and for any reason without prejudice to their 
future medical care by the study personnel or institution. If a subject decides to withdraw, all study 
evaluations and procedures will be stopped, and an inquiry will be made about the cause of withdrawal. 
Climb will account for and document all subjects enrolled in the study, including those withdrawn from the 
study or lost to follow-up. If a subject withdraws from the clinical investigation, the reason(s) shall be 
reported in ePRO.  
Reasons for withdrawal include, but are not limited to:  
● Subject’s rescission of consent.   
● Any unexpected adverse device effect which is, in the opinion of the Principal Investigator, related 
to the device and will endanger the wellbeing of the subject if the treatment is continued.  
● The development of any undercurrent illness(es), infection or condition(s) that might interfere with 
the Clinical Investigation Plan.  
● Any problem deemed by the Principal Investigator and Sponsor to be sufficient to cause 
discontinuation.   
● Lost to follow-up  
● Death  
Additional study data may no longer be collected after the point at which a subject has been withdrawn from 
the study or withdraws his/her consent. Data collected up to the point of subject withdrawal will be used for 
analysis.  
Subjects who are withdrawn will not be replaced if they have received the investigational device. If possible, 
any assessments planned for the subject on withdrawal from the clinical investigation, including adverse 
event collection, should be performed when intention to withdraw the subject is announced.  
Subjects who are withdrawn prior to receiving an investigational device will be replaced, including screen 
failures.  
7.3.15.2 SUBJECT REPLACEMENT  
Subjects may be replaced if they are screen failures.    

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7.3.15.3 LOST TO FOLLOW-UP  
The effort to obtain follow-up information should include 3 attempts to make contact with the subject via 
telephone or text. All contact efforts to obtain follow-up information should be documented in ePRO.   
7.4  MONITORING  
All source data and documentation will be reviewed for completeness and appropriateness by investigative 
staff.    
The Principal Investigator and Climb will permit the Sponsor (or designee) and the FDA to inspect source 
documentation and data for this study. These inspections are for the purpose of verifying adherence to the 
protocol and the completeness and accuracy of the data recorded in ePRO.   
7.4.1 Source Data and Documentation  
For this patient-reported decentralized clinical trial, source data is defined as all information in original 
records of clinical findings, observations, or other activities in a clinical investigation, necessary for the 
reconstruction and evaluation of the clinical investigation. Data entered into ePRO by subjects and/or 
investigative staff will be considered one form of source data for this study.  
Source documents are defined as printed, optical, or electronic documents containing source data, e.g., 
prescriptions for the device, device accountability records, and any medical records kept by the investigative 
staff in support of this clinical investigation.   
7.4.2 Audits and Inspections  
The FDA and the Notified Body have the right to conduct an audit of the clinical investigation to ensure that 
the clinical investigations was, in fact, performed by the investigative staff and that the data reported in 
support of a marketing application accurately reflects the data in the records. The authority may also inspect 
such studies to verify that the clinical investigation was conducted in accordance with national regulations 
relating to the IRB and informed consent.  It is the joint responsibility of the Sponsor and the Principal 
Investigator to ensure that the clinical investigation has been conducted in line with all national and local 
regulations.  
In the event that the FDA or Notified Body desires to inspect this clinical investigation, the Sponsor, 
Principal Investigator, Climb, and NAMSA will permit authorized inspectors to inspect all facilities and 
records relating to the clinical investigation and aid the Inspector to perform the audit in a timely fashion.   
Separately, during the conduct of this clinical investigation, Fisher Wallace  may appoint Quality Assurance 
(QA) personnel to audit the administration and conduct of the clinical investigation.  
8  
STATISTICAL DESIGN AND ANALYSIS  
Statistical analysis for the study will focus on the randomized comparison of groups for study endpoints. 
Key elements of the planned statistical analysis are outlined below. Additional details, including more 

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details regarding plans for analysis populations, subgroups, secondary endpoints, handling missing data, and 
sensitivity analyses will be provided in a separate standalone Statistical Analysis Plan.  
8.1  ANALYSIS POPULATION  
The primary analysis will be based on intent-to-treat, with subjects analyzed as randomized regardless of 
treatment actually received.    
8.2  DESCRIPTIVE STATISTICS  
Continuous data will be summarized with mean, standard deviation, median, minimum, maximum, and 
number of evaluable observations. Categorical variables will be summarized with frequency counts and 
percentages. Confidence intervals may be presented, where appropriate, using the t-distribution for 
continuous data and Clopper-Pearson Exact method for categorical variables.  
8.3  ANALYTICAL PROCEDURES  
The primary endpoint is the change in BDI-II at week 2 compared to baseline. Analysis will be based on a 
linear model for change, adjusted for each subject’s baseline value. The mathematical statement of the null 
and alternative hypothesis for primary endpoint is:  
Ho: B2 ≤ 0   
Ha: B2 > 0 where B2 represents the regression coefficient from the linear model corresponding to 
study arm, parameterized so a regression coefficient greater than zero represents a greater mean change 
for the treatment group compared to the control group. The general form of the linear model for each 
endpoint is:  
ΔY = B0 + B1Y0 B2*X  
where ΔY is the change in outcome from baseline at week 2, B0 is the intercept term, B1 is the coefficient 
for the subject’s baseline value Y0, and X is the treatment group indicator (1 = treatment, 0 = sham). 
Multiple imputation will be employed to address missing data.   
Study success will be based on successful rejection of the null hypothesis for the primary endpoint.  
Subgroup analysis will be provided based on sex and race as well as potentially other baseline factors, 
including baseline BDI-II score.   
8.4  SIGNIFICANCE LEVEL AND POWER OF THE PRIMARY ENDPOINT AND OVERALL STATISTICAL 
TESTING STRATEGY  
The primary endpoint analysis will be performed at the one-sided 0.025 alpha level. Any other p-values and 
confidence intervals will be based on a nominal two-sided 0.05 alpha level (or equivalently a one-sided 
0.025 alpha level as appropriate) without adjustment for multiple comparisons.   

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8.5  
SAMPLE SIZE CALCULATION AND JUSTIFICATION  
A total of 250 evaluable subjects (in a 1:1 allocation ratio) will provide 80% power assuming a population 
mean difference between groups of 3.2 and a common standard deviation of 9 based on a two-sided 
twosample t-test with an alpha of 0.05. Previous data suggests the standard deviation for 2 week 
improvement to be approximately 6.5; however, a conservative estimate of 9 was used for these 
calculations. If the observed standard deviation is less than 9, a smaller effect size will provide 80% power. 
In addition, this calculation is conservative since the planned test adjusting for baseline is expected to 
provide additional power. Sample size calculations were performed using PASS 2021 (NCSS, LLC).  While 
some amount of missing data is expected, the primary analysis will be based on the randomized cohort of 
subjects and will employ multiple imputation to mitigate the impact of missing data.   
The sample size for the study is practically constrained by regulatory requirements for timely submission 
and the impact of the COVID-19 pandemic. Accordingly, while the final formal analysis is planned for the 
final planned sample size, circumstances may dictate initial regulatory submission based on data available 
with supplemental updates provided later based on the final data set. Since the formal analysis will be based 
on the final planned sample size, there are no alpha implications.   
9  DATA MANAGEMENT  
9.1  
PROCEDURES FOR DATA MANAGEMENT  
Climb will be responsible for study data management according to a project plan developed for this study in 
collaboration with the Sponsor and designee(s).  
  
The details of data review and querying will be described in a Data Management Plan (DMP) that will be 
maintained by Climb, the Principal Investigator, and the Sponsor. This plan may be updated throughout the 
investigation as amended data management requirements and investigation-specific data conventions are 
determined.  
9.1.1 Electronic Patient Reported Outcomes  
The Climb web-based ePRO digital health technology will be used to record and manage study data. 
Subjects who have been screened for study participation and signed an Informed Consent Form will 
selfreport their experiences during the trial using the ePRO. Subject training on ePRO usage will be 
conducted prior to starting study treatment with the investigational device. Investigative staff will be 
available to answer questions from subjects about ePRO usage and assist them with technological issues or 
clarifications.   
Investigative staff will review all subject-entered ePRO data to monitor subject safety and identify any 
issues pertaining to study design or the investigational product. A subject may contact the investigative team 
should they wish for their reported data to be reised or corrected. An investigative team member will make 
the change in ePRO and enter a reason for change in ePRO as well. The ePRO includes an audit history to 
display changes to reported data.   

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9.1.2 Data Queries   
Sponsor representatives reviewing subject ePRO data may contact the subject for clarification of data or to 
follow up for missing data. All changes to ePRO data will be captured in an audit trail.  
9.1.3 Confidentiality  
  
This clinical investigation will comply with HIPAA and any additional requirements imposed by national 
law concerning data protection.  
A study code identification number will be used to facilitate creation of de-identified reports. Subject 
personal data will be processed at all times in accordance with applicable legal requirements and will be 
used solely for the purposes of conducting this clinical study and to aid future scientific research in the 
treatment of moderate to severe depressive disorder. In general, only the Sponsor or authorized designees 
will have direct access to subject personal data. It may also happen that representatives of national or 
international public health authorities (e.g., Competent Authorities) are granted direct access to subject 
personal data, if required by applicable law.  
9.2  PROCEDURES FOR VERIFICATION AND VALIDATION OF EPRO SYSTEM  
The ePRO used for this trial was verified and validated by Climb’s procedures for data capture validation 
and verification.   
9.3  
PROCEDURES FOR DATA RETENTION   
The Climb procedures for study data retention will be followed. All information in the ePRO will be stored 
in a secure validated database.  
9.4  SPECIFIED RETENTION PERIOD  
  
The Sponsor shall maintain the records of the study during this investigation and for a period of 2 years after 
the later of the following two dates: The date on which the investigation is terminated or completed, or the 
date that the records are no longer required for purposes of supporting a premarket approval application, a 
notice of completion of a product development protocol, a humanitarian device exemption application, or a 
premarket notification submission.  
9.5  CLINICAL QUALITY ASSURANCE  
  
The study will be conducted and monitored by the Sponsor and authorized designees. The Sponsor may 
appoint a Quality Assurance (QA) auditor to review the records and conduct of the study.  
10 AMENDMENTS TO THE PROTOCOL  
Any modifications to the protocol require Sponsor approval.  Once completed, the revised protocol needs to 
be submitted to the IRB. The protocol must receive written approval as an Amendment prior to 
implementing the modifications.  

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11 DEVIATIONS FROM THE PROTOCOL   
11.1 INVESTIGATOR DEVIATIONS FROM PROTOCOL  
Major deviations from this protocol, except in emergency situations, require prior approval by the Sponsor. 
This provision does not apply to those changes made to reduce discomfort or overt risks to the subject. All 
major deviations and any procedures or actions taken by investigative staff must be documented in the 
ePRO and reported to the Sponsor within 2 days.  
Minor deviations (e.g. assessment unable to be completed or outside visit window) may occur from time to 
time.  The investigative staff should make their best effort to minimize such occurrences.  Should a minor 
deviation occur, it should be documented in the ePRO in a timely manner.    
11.2 PROCEDURES FOR DEVIATION RECORDING, REPORTING AND ANALYZING  
All deviations will be documented in the subject's ePRO Case Report Form and reported to the Sponsor 
within 2 days.  
11.3 CORRECTIVE AND PREVENTIVE ACTIONS AND PRINCIPAL INVESTIGATOR DISQUALIFICATION CRITERIA  
Protocol deviations will be reviewed during monitoring visits. As appropriate, investigators will be required 
to identify corrective and preventive actions to prevent further deviations. An investigator may be 
disqualified from the study for repeated and/or egregious protocol deviations.  
12 DEVICE ACCOUNTABILITY   
12.1 INVESTIGATIONAL DEVICE DISPOSITION  
  
Access to investigational devices shall be controlled by the Sponsor and authorized designee. The 
investigational devices shall be used only in this clinical investigation and according to the clinical trial 
protocol. The Sponsor shall keep records of the type and number of all investigational devices shipped to 
subjects including device return or disposal.   
12.2 CLINICAL SUPPLIES ACCOUNTABILITY  
  
The investigational devices provided for use in this study are intended for use only in the clinical trial 
outlined in this protocol and will be used only in subjects appropriately consented in this trial. The use of the 
supplies for other clinical or preclinical situations is strictly prohibited. The use of the investigational 
supplies by any third party, outside of the provisions stated in this protocol, without the express written 
permission of Sponsor, is strictly prohibited. The possession and use of the supplies by subjects must be 
closely controlled and monitored. Subjects will be required to return the used devices at the conclusion of 
their study participation (End of Therapy or early withdrawal/termination). All investigational supplies that 
are not used on a subject will be returned to the Sponsor at the end of the study.  

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The Sponsor or authorized designee shall keep records documenting the receipt, use, return and disposal of 
the investigational devices, which shall include:  
● the date of receipt,  
● identification of each investigational device (lot number/serial number or unique code),  
● the expiry date, if applicable,  
● the date or dates of use,  
● subject identification,  
● date on which the investigational device was returned/removed from subject, if applicable, 
and,  
● the date of return to the Sponsor of unused, expired or malfunctioning investigational 
devices, if applicable.  
12.3 INVESTIGATIONAL DEVICE ACCOUNTABILITY RECORD  
  
Investigational devices will be shipped directly to subjects by the Sponsor’s authorized blinded designee.  
Upon receipt of the investigational device, the subject will record confirmation of receipt in ePRO. The 
Sponsor’s authorized designee will review ePRO device accountability data in a timely manner to ensure 
accurate record keeping of final disposition of all investigational materials. Device accountability data in 
ePRO will be reconciled with the Sponsor’s investigational device shipping and return records during the 
trial.  
13 REGULATORY COMPLIANCE  
13.1 STATEMENTS OF COMPLIANCE  
● This clinical investigation will be conducted in compliance with the principles that have their origin 
in the latest version of the Declaration of Helsinki, October 2013.  
● This clinical investigation will comply with 21 CFR Parts 11, 50, 54, 56, and 812 requirements of 
FDA, the requirements of the IRB, ISO 14155:2020, and other applicable regional or national 
regulations, whichever provides the greater protection of the individual.  
● This clinical investigation will not begin until required approval(s)/favorable opinion(s) have been 
obtained from the applicable IRB or regulatory authority.  
● Any additional requirements imposed by an IRB or regulatory authority will be followed in the 
conduct of this clinical trial.  
● The Sponsor has obtained clinical trial insurance that will cover expenses in the event of any 
physical injury resulting from research procedures.   

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13.2 INSTITUTIONAL REVIEW BOARD   
Prior to the initiation of this clinical investigation, on behalf of the Principal Investigator, Climb will submit 
the protocol, patient-facing materials, informed consent form template, and any other required documents to 
the IRB for review and approval.  The Principal Investigator, and any other member of the investigative 
team, if a member of the IRB, must not participate in the decision-making. A list of the members of the IRB 
reviewing this protocol will be requested.  
A signed and dated letter from the IRB granting approval/favorable opinion must be received prior to the 
initiation of the clinical investigation.    
13.3 PROVISION OF INVESTIGATIONAL DEVICE  
Investigational products will not be shipped to the first enrolled subject until investigative staff responsible 
for conducting device training with subjects have themselves completed the required training on device 
usage/handling and this clinical study protocol.   
  
13.4 PRINCIPAL INVESTIGATOR’S STUDY REPORTING RESPONSIBILITIES  
The Investigator agrees to the following reporting responsibilities:  
● Collaborate with the Sponsor, NAMSA, and Climb to provide the required reports to the IRB for the 
duration of the study. Copies of IRB correspondence must be provided to the Sponsor for Trial 
Master File filing.  
● Collaborate with Climb and NAMSA to submit the Investigator’s Final Report to the IRB per the 
IRB’s requirements after the study’s completion or termination.  
● Collaborate with the Sponsor, Climb, NAMSA, and investigative staff to receive any pertinent 
details that may impact the conduct of the clinical study and require IRB reporting per IRB policy.  
14 INFORMED CONSENT PROCESS  
14.1 GENERAL INFORMED CONSENT PROCESS  
  
The Sponsor will provide a template informed consent form (ICF) for IRB review/approval.   
The Principal Investigator or investigative staff designee must administer this approved ICF to each 
prospective study subject, and obtain the subject's signature along with the date of consent prior to 
enrollment in the study. The ICF for this study will be electronic and signatures will be obtained via 
DocuSign or a similar platform. The ICF must be obtained in accordance with the applicable guidelines 
of the Declaration of Helsinki, or local regulations and laws, whichever represents the greater protection 
of the individual.  Subjects must be informed about their right to withdraw from the study at any time 
and for any reason without sanction, penalty, or loss of benefits to which the subject is otherwise entitled 
and also be informed that withdrawal from the study will not jeopardize their future medical care.  A 

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copy of their signed ICF must be given electronically to each subject enrolled in the study.  This will be 
provided electronically for their records. The institutional standard subject consent form does not replace 
the study ICF.  
15 ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND DEVICE 
DEFICIENCIES  
  
In this trial, all adverse events (AEs) and device deficiencies that occur will be reported by the subject using 
ePRO and reviewed by the Sponsor (or designee) and Principal Investigator in a timely manner. All AEs will 
be followed by the Sponsor and Principal Investigator or designee until the last event has resolved, the 
condition has stabilized, or the subject exits the trial, whichever comes last. All follow up reports for AEs 
will be documented in detail in the ePRO.   
15.1 DEFINITIONS  
  
Adverse Event (AE): Any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to 
the investigational medical device and whether anticipated or unanticipated.  
1. This definition includes events related to the investigational medical device.  
2. This definition includes events related to the procedures involved.  
3. For users or other persons, this definition is restricted to events related to investigational medical 
devices.  
Adverse Device Effect (ADE): Adverse Event related to the use of an investigational medical device.  
1. 
This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device.  
2. 
This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device.  
Device Deficiency: Inadequacy of a medical device with respect to its identity, quality, durability, reliability, 
usability, safety, or performance. Device deficiencies include malfunctions, use errors, and inadequacy in 
the information supplied by the manufacturer including labeling.  
Serious Adverse Device Effect (SADE): Adverse Device Effect that has resulted in any of the 
consequences characteristic of a serious adverse event.  
Serious Adverse Event (SAE): Adverse Event that led to any of the following:  

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(a) 
death;  
(b) 
serious deterioration in the health of the subject, that resulted in any of the following:  
i. 
a life-threatening illness or injury, or  
ii. 
permanent impairment of a body structure or a body function including chronic 
diseases, or iii.     
inpatient or prolonged hospitalization, or  
iv.     medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function,  
(c) 
fetal distress, fetal death or a congenital physical or mental impairment or birth defect.  
NOTE: Planned hospitalization for a pre-existing condition, without serious deterioration in health, 
is not considered a serious adverse event.  
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or any 
lifethreatening problem or death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the investigational plan or application 
(including a supplementary plan or application), or any other unanticipated serious problem associated with 
a device that relates to the rights, safety, or welfare of subjects.  
NOTE: An anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity, or outcome has been identified in the risk assessment.  
15.2 REPORTING  
  
15.2.1 Investigator Responsibilities  
All Serious Adverse Events (SAEs), Serious Adverse Device Effects (SADEs, both Anticipated or  
Unanticipated), including any Device Deficiency that could have led to an SADE, must be reported to the 
Sponsor or designee within 24 hours of knowledge of the event. It is the responsibility of the Sponsor or 
designee to report the occurrence of any SAE, SADE, and/or UADE to the IRB according to IRB guidelines 
and national laws and regulations.  
The Principal Investigator or designee will contact all subjects who record an adverse event or potential 
adverse event in ePRO. The subject will be asked to provide the following for the event:  
● Any further details about the event or the subject’s experience using the investigational product not 
already recorded in ePRO, if deemed necessary by the investigator  ● Outcome, with options to 
include:  
○ Ongoing/Not Resolved/Not Recovered  
○ Recovering/Resolving  
○ Recovered/Resolved   

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○ Recovered/Resolved with Sequelae  
○ Unknown  
● Resolution date if the outcome is reported as recovered/resolved, with or without sequelae ● Any 
treatments taken for the event and/or any actions taken to receive or schedule treatment ● Action 
taken with the study treatment in response to the event, with options including:  ○ No action  
○ Discontinuation of study treatment  
○ Temporary halt of the study treatment; if temporary halt, the subject will be asked if the event 
resolved or continued after stopping the study treatment and the dates when treatment was 
paused.  
● Relationship of the event to the use of the investigational device, reported as either Related or Not 
related  
The investigator will review all of the reported information from the subject and separately record their 
causality using the following options:   
● Not Related: An AE which cannot be attributed to the study device.  
● Unknown Relationship: The relationship of the AE to the device cannot be determined.  
● Possible: The AE occurs within a reasonable time sequence to study device usage and there is some 
evidence to “possibly” suggest a causal relationship. However, the influence of other factors such as 
underlying disease, concomitant medications, or concurrent treatment may have contributed to the 
event.  
● Probable: The temporal sequence between the device use and the event is such that the relationship 
is likely or subject’s condition or concomitant therapy could have caused the AE.  
● Definite: The AE occurs in a plausible time relationship to study device usage and cannot be 
explained by any concurrent disease or other devices, drugs or chemicals.  
Additionally, the investigator will record in ePRO if the AE meets the definition of a Serious Adverse Event 
(SAE) as per the definition in Section 15.1.  
  
15.2.2 Sponsor Responsibilities  
  
All adverse events and device deficiencies will be reviewed by the Sponsor to assess regulatory reporting 
responsibilities for the event. The Sponsor will maintain records concerning adverse device effects, whether 
anticipated or unanticipated.  
The Sponsor will immediately conduct an evaluation of any unanticipated adverse device effects (UADEs). 
If it is determined that a UADE presents an unreasonable risk to subjects, the Sponsor will terminate the 
study or the parts of the study presenting that risk as soon as possible. The results of a UADE investigation 
will be reported to FDA and to the IRB within 10 working days after the Sponsor first receives notice of the 
effect. Thereafter, the Sponsor will submit such additional reports concerning the effect as requested by 
FDA.  

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15.3 ANTICIPATED POTENTIAL ADVERSE EVENTS  
Anticipated potential adverse events (AEs) consist of those related to the investigational medical device or 
the procedures involved in using the device, as well as AEs that occur in this study’s patient population who 
may be receiving treatment for comorbidities. Anticipated potential AEs that may be encountered in the 
conduct of this study including potential AEs related to the use of the FW-200 are listed in Section 5.2 
Potential Anticipated Adverse Events. It is possible that there are additional risks that have not been 
foreseen.  
15.4 EMERGENCY CONTACT DETAILS  
  
In case of an immediately reportable adverse event (UADE), contact the Sponsor:   
Gordon Levites, Quality Assurance Manager  
1-631-813-8612 gordon@fisherwallace.com   
16 VULNERABLE POPULATIONS  
ISO 14155:2020 defines a vulnerable subject as an individual whose willingness to volunteer in a clinical 
investigation could be unduly influenced by the expectation, whether justified or not, of benefits 
associated with participation or of retaliatory response from senior members of a hierarchy in case of 
refusal to participate. Individuals who suffer from Major Depressive Disorder would be considered a 
vulnerable population and therefore included within this clinical investigation.    
These vulnerable subjects according to the ISO 14155 definition will be asked to provide their informed 
consent if they are capable of providing it themselves and the consent process will be performed without 
undue delay. Informed consent processes shall be conducted according to national law and IRB procedures.  
The protection of the rights and welfare of study participants will be overseen by the responsible IRB and 
the Principal Investigator.  
17 SUSPENSION OR PREMATURE TERMINATION OF THE CLINICAL 
INVESTIGATION  
17.1 CRITERIA FOR SUSPENSION OR PREMATURE TERMINATION  
The clinical study may be stopped at any time at the Sponsor’s discretion.  
In addition, further recruitment in the study may be stopped due to insufficient compliance with the 
protocol, GCP-related issues, and/or other applicable  regulatory requirements, procedure-related problems, 
lack of enrollment, or if the number of subject discontinuations for administrative reasons is deemed too 
high.  

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17.2 SUBJECT FOLLOW-UP IN THE CASE OF STUDY TERMINATION  
In the event of early study termination, all subjects will be contacted via telephone by the Sponsor or 
designee. A record of contact(s) with each subject will be maintained in the ePRO.  
18 PUBLICATION POLICY  
Publication policy will be addressed in the Principal Investigator clinical trial agreement.  
18.1 CLINICAL TRIAL REGISTRATION  
This study will be registered on www.clinicaltrials.gov per federal regulations. This study is required by the 
FDA to be registered in the US government database for the registration of clinical trials. Information that 
can be viewed by all who access the website will only include the study design, the clinicians interacting 
with subjects in the study, and the study results at the completion of the study. No personal information and 
no protected health information (PHI) will be entered into the database.  
  
  
 

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19 BIBLIOGRAPHY  
  
Beck Depression Inventory-Second Edition | The National Child Traumatic Stress Network. Accessed 
March 8, 2022. https://www.nctsn.org/measures/beck-depression-inventory-second-edition   
Czeisler MÉ , Lane RI, Petrosky E, et al. Mental Health, Substance Use, and Suicidal Ideation During the 
COVID-19 Pandemic – United States, June 24–30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1049– 
1057.  
Datta A, Dmochowski JP, Guleyupoglu B, Bikson M, Fregni F (2013a). Cranial electrotherapy stimulation 
and transcranial pulsed current stimulation: a computer based high-resolution modeling study. Neuroimage. 
Jan 15;65:280-7. https://pubmed.ncbi.nlm.nih.gov/23041337/    
Datta A, Zhou X, Su Y, Parra LC, Bikson M (2013b). Validation of finite element model of transcranial 
electrical stimulation using scalp potentials: implications for clinical dose. J Neural Eng. Jun;10(3):036018. 
https://pubmed.ncbi.nlm.nih.gov/23649036/   
Federal Register : Neurological Devices; Reclassification of Cranial Electrotherapy Stimulator Devices  
Intended To Treat Anxiety and/or Insomnia; Effective Date of Requirement for Premarket Approval for  
Cranial Electrotherapy Stimulator Devices Intended To Treat Depression. (n.d.). Retrieved February 27, 
2022, from https://www.federalregister.gov/documents/2019/12/20/2019-27295/neurological-
devicesreclassification-of-cranial-electrotherapy-stimulator-devices-intended-to-treat   
Gelenberg, A.J., et. al. (2010, October). Practice Guideline for the Treatment of Patients With Major  
Depressive Disorder, 3rd Edition. Psychiatryonline. Retrieved from  
PG_Depression3e.book(PG_Depression_3e00Pre.fm) (psychiatryonline.org)  
Ghobadi-Azbari P, Jamil A, Yavari F, Esmaeilpour Z, Malmir N, Mahdavifar-Kayati R, Soleimani G, Cha Y-
H, Shereen AD, Nitsche MA, Bikson M, Ekhtiari H (2020). fMRI and transcranial electrical stimulation 
(tES): A systematic review of parameter space and outcomes. Prog Neuropsychopharmacol Biol Psychiatry. 
Oct 21;110149. https://pubmed.ncbi.nlm.nih.gov/33096158/   
Khadka N, Bikson M (2020). Neurocapillary-Modulation. Neuromodulation: Technology at the Neural 
Interface. 19 December. https://pubmed.ncbi.nlm.nih.gov/33340187/   
Mann, D. (2011). Antidepressants Prescribed Without Psychiatric Diagnosis; Study Documents Rise in Use 
of Antidepressants From Non-Psychiatric Illnesses. WebMD. Retrieved from  
https://www.webmd.com/depression/news/20110804/antidepressants-prescribed-without-
psychiatricdiagnosis   
Merlet I, Birot G, Salvador R, Molaee-Ardekani B, Mekonnen A, Soria-Frish A, Ruffini G, Miranda PC, 
Wendling F (2013). From oscillatory transcranial current stimulation to scalp EEG changes: a biophysical 

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and physiological modeling study. PLoS One;8(2):e57330. https://pubmed.ncbi.nlm.nih.gov/23468970/ 
Mindes J, Dubin MJ, Altemus M (2015). Cranial Electrical Stimulation. Chapter 11 in H Knotkova and D 
Rasche (Eds.), Textbook of Neuromodulation. New York: Springer. 
https://link.springer.com/chapter/10.1007/978-1-4939-1408-1_11   
Miniussi C, Debora Brignani D, Pellicciari MC (2012). Combining transcranial electrical stimulation with 
electroencephalography: a multimodal approach. Clin EEG Neurosci. Jul;43(3):184-91. 
https://pubmed.ncbi.nlm.nih.gov/22715493/   
Nida. (n.d.). Patient Health Questionnaire-9. Retrieved March 8, 2022, from 
http://www.drugabuse.gov/nidamed-medical-health-professionals   
Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., Markowitz, J. C., 
Ninan, P. T., Kornstein, S., Manber, R., Thase, M. E., Kocsis, J. H., & Keller, M. B. (2003). The 16-Item 
quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report 
(QIDSSR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry, 
54(5), 573–583. https://doi.org/10.1016/S0006-3223(02)01866-8  
Sheehan, D. v., Sheehan, K. H., Shytle, R. D., Janavs, J., Bannon, Y., Rogers, J. E., Milo, K. M., Stock, S.  
L., & Wilkinson, B. (2010). Reliability and validity of the mini international neuropsychiatric interview for 
children and adolescents (MINI-KID). Journal of Clinical Psychiatry, 71(3), 313–326. 
https://doi.org/10.4088/JCP.09M05305WHI   
  
20 APPENDICES  
20.1 APPENDIX 1:  DEVICE COMPONENT NAMES, MODEL NUMBERS AND VERSIONS  
The FW-200 CES Device consists of the following components:  
Component  
Part/Model Number  
CES device controller  
DR-9001  
Electrode receptacle with sponge  
DR-9010  
Electrode lead wires - Red  
DR-9009  
Electrode lead wires - Black  
 
 
DR-9008  

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Headband  
DR-9005  
Sponge pack (4 sponges)  
DR-9010  
Velcro headbands  
DR-9005   
Carry case  
DR-9011  
User guide  
PL 1002