Remotely Monitored Transcranial Direct Current Stimulation in Children With Cerebral Palsy
Phase: NA
Conditions: Cerebral Palsy (CP)
Sponsor: University of Wisconsin, Madison

 
 
 
 
Remotely Monitored Transcranial Direct Current Stimulation in 
Children With Cerebral Palsy  
 
NCT05071586  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PI:  Bernadette Gillick 
Document Date: 5/4/2023 

 
 
~ ii ~ 
 
 
 
 
 
 
 
 
 
Remotely Monitored Transcranial Direct Current Stimulation in 
Children with Cerebral Palsy 
 
 
 
 
Protocol Number: 2021-0691 
 
Principal Investigator: Bernadette Gillick 
 
 
 
IDE Sponsor: [Bernadette Gillick] 
 
PreviousFunding Sponsor: C-PROGRESS / NIH / Virginia Polytechnic Institute 
and State University 
Current Funding Sponsor: UWF – University of Wisconsin Foundation 
 
This document is confidential. 
No part of it may be transmitted, reproduced, published, or used by other persons without prior 
authorization from the Sponsor or Principal Investigator. 
 
 
 
Protocol Version History 
 
Protocol 
Version 
Version 
Date 
Summary of Revisions Made 
Rationale 
1.0 
08/30/2021 
Initial version 
 
2.0 
07/18/2022 
- 
Add safety monitor team member 
to be on site to monitor safety  
- 
Change the Soterix Medical 1x1 
tDCS mini-CT stimulator to the 
Soterix 1x1 LTE tDCS stimulator.  
- 
Add recruitment methods: self-
identify and flyers 
- 
 Study Coordinator changed 
- 
Remove Preparation 
-Increases the safety for the 
participants within the study 
-The Soterix LTE tDCS device 
has been safely and feasibly 
used over the last decade with 
IRB approvals and FDA IDE 
exemptions 

 
 
~ iii ~ 
- 
Add references  
- 
Device will not be mailed to 
home  
-Preparation referred only to the 
mini-CT stimulator device and 
not the LTE device 
- Safety monitor will bring device 
and take after each session 
3.0 
9/15/22 
- 
Change inclusion criteria to 
specify hemiparetic CP with 
history of perinatal brain 
bleed/stroke  
- 
Add the possibility to use mock 
device in training 
- 
Editorial changes 
- 
The study was intended to 
specifically include children 
with CP as a potential future 
target for interventions 
- 
The goal of the study to 
justify feasibility of 
teleneuromodulation is 
enhanced by giving 
participants as much 
independent training as 
possible 
- 
Clarity 
4.0 
10/18/22 
-Addition of vital measurements 
pre/post stimulation sessions 2-5 
-Box and blocks test and adverse 
event survey will now also be during 
session 2 as it is during 3-5 
-Addition of new recruitment 
strategies 
-clarification of intellectual disability 
population 
- removal of device log which is not 
needed 
- clarification of screening 
procedures and inclusion of more 
parental demographic information 
-potential for more than one study 
monitor in the home 
-Increase safety of participant by 
monitoring vitals throughout and  
motor function and adverse 
events even during sham 
stimulation 
-Other changes were to clarify 
procedures already approved 
- added additional recruitment 
measures to ensure we could 
enroll enough participants in the 
short timeframe we have 
- ensuring safety for the study  
monitors 
5.0 
12/14/22 
- 
Adding MRI screening visit 
- 
Adding AE surveys to Session 
Day 1  
- 
Adding a therapy questionnaire  
- 
Adding AE surveys to Day 1 
will give us good baseline 
information for whether just 
wearing the device without 
stimulation affects the 
subject 
- 
Previously we have 
discussed acquiring 
information but did not have 
a formal survey for 
assessing this information 
6.0 
 
Expanding age range to 21 years 
 
7.0 
3/23/23 
Allow participation from participants 
18-21 who have a legally authorized 
representative and lack the capacity 
to consent to study participation 
 

 
 
~ iv ~ 
8.0 
5/4/23 
-Changing funding source 
-Adding an optional 6 month follow 
up study 
Allows us to follow up on the 
health and motor function of 
individuals who participated in 
receiving tDCS stimulation in this 
study 
 
 

 
 
- i - 
Table of Contents 
 
1.0 
STATEMENT OF COMPLIANCE .................................................................................................................................................... 1 
2.0 
LIST OF ABBREVIATIONS ............................................................................................................................................................ 2 
3.0 
STUDY SUMMARY ......................................................................................................................................................................... 3 
 
Synopsis ............................................................................................................................................................................ 3 
 
Schematic of Study Design ............................................................................................................................................... 5 
4.0 
KEY ROLES .................................................................................................................................................................................... 6 
5.0 
INTRODUCTION ............................................................................................................................................................................. 7 
 
Cerebral Palsy and Motor Rehabilitation ........................................................................................................................... 7 
 
Investigational Procedure .................................................................................................................................................. 7 
 
Rationale ........................................................................................................................................................................... 7 
6.0 
STUDY OBJECTIVES AND ENDPOINTS ...................................................................................................................................... 8 
 
Aims .................................................................................................................................................................................. 8 
7.0 
STUDY DESIGN .............................................................................................................................................................................. 9 
 
General Design ................................................................................................................................................................. 9 
 
End of Study Definition ...................................................................................................................................................... 9 
8.0 
SUBJECT SELECTION .................................................................................................................................................................. 9 
 
Inclusion & Exclusion Criteria ............................................................................................................................................ 9 
 
Vulnerable Populations ................................................................................................................................................... 10 
 
Lifestyle Considerations .................................................................................................................................................. 12 
 
Subject Identification ....................................................................................................................................................... 12 
8.4.1 
Self-Identification .............................................................................................................................................. 12 
8.4.2 
Pediatric Neuromodulation Laboratory Database ............................................................................................. 12 
 
Subject Recruitment ........................................................................................................................................................ 12 
8.5.1 
Email ................................................................................................................................................................. 12 
8.5.2 
Self-Identify ....................................................................................................................................................... 12 
8.5.3 
Flyers ................................................................................................................................................................ 13 
8.5.4 
Health Records ................................................................................................................................................. 13 
8.5.5 
Mailing Opt-Out Letters ..................................................................................................................................... 13 
8.5.6 
Calling ............................................................................................................................................................... 13 
8.5.7 
Waisman Registry ............................................................................................................................................. 13 
8.5.8 
Clinical Practice ................................................................................................................................................ 13 
 
Remuneration and Retention Strategies ......................................................................................................................... 13 
 
Early Termination and Withdrawal .................................................................................................................................. 14 
9.0 
STUDY INTERVENTION ............................................................................................................................................................... 14 
 
Study Intervention Description ........................................................................................................................................ 14 
9.1.1 
Source .............................................................................................................................................................. 15 
9.1.2 
Packaging and Labeling .................................................................................................................................... 15 
9.1.3 
Storage and Stability ......................................................................................................................................... 15 
9.1.4 
Accountability .................................................................................................................................................... 16 
9.1.5 
Dosing and Administration ................................................................................................................................ 16 
 
Study Procedural Intervention(s) Description .................................................................................................................. 16 
9.2.1 
Administration of Procedural Intervention ......................................................................................................... 16 
 
Method for Assigning to Treatment Groups ..................................................................................................................... 16 
 
Study Intervention Compliance ....................................................................................................................................... 16 
 
Concomitant Therapy ...................................................................................................................................................... 16 
9.5.1 
Permitted Concomitant Therapy ....................................................................................................................... 16 
9.5.2 
Prohibited Concomitant Therapy ....................................................................................................................... 16 
10.0 
STUDY VISITS AND PROCEDURES ........................................................................................................................................... 17 
 
Study Calendar ............................................................................................................................................................... 17 

 
 
- ii - 
 
Overview of Study Procedures ........................................................................................................................................ 18 
10.2.1 
Transcranial Direct Current Stimulation ............................................................................................................ 18 
10.2.2 
Setup ease/comfort survey ............................................................................................................................... 19 
10.2.3 
Vitals 
19 
10.2.4 
Motor assessments – Box and Blocks Test ...................................................................................................... 19 
10.2.5 
Adverse events survey ...................................................................................................................................... 19 
10.2.6 
Follow-up .......................................................................................................................................................... 20 
 
Screening and Enrollment ............................................................................................................................................... 20 
10.3.1 
Pre-screening .................................................................................................................................................... 21 
10.3.2 
Informed Consent and Assent ........................................................................................................................... 22 
10.3.3 
Enrollment ......................................................................................................................................................... 23 
10.3.4 
Screen Failure and Re-enrollment .................................................................................................................... 23 
10.3.5 
Optional MRI Screening .................................................................................................................................... 23 
 
On-Study/Follow-up Visits ................................................................................................. Error! Bookmark not defined. 
10.4.1 
Day 1 (Session 1)- Mock Setup Practice 1.......................................................... Error! Bookmark not defined. 
10.4.2 
Day 2 (Session 2)- Sham Stimulation Practice 2 ................................................ Error! Bookmark not defined. 
10.4.3 
Day 3 (Session 3-5)- Active stimulation 1-3 ........................................................ Error! Bookmark not defined. 
10.4.4 
Post Sessions/Follow up ..................................................................................... Error! Bookmark not defined. 
 
Unscheduled Visits ............................................................................................................ Error! Bookmark not defined. 
 
Early Termination/Withdrawal Visit .................................................................................... Error! Bookmark not defined. 
 
Long-Term Follow-up | Re-contacting Subjects................................................................. Error! Bookmark not defined. 
11.0 
DATA COLLECTION, HANDLING, SHARING, AND RECORD KEEPING ........................ ERROR! BOOKMARK NOT DEFINED. 
 
Data Collection .................................................................................................................. Error! Bookmark not defined. 
11.1.1 
Data Collection Forms ........................................................................................ Error! Bookmark not defined. 
11.1.2 
Data Management Software System(s) .............................................................. Error! Bookmark not defined. 
 
Confidentiality and Privacy ................................................................................................ Error! Bookmark not defined. 
 
Records Retention............................................................................................................. Error! Bookmark not defined. 
 
Retention for Future Research: Data and Image Banking ................................................. Error! Bookmark not defined. 
11.4.1 
Purpose of Storage ............................................................................................. Error! Bookmark not defined. 
11.4.2 
Data Being Stored ............................................................................................... Error! Bookmark not defined. 
11.4.3 
Duration of Storage ............................................................................................. Error! Bookmark not defined. 
11.4.4 
Access to Data and Images and Security Measures ........................................... Error! Bookmark not defined. 
11.4.5 
Procedures to Release Data ............................................................................... Error! Bookmark not defined. 
11.4.6 
Process for Tracking Subject Consent and Authorization ................................... Error! Bookmark not defined. 
 
Protocol Deviations ........................................................................................................... Error! Bookmark not defined. 
 
Publication and Data Sharing Policy ................................................................................. Error! Bookmark not defined. 
12.0 
STUDY ANALYSIS ............................................................................................................. ERROR! BOOKMARK NOT DEFINED. 
 
Statistical Hypotheses ....................................................................................................... Error! Bookmark not defined. 
 
Sample Size Justification .................................................................................................. Error! Bookmark not defined. 
 
Statistical Methods ............................................................................................................ Error! Bookmark not defined. 
 
Planned Interim Analysis ................................................................................................... Error! Bookmark not defined. 
 
Handling of Missing Data .................................................................................................. Error! Bookmark not defined. 
13.0 
RISK/BENEFIT ASSESSMENT .......................................................................................... ERROR! BOOKMARK NOT DEFINED. 
 
Potential Benefits to the Subjects ...................................................................................... Error! Bookmark not defined. 
 
Known Potential Risks ....................................................................................................... Error! Bookmark not defined. 
13.2.1 
Known Interventional Risks ................................................................................. Error! Bookmark not defined. 
 
Risk/Benefit Analysis ......................................................................................................... Error! Bookmark not defined. 
14.0 
DATA AND SAFETY MONITORING .................................................................................. ERROR! BOOKMARK NOT DEFINED. 
 
Adverse Event (AE) Definition ........................................................................................... Error! Bookmark not defined. 
 
Serious Adverse Event (SAE) Definition ........................................................................... Error! Bookmark not defined. 
 
Classification of an Adverse Event .................................................................................... Error! Bookmark not defined. 
14.3.1 
Severity of Event ................................................................................................. Error! Bookmark not defined. 
14.3.2 
Relationship to Study, Study Procedure(s) and/or Study Intervention(s) ............ Error! Bookmark not defined. 
14.3.3 
Expectedness for Study, Study Procedure(s) and/or Study Intervention(s) ........ Error! Bookmark not defined. 

 
 
- iii - 
 
Time Period and Frequency for Event Assessment and Follow-Up .................................. Error! Bookmark not defined. 
 
Reporting AEs and SAEs .................................................................................................. Error! Bookmark not defined. 
14.5.1 
Reporting AEs ..................................................................................................... Error! Bookmark not defined. 
14.5.2 
Reporting SAEs .................................................................................................. Error! Bookmark not defined. 
 
Reporting of Pregnancy ..................................................................................................... Error! Bookmark not defined. 
 
Unanticipated Problems .................................................................................................................................................. 25 
 
Unanticipated Adverse Device Effect .............................................................................................................................. 25 
 
Protocol Deviations ......................................................................................................................................................... 25 
 
Incidental Findings .......................................................................................................................................................... 25 
 
Safety Oversight .............................................................................................................................................................. 26 
 
Study Monitoring ............................................................................................................................................................. 26 
 
Study Stopping Rules ...................................................................................................................................................... 27 
 
Economic Burden to Subjects ......................................................................................................................................... 27 
 
Facilities and Locations ................................................................................................................................................... 27 
 
Feasibility of Recruiting the Required Number of Subjects ............................................................................................. 28 
 
Principal Investigator Considerations .............................................................................................................................. 28 
14.17.1 Time Devoted to Conducting the Research ...................................................................................................... 28 
14.17.2 Process for Informing Study Teams .................................................................................................................. 28 
 
Availability of Medical or Psychological Resources ......................................................................................................... 29 
15.0 
REFERENCES .............................................................................................................................................................................. 29 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 1 of 38  
 
1.0 
STATEMENT OF COMPLIANCE 
I confirm that I have read this protocol. I will comply with the IRB-approved protocol, and applicable 
regulations, guidelines, laws, and institutional policies.  
 
I agree to ensure that all study team members involved in the conduct of this study are informed about their 
obligations in meeting the above commitment.  
 
Name 
Signature 
Date 
 
 
__________________________________ 
_____________________________ 
___________________ 
Principal investigator 
 
 
__________________________________ 
_____________________________ 
___________________ 
Sponsor 
 
 
 
 
 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 2 of 38  
 
2.0 
LIST OF ABBREVIATIONS 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CP 
Cerebral Palsy 
C-PROGRESS 
Center for Pediatric Rehabilitation: Growing Research, Education, and Sharing 
Science 
CTMS 
Clinical Trial Management Software 
DHHS 
Department of Health and Human Services 
DSMC 
Data & Safety Monitoring Committee 
DSMP 
Data & Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IDE 
Investigational Device Exemption 
ICTR 
Institute for Clinical and Translational Research 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
MRI 
Magnetic Resonance Imaging 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
OnCore 
Online Collaborative Research Environment 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SMC 
Safety Monitoring Committee 
SMP 
Study Monitoring Plan 
tDCS 
Transcranial Direct Current Stimulation 
UP 
Unanticipated Problem 
UP 
Unanticipated Problem 
 
 
 
 
 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 3 of 38  
 
 
 
3.0 
STUDY SUMMARY 
 Synopsis 
Full Title 
Remotely Monitored Transcranial Direct Current Stimulation in Children with 
Cerebral Palsy 
Short Title 
Pediatric Brain and Movement 
Protocol Number 
[HS IRB] 
ClinicalTrials.gov 
Identifier & 
Summary 
 
This study is being performed to determine the safety, tolerability and feasibility of remotely 
monitored transcranial direct current stimulation for children with cerebral palsy.  
 
Number of 
Site(s) 
This study is being done at one site: The University of Wisconsin Madison. 
Main Inclusion 
Criteria 
• 
Children with hemiparetic cerebral palsy with a radiologically confirmed perinatal brain 
bleed/stroke 
• 
Ability to follow 2-step commands 
• 
Aged between 8 years 0 days and 21  years. 
Main Exclusion 
Criteria 
• 
Inaccessibility to internet and a working computer/laptop/device 
• 
Neoplasm 
• 
Presence of metal implants 
• 
Epilepsy 
• 
History of seizure within 2 years preceding the study 
Objective(s) 
Primary Objective  
• 
To assess safety and tolerability of remotely monitored tDCS using our safety survey 
and optional 6-month/12-month follow up 
Secondary Objectives  
• 
To evaluate the quality, ease and comfort of in-home device set-up. 
• 
To evaluate the quality of tDCS stimulation. 
Endpoints 
Primary Endpoint 
Adverse events survey (pre, during, and post stimulation on sessions 1-5) and Box 
and Blocks test (pre and post stimulation sessions 2-5) will assess possible adverse 
effects.  
Secondary Endpoints 
• 
Setup speed  
• 
SMARTscanTM electrode contact quality 
Study Design 
This is an exploratory pilot open label trial that will assess the safety and feasibility 
of active tDCS in the home setting under caregiver and remote investigator 
supervision and direction, with a study safety monitor in the home on days when 
there is an active device present. An optional 6 month/12-month follow up session 
will be completed to to assess Box and Blocks scores and medical status since r 
participation in the primary study.  

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 4 of 38  
 
IND or IDE 
Number 
Abbreviated IDE requirements apply for Non-Significant Risk Device 
Study 
Intervention 
Participants will receive 20 minutes of 1.5 mA transcranial direct current stimulation 
(tDCS) for three consecutive days. 
Total Number of 
Subjects 
A total of 10 subjects will be recruited. 
Study Population Male and females aged 8 to 21  with established diagnosis of hemiparetic cerebral 
palsy with a history of perinatal stroke/brain bleed who are US residents. 
Statistical 
Methodology 
Adverse event reporting frequency (% of total participants enrolled) and tolerability 
will be compared to pediatric tDCS studies performed within the laboratory setting 
and administered by trained research personnel.  This data is publicly available in 
the form of published trials from our group and other groups. For participants in the 
6-month/12-month follow-up, we will monitor for any change in motor function by 
comparing box and blocks scores from the primary study and 6-month/12-month 
study follow up visits. We will also assess current medical status by pursuing 
updated medical records.  
Estimated 
Subject Duration 
The duration of the study for each subject is approximately 5 days. 
Estimated 
Enrollment 
Period & Study 
Duration 
Study enrollment and follow-up will occur over 10 months with the total expected 
duration of the trial to be 12 months. 
 
 
 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 5 of 38  
 
 Schematic of Study Design 
 
 
 
 
 
 
 
 
         
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Session 1 (Practice 1)  
Pre-stimulation: adverse events survey, 
Stimulation montage setup (efficiency and quality) 
End: setup ease/comfort survey, adverse event survey 
Contact participants from our previous tDCS trials that have hemiparetic cerebral 
palsy with a history of brain bleed/stroke, a diagnosis of CP, and no safety 
contraindications (e.g. seizures); screen participants by inclusion and exclusion 
Session 2 (Sham Stimulation / Practice 2)  
Study Staff Safety Monitor is present in the home 
Pre-stimulation: adverse events survey, motor function test, vitals 
Stimulation montage setup (efficiency and quality) with sham stimulation 
End: setup ease/comfort survey, adverse event survey, motor function test, vitals 
Session 3 (Active Stimulation 1) 
Study Staff Safety Monitor is present in the home 
Pre-stimulation: adverse events survey, motor function test, vitals 
Stimulation montage setup (efficiency and quality) with active stimulation 
Post-stimulation: setup ease/comfort survey, adverse events survey, motor 
function test, vitals 
Session 4 (Active Stimulation 2) 
Study Staff Safety Monitor is present in the home 
Pre-stimulation: adverse events survey, motor function test, vitals 
Stimulation montage setup (efficiency and quality) with active stimulation 
Post-stimulation: setup ease/comfort survey, adverse events survey, motor 
function test, vitals 
Prior to Enrollment 
Day 1 
Day 3 
 
Day 4 
 
Day 2 
Day 5 
 
Total N= 10. Obtain family/caregiver informed consent. Provide information 
including supplies, instructional videos and login information.   
Session 5 (Active Stimulation 3) 
Study Staff Safety Monitor is present in the home 
Pre-stimulation: adverse events survey, motor function test, vitals 
Stimulation montage setup (efficiency and quality) with active stimulation 
Post-stimulation: setup ease/comfort survey, adverse events survey, motor 
function test, vitals 
Recruitment 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 6 of 38  
 
 
 
 
 
 
 
 
 
4.0 
KEY ROLES 
The following is a list of all key personnel and roles: 
 
Principal Investigator 
Bernadette T. Gillick, PhD, MSPT, PT  
Associate Professor, Departments of Pediatrics  
University of Wisconsin-Madison 
Waisman Center 
1500 Highland Ave 
Madison, WI 53705 
Phone Number:608-262-7457 
bgillick@wisc.edu 
Participating Site(s) 
Waisman Center 
University of Wisconsin-Madison 
1500 Highland Avenue 
Madison, WI 53705 
Consultant 
Daniel Lench, PhD 
Medical University of South Carolina 
208 Rutledge Avenue 
Charleston, SC 29425 
Phone Number (203)505-5814 
lenchd@musc.edu 
Study Coordinator 
Preston Christopher, BS 
Waisman Center 
1500 Highland Ave 
Madison, WI 53705 
608-381-2699 
Pmchristoph2@wisc.edu 
Medical Director 
Dr. Chris Ikonomidou, MD, PhD 
University of Wisconsin Madison 
MFCB 7th Floor  
1685 Highland Ave. 
Madison, WI 53705-2281 
608-265-6470  
ikonomidou@neurology.wisc.edu 
Medical Monitor 
Melissa Villegas, MD 
Assistant Professor (CHS), Department of Pediatrics 
1500 Highland Avenue 
Madison, WI 53705 
608-263-8663  
mvillegas3@wisc.edu 
Study Monitoring Contact  
ICTR 
750 Highland Avenue 
2112 HSLC 
Madison, WI 53706 
Funding Sponsor 
UWF – University of Wisconsin Foundation 
Contact: Univeristy of Wisconsin Foundation 
1848 University Avenue 
Madison, WI 53726 
 Optional 6 month/12-month Follow up 
Informed Assent and Consent obtained 
Medical Records Obtained 
In home remote Box and Blocks motor assessment 
GMFCS, Pediatric Cognition, Current Therapy, tDCS tolerance, and tDCS Subject 
Report of Symptoms surveys 
6 month//12-month 
follow up

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 7 of 38  
 
608-263-4545 
uwf@supportuw.org 
 
5.0 
INTRODUCTION 
 Cerebral Palsy and Motor Rehabilitation 
An estimated 3.6 per 1,000 births in the United States are affected by stroke or brain bleeds which can lead 
to Cerebral Palsy (CP), a developmental disorder associated with motor impairment(1,2). While, the majority 
of rehabilitation approaches focus on behavioral repetition to improve gait and upper extremity function, 
these therapies can require extensive practice times and extent of recovery is variable. Thus, there is a 
need for novel strategies which can optimize the speed and consistently of rehabilitation outcomes for this 
population (3,4). Brain development during childhood is characterized by heighted neuroplastic potential(5) 
stressing the importance for intervention methods that harness neuroplasticity. Accordingly, several 
therapies (e.g., intensive training of the upper extremities) are theoretically based in mechanisms of motor 
learning and use-dependent plasticity(6). 
 Investigational Procedure 
Non-invasive brain stimulation (NIBS), specifically transcranial direct current stimulation (tDCS), provides 
an approach for modulation of neuroplasticity that is safe, inexpensive, and portable. Furthermore, 
rehabilitation approaches combined with tDCS have shown promise to improve motor function recovery 
and quality of life after stroke in adults(7). Integrating the application of NIBS may allow for enhanced 
rehabilitation during the enhanced neuroplastic period of childhood and NIBS has demonstrated promising 
outcomes in increasing the rate and extent of recovery(8). The Pediatric Neuromodulation Laboratory has 
pioneered the development of combined pediatric rehabilitation interventions and tDCS to improve motor 
function(9–11). Our studies have shown that in children with CP the use of tDCS is safe, feasible, and 
successful at modifying motor performance when in combination with other physical therapy interventions. 
tDCS is not currently available to subjects without taking part in the study. In this study, we plan to have a 
trained study team member instruct administration of tDCS in the remote setting during a synchronous 
zoom call with another trained study team member at the site of stimulation to monitor safety during 
sessions with the active device. To ensure the device is safely used in the home setting, and only during 
designated times, the safety monitor will bring the active device to each stimulation session and remove 
the device from the home after the session is finished. 
 Rationale 
Several studies have demonstrated improved effects of rehabilitation interventions when they are 
combined with tDCS(12). However, traveling to the laboratory or clinic may increase the difficulty and burden 
on families to complete an intervention with multiple sessions. This highlights the opportunity for remotely 
supervised at-home interventions. In adults, telerehabilitation, including integration of tDCS in the at-home 
environment, has offered the opportunity to improve access, lower the cost, and improve compliance with 
such treatments that require repetitive practice(13,14). However, there is further need to explore the feasibility 
and tolerability in pilot studies for pediatric application, and to expand the investigation in larger randomized 
controlled clinical trials to assess reproducibility and efficacy(15). 
 
To advance the reach of teleneuromodulation in pediatric rehabilitation it is crucial to extend the safety and 
accessibility of this affordable intervention. However, prior to the COVID-19 pandemic, there were no 
studies remotely performing tDCS for pediatric populations. During the pandemic Stay-at-Home mandate, 
we completed a novel feasibility investigation of performing remote mock tDCS in children by working with 
a child-caregiver pair. We found that remote mock tDCS is feasible in the home-setting without 
compromising the efficiency, quality, and comfort of administration. Children and their caregivers were able 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 8 of 38  
 
to follow remote instructions without compromising the quality of placement and comfort while wearing the 
tDCS device(16). 
 
With this proposal, we aim to follow-up and build upon our study that demonstrated mock tDCS setup 
feasibility, to assess ease of use and tolerability of at-home active tDCS in children with CP due to perinatal 
stroke. Together with gathered feedback about the experiences of children and caregivers during the 
procedure, knowledge gained will allow us to design a larger scale effectiveness study of a combined 
teleneuromodulation and rehabilitation intervention for recovery of motor deficits by targeting 
neuroplasticity and motor skills in pediatrics. Effective remote neuromodulation therapy can provide access 
to in-person rehabilitation and aid in accommodating mobility and financial challenges. This intervention 
has the potential to improve motor rehabilitation outcomes and can offer telehealth access, which may 
reduce treatment cost and improve outcomes when there is limited access to clinic or hospital facilities. 
Ultimately, this will contribute to a wider reach in improving quality of life across the lifespan in individuals 
with CP. 
6.0 
STUDY OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
To assess safety and tolerability of 
remotely monitored tDCS using our safety 
survey. 
 
-Reporting of adverse events/discomfort  
-Optional 6 month/12-month follow up 
Secondary 
To evaluate speed of device setup. 
Time to complete montage setup 
To assess the quality of stimulation. 
SMARTscanTM electrode contact quality 
Correlative/exploratory  
To assess interest and engagement in 
future teleneuromodulation rehabilitation 
interventions 
 
Follow-up feedback 
Box and Blocks test assesses hand function pre-
stimulation and post-stimulation sessions 3-5. 
 
 Aims 
Aim 1. Determine the safety and tolerability of 20 minutes of at-home active tDCS with remote instruction.  
Hypothesis 1: Children will tolerate the stimulation well with no serious adverse effects. 
Hypothesis 2: The repeated and guided sessions will result in increased comfort and confidence reported 
by the caregivers and children in performing tDCS at home. 
 
Aim 2. Determine the feasibility of remotely instructed teleneuromodulation with active tDCS.  
Hypothesis 1: Based on our preliminary feasibility study, we expect caregivers and children to correctly and 
reliably setup a stimulation montage with children after following remote instructions over two practice 
sessions. 
Hypothesis 2: Participants will be able to initiate and successfully complete active tDCS over repeated 
sessions, with increasing quality of stimulation delivery. 
 
Exploratory Aim 3 - Integrate feedback from the child and caregivers to assess their interest or 
commitment to engaging in future at-home tDCS interventions towards the construct of an advanced 
clinical trial. 
Hypothesis 1: The majority of families will express interest in future participation. 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 9 of 38  
 
7.0 
STUDY DESIGN 
 General Design  
Exploratory single site open label unblinded trials will assess the feasibility of active tDCS in the home 
setting under caregiver, remote investigator supervision and direction, and in-home safety monitoring. The 
study population will consist of 10 children and adults between ages 8 – 21 years and 365 days that have 
hemiparetic cerebral palsy with a history of a perinatal brain bleed or stroke. Medical records will be 
obtained for confirmation of hemiparetic cerebral palsy with a perinatal brain bleed or stroke. Medical 
records for current medical status will be gathered and reviewed by our medical director Dr. Chris 
Ikonomidou to confirm diagnosis and that the participant meets the study criteria. The study will occur over 
five consecutive days with 20 minutes of active 1.5 mA tDCS stimulation on days 3-5. We will conduct 
optional 6 month/12-month follow up sessions where we will reassess Box and Blocks performance , 
responses to surveys, and review medical records. Participants can be involved in the “6-month/12-month 
follow up” +/- 1 month (5-7 months after participation in primary study for 6-month visit, 11-13 months after 
participation in primary study for 12-month visit).  
 
 
Figure 1. Study design and assessments. 
 
 
 End of Study Definition 
A participant is considered to have completed the primary study if they have completed all phases of the 
study including return of equipment to study team and the 1 week follow-up to assess the family’s overall 
experience. Additionally, participants will be given the option to participate in 6-month/12-month follow-up. 
After these sessions are completed and the medical records are obtained, a participant is considered to 
have completed the follow-up study visits. 
8.0 
SUBJECT SELECTION 
 Inclusion & Exclusion Criteria   
Inclusion Criteria  
1. Aged between 8 years 0 days and 21 years 365 days 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 10 of 38  
 
2. Children who have hemiparetic cerebral palsy with a history of perinatal brain bleed/stroke 
3. Receptive language function to follow two-step commands  
4. Able to give informed assent along with the informed consent of the legal guardian. If the 
participant is 18-21 (with the capacity to consent), they must be able to give informed consent. 
5. Intentional about representing the sub-population of children with CP who experience 
intellectual disability (at least 2/10 participants with mild intellectual disabilities will be recruited) 
6. ≥ 10 degrees of active motion at the metacarpophalangeal joint 
7. Children who have had surgeries, which may influence motor function e.g.- tendon transfer, will 
be included, yet surgical history will be documented and included in any publication within a 
participant characteristics table. 
 
Exclusion Criteria 
1. Inaccessibility to internet and a working computer/laptop/device. 
2. Implants 
3. Neoplasm 
4. Metabolic Disorders 
5. Epilepsy 
6. Seizure within two years preceding the study 
7. Acquired Traumatic Brain Injury  
8. Pregnancy 
9. Indwelling metal or incompatible medical devices 
10. Evidence of skin disease or skin abnormalities 
11. Botulinum toxin or Phenol block within [six-months] preceding the study 
12. Disorder of Cellular Migration and Proliferation 
8.1.1 
Inclusion/Exclusion Criteria for Optional 6 Month/12-month Follow-up 
To be eligible for the optional 6-month/12-month follow-up, participants must have previously 
participated in the primary study and have access to a reliable internet connection and a functioning 
computer, laptop, or mobile device. Apart from these requirements, there are no other exclusion 
criteria. 
 Vulnerable Populations 
Vulnerable populations excluded from participation in the study 
1. Pregnant women/fetuses/neonates for the primary study. If participants become pregnant after 
participating in primary study, they may participate in the 6- and 12-month follow up sessions.. 
 
2. Non-English speakers. 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 11 of 38  
 
3. Those unable to read (illiterate).   
4. Employees of the researcher. 
5. Students of the researcher. 
6. Individual or group that is approached for participation in research during a stressful situation 
such as emergency room setting, childbirth (labor), etc. 
7. Individual or group with a serious health condition for which there are no satisfactory standard 
treatments. 
8. Individual or group with a fear of negative consequences for not participating in research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior). 
9. Any other circumstance/dynamic that could increase vulnerability to coercion or exploitation that 
might influence consent to research or decision to continue in research. 
 
This study will enroll children because the research is critical to advance the care and rehabilitation of 
children with CP and presents minimal risk to the children. From enrollment in past studies, we have found 
children with a CP diagnosis may be receiving physical or occupational therapy. If a child is receiving any 
concurrent therapies, all of the therapies will be documented. Data collected will inform future larger clinical 
trial evaluating the efficacy of at-home combined tDCS and rehabilitation in CP. Integrating tDCS as an 
adjuvant modality to telerehabilitation has the potential to enhance the efficacy of telerehabilitation 
therapies and offers a novel approach for remote intervention access, particularly relevant to reduce 
treatment cost and burden in case of limited access to clinic or hospital facilities. To further minimize risks 
to children, a trained study team member will supervise for safety concerns during all tDCS sessions in 
person and permission will also be obtained from a parent/guardian. If the participant is 18-21 years of age 
and has the capacity to give consent (adult child), permission will be obtained from the participant and the 
parent as participation is required from both parent and child.  
When in contact with potential participants between the ages of 18-21, we will determine if they have the 
capacity to consent (10.3.3 Adults Unable to Consent).  
 
We will NOT enroll participants whose capacity to consent may fluctuate throughout their involvement in 
the study. Using videoconferencing, a lab member will instruct the participants on how to perform tDCS 
stimulation. This will include 1 day of practice with inactive tDCS, 1 day of sham stimulation, and 3 days of 
active tDCS.   
We are studying children and young adults aged 8-21 who have hemiparetic cerebral palsy with a history of 
perinatal brain bleed/stroke. The knowledge to be gained from this study will be beneficial in developing 
protocols for continuing pediatric rehabilitation therapy during mandated Stay-At-Home directives and other 
access restrictions (e.g., rural communities). We anticipate minor adverse events as listed in the adverse 
events section below.  During the testing session, behavioral and environmental strategies will be shared, 
as needed, with the parent/caregiver for all children to optimize tolerance and completion of each session. 
These may include but are not limited to predictable routines, a visual timer, distraction techniques and 
child-friendly descriptive language. As we are a pediatric laboratory with experienced pediatric researchers, 
clinicians and trainees, comprehensive efforts have been made to ensure that our procedures are 
developmentally appropriate to both participant and family. Recruitment materials, study information, and 
conversations are tailored to a pediatric population. Participant-specific study materials are provided before 
participation in testing sessions, and age-appropriate adaptations for each procedure/test are used. Our 
team has created videos that help explain the research and videos specific to the procedures of this study 
will be shared with families. 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 12 of 38  
 
 Lifestyle Considerations 
Not applicable 
 Subject Identification 
8.4.1 
Self-Identification 
Since study subjects will need to be in an age range between 8 years to 21 years potential subjects will 
not be able to self-identify.  However, parents/legal guardians of children that meet inclusion criteria 
could ‘self-identify’ due to their parental role. Participants who are between 18-21 years of age can self-
identity as long as they have consent capacity. Parents/legal guardians, and participants 18-21 with 
consent capacity can respond to Institutional Review Board (IRB)-approved recruitment efforts, such as 
web postings, posters/flyers, radio or TV ads, newspaper ads, mass mailings, email blasts, etc. IRB-
approved screening scripts, eligibility questionnaires, and email response templates will be utilized 
when communicating with parents/legal guardians of potentially eligible subjects who respond to these 
recruitment methods. Information collected from the parents/legal guardians of potential subject is to be 
limited to protect the potential subject’s privacy, and information collected from potential subjects who 
fail pre-screening will be destroyed. Indirect recruitment materials and response communications will 
not contain subject health information. 
8.4.2 
Pediatric Neuromodulation Laboratory Database 
We will use our own database from participants who have previously participated in our studies and 
have signed consent to be contacted for this study.  
 Subject Recruitment 
A total of 10 subjects will be recruited. Several recruitment strategies are as detailed below. The phone 
screening script will be used in response to calls or emails from potential subjects. 
 
Based on recruitment in previous studies in this population performed by our lab, we expect that about 75% 
of our sample of children will reside within the state where the laboratory exists, i.e., Wisconsin. The 
remaining participants will be recruited from the greater Midwestern and Western regions. We have 
experienced exceptional participation (increase in overall enrollment from initial inquiries in our studies from 
9% to 14% over the last 5 years), retention (100% in 3 studies of 50 total children), and adherence (99.8%) 
in our trials of over 539 total visits. 7 participants from the pilot study in our lab expressed interest for future 
studies and agreed to be re-contacted for participation. Recruitment will take place immediately after IRB 
approval and continue for 12 months. The baseline diagnosis for children who have hemiparetic cerebral 
palsy with stroke/brain bleeds has been established and documented through previous involvement in our 
studies; however, we will gather medical records for current medical status to confirm there are no changes 
in medical status.  
8.5.1 
Email 
Children who have hemiparetic cerebral palsy with a history of perinatal brain bleed or stroke will be 
recruited from our database of previous participants. We will contact the list of previous participants in 
our laboratory studies who have agreed to be re-contacted and expressed interest in participation in 
future studies. We will recruit participants through email and establish a time to screen via telephone.  
8.5.2 
Self-Identify 
Self-identify: Parents/legal guardians of children who meet inclusion criteria could self-identify in 
response to IRB-approved recruitment materials, such as web posters/flyers, social media posts, 
emails, mailings, etc. Anyone who sees information about this study may pass the information onto 
potentially eligible families, who may choose to contact the study team. Relevant local and national 
groups will be provided with IRB-approved recruitment materials and language to be posted on their 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 13 of 38  
 
websites and social media platforms. Participants 18-21 with capacity to consent are able to self-
identify in response to any IRB approved recruitment materials.  
8.5.3 
Flyers 
Flyers announcing that volunteers are needed for the study will be posted or sent out to various 
specialty clinics or schools serving our population of interest. Several key details of the study will be 
included in the flyer (key eligibility criteria, number and length of visits. location of study site, type of 
remuneration) along with a call back number for people to call in case they are interested.  
8.5.4 
Health Records 
We will work with UW ICTR’s Clinical Research Data Service (CRDS) to identify eligible patients at 
within UW Health. 
 
Additionally, study team with electronic medical record access may search patient lists made available 
to them as part of their research access to identify potential subjects at recruiting sites for study 
eligibility evaluation. The research team will conduct further prescreening of individual records to 
identify potential participants.  
8.5.5 
Mailing Opt-Out Letters 
Study team with research access to the electronic medical record system will use appropriate ICD 
codes to identify potential participants. Families at UWHealth will be mailed the opt-out letter. This letter 
informs families that a study team member will be calling within two weeks to discuss the study and 
inquire about the family’s interest. Upon receipt of the letter, the family may choose to email the study 
team to express interest in the study or opt-out of contact. 
8.5.6 
Calling 
Within 2 weeks of mailing the opt-out letter, a study team member will reach out to the potential 
participant family. Up to three call attempts will be made by the study team. If call goes to voicemail, the 
approved voicemail phone script will be used. 
8.5.7 
Waisman Registry 
We will work with the Intellectual & Developmental Disabilities Research Registry at the Waisman 
Center. The individuals enrolled in this registry may be contacted to potentially participate in this study. 
The research team will set up a time to screen the participants if they are interested in participating in 
this study.  
8.5.8 
Clinical Practice 
Hospital/clinic care providers at institutions serving our target population may identify potential 
participants during routine clinical care based on inclusion/exclusion criteria. They may provide IRB-
approved recruitment materials to patient families and invite them to contact the study team if they are 
interested in learning more. 
 Remuneration and Retention Strategies 
Based on our previous experience in pediatric non-invasive stimulation and infant stroke studies, we will 
utilize the following retention tools:  
• 
Once eligibility has been confirmed, we will contact the parents/legal guardians or adult child participant 
and their parent to schedule a conversation in-person or a video chat to answer any additional 
questions and to introduce our team and put a face with a name. 
• 
Throughout the five consecutive days of the study, we will check in with the parents/legal guardians or 
adult child participant to answer questions and provide any pertinent information. 
• 
We will contact the parents/legal guardians or adult child participant via phone one week before their 
visits to answer any questions/concerns. 
• 
We have a dedicated laboratory study phone number which we share with parents/legal 
guardians/adult child participants, and to which we attend regularly. 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 14 of 38  
 
• 
We will invite parents/legal guardians/adult child participants to be on our mailing list to receive 
biannual Pediatric Neuromodulation Lab newsletters for updates. 
• 
A consistent point of contact will be maintained with parents/legal guardians/adult child participants, 
from recruitment to study completion, to establish rapport and build a positive relationship between the 
family and research team. 
• 
A thank-you letter with a summary of participation will be sent to parents/legal guardians/adult child 
participants after completion of all sessions. Upon completion of the 5 sessions, each family will receive 
$100 for participation. If the study is stopped due to an adverse event or because the participant wants 
to stop for any reason, they will receive compensation at a prorated rate based upon the number of 
sessions completed. Participants will receive $50 for each additional optional follow-up visit they 
complete. This will total to an additional $100 for completing both the 6-month and 12-month follow-up 
visits. 
 Early Termination and Withdrawal 
Families are free to withdraw from participation in the study at any time upon request. 
 
The Principal Investigator (PI) may discontinue or withdraw a subject from the study for the following 
reasons at his/her discretion: 
• 
Legal guardian/parent of the child voluntarily withdraw from the study 
• 
Participant death 
• 
Pregnancy 
• 
Subject non-compliance with study requirements (e.g., study intervention non-compliance)  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation occurs 
such that continued participation in the study would not be in the best interest of the subject 
• 
If the subject is no longer an appropriate candidate for participation   
• 
There is evidence of progressive disease or unacceptable toxicity 
• 
Subject unable to complete the 5 sessions within two weeks 
 
Participants withdrawn from study will be replaced, and the details surrounding the circumstances for 
withdrawing the participant from the study will be reported, with no identifiers included. Data collected up to 
the point of withdrawal will be kept and used for analysis. Participants who withdraw from the study will be 
given the opportunity to be involved in the 6-month/12-month follow up study visits. 
 
If the study ends prior to the study completion, all scheduled participants and families will be notified, and 
study sessions will be terminated. All research investigators on the study will be notified.  The funding 
agency will also be notified. 
 
9.0 
STUDY INTERVENTION 
 Study Intervention Description 
The device used for this intervention will be the Soterix 1x1 Limited Total Energy tDCS Stimulator 
Model 1401.  
With IRB approvals and FDA IDE exemptions, we have safely and feasibly used the Soterix LTE tDCS 
model over the last decade. Previous IRB approval has been obtained using an FDA IDE exemption with 
NSR status (see FDA letter/Wasserman). The Soterix LTE tDCS model will be used to deliver low-intensity 
tDCS in the home setting, to children with CP assisted by the parent/legal guardian and monitored by the 
safety monitor team member – henceforth referred together as the ‘participant team’ - and with 
synchronous remote instruction by the investigative team. The procedure will target the primary motor 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 15 of 38  
 
cortex (M1) using a bilateral M1 electrode montage. The M1 is a cortical area of interest for interventions 
aimed at improving motor skills in our participant population who have hemiparetic cerebral palsy with 
perinatal stroke and brain bleed, and as is conventional using this montage, we will place the anode over 
the lesioned or more-involved hemisphere. We intend to deliver tDCS in three active sessions, at a current 
intensity of 1.5 mA (based on child tolerance) and 20 min duration in each of the three active stimulation 
sessions.    
 
9.1.1 
Source 
Soterix Medical will distribute LTE Transcranial Direct Current Stimulator to the study site. The contents 
of the shipment will then be reviewed and verified against the packing slip and will be documented as 
instructed at the initiation visit.  
 
Soterix Medical Inc.  
Aspen Corporate Park, 
1480 US Highway 9 North, 204, Woodbridge, NJ 07095 
Email: contact@soterixmedical.com Phone: +1 888 990 8327 
Fax: 212-315-3232  
 
The study team will be responsible for procuring the LTE tDCS stimulator. 
9.1.2 
Packaging and Labeling 
Device installation and maintenance will follow manufacturers’ instructions for approved use. The 
device will be delivered by the safety monitor study team member to the participant. 
9.1.3 
Storage and Stability 
Investigational product must be stored in a secure area accessible only to authorized trial personnel. 
When not out at participants’ homes, the device will be installed and housed in the Pediatric 
Neuromodulation Laboratory, in a dedicated and locked research space, accessible only by/with 
authorized study team personnel. The Pediatric Neuromodulation Laboratory is located within the 
Waisman Center, and the facility meets all the requirements needed for appropriate installation, 
functioning, and storage of the device following manufacturer’s instructions. The device must be stored 
away from fluids and heat sources. The storage temperature of the device must be between 50°F - 
80°F with a maximum humidity of 70%. The temperature must be monitored and documented on the 
appropriate form for the entire time that the investigational product is at the trial site. If the storage 
temperature deviates from the permitted range, the investigational product must not be administered, 
and the site investigator or responsible person should contact Soterix Medical for further instructions.  
The device will also follow these precautions and warnings: 
• 
The Soterix Medical LTE tDCS Stimulator must be stored away from fluids and heat sources.  
• 
To clean the Soterix Medical LTE tDCS Stimulator, use a dry cloth to wipe dust from the external 
surface when necessary. Do not spray liquid cleaners directly on the Soterix Medical LTE 
tDCSStimulator, as this will void your warranty.  
• 
Do not disinfect the Soterix Medical LTE tDCS Stimulator  
• 
Do not immerse the Soterix Medical LTE tDCS Stimulator in water or any other fluids.  
• 
The Soterix Medical LTE tDCS Stimulator should not be used in a moist environment or if any parts 
of the stimulator are damp or wet.  
• 
Do not drop the device.  
• 
The Soterix Medical LTE tDCS Stimulator should not be used if there are any signs of external 
damage.  
• 
Carefully inspect the device on arrival and prior to each use.  

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 16 of 38  
 
• 
If any controls or displays are not working as indicated in the manual. Immediately return the device 
to Soterix Medical Inc. for repair.  
• 
Storage and operation temperature must be between 50° F and 110° F  
At the start of each experimental session, the investigative team will carefully inspect the device, 
together with the participant team, via video conference.  
9.1.4 
Accountability 
The study coordinator will maintain records of product delivery, site inventory, and product return. The 
safety monitor will be responsible for bringing the device to the participants home for every session and 
taking it after completing the session. 
 
In the event of a quality issue, the site should quarantine the investigational product and contact Soterix 
Medical for further instructions.  
9.1.5 
Dosing and Administration  
tDCS stimulation will be delivered at 1.5mA for 20 minutes while the caregiver and study team 
members evaluate the participant for any potential adverse event. Refer to the adverse events section 
below for more information. If it is uncomfortable to go to the full intensity, we will adapt and modify the 
stimulation to 1.0 mA by adjusting the device’s dial in person by the caregiver or safety monitor as 
directed by the study coordinator. 
 Study Procedural Intervention(s) Description  
9.2.1 
Administration of Procedural Intervention 
Active tDCS stimulation will be delivered to the participants during sessions 3-5 of the study after 
participants have been evaluated and cleared for quality set-up of the tDCS montage. A trained study 
team member will interact virtually with the caregiver to activate the tDCS stimulation device while a 
safety monitor team member will be located in person to supervise any safety concerns. 
 Method for Assigning to Treatment Groups 
This is an open label study; there are no blinding procedures. 
 Study Intervention Compliance 
Protocol compliance will be assessed directly by trained lab members. The lab team will witness and 
monitor the activation of the LTE device by the trained caregiver. The caregiver administering stimulation 
must be the individual who was successfully trained during the practice sessions. The safety supervision 
lab member will assess any safety concerns throughout the process at the site of the stimulation. 
 
 
 Concomitant Therapy 
9.5.1 
Permitted Concomitant Therapy 
Concomitant therapies and medication are permitted and will be documented during the screening visit. 
This is not expected to affect the primary or secondary outcome measures of the study.  
9.5.2 
Prohibited Concomitant Therapy 
Concomitant participation in another neuromodulation study is prohibited considering concurrent 
neuromodulation may directly affect the endpoints of the study. Additionally, participants who received 
Botulinum toxin or phenol block within the last six months preceding the study are prohibited from 
participating. However, after completion of the tDCS stimulation sessions, participants will be eligible to 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 17 of 38  
 
participate in the optional 6 month/12-month visits as long as they have participated in the study before 
and have access to working internet and computer/laptop/device.  
 
10.0 
STUDY VISITS AND PROCEDURES 
 
Study Calendar 
The procedures performed at each study visit are listed in the table below. 
 
Procedure 
Screening 
 
Session 
1 
Session 
2 
 Active 
stimulation 
Session 
 3-5 
1 week 
post day 5 
completion 
Informed Consent 
x 
 
 
 
 
Review Eligibility 
Criteria 
x 
 
 
 
 
Obtain Medical History 
x 
 
 
 
 
Vitals Measured 
 
 
x 
x 
 
Stimulation montage 
setup  
 
x 
x 
x 
 
Setup ease/comfort 
survey 
 
x 
x 
x 
 
Safety Monitor Present 
In-home (active device 
use) 
 
 
x 
x 
 
Motor Behavior 
Assessment1 pre, post 
stimulation 
 
 
x 
x 
 
Adverse Events Survey 
pre, during, post 
stimulation 
 
x 
x 
x 
 
Device stimulation 
administration 
 
 
Sham 
Active 
 
Follow-up 
 
 
 
 
x 
 
Procedure 
Optional 6-month/12-month follow up 
Informed Consent/Assent 
X 
Obtain Medical History 
X 
Motor Behavior Assessment1 
X 
Surveys2  
X 
 
1 Box and Blocks Test 
2 Gross Motor Function Classification System, Pediatric Cognition Survey, Current Therapy 
survey, Demographic Survey, tDCS Tolerance Survey, tDCS Subject Report of Symptoms 
Questionnaire 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 18 of 38  
 
 
 
Overview of Study Procedures 
 
Individuals who respond as being interested in the study will scheduled for a phone or video call to discuss 
study procedure. At this point we will evaluate whether the family has appropriate computer/ internet 
access.  If the family (e.g. parent/caregiver and child) are interested in participating, we will proceed to 
performing consent/assent via phone call or video conference. As we will request for photos/video of 
electrode placement, a photo/video authorization form will also be required. We will request for permission 
to record the videoconference call via the consent form. Following these enrollment procedures, the 
parent/legal guardian – henceforth referred to as ‘caregiver’ throughout the protocol- will be asked to 
participate in a pre-visit which may occur in the same visit as the enrollment. If the participant is an adult 
with consent capacity (between the ages of 18-21) both the adult and the parent of that adult will be 
involved in the call. During the pre-visit, an address for the safety monitor study team member, and 
videoconferencing times will be scheduled for completion of the five-day study. There are two types of 
sessions that will occur throughout the study (practice and active stimulation). A trained study team 
member will be present via videoconference with the caregiver/child during the entirety of the sessions. A 
study team member will be on-site, in-home during active device use to solely ensure safety of the 
participant. Unless indicated for safety, the safety monitor will not provide guidance in setting up the device 
or delivering tDCS to the participant.  The protocol for survey’s, questionnaires, and assessments are 
detailed below. 
 
10.2.1 Transcranial Direct Current Stimulation  
Montage Set-up Protocol  
The Soterix Medical bilateral M1 tDCS montage set-up protocol will be completed during all five 
sessions of the study. Participants will be sent instructional videos on how to perform the following 
procedures via REDCap. They will be asked to view these videos prior to the videoconferencing call on 
practice session 1. Participants will receive a mock device that does not have the ability to stimulate to 
allow them to practice setup with the instructional videos.  
 
For all sessions: the lab team will press the “now” button on the survey to begin recording the time 
duration to place the tDCS headgear on the head appropriately. Parent Participants will be instructed 
to: 
1) Connect the provided cables to the device using the banana plugs on the back of the device  
2) Place the tDCS headgear on the child’s head with the arrow aligned with the nose and 
upload an image of the step 
3) Mark locations below the red and black markers with the provided pen/pencil 
4) Use the provided alcohol pads to clean the skin at the marked locations and identify any 
redness, cuts, pimples, etc. 
5) Insert the connector cord pin securely into the opening of the receptacle on the rubber insert 
6) Snap on the two tDCS sponge pads saturated in saline to the red and black markers and 
upload an image. 
Both the caregiver and the laboratory team will record the time these steps were completed.  
 
Non-active Mock Device 
 
Practice Day 1: Now, participants will be asked to leave the tDCS setup in place for 20 minutes. 
Caregivers will observe the child during this time to see if the electrode sponges move or if the child 
adjusts the headgear. After the 20 minutes, the caregiver will be instructed to mark the new location of 
the arrow and measure the distance the arrow may have moved during the 20 minutes. An adverse 
event survey will be conducted prior to the session, at the 10-minute mark, and post stimulation 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 19 of 38  
 
 
Active Device – At least one safety monitor study team member is present in the home of the 
participant team 
 
Sham Day 2: The study team staff will evaluate the tDCS montage set-up for successful set-up. If set-
up is completed correctly, the caregiver will activate the tDCS device for a sham stimulation. 
Participants will receive 30 seconds current ramp-up to 1.5mA immediately followed by ramp-down 
back to 0. They will continue to wear the headgear with no stimulation until the end of the 20-minute 
session when the current will once again receive ramp up to 1.5mA immediately followed by 30 second 
ramp-down. This will allow the child to potentially experience the mild skin tingling in order to adjust and 
prepare for the active sessions.  The level of stimulation will be adjusted if necessary. An adverse event 
survey will be conducted prior to the session, at the 10-minute mark, and post stimulation. Vitals (blood 
pressure, respiration rate, and heart rate) will also be taken before and after stimulation. The participant 
will be given the option to use an iPad to watch videos during the 20-minute session. 
Active Days 3-5: Same as Day 2, except participants will receive 20 minutes of tDCS stimulation. 
Caregivers and the investigative team will observe the child during this time to see if the electrode 
sponges move or if the child adjusts the headgear. After the 20 minutes, the caregiver will be instructed 
to mark the new location of the arrow and measure the distance the arrow may have moved during the 
20 minutes of stimulation. If the child were to experience a mild adverse event, the caregiver and study 
team staff will opt to stop the active stimulation, assess the event, discuss with the study Medical 
Monitor and reassess. If deemed appropriate by the Medical Monitor the laboratory investigative team 
would discuss the plan to move forward with the Participant Team and make adjustments to stimulation 
intensity for future sessions for comfort.  
10.2.2 Setup ease/comfort survey 
This survey will be completed at the end of all five sessions. The survey will evaluate the participant’s 
overall experience of the session by addressing the following topics:  
• Caregiver: - How difficult were the tDCS setup instructions to understand?  
• Caregiver: - How could instructions be improved in the future? 
• Child - How comfortable was wearing the tDCS cap and sponges? 
• Child – How could we make wearing the cap more comfortable?  
• Any general comments  
 
10.2.3 Vitals 
Blood pressure, heart rate, and respiration rate will be taken pre and post stimulation on days 2-5 to 
ensure participant safety and monitor any changes in vitals. The safety monitor will take all vital 
measurements. These will be recorded on REDCap. 
 
10.2.4 Motor assessments – Box and Blocks Test 
Hand motor function will be assessed as a control measure before and after stimulation on days 2-5 
with the Box and Blocks test. Instructions to this task will be read directly to the participant during the 
videoconferencing call. The testing researcher will guide testing with the Box and Blocks test (wherein 
the child moves as many 1” wooden blocks within 1 minute). There will be 1 trial period and 4 
subsequent tests of the dominant and non-dominant hand (2 tests per hand). 
10.2.5 Adverse events survey 
Tolerance and report of any symptoms will be formally assessed using tDCS-specific participant safety 
questionnaires. This includes common mild effects like skin tingling and itching, as well as others such 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 20 of 38  
 
as headache, anxiety and mood changes, or any other events. This survey is filled out before, during at 
the 10-minute mark, and after tDCS stimulation sessions 1-5.  
 
10.2.6 1-week Follow-up 
We will ask the participants an open-ended question to check-in, assess the family’s experience with 
the overall procedure and potential interest in future studies. This will be called the tDCS tolerance 
survey. This will occur via telephone one week after completion of the session. 
10.2.7 Optional 6-month/12-month Follow-up 
10.2.7.1 
Medical Records 
To conduct a medical record review and assess medical status and the potential for new onset 
seizures since participation in the primary study, we will obtain a consent for a standardized medical 
record release under the Health Insurance Portability and Accountability Act (HIPAA), provided the 
previous HIPAA consent for medical record release has not expired. Our goal is to collect medical 
records that reflect the participant's current medical status.  We will obtain participant's most 
updated medical records to review their current health status and review any changes since 
participation in the primary study. We are more specifically looking for any key factors relevant to 
our study inclusion/exclusion criteria such as new onset of seizures, development of epilepsy, 
changes in motor function, and development of long-lasting symptoms potentially relating to tDCS. 
 
We are also collecting information regarding the pregnancy status of participants as it is crucial for 
our research and subsequent follow-up visits. Understanding the pregnancy status is important due 
to the wide-ranging effects that pregnancy can have on the physiological and anatomical systems, 
including its impact on motor function. By identifying if participants are pregnant, we can accurately 
analyze and interpret their medical status since participation in the primary study. This knowledge 
will enable us to account for any potential influences that pregnancy may have on the outcomes 
and ensure that our analysis is comprehensive and accurate. 
10.2.7.2 
Motor Assessments – Box and Blocks Test 
At the 6-month/12-month timepoint, we will administer the Box and Blocks test. We will send the 
necessary supplies to the participant and provide them with instructions over videoconference call. 
Participants will return Box and Blocks in the same packaging with a return label. The test will 
consist of one trial period followed by four tests, with two tests for each hand (dominant and non-
dominant).  
 
10.2.7.3 
Survey(s) 
At the 6-month/12-month timepoint, we will send the Gross Motor Function Classification System 
survey, Pediatric Cognition Survey, Current Therapy Survey, Demographics Survey, tDCS 
tolerance survey, all which were completed in the primary study, to the participant over REDCap. 
We will also include a tDCS Subject Report of Symptoms Questionnaire which will be a guided 
interview of questions investigating potential adverse events that may have occurred since 
participation in the primary study.  
 
 
 
Screening and Enrollment 
The Screening and Enrollment visits and procedures are described in detail below. 
Commented [JF1]: I searched for the word "records" 
throughout the protocol and found that previous descriptions 
indicate that medical records will be reviewed only to confirm 
eligibility. Please revise 10.2.7.1 to describe more specifically 
what information will be collected during follow up to assess 
current medical status. This would also be a good place to 
provide the rationale for identifying pregnancy status.  
Commented [PC2R1]: This has been included, thank you 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 21 of 38  
 
10.3.1 Pre-screening 
 
When caregiver(s) of potential subjects or adult potential participants contact the study team, a study 
team member will review a brief description of the study’s purpose and participation requirements with 
them. This must also include a statement that participation is voluntary. The screener will ask the 
callers if they have questions and whether they are interested in participating. This portion must be 
completed with the participant and the parent if the participant is above the age of 18 years old with 
consent capacity. If the potential participant is between 18-21 and does not have the capacity to 
consent, the screening call must be completed by the guardian.. If the participant is below the age of 
18, they do not need to be a part of this screening call. 
 
If the caregiver and\or adult participant expresses interest, the study team will ask to collect the 
demographic information listed below.  
 
Demographics  
The demographics section will include background information of the caregiver/child including:  
• 
Age of child 
• 
Child’s full name 
• 
Sex of child 
• 
Child’s date of birth 
• 
Child’s race and ethnicity 
• 
Legal guardian’s full name 
• 
Preferred phone number 
• 
Home address 
• 
Previous participation in a brain stimulation study (TMS or tDCS) 
• 
Relationship of child and caregiver 
• 
Caregivers highest education (high school, bachelors, etc.) 
We will potentially collect more demographic information if the participant enrolls into the study. We will 
once again ask to collect demographic information if participations are willing to participate in the 
optional 6 month/12-month follow up sessions.The consenting parent/guardian will be asked if they 
would be willing to fill out demographic survey using a secure REDCap link. Demographic information 
collected from the consenting parent/guardian may be used in analysis and reporting. We will request: 
• 
Age 
• 
Zip code 
• 
Race and ethnicity 
• 
Educational level  
• 
Employment status 
• 
Total annual gross income of house hold 
• 
Number of people supported by this income 
• 
 
After the team member collects the first half of the demographic information, they will do an initial 
screen for inclusions/exclusion criteria and any tDCS contraindications. This call is estimated to take 20 
minutes.  
 
After all questions have been answered and if no exclusion criteria are found during the prescreening 
call, the study team member will ask if the caregiver\legal guardian and\or adult child participant are 
interested in proceeding to the next step for further screening for inclusion/exclusion criteria. A Health 
Insurance Portability and Accountability Act (HIPAA) consent for a standardized medical record release 
is obtained in order to perform a medical record review. We will gather a medical record with current 
medical status to confirm inclusions and exclusion criteria are met. Information for all subjects will be 
collected and managed in accordance with HIPAA policies. This review is completed by the study 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 22 of 38  
 
physicians for review of inclusion/exclusion by history and MRI/CT radiographic reports of the brain. 
Eligibility will be verified by the principal investigator after this review. The medical director will confirm 
participant eligibility in the study.  
 
If a participant is excluded or declines participation, parents/guardians and\or adult child participant will 
be asked if they would like to have their contact information retained for future studies and/or to receive 
biannual lab newsletters. If yes, contact information will be kept separately from screening data. The 
parent/guardian and\or adult child participant will be notified of the information to be kept, including 
child name, child date of birth, child diagnosis, parent name, and parent contact information (phone 
number, email address and/or address). 
 
Ineligible screening data will be stored until the close of enrollment to prevent re-contacting 
parents\legal guardians and\or adult child participants after screening. Once enrollment is completed, 
identifiers will be destroyed. De-identified screening information will be used to describe and analyze 
the recruitment process. The data will be stored securely in our HIPAA-compliant database to prevent 
unauthorized use of the information. This database will be accessible to a select number of study team 
members. 
 
 
10.3.2 Informed Consent and Assent 
All study team staff are trained to guide participants through the consent/assent process.  
 
Preliminarily eligible subjects will be contacted via phone and/or email for informed consent and assent. 
The informed consent process will be conducted following all federal and institutional regulations 
relating to informed consent. Informed consent will be obtained prior to conducting any study-related 
activities. After families respond to the email recruitment script and express interest in participating in 
our study, we will send the consent form via email for them to review and follow up with a phone call.  
During the phone call, trained study personnel will explain the study and complete pre-screening. 
Participants, under the age of 18 and 18-21 without the capacity to consent will then be asked if they 
would like to discuss the assent form at this time and be invited to a video session or schedule a 
separate session.  The Teach Back practice will be used to obtain informed consent/assent and confirm 
their understanding. Participants are welcome to complete the consent/assent at the time of review with 
trained study personnel or take their time to think about participation before completing the form. This 
consent form must be signed by one parent/legal guardian. We will require only one parental/legal 
guardian signature for consent due to the minimal risk of this study. If the participant is between 18-21 
and does not have the capacity to consent, an LAR will sign the consent form. Assent will be obtained 
from all participants who lack the capacity to consent (8-17 year-olds and adults 18-21 lacking consent 
capacity).  The study procedures will be explained to the participant in an understandable way and the 
participant’s assent will then be requested. Only participants who can provide affirmative agreement 
that they wish to participate will be included. The consent form has a signature block to document the 
participant’s assent. If the child is over 18 years old and has the capacity to give consent, they must 
sign the consent form themselves in addition to their parent as they both are involved in the study as an 
adult child/parent dyad.  Neither children nor adults will be required to provide justification if they do not 
wish to participate. This will facilitate refusal to participate due to reasons that the child does not wish to 
disclose (e.g. possible pregnancy) Abbreviated IDE requirements apply for Non-Significant Risk Device. 
Individuals who are 18-21 that lack the capacity to consent will not be able to participate in the optional 
MRI study. 
 
10.3.3 Adults with Impaired Decision-Making Capacity 
Before enrolling potential participants aged between 18-21, we will evaluate whether they have the 
ability to provide informed consent. To assess their capacity to consent, we will utilize the teach-back 
method to ensure they understand the research's purpose, potential risks, absence of direct benefit, 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 23 of 38  
 
and voluntary nature of participation. If the evaluation confirms their consent capacity, they will be 
asked to provide consent to participate in the study, unless guardianship requires the guardian's 
consent. We will adhere to HRP-013 and consult the Office of Legal Affairs to determine the 
appropriate Legal Authorized Representative (LAR) for individuals deemed to lack consent capacity, as 
well as any legal queries regarding consent. We will obtain assent from all participants who lack the 
capacity to consent, and we will describe the study processes in simple language using the teach-back 
method. Only those participants who give affirmative agreement to participate will be included in the 
study. 
Video sessions will be conducted via HIPAA-compliant WebEx version, secure Zoom, or Microsoft 
Teams available to UW researchers. In case of remote consent, a 21 Code of Federal Regulations 
(CFR) Part 11 compliant version of DocuSign, provided by UW, will be used. The authorized member of 
the research team who obtained consent/assents will sign the form. Printed signed forms will be kept in 
a locked cabinet in the lab’s office, which is only accessible to certain study team members.   
 
Following enrollment, the research team will consistently communicate with the parent/child team 
during study interactions to confirm their understanding and comfort with the procedures. Specific 
questions asked by the parent/legal guardian or child will be documented to assist us with determining 
how best to support their understanding.  
 
 
10.3.4 Enrollment 
A research subject will be defined as “enrolled” in the study when they meet the following criteria: 
• 
The subject has been consented and assented by study staff.  
• 
The subject and study staff have completed all screening documentation. 
• 
The PI has verified that the subject meets all of the inclusion criteria. 
• 
The PI has verified that subject meets none of the exclusion criteria. 
 
10.3.5 Screen Failure and Re-enrollment 
A screen failure will occur if, after review of the medical records, the caregiver/child do not fit the criteria 
to participate. In that case, enrollment will not take place and the study team will discuss the findings 
with the family/caregivers. No re-enrollment will be considered due to age range and inclusion criteria. 
 
10.3.6 Optional MRI Screening 
If subjects meet all other enrollment criteria and confirm interest in being a part of the study, but their 
medical records do not include radiological confirmation of brain breed or stroke, we will offer them an 
MRI screening visit.  This MRI will be paid for by research funds and will be consented separately as an 
optional screening visit.  Separate consent is preferable, given that the findings of the MRI will 
determine if subjects can enroll in the main study. The consent/assent process follow the procedure 
detailed on 10.3.2. 
 
The potential participant will be provided with a link to a walk though guide of how an MRI is completed 
at the Waisman Center: (https://pnl.waisman.wisc.edu/tests-and-interventions/), or 
(https://www.youtube.com/watch?v=jFxO_XGp3UM&t=2s). The potential participant will also be 
provided with a link to listen to what an MRI scan may sound like, such as: 
(https://www.youtube.com/watch?v=S4DHUim_Lc8). In addition, if the subject is particularly anxious, 
s/he will be offered an additional mock scan. At the Waisman Center, the mock scanning room has 
been designed to very closely enact a neuroimaging procedure with the exception that the scanning 
apparatus is not capable of generating a magnetic field. Importantly, it also allows for a practice session 
prior to data collection. The participants will hear an audio file that replicates the scanner noise that 
occurs during the real scanning session. Study personnel will support and coach subjects if they have 
any difficulties accommodating to the scanner environment. During this mock practice session the 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 24 of 38  
 
importance of keeping the head still during the scan is emphasized, and participants have a chance to 
practice this. These methods have been standard child MRI scans and work well with children. 
  
After completion of an MRI safety screening form, participants will receive an MRI scan at the Waisman 
Center for Brain Imaging (1500 Highland Ave.; Madison, WI 53705) or at WISPIC (6001 Research Park 
Blvd.; Madison, WI 53719.  The parent/legal guardian may be permited to be in  the scanning control 
room during the session, after completing a safety screening, in accordance with facility policy.  
 
Scanning Protocol: The MRI will be done using a 3 Tesla Discovery MR750 MRI scanner (GE 
Healthcare, Waukesha, WI). Our imaging protocol includes structural imaging and diffusion MRI. The 
exact scan length and parameters of each scan type (T1, T2, DWI) will be set for this study in 
coordination with the Waisman Brain Imaging Core staff and the UW radiology team to optimize the 
quality of data for purposes of determining study eligibility.  All of the imaging methods have been 
previously implemented at UW-Madison. Each sequence will take approximately 5-10 minutes and the 
total scan time will be approximately 60 minutes. 
• 
Structural Imaging 
o T1-weighted: Anatomical T1-weighted imaging will be obtained using techniques the 
custom MPnRAGE sequence(25,26), which inherently removes the intensity variations from 
inhomogeneities in the coil sensitivities and motion artifacts. This technique has been 
widely utilized across imaging studies at the Waisman Center, including infant and pediatric 
populations. The T1-weighted scan will be used in the analysis pipeline to confirm lesion 
location. 
o T2-weighted: T2-weighted images will be acquired using GE’s 3-dimensional CUBE 
sequence, allowing for high resolution T2-weighted images.  
• 
Diffusion Weighted Imaging: DWI uses extra gradients applied after excitation and before data 
sampling to encode information amount small displacements of water. The strength, direction, 
and timing of the gradients (called b-value) determine sensitivity of diffusion. A multiple b-value 
dataset will be acquired, with the number and strength of the b-values and gradient directions 
optimized for the age range of infants studied. Diffusion imaging data will be acquired with 
reverse phase encoding schemes in order to correct for susceptibility distortions. Multiband 
imaging (factor=3) will be used to make the acquisition faster. 
 
A neuroradioligist will review the scan and produce a radiological report to be reviewed by the study 
medical director who will ultimately determine eligibility.  At the request of the subject and caregiver, the 
medical director will meet also with the subject and their parent to discuss the results of the radiological 
report within 30 days if the recommendation of the radiologist is to further investigate the unusual results of 
the images with the participant’s own physician.  Study teams will not inform subjects of their eligibility until 
after the results have been communicated by the medical director to the subject and their caregiver or they 
have declined this discussion.  
• 
“Souvenir” Radiology Images: If an MRI scan was completed with an participant, per IRB policy a three-
view research radiology souvenir will be offered for families. The images will be labelled as “Research 
images, not for diagnostic use”. Images will be emailed in an encrypted document to the 
parent/caregiver after the neuroradiologist review. Families can choose not to receive these images. 
Images will be sent to the parent/legal guardian in a password protected document through encrypted 
email or mail, as preferred by the parent/legal guardian.  
 
10.3.7 Optional 6 month/12-month follow up  
Participants who completed any number of sessions during the primary study a 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 25 of 38  
 
 
Unanticipated Problems 
An unanticipated problem (UP), as defined by the Department of Health and Human Services (DHHS) 
Office for Human Research Protection (OHRP), is any incident, experience, or outcome that meets all of 
the following criteria:  
• 
The incidence, experience, or outcome is unexpected given the research procedures described in 
protocol-related documents (e.g., the study protocol, the informed consent documents) and the 
characteristics of the subject population being studied. An event may be considered unexpected if it 
exceeds the nature, severity, or frequency described in the study-related documents, Investigator’s 
Drug Brochure, product labeling, or package insert. 
• 
The incidence, experience, or outcome is related or probably related to participation in the research 
study. “Probably related” means the incidence, experience, or outcome is more likely than not to be 
caused by the research study procedures. 
• 
The occurrence of the incidence, experience, or outcome suggests that the research places subjects or 
others at a greater risk of harm (physical, psychological, economic, or social) than was previously 
known or recognized.  
 
The investigator will report UPs to the reviewing IRB and to the PI. The UP report will include the following 
information: 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome represents 
an UP;  
• 
A description of any changes to the protocol, informed consent documents, or other corrective actions 
that have been taken or are proposed in response to the UP. 
 
 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect means any serious adverse effect on health or safety or any life-
threatening 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. 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review Board (IRB) a report of 
any unanticipated adverse device effect occurring during an investigation as soon as possible, but in no 
event later than 10 working days after the investigator first learns of the effect. 
 
Protocol Deviations 
Refer to section 11.5. 
Any planned protocol deviations will be submitted to the sponsor, the FDA and the IRB before 
implementation when applicable. If an unplanned deviation occurs in case of emergency to protect the life 
or physical well-being of the participant, it will be reported no later than 5 working days. 
 
 
Incidental Findings 
N/A 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 26 of 38  
 
 
Safety Oversight 
The full details of the planned study monitoring are included in the Data Safety and Monitoring Plan 
(DSMP). 
 
The PI will oversee the safety of the entire study, including careful assessment and appropriate reporting of 
all AEs and SAEs. A trained study team member will be present during stimulation to monitor the safety of 
the participant. The parent/legal guardian or adult participant and study team will report any adverse events, 
which arise after any session of tDCS or behavioral assessment, to the investigator and the investigator will 
convey the concerns to the Medical Monitor immediately upon receipt of this information to determine the 
optimal recommendation for care. The Medical Monitor will review each case after independent analysis of 
vital signs/symptoms and the occurrence of any minor or SAE. Incorporation of this Medical Monitor review 
will occur in addition to the safety and risk mitigation plans that we have established during each active 
session with the child and family. The Medical Monitor will review these reports and determine continuation of 
study based on comparative analysis of study stopping rules. 
 
The Medical Monitor for this study is:  
Melissa Villegas, MD 
Assistant Professor (CHS), Department of Pediatrics 
1500 Highland Avenue 
Madison, WI 53705 
608-263-8663  
 
Dr. Villegas holds board certifications in General Pediatrics, Physical Medicine and Rehabilitation, and 
Pediatric Rehabilitation Medicine. Dr. Villegas will utilize this background and her experience evaluating 
patients with cerebral palsy as the Waisman Center Cerebral Palsy Clinic Director to fulfill the role of 
Medical Monitor. 
 
Study Monitoring 
We have contracted with the UW Institute for Clinical and Translational Research (ICTR) Study Monitoring 
Service (SMS) for the proposed study to provide ongoing monitoring services to conduct and follow-up of 
monitoring visits throughout the life cycle of the study. The purpose of the SMS Program is to provide 
independent, ongoing monitoring to support compliance with good clinical practice (GCP) guidelines, 
federal, state and institutional regulations, policies, and guidance. The primary role of the SMS is to 
validate the integrity of the data collected and to assess compliance with the IRB approved protocol and 
applicable regulatory requirements, while ensuring the rights, safety and welfare of subject are protected. 
 
For this study, SMS personnel will conduct a Site Initiation Visit (SIV) and ongoing Interim Monitoring Visits 
(IMVs), either on-site, remotely, centrally or a combination thereof, throughout the duration of the study. 
During IMVs, the monitors will review study materials, including but not limited to: regulatory files, consent 
forms, and drug accountability logs.  SMS will review FDA communications to ensure compliance with 
applicable FDA IDE IND regulations, guidelines, and institutional policies.  SMS personnel will conduct a 
Close-Out Visit (COV) upon completion of the study at the study site.  
 
Monitoring will consist of all (100%) consent and screening documents for each enrolled subjects along 
with all (100%) study-related records for a minimum of 20% of subjects enrolled. SMS personnel could 
increase the percentage of study or subject records to be reviewed if warranted by the ongoing monitoring 
findings, resulting in a partial or full review of up to 100% of the study-related subject records. In addition, 
the SMS staff will verify adherence to protocol eligibility criteria, verify documentation for the accountability 
and administration of the study product, verify documentation of study procedures, and verify that FDA 
required SAE reports were appropriately submitted. 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 27 of 38  
 
 
Study Stopping Rules 
Both Individual and Entire Study stopping rules are described below: 
 
Death. Study stopped for both individual and entire study. A full investigation of event will be explored by 
entire study team. The medical monitor will review all details. Report of event will be distributed to all 
governing and monitoring committees. 
 
Seizure: Individual- Immediate suspension of tDCS application for this particular child and initiation and 
follow-through of safe and effective seizure management. Refer to seizure management outline. Provide 
physician letter to subject which describes the research-related adverse event with physician interpretation. 
 
Pregnancy: If at any time during the study, the participant states that they are pregnant, the participation 
will not be allowed to continue within the primary study. They will be allowed to participate in the 6 and 12-
month follow up visits as described in 14.6 Reporting of Pregnancy. 
 
Transient Decline in Motor Function (Individual). Immediate suspension of TMS intervention for the 
particular participant and initiation of assessment of the change. A written report with detailed 
documentation of decline in function will be submitted to the Medical Monitor.  The participant’s pediatrician 
and neurologist will also be contacted.  Follow-up testing will then occur one week after suspension of the 
study to track progress and change in status with physicians contacted with results directly thereafter.   
 
Transient Decline in Motor Function (Entire Trial).  If any participant shows a decrease in function following 
any component of the proposed study (tDCS or behavioral assessment), the study will be stopped at that 
time for review by the Medical Monitor.  If the Medical Monitor deems that the change in function does not 
indicate need for termination of the study, the study will recommence.  If the Medical Monitor deems that 
the protocol has indications for change, the study will be reviewed by the investigative team, including 
consultants and will be changed and submitted for re-approval by the IRB before recommencing the study.  
 
Entire Study- If another subject incurs a seizure proceed with steps for Individual Stopping Rules as noted 
above.  Study will be suspended at this point and a thorough review by research team, medical monitor 
and consultants will occur in order to assess the need for amendment of the protocol or full 
stop/termination of study for future safety concerns.  
 
Study Medical Director Evaluation. Recommend further evaluation to the participant and legal guardian by 
a neurologist if not the pediatrician\physician routinely involved in the participant’s care. An identification of 
causality and re-evaluation of treatment design will occur by study researchers, including consultants, 
medical monitor and physicians in order to proceed. All procedures will be assessed for strict adherence 
to all intervention steps listed in the protocol.  If deviation is found, error will be corrected. Proceed with 
study. 
 
 
Economic Burden to Subjects 
Subjects will not have to pay for study procedures (tDCS equipment). The subject will not be billed by the 
healthcare system or their health insurance company for any costs related to a study procedure.  
 
Subjects will be responsible for any costs related to follow-up as directed by their healthcare team, such as 
clinic visits, including all out-of-pocket costs. 
 
Facilities and Locations 
All recruitment and study procedures will be performed at a single site: The University of Wisconsin-
Madison. All interventions will occur in the participants home during a videoconferencing session with 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 28 of 38  
 
trained study team members giving instructions. A study team member will also be on site of active device 
use to monitor safety. Unless indicated for safety, the safety monitor will not provide guidance in setting up 
the device or delivering tDCS to the participant. 
 
Feasibility of Recruiting the Required Number of Subjects 
We have experienced exceptional participation (increase in overall enrollment in our studies from 9% to 
14% over the last 5 years), retention (100% in 3 studies of 50 total children), and adherence (99.8%) in our 
trials of over 539 total visits. We will be in contact with 15 participants who have received tDCS in our 
previous studies (67% of these subjects are needed for our project enrollment of 10). 7 participants from 
the pilot study in our lab expressed interest for future studies and agreed to be re-contacted for 
participation (70% of our projected subject enrollment of 10). Recruitment will take place immediately 
after IRB approval and continue for 12 months.  
 
Principal Investigator Considerations 
10.14.1 Time Devoted to Conducting the Research 
The Principal Investigator has 2% time effort devoted to this study, recognized by the Department of 
Pediatrics. 
10.14.2 Process for Informing Study Teams 
All research procedures will be performed by qualified personnel who have completed required training, 
including human subjects training. Dr. Bernadette Gillick has been investigating NIBS since 2007 with 
PhD training in TMS and Neuroimaging. Additionally, she has been trained by the Harvard Berenson 
Center for Non-Invasive Brain Stimulation 2012 and NYC Neuromodulation Conference 2013 on the 
use and application of tDCS, and by Brainsight Stereotactic Neuronavigation President Roch Comeau 
in 2013. 
 
Staff will participate in initial training, follow-up training, and ongoing monitoring and supervision, to 
ensure understanding of ethical issues involved in this research that includes, but is not limited to, 
courses offered by UW-Madison’s Human Research Protection Program, and a training on HIPAA and 
measures to protect confidentiality. 
 
All study personnel involved in tDCS stimulation will receive formal training including but not limited to 
review of critical safety literature and device manuals, hands-on procedural training by PI’s, and 
mentoring by trained graduate students or post-doctoral fellows within the lab familiar with study 
techniques. All study personnel involved in the use and application of tDCS will demonstrate 
competence prior to use with study participants. All study personnel involved in neuromodulation will be 
supervised by the site PIs. 
 
As a lab team, every lab member will be trained by Dr. Gillick on how to conduct a remote tDCS 
session. We will walk through each component of the session (surveys, Box and Blocks test, tDCS 
stimulation, etc.) as a team from start to finish. Each team member will perform two mock sessions: one 
with another team member and one with a community partner. The safety monitor will be trained to be 
able to prevent, assess, and monitor safety during each session.  
 
Dr. Lench, a postdoctoral researcher, will be acting as a consultant at the Medical University of South 
Carolina. He will not be interacting directly with participants during videoconferences, analyzing 
identifiable data, conducting experiments, participant recruitment, or consent. He will only assist with 
data analysis and manuscript preparation with access to no identifiable data. All experiments will be 
performed remotely, therefore no participants will be recruited through, or experiments conducted in 
other physical location, such as MUSC. The communication plan between the UW research team and 
MUSC team is detailed in HRP-830 -WORKSHEET -Communication and Responsibilities (uploaded 
separately). This communication plan will ensure MUSC will have the most current version of the 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 29 of 38  
 
protocol, consent document, and HIPAA authorization throughout the study. Dr. Lench will request a 
determination from MUSC IRB that they do not consider him engaged in the research. The PI will 
ensure via regular project meetings that all required approvals will be obtained at each site (including 
approval by the site’s IRB of record) and all modifications will be communicated to MUSC and Dr. 
Lench and approved (including approval by the site’s IRB of record) before the modification is 
implemented. No identifiable data will be shared outside of UW servers. All local site researchers will 
conduct the study in accordance with applicable federal regulations and local laws.   
 
 
Availability of Medical or Psychological Resources 
All participants will have virtual availability to the medical monitor as needed. In the case of an adverse 
event, a response protocol has been developed to include a call to 9-1-1 as needed.  
11.0 
REFERENCES 
1.  
O’Shea M. Diagnosis, Treatment, and Prevention of Cerebral Palsy in Near- Term/Term 
Infants. Clin Obs Gynecol. 2008;51(4):816–28.  
2.  
Yeargin-Allsopp M, Van Braun KN, Doernberg NS, Benedict RE, Kirby RS, Durkin MS. 
Prevalence of cerebral palsy in 8-year-old children in three areas of the united states in 2002: A 
multisite collaboration. Pediatrics. 2008;121(3):547–54.  
3.  
Morgan C, Darrah J, Gordon AM, Harbourne R, Spittle A, Johnson R, et al. Effectiveness of 
motor interventions in infants with cerebral palsy: a systematic review. Dev Med Child Neurol. 
2016;58(9):900–9.  
4.  
Moreau NG, Bodkin AW, Bjornson K, Hobbs A, Soileau M, Lahasky K. Effectiveness of 
rehabilitation interventions to improve gait speed in children with cerebral palsy: Systematic 
review and Meta-Analysis. Phys Ther. 2016;96(12):1938–54.  
5.  
Ballantyne AO, Spilkin AM, Hesselink J, Trauner DA. Plasticity in the developing brain: 
Intellectual, language and academic functions in children with ischaemic perinatal stroke. Brain. 
2008;131(11):2975–85.  
6.  
Chen CY, Georgieff M, Elison J, Chen M, Stinear J, Mueller B, et al. Understanding brain 
reorganization in infants with perinatal stroke through neuroexcitability and neuroimaging. 
Pediatr Phys Ther. 2017;29(2):173–8.  
7.  
Feng W, Kautz SA, Schlaug G, Meinzer C, George MS, Chhatbar PY. Transcranial Direct 
Current Stimulation for Poststroke Motor Recovery: Challenges and Opportunities. PM R. 
2018;10(9):S157–64.  
8.  
Saleem GT, Crasta JE, Slomine BS, Cantarero GL, Suskauer SJ. Transcranial Direct Current 
Stimulation in Pediatric Motor Disorders: A Systematic Review and Meta-analysis. Arch Phys 
Med Rehabil [Internet]. 2019;100(4):724–38. Available from: 
https://doi.org/10.1016/j.apmr.2018.10.011 
9.  
Gillick B, Rich T, Nemanich S, Chen CY, Menk J, Mueller B, et al. Transcranial direct current 
stimulation and constraint-induced therapy in cerebral palsy: A randomized, blinded, sham-
controlled clinical trial. Eur J Paediatr Neurol [Internet]. 2018;22(3):358–68. Available from: 
https://doi.org/10.1016/j.ejpn.2018.02.001 
10.  Nemanich ST, Rich TL, Chen CY, Menk J, Rudser K, Chen M, et al. Influence of combined 
transcranial direct current stimulation and motor training on corticospinal excitability in children 
with unilateral cerebral palsy. Front Hum Neurosci. 2019;13(April):1–12.  
11.  Nemanich ST, Rich TL, Gordon AM, Friel KM, Gillick BT. Bimanual Skill Learning after 
Transcranial Direct Current Stimulation in Children with Unilateral Cerebral Palsy: A Brief 
Report. Dev Neurorehabil [Internet]. 2019;22(7):504–8. Available from: 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 30 of 38  
 
https://doi.org/10.1080/17518423.2019.1600065 
12.  Charvet LE, Kasschau M, Datta A, Knotkova H, Stevens MC, Alonzo A, et al. Remotely-
supervised transcranial direct current stimulation (tDCS) for clinical trials: Guidelines for 
technology and protocols. Front Syst Neurosci. 2015;9(MAR):1–13.  
13.  Charvet LE, Shaw MT, Bikson M, Woods AJ, Knotkova H. Supervised transcranial direct 
current stimulation (tDCS) at home: A guide for clinical research and practice. Brain Stimul 
[Internet]. 2020;13(3):686–93. Available from: https://doi.org/10.1016/j.brs.2020.02.011 
14.  Gough N, Brkan L, Subramaniam P, Chiuccariello L, De Petrillo A, Mulsant BH, et al. Feasibility 
of remotely supervised transcranial direct current stimulation and cognitive remediation: A 
systematic review. PLoS One [Internet]. 2020;15(2):1–27. Available from: 
http://dx.doi.org/10.1371/journal.pone.0223029 
15.  Palm U, Kumpf U, Behler N, Wulf L, Kirsch B, Wörsching J, et al. Home Use, Remotely 
Supervised, and Remotely Controlled Transcranial Direct Current Stimulation: A Systematic 
Review of the Available Evidence. Neuromodulation. 2018;21(4):323–33.  
16.  Lench DH, Simpson E, Sutter EN, Gillick BT. Feasibility of remote transcranial direct current 
stimulation for pediatric cerebral palsy during the COVID-19 pandemic. Brain Stimul [Internet]. 
2020;13(6):1803–4. Available from: https://doi.org/10.1016/j.brs.2020.10.010 
17.  Brunoni AR, Amadera J, Berbel B, Volz MS, Rizzerio BG, Fregni F. A systematic review on 
reporting and assessment of adverse effects associated with transcranial direct current 
stimulation. Int J Neuropsychopharmacol. 2011;14(8):1133–45.  
18.  Van De Winckel A, Carey JR, Bisson TA, Hauschildt EC, Streib CD, Durfee WK. Home-based 
transcranial direct current stimulation plus tracking training therapy in people with stroke: An 
open-label feasibility study 11 Medical and Health Sciences 1117 Public Health and Health 
Services. J Neuroeng Rehabil. 2018;15(1):1–10.  
19.  
[National Research Council. The Prevention and Treatment of Missing Data in Clinical Trials. 
Washington, DC: National Academies Press, 2010.  
 
20. 
Little RJ, D'Agostino R, Cohen ML, Dickersin K, Emerson SS, Farrar JT, Frangakis C, Hogan JW, 
Molenberghs G, Murphy SA, Neaton JD, Rotnitzky A, Scharfstein D, Shih WJ, Siegel JP, Stern H. The 
prevention and treatment of missing data in clinical trials. N Engl J Med. 2012 Oct 4;367(14):1355-60.] 
21.  
Rich T**, Nemanich ST, Chen M, Friel KM, Feyma T, Krach LE, Nawshin T**, Meekins G, Gillick BT. 
"Transcranial direct current stimulation (tDCS) paired with occupation-centered bimanual training in 
children with unilateral cerebral palsy: A preliminary study 
22.  
Groth S, Rich T*, Kubat K*, Martin J*, Miller T*, Morse S*, Myhrman K*, Tobias A*, Gillick BT, 
“Localizing the primary motor cortex as a target for transcranial direct current stimulation (tDCS): A 
comparison of the 10-20 Electroencephalogram (EEG) System and Transcranial Magnetic Stimulation 
(TMS) methods: Study in Progress.” 
23.  
Nemanich S*, Rich T*, Chen CY*, Lixandrao M*, Meekins G, Feyma T, Ward M, Krach LE, Gillick BT . 
“Changes in Hand Function and Motor Cortex Excitability Following tDCS and CIMT Therapy in Children 
with Unilateral Cerebral Palsy with Different Patters of Corticospinal Organization.” 
24.  
Nemanich ST*, Sutter E*, Kowalski J*, Nawshin T*, Francis S*, Gillick BT. Targeted applications of 
tDCS based on corticospinal connectivity patterns in children with hemiparesis: study protocol and 
preliminary results 
25.      Kecskemeti S, Samsonov A, Hurley SA, Dean DC, Field A, Alexander AL. MPnRAGE: A technique to 
simultaneously acquire hundreds of differently contrasted MPRAGE images with applications to 
quantitative T1 mapping. Magn Reson Med. 2016;75(3):1040-1053. doi:10.1002/mrm.25674 
26.  
Kecskemeti S, Samsonov A, Velikina J, et al. Robust Motion Correction Strategy for Structural MRI in 
Unsedated Children Demonstrated with Three-dimensional Radial MPnRAGE. Radiology. 
2018;289(2):509-516. doi:10.1148/radiol.2018180180 
 
 

Pediatric Brain and Movement 
 
Gillick 
 
 
 
Version #: [7] 
Version Date: [5/4/2023] 
Page 31 of 38