Remotely Supervised Transcranial Direct Current Stimulation (tDCS) for Primary Progressive Aphasia (PPA)
Phase: PHASE2
Conditions: Primary Progressive Aphasia
Sponsor: NYU Langone Health

 
 
Official Title: 
Remotely Supervised (RS) tDCS for Primary Progressive Aphasia 
(PPA) 
NCT Number: 
NCT05615922 
Study Number: 
s22-01155 
Document Type:  
Study Protocol and Statistical Analysis Plan 
Date of the 
Document: 
• 
March 27, 2023 
 
 

Study #: s22-01155 
 
 
 
 
Page 1 of 37 
 
Remotely Supervised (RS) tDCS for Primary Progressive Aphasia (PPA) 
 
 
Principal Investigator: 
 
Leigh Charvet, PhD 
Department of Neurology, NYU Langone Health  
222 East 41st Street, 10th floor 
New York, NY 10016, USA 
Leigh.Charvet@nyulangone.org  
929-455-5141 
 
Additional Investigators: 
 
Amy Vogel-Eyny, PhD, CF-SLP 
222 East 41st Street, 10th floor 
New York, NY 10016, USA 
Amy.Vogel-Eyny@nyulangone.org  
 
Eric McConathey, MA 
222 East 41st Street, 10th floor 
New York, NY 10016, USA 
eric.mcconathey@nyulangone.org 
 
Lauren Krupp, MD 
222 East 41st Street, 10th floor 
New York, NY 10016, USA 
Lauren.krupp@nyulangone.org  
 
Giuseppina Pilloni, PhD 
222 East 41st Street, 10th floor 
New York, NY 10016, USA 
Giuseppina.pilloni@nyulangone.org  
 
Elizabeth Galletta, PhD, CCC-SLP 
240 East 38th Street, 15th floor 
New York, NY 10016, USA 
Elizabeth.Galletta@nyulangone.org 
 
NYULMC Study Number: 
i22-01155 
Regulatory Sponsor:  
Leigh Charvet, PhD 
Study Product: 
tDCS 1x1 mini CT tDCS 
Study Product Provider:  
Soterix Medical Inc. 
ClinicalTrials.gov 
Number  
NCT05615922 
 
Initial version: 10/07/2022 version 1.0 
Amended: 3/27/2023 version 5.0 
 
 

Study #: s22-01155 
 
 
 
 
Page 2 of 37 
 
Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of Human 
Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as applicable, any other applicable US government 
research regulations, and institutional research policies and procedures. The International Conference on 
Harmonisation (“ICH”) Guideline for Good Clinical Practice (“GCP”) (sometimes referred to as “ICH-GCP” or “E6”) 
will be applied only to the extent that it is compatible with FDA and DHHS regulations. The Principal Investigator 
will assure that no deviation from, or changes to the protocol will take place without prior agreement from the 
sponsor and documented approval from the Institutional Review Board (IRB), except where necessary to eliminate 
an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection Training. 
 
 

Study #: s22-01155 
 
 
 
 
Page 3 of 37 
 
Table of Contents 
 
STATEMENT OF COMPLIANCE ................................................................................................................ 2 
LIST OF ABBREVIATIONS ......................................................................................................................... 6 
PROTOCOL SUMMARY .............................................................................................................................. 8 
SCHEMATIC OF STUDY DESIGN .............................................................................................................. 3 
1 
KEY ROLES ........................................................................................................................................ 4 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................... 4 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE ............................................................... 4 
2.2 
NAME AND DESCRIPTION OF THE INVESTIGATIONAL DEVICE ............................................................. 5 
2.2.1 
Preclinical Data ....................................................................................................................... 6 
2.2.2 
Clinical Data to Date ............................................................................................................... 6 
2.2.3 
Dose Rationale ....................................................................................................................... 6 
2.3 
RATIONALE .................................................................................................................................... 6 
2.4 
POTENTIAL RISKS & BENEFITS ....................................................................................................... 7 
2.4.1 
Known Potential Risks ............................................................................................................ 7 
2.4.2 
Known Potential Benefits ........................................................................................................ 8 
3 
OBJECTIVES AND PURPOSE ........................................................................................................... 8 
3.1 
PRIMARY OBJECTIVE ..................................................................................................................... 8 
3.2 
SECONDARY OBJECTIVES .............................................................................................................. 8 
4 
STUDY DESIGN AND ENDPOINTS ................................................................................................... 8 
4.1 
DESCRIPTION OF STUDY DESIGN .................................................................................................... 8 
4.2 
STUDY ENDPOINTS ........................................................................................................................ 9 
4.2.1 
Primary Study Endpoints ........................................................................................................ 9 
4.2.2 
Exploratory Endpoints ............................................................................................................. 9 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................................... 9 
5.1 
INCLUSION CRITERIA ...................................................................................................................... 9 
5.2 
EXCLUSION CRITERIA .................................................................................................................... 9 
5.3 
VULNERABLE SUBJECTS ................................................................................................................ 9 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION ......................................................................... 10 
 5.4.1 Use of Epic Information for Recruitment Purposes 
5.5 
DURATION OF STUDY PARTICIPATION ........................................................................................... 10 
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES ............................................................................... 10 
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION ............................................................................... 10 
5.7.1 
Reasons for Withdrawal or Termination ............................................................................... 10 
5.7.2 
Handling of Participant Withdrawals or Termination ............................................................. 11 
5.8 
PREMATURE TERMINATION OR SUSPENSION OF STUDY ................................................................. 11 
6 
STUDY DEVICE INTERVENTION..................................................................................................... 11 
6.1 
STUDY DEVICE DESCRIPTION ....................................................................................................... 11 
6.1.1 
Acquisition ............................................................................................................................. 12 
6.1.2 
Product Storage and Stability ............................................................................................... 12 
6.1.3 
Device Programming ............................................................................................................ 12 
6.1.4 
Dosing and Administration .................................................................................................... 12 
6.1.5 
Route of Administration ......................................................................................................... 12 
6.1.6 
Duration of Intervention ......................................................................................................... 12 
6.1.7 
Device Specific Considerations ............................................................................................ 12 
6.2 
STUDY DEVICE ACCOUNTABILITY PROCEDURES ............................................................................ 13 
7 
STUDY BEHAVIORAL INTERVENTION .......................................................................................... 13 
7.1.1 
Word Naming Practice .......................................................................................................... 13 
7.1.2 
Administration of Intervention ............................................................................................... 15 

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8 
STUDY PROCEDURES AND SCHEDULE ....................................................................................... 15 
8.1 
STUDY PROCEDURES .................................................................................................................. 15 
8.2 
STUDY ASSESSMENTS ................................................................................................................. 16 
8.2.1 
Self Report Questionnaires ................................................................................................... 16 
8.2.2 
Cognitive and PPA symptoms Assessments (Exploratory) .................................................. 16 
8.2.3 
Additional Assessments ........................................................................................................ 16 
8.3 
STUDY SCHEDULE ....................................................................................................................... 16 
8.3.1 
Pre-Screening ....................................................................................................................... 16 
8.3.2 
Consent & Telehealth medical screening (Visit 1) ................................................................ 16 
8.3.3 
Baseline Visit ........................................................................................................................ 16 
8.3.4 
tDCS Session 1 (Visit 2) ....................................................................................................... 16 
8.3.5 
Remotely-Supervised tDCS sessions 2-20 (Visits 3-20) ...................................................... 17 
8.3.6 
Treatment-end Visit (Visit 21) ............................................................................................... 17 
9 
ASSESSMENT OF SAFETY ............................................................................................................. 17 
9.1 
DEFINITION OF ADVERSE EVENTS (AE) ......................................................................................... 17 
9.1.1 
Definition of Serious Adverse Events (SAE) ......................................................................... 17 
9.1.2 
Definition of Unanticipated Problems (UP) ........................................................................... 18 
9.2 
CLASSIFICATION OF AN ADVERSE EVENT ...................................................................................... 18 
9.2.1 
Severity of Event ................................................................................................................... 18 
9.2.2 
Relationship to Study Agent ................................................................................................. 18 
9.2.3 
Expectedness ....................................................................................................................... 19 
9.3 
TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ................................... 19 
9.4 
REPORTING PROCEDURES – NOTIFYING THE IRB .......................................................................... 19 
9.4.1 
Adverse Event Reporting ...................................................................................................... 19 
9.4.2 
Serious Adverse Event Reporting ......................................................................................... 20 
9.4.3 
Unanticipated Problem Reporting ......................................................................................... 20 
9.5 
REPORTING PROCEDURES – NOTIFYING THE STUDY SPONSOR ...................................................... 20 
9.6 
STUDY HALTING RULES ............................................................................................................... 21 
9.7 
SAFETY OVERSIGHT .................................................................................................................... 21 
9.7.1 
Data Safety Monitoring ......................................................................................................... 21 
9.7.2 
Medical Monitoring ................................................................................................................ 21 
9.7.3 
Clinical Monitoring ................................................................................................................. 21 
10 
STATISTICAL CONSIDERATIONS .................................................................................................. 21 
10.1 
STATISTICAL AND ANALYTICAL PLANS (SAP)................................................................................. 21 
10.2 
STATISTICAL HYPOTHESES ........................................................................................................... 21 
10.3 
ANALYSIS DATASETS ................................................................................................................... 22 
10.4 
DESCRIPTION OF STATISTICAL METHODS ...................................................................................... 22 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................................ 22 
12 
QUALITY ASSURANCE AND QUALITY CONTROL ....................................................................... 23 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................................ 23 
13.1 
ETHICAL STANDARD ..................................................................................................................... 23 
13.2 
INSTITUTIONAL REVIEW BOARD .................................................................................................... 23 
13.3 
INFORMED CONSENT PROCESS .................................................................................................... 23 
13.3.1 Consent and Other Informational Documents Provided to Participants ............................... 23 
13.3.2 Consent Procedures and Documentation ............................................................................. 23 
13.4 
Posting of Clinical Trial Consent Form ...................................................................................... 23 
13.5 PARTICIPANT AND DATA CONFIDENTIALITY ......................................................................................... 23 
14 
DATA HANDLING AND RECORD KEEPING .................................................................................. 25 
14.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ............................................................. 25 
14.2 
STUDY RECORDS RETENTION ...................................................................................................... 25 
14.3 
PROTOCOL DEVIATIONS ............................................................................................................... 25 
15 
STUDY FINANCES ........................................................................................................................... 26 

Study #: s22-01155 
 
 
 
 
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15.1 
FUNDING SOURCE ....................................................................................................................... 26 
15.2 
COSTS TO THE PARTICIPANT ........................................................................................................ 26 
15.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ............................................................................ 26 
16 
STUDY ADMINISTRATION ............................................................................................................... 26 
16.1 
STUDY LEADERSHIP ..................................................................................................................... 26 
17 
CONFLICT OF INTEREST POLICY ................................................................................................. 27 
18 
REFERENCES .................................................................................................................................. 29 
19 
SCHEDULE OF EVENTS .................................................................................................................. 33 
  
 

Study #: s22-01155 
 
 
 
 
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List of Abbreviations 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
COWAT 
Controlled Oral Word Association Test 
CRF 
Case Report Form 
CSOC 
Clinical Study Oversight Committee 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data and Safety Monitoring Board 
FFR 
Federal Financial Report 
FWA 
Federal Wide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IFG 
Inferior Frontal Gyrus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
lvPPA 
Logopenic Variant PPA 
mA 
Milliamperes  
MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
NSR 
Non-significant risk 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PI 
Principal Investigator 
PPA 
Primary Progressive Aphasia 
QA 
Quality Assurance 
QAB 
Quick Aphasia Battery 
QC 
Quality Control 
RS-tDCS 
Remotely-supervised transcranial direct current stimulation 
SD 
Standard Deviation 
SAE 
Serious Adverse Event/Serious Adverse Experience 

Study #: s22-01155 
 
 
 
 
Page 7 of 37 
 
SOP 
Standard Operating Procedure 
svPPA 
Semantic Variant PPA 
tDCS 
Transcranial Direct Current Stimulation 
US 
United States 
WAIS-IV 
Wechsler Adult Intelligence Scale – 4th Edition 
 
 
 

Study #: s22-01155 
 
 
 
 
Page 8 of 37 
 
Protocol Summary 
Title 
Remotely Supervised Transcranial Direct Current Stimulation (tDCS) for 
Primary Progressive Aphasia (PPA) 
Short Title 
RS-tDCS for PPA 
Brief Summary 
Approximately 30 participants with PPA will be nationally-recruited in an open-
label trial of a completely remote intervention to receive four weeks (5 x 30 min 
daily sessions per week) of active tDCS (2.0 mA, F7: left anodal) paired with 
simultaneous word naming practice 
Objectives 
- Evaluate the feasibility of RS-tDCS paired with word naming practice in 
patients with PPA 
- Collect preliminary efficacy data measured by change in scores on language 
assessment to support future grant applications 
Methodology 
Open Label Design 
Endpoint 
Primary Endpoints: 
- Feasibility judged by study completion percentage. The study will be deemed 
feasible if participants complete 16/20 RS-tDCS sessions  
 
Secondary Endpoints: 
- language assessment scores (QAB, BNT, COWAT) 
- The number of trained and untrained language probes identified at treatment 
end 
- Self-report questionnaires (ACOM, SAQOL-39, PROMIS Social Roles and 
Activities, and PROMIS Global Health) 
Study Duration 
2 years 
Participant Duration 
Approximately 1 month (4 weeks of intervention) 
Duration 
of 
IP 
administration 
20x30 minutes daily sessions of IFG tDCS combined with word naming 
practice  
Population 
N=30 participants (ages 45-85) diagnosed with early-stage primary 
progressive aphasia 
Study Sites 
NYU Langone Health 
222 East 41st Street, 10th Floor 
New York, NY 10017 
Number of participants 
N=30 participants  
Description of Study 
Procedure 
tDCS is noninvasive brain stimulation device that modulate brain activity 
delivering a low-intensity electrical current (2.0 mA) through scalp sponge 
electrodes. The device is preprogrammed to ramp up to 2.0 mA (for 30 
seconds), provide constant current throughout session (29 minutes), and then 
ramp down (for 30 seconds) at the end. 
 
Treatment is via telehealth visits, remotely and monitored through live 
videoconference using the established remotely supervised (RS) tDCS 
procedure. 
 
During the stimulation period, participants will engage in a picture naming 
exercise during the stimulation as guided by the study tDCS clinicians. 
 
Key Procedures 
Active tDCS with simultaneous word naming practice. 

Study #: s22-01155 
 
 
 
 
Page 9 of 37 
 
Statistical Analysis 
To measure feasibility, individuals will be categorized as “compliant” based on 
the percentage of study visits completed (16/20). Compliance with the 
interventions will be assessed by summarizing the distributions of numbers and 
proportions of completed sessions.  
 
Preliminary efficacy will be measured by performance at baseline and study 
end across study measures (QAB, BNT, COWAT, self-report questionnaires). 
Change in scores, indicating change following intervention, will be calculated 
for each compliant participant (defined as above). 
 
 
 

Study #: s22-01155 
 
 
 
 
Page 10 of 37 
 
SCHEMATIC OF STUDY DESIGN 
 
Prior to  
Enrollment 
 
 
 
Baseline 
Day 1 
 
 
 
 
Intervention 
Day 2 – Day 19 
 
 
Final Treatment Day 
Day 20 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirm eligibility criteria via medical records and self-report;  
Obtain informed consent 
Self-report questionnaires (ACOM, SAQOL-39, PROMIS Social Roles and 
Activities, PROMIS Global Health) 
Baseline Language Assessment (Trained and Untrained Words, QAB, BNT, 
COWAT) 
tDCS training and tolerability testing 
RS-tDCS + word naming practice 
5 Days a week: RS-tDCS + word naming practice 
RS-tDCS + word naming practice 
Post-intervention assessment 
Post-stimulation language assessment (Trained and Untrained Words, QAB, 
BNT, COWAT) 
Self-report questionnaires (ACOM, SAQOL-39, PROMIS Social Roles and 
Activities, PROMIS Global Health) 

Study #: s22-01155 
 
 
 
 
Page 11 of 37 
 
1 
Key Roles 
Leigh Charvet, PhD, Principal Investigator  
NYU Langone Health — Neurology 
240 E38th Street, New York, NY 11211 
Leigh.Charvet@nyumc.org  
  
929-455-5141 
2 
Introduction, Background Information and Scientific Rationale 
2.1 
Background Information and Relevant Literature 
The goal of this open-label pilot study is to establish the feasibility of a program of remotely supervised transcranial 
direct current stimulation (RS-tDCS) paired with word naming practice for people living with the semantic or 
logopenic variants of primary progressive aphasia (PPA). We will also collect preliminary efficacy data for speech 
and language outcomes following treatment. These data will be used to inform a grant application to complete the 
next step of a randomized controlled trial. 
 
Primary Progressive Aphasia (PPA) is a neurological condition associated with a gradual progressive 
decline in language function, affecting three in 100,000 people annually1, which is a conservative estimate. 
PPA is a devastating language-led neurodegenerative syndrome that is associated with atrophy of predominately 
left-hemisphere brain regions governing language. The three variants of PPA – semantic, logopenic, and 
nonfluent/agrammatic – are characterized by distinct neural areas of atrophy including frontal, temporal, and parietal 
regions2,3. The semantic variant is characterized by word knowledge loss; the logopenic variant by difficulties in 
word retrieval and repetition that are primarily phonologically mediated, and the nonfluent/agrammatic variant is 
differentiated by impairment in syntax and motor speech4. Beyond the devastating impact that PPA has on 
language, individuals living with PPA are often middle-aged when diagnosed, which negatively impacts family, work, 
and overall participation in social roles and activities1.  
 
Word naming is impaired across all three clinical variants of PPA4.  
Word-finding difficulties are most pronounced in the early stages of PPA in the semantic and logopenic variants. 
However, word naming problems are not a salient feature of the nonfluent/agrammatic variant until an advanced 
stage of disease progression5,6. Targeting word naming training in PPA is of clinical relevance since difficulty finding 
words is among the chief early complaints2. Research suggests that word naming training in PPA can lead to 
improved language outcomes7. However, gains following language training alone remain relatively small8. 
Therefore, researchers have utilized neuromodulation as an adjunctive technique to improve word-naming 
outcomes.  
 
One such neuromodulatory technique is tDCS, which is a type of noninvasive brain stimulation wherein a 
mild electrical current is passed through electrodes placed on the scalp. Delivering weak electrical currents 
(1.0-2.5 mA) via scalp electrodes, tDCS modulates neuronal excitation in the region where applied. tDCS has been 
extensively studied for a wide range of clinical applications and has a well-established record of safety and 
tolerability9. 
 
tDCS delivered while completing a trainingactivity can reinforce the learning that occurs to improve training 
outcomes. One established use of tDCS is to pair the stimulation with an ongoing or paired training activity to 
“boost” the training effect10–12. In this manner, the use of tDCS has been shown to lead to greater training outcomes 
from a range of training activities (motor, cognitive, speech and language) by increasing or decreasing the resting 
potential and/or firing rates13. Thus, repeated applications of stimulation facilitate neuroplasticity14 through 
mechanisms of LTP of synapses14–20.  
 
tDCS must be dosed in a sustained and cumulative manner for adequate evaluation of its efficacy.  
It is clear that tDCS effects are cumulative with adequate evaluation of behavioral effects requiring a period of 
multiple repeated applications21. Preclinical studies have demonstrated that stimulation results in sustained 
neuronal response22, with increased sensitization following repeated application21. This effect is mirrored through 
consistent findings across clinical studies in that: 1) a single tDCS session doesn’t cause any meaningful behavioral 
response, and 2) behavioral changes only follow a sustained period of daily treatment23,24. 

Study #: s22-01155 
 
 
 
 
Page 12 of 37 
 
 
tDCS is a safe and tolerable treatment that can be delivered to participants at home using the remotely-
superviced tDCS protocol25. We developed a remote protocol for use in clinical trials referred to as RS-tDCS, 
where each daily tDCS session is supervised live via videoconference in order to provide patients with access to 
the treatment remotely. We have extensive experience in delivering remote tDCS treatment to people living with 
multiple sclerosis (MS) and an extensive range of other neurological and psychiatric conditions. We also have a 
clinical tDCS virtual health program where we provide remote tDCS to patients with many different conditions26,27. 
 
When targeted to the inferior frontal gyrus (IFG), tDCS has been shown to improve word naming among 
individuals with word finding difficulties. The IFG is a key neural circuit for word naming28–30. tDCS has been 
used in people with aphasia when it is paired with language training. Through both research26,31 and our clinical 
service27, we have initial experience providing RS-tDCS paired with language activities to people living with aphasia. 
Among individuals with PPA, a recent meta-analysis strongly suggests that language training alongside tDCS 
exceeds the gains made through language training alone32, with the left IFG as a common neural target across 
naming studies. Furthermore, we have led the field in determining the feasibility of remotely-supervised tDCS (RS-
tDCS) for individuals with PPA with differing typologies and various degrees of severity31. However, no study to 
date has systematically investigated the feasibility and acceptability of RS-tDCS paired with language training in 
PPA.  
 
In the context of this progressive condition, the treatment goal is to extend the preservation of language 
functioning through the use of tDCS paired with word naming practice. In this open-label pilot study, we will 
measure the use of RS-tDCS in people with PPA. It is important for us to first demonstrate the acceptability and 
feasibility of the treatment. We will also pilot secondary clinical efficacy outcomes, to target personally relevant 
known words rather than attempting to restore access to forgotten words33,34. Research suggests that recall is 
higher among those with PPA who have trained words of functional relevance compared to an untrained set of 
words33,35,36. This study uniquely pairs the evidence from behaviorally-based language training studies in PPA 
alongside our established RS-tDCS protocol, allowing for determination of the clinical efficacy of tDCS as an 
adjuvant to PPA treatment. 
2.2 
Name and Description of the Investigational Device  
• 
1x1 Mini-CT tDCS device (Soterix Medical Inc.): The 1x1 Mini-CT tDCS device (see Fig.1, Panel A), 
through the accompanying headset (Fig. 1, Panel B) and sponge electrodes (Fig.1, Panel C), delivers a 
weak electrical current (1.0-2.0 mA) to target a specific area of the brain. It is a powered device (9 V) and 
is easily operated, with a user-friendly large-button keypad interface. The device has specific functions and 
features that guarantee safety in the remote supervised administration and uniform stimulation dose across 
sessions and participants. The device allows strict dose control and usage control, employing a one-time 
use code provided by the study technician to unlock the device for each stimulation session. 
 
Figure 1. Equipment for tDCS intervention 
A 
B 
C 
 
 
 
Panel A: 1x1 Mini-CT tDCS device; Panel B: SNAPstrap Headgear; Panel C: EASYpad Electrodes  
 
2.2.1 Preclinical Data 
N/A  

Study #: s22-01155 
 
 
 
 
Page 13 of 37 
 
2.2.2 Clinical Data to Date 
Feasibility of RS-tDCS. We have led the field in remote brain stimulation with the development of the RS-tDCS 
platform37–47. In our protocol, participants are provided with remotely-controlled tDCS device, trained in safe and 
effective operation, and then supervised for daily use through live videoconference48 (VSee48). Our updated 
videoconference software for this study will be Zoom. The telehealth connection has resulted in high retention rates 
across repeated and extended sessions (e.g., >97% completion rates across RCTs to date37–47). Extensively tested 
over > 7 years (>9000 remote tDCS sessions in >400 patients to date), it is well validated for use in MS and 
generalizable for use across most other clinical populations37–47 (ages 18-85 years, range of neurological and 
psychiatric conditions, including those with advanced disabilities and/or limited technical experience, and reaching 
those at socioeconomic disadvantage). Further, the RS-tDCS platform has allowed for continued enrollment of 
patients with MS in ongoing RCTs during the COVID-19 onsite clinical research pause49–52 (with >100 participants 
by completing all study procedures remotely).  
 
IFG tDCS regulates language difficulties. IFG tDCS has been established to regulate language difficulties (e.g., 
in PPA and post-stroke aphasia). In subanalyses of nondepressed MS participants with high baseline negative 
affect53, 10 or more RS-tDCS sessions, led to reliable negative affect reduction, and the negative affect reduction 
was maintained at 1-month follow-up. Importantly, these changes have also been linked to increased functional 
connectivity in Broca’s area following treatment54. 
2.2.3  Dose Rationale  
The tDCS protocol of this proposed research will use a stimulation intensity of 2.0 mA that falls well within safety 
limits established by numerous previous studies applying tDCS with human subjects. 
 
2.3  Rationale 
The application of tDCS for language difficulty is not novel on its own32. However, all studies of tDCS in PPA have 
required onsite delivery of treatment, resulting in small sample sizes and few sessions administered (likely 
underdosing)2,55,56. Therefore, our main objective is to evaluate the feasibility of reaching PPA participants for study 
remotely. We will evaluate preliminary efficacy by measuring language output before and after the treatment period. 
2.4  Potential Risks & Benefits 
2.4.1 Known Potential Risks 
Risks of tDCS: The repeated application of tDCS as proposed in this study poses a non-significant risk (NSR) to 
participants. The safety of this technique has been addressed and tested by multiple researchers who have 
concluded that tDCS, as applied in a manner similar to our proposed protocol, induces only mild and transient side 
effects with no report of serious adverse event related to tDCS across clinical trials to date. In >9,000 participant, 
no undesirable or long-lasting effects have been reported, nor have any subjects reportedly abandoned a study due 
to discomfort. The most common side effects are warming sensation, itching or tingling sensation under the area of 
the electrodes. The tDCS protocol of this proposed research will use a stimulation intensity of 2.0 mA that falls well 
within safety limits established by numerous previous studies applying tDCS with human subjects. In both active 
and sham tDCS treatment arms, there could be mild discomfort from wearing the headgear. 
 
The protocol is designed to have a decision-tree series of checkpoints with "STOP" criteria that must be cleared in 
order to proceed at each step (see Fig.2).  
 
Risks of RS-tDCS: Extensively verified safety and tolerability of RS-tDCS in the context of research26 and 
specifically in people with aphasia31 based on this experience and well-established safety/tolerability of tDCS in 
general, we do not anticipate adverse events to be frequent or treatment limiting. No serious adverse events 
occurred following 6,779 sessions of RS-tDCS26. However, adverse event reporting will occur at each session and 
risk will be systemically monitored and minimized as outlined in Section 9.7.1. Dr. Krupp will serve as medical 
monitor for this study as she has served for all NYU Langone MS Comprehensive Care Center tDCS studies to 
date. Quarterly meetings will be help with Dr. Krupp to review adverse events and any adverse event that is judged 
to be treatment limiting or severe will be immediately addressed by Dr. Krupp per standard medical care and 
reported to IRB following guidelines. If a serious adverse event occurs, stimulation will be stopped, participants will 
be instructed to remove the headset, and to either dial 911 or contact their treating neurologist for follow-up. A 

Study #: s22-01155 
 
 
 
 
Page 14 of 37 
 
member of the study team will follow up with subjects within the next 1-7 days after such events to document the 
resolution. This process will be same for both NYU and non-NYU patients. If these cases do occur, treatment will 
not resume until Dr. Krupp gives medical clearance to proceed.  
 
Participants will be visually surveyed to rate discomfort on a Likert scale from 1-10 at 3 time points during treatment 
(session 1, midway, and session 20). If a participant reports a score of 7 or higher for discomfort, the session will 
be stopped and the study member will consult with the participant for any adjustments needed. Session will start 
one time again with participant agreement, but will be terminated if a second discomfort score of 7 or higher is 
reported. Sessions will also be ended if at any point in time if a participant spontaneously reports a discomfort score 
of 7 or higher. Based on extensive experience26, we have established that this type of discomfort rating will capture 
any potential type of adverse events as they may occur. 
 
Figure 2. Session safety and tolerability checkpoints and stop criteria 
* the supervising study technician intervenes to assess the subject’s safety and abort the session when necessary. 
 
 
Word naming practice: Word naming practice is not associated with any known risk. To minimize possible 
frustrating feeling, each session will be monitored in real-time via HIPAA-compliant videoconference with a trained 
study technician. 
 
Self-report questionnaires: Completing questionnaires about one’s language use may produce some discomfort 
and/or emotional distress in some patients. Participants will be allowed to take breaks as needed and may skip 
questions they do not feel comfortable answering so long as the questions do not affect analysis of primary 
endpoints or eligibility criteria. Individuals with diagnosed psychiatric disorders will be identified by their physician 
prior to enrollment and would therefore not meet inclusion criteria. While we don’t anticipate this population to have 
suicidal ideation, the study will follow standard clinical procedures if a subject is suicidal (e.g. refer subject to closest 
emergency room).  
 
2.4.1.1 
Other Risks 
Breach of Confidentiality: There is minimal risk of breach of confidentiality. Participants will be assigned a unique 
study ID and their name will not be used on any of the data collected. All study data survey will be acquired through 
REDCap and the printed records will be stored in lock cabinet at 222 E 41st Street, 10th Floor. Any study data stored 

Study #: s22-01155 
 
 
 
 
Page 15 of 37 
 
on secure NYU computers and servers will be de-identified. The results of these data collected may be used for 
publication but will not include the participants’ names. 
Unforeseeable Risks: While not expected, there may be risks associated with tDCS that are not known at this 
time. 
2.4.2 Known Potential Benefits 
Some participants may receive benefit from the word naming practice. There is robust research on the benefits of 
such interventions among individuals with aphasia. 
 
Based on the literature to date, we anticipate that tDCS combined with word naming practice may improve language 
functioning among individuals with PPA56,57.  
 
This will be one of the first studies to evaluate a tele-intervention program of tDCS for speech and word naming 
practice among patients with PPA. The project has the potential to produce an immediately available treatment 
option for language difficulties among individuals with PPA. This would have immediate and significant clinical utility. 
In particular, the benefit to the field is the availability of a treatment option for managing symptom burden associated 
with PPA. 
3 Objectives and Purpose 
3.1 Primary Objective 
To evaluate the feasibility of an RS-tDCS service and concurrent word naming practice. 
3.2 Secondary Objectives  
Secondary objectives include exploratory analyses to evaluate the potential benefits of tDCS + word naming 
practice through change scores on language outcomes. This data will inform the power analysis for future study 
development. 
4 Study Design and Endpoints 
4.1 Description of Study Design 
This study will recruit n=30 PPA patients to receive 20x30 min sessions of active 2.0mA tDCS, combined with 
simultaneous word naming practice over a 4-week period. 
 
All participants will have a remote consent/research screening visit, baseline visit, 20 tDCS treatment visits, and 
post-treatment assessment. All visits will be completed remotely using Zoom. 
 
This will be a single site study at NYU Langone Health and will take place over a 2-year period.  
4.2 Study Endpoints 
4.2.1 Primary Study Endpoints 
• 
Feasibility judged by study completion percentage (16/20 sessions completed per participant) 
4.2.2 Exploratory Clinical Endpoints 
• 
Change in language assessment scores (QAB, BNT, COWAT) and self-report questionnaires (ACOM, 
SAQOL-39, PROMIS Social Roles and Activities, PROMIS Global Health) will be assessed. 
5 Study Enrollment and Withdrawal 
 
5.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 

Study #: s22-01155 
 
 
 
 
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1. Ages 45-85 (inclusive) 
2. Primary progressive aphasia diagnosis (logopenic or semantic variant) 
3. Wide Range Achievement Test (WRAT) score < -1.5 SD, serving as a literacy proxy for premorbid cognitive 
ability and ensuring English language fluency sufficient for participation in the study procedures. If 
participants are not fluent enough to perform this task, the Peabody Picture Vocabulary Test (PPVT) will 
instead be administered with the same cut-off score of < -1.5 SD.  
4. WAIS-IV Matrix Reasoning T score < 20, serving as an index of current general cognitive functioning to 
exclude those with severe cognitive impairment 
5. Stable and continuous access to internet service, email (WiFi “hotspot” to be provided if needed) 
6. Fluent in English language (due to outcomes validated in English versions only) 
 
Inclusion criteria may be confirmed through medical records, screening assessments and self-report. 
5.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Disorder other than PPA known to cause language dysfunction 
2. Diagnosis of nonfluent/agrammatic subtype of primary progressive aphasia 
3. History of traumatic brain injury 
4. Uncontrolled seizure disorder and/or recent (<5 years) history of seizure  
5. Metal implants in the head or neck 
6. Any skin disorder or skin sensitive area near stimulation locations 
7. Pregnant or breastfeeding. Given the age range of our potential participants, we do not anticipate excluding 
anyone on the basis of pregnancy or breastfeeding. While there are no known or theoretical safety risks of 
tDCS in this special population, we routinely have included this eligibility in all our tDCS studies to date out 
of an abundance of caution. Further, in reference to our outcomes for this study, pregnancy and/or 
breastfeeding status may have unique cognitive features secondary to the influence of hormones. 
Participants should not become pregnant while participating in this study. If they are able to become 
pregnant, they will be required to use a medically-accepted method of birth control while they participate in 
the study:  
o 
Hormonal methods like birth control pills, patches, vaginal rings or implants 
o 
Barrier methods such as condoms or a diaphragm used with spermicide (a foam, cream or gel that kills 
sperm) 
o 
Intrauterine device (IUD)  
o 
Abstinence (no sex) 
 
Exclusion criteria may be confirmed through medical records, screening assessments and self-report. 
5.3 Vulnerable Subjects 
We will enroll PPA patients early in the disease course and with language loss as their primary impairment. To 
ensure the ability to meaningfully participate, consistent with all of our RS-tDCS protocols, we will screen to include 
participants with premorbid intellectual functioning in at least the average range, and screen to exclude those 
participants with severely impaired current level of cognitive functioning. Consistent with our RS-tDCS protocol, 
premorbid cognitive impairment will be estimated using the verbal Wide Range Achievement Test-4th edition 
(WRAT-IV) or the nonverbal Peabody Picture Vocabulary Test-4th edition (PPVT-4) as a proxy of expressive 
vocabulary, which is an established method to estimate premorbid cognitive ability. A cut off of 1.5 SD below age 
normative means will be used for exclusion criteria. Current level of cognitive functioning cognitive functioning will 
be estimated using the nonverbal Matrix Reasoning subtest from the Wechsler Adult Intelligence Scale-4th Edition 
(WAIS-IV) that measures abstract reasoning. A cut-off of 3 SD below age normative means (indicating greater than 
moderate impairment) will be used for exclusion criteria. 
5.4 Strategies for Recruitment and Retention 
Potential subjects who meet the eligibility requirements as determined by the inclusion and exclusion criteria will be 
contacted by a trained member of the study team. Diagnosis of PPA and tDCS eligibility will be confirmed by medical 
record review and a signed tDCS safety form sent to study staff prior to study enrollment.  
 

Study #: s22-01155 
 
 
 
 
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A patient who is seeing one of these medical staff members as their treating clinician will be introduced to the study 
by that medical staff member. If the patient is interested and agrees to be contacted, a team member will contact 
them on the phone (or in-person if participant is already in clinic) using an IRB-approved phone script to provide 
additional study information and pre-screen to assess eligibility. Verbal responses will be recorded on a separate 
pre-screen verbal checklist. For any subject who is ineligible, or who is eligible but decides not to participate, we 
will immediately destroy the data collected during the pre-screen.  
 
An IRB approved flyer will be posted in local physician offices and waiting rooms and throughout NYU and support 
organizations. In addition to recruitment at NYU, we will post these flyers around the Ambulatory Care Center (ACC) 
for patients to recruit from the entirety of the Neurology department and from any number of people who come to 
visit the ACC on E38th Street or have an appointment at E41st Street.  
 
An IRB approved study description will be posted on PPA related websites and shared with appropriate list-services 
related to those websites. 
 
Diagnosis of PPA will be confirmed by patient medical records. Non-NYU patients will be asked to submit their 
medical records for confirmation. All patients will complete a tDCS safety questionnaire to confirm eligibility for tDCS 
administration (e.g. no metal in head or neck, history of epilepsy, etc.)  
 
A description of the study including objectives and the expectations of the subject’s participation will be explained. 
Potential participants will be clearly informed that they have the right not to participate in the study and that declining 
participation will not in any way affect their clinical care at NYU Langone Health. Subjects will additionally verbally 
confirm if they meet eligibility criteria. 
 
Consent and assent of study participants will take place in a private telecommunication room (Zoom).  
 
Recruitment procedures will be conducted in private patient rooms during direct subject encounters with their 
healthcare provider. Any identifiable data that is collected during recruitment will be kept in a locked filing cabinet 
in a locked office. Any identifiable data from screening failures will be destroyed immediately after the recruitment 
period has ended. If a subject requests information regarding opting out of further recruitment for all research, 
subjects will be directed to contact study coordinator or have subjects contact research-contact-optout@nyumc.org 
or 1-855-777-7858. 
5.1 
Informed Consent Process 
Consent forms describing in detail the study device, study procedures, and risks are given to the participant and 
written documentation of informed consent is required prior to starting intervention / administering study product. 
The following consent materials are submitted with this protocol: informed consent form. 
5.1.1 Consent Procedures and Documentation 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the study and 
continues throughout the individual’s study participation. Extensive discussion of risks and possible benefits of 
participation will be provided to the participants and their families. Consent forms will be IRB-approved and the 
participant will be asked to read and review the document. The investigator will explain the research study to the 
participant and answer any questions that may arise. All participants will receive a verbal explanation in terms suited 
to their comprehension of the purposes, procedures, and potential risks of the study and of their rights as research 
participants. Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their relatives or think about 
it prior to agreeing to participate. The participant will sign the informed consent document prior to any procedures 
being done specifically for the study. The participants may withdraw consent at any time throughout the course of 
the trial. A copy of the signed informed consent document will be given to the participants for their records. The 
rights and welfare of the participants will be protected by emphasizing to them that the quality of their medical care 
will not be adversely affected if they decline to participate in this study. 
 
Subjects may be mailed an informed consent form and a link to the Zoom room to meet in after they have reviewed 
the consent. The study team member will then explain the consent to the subject, and ask if the subject has any 

Study #: s22-01155 
 
 
 
 
Page 18 of 37 
 
questions. If the subject agrees to participate, they will sign the informed consent document and mail it back to the 
study team via a provided return label. Alternatively, the consent form may be sent via email by a study team 
member for the participant to print, sign, and return via SendSafe. The consent process, including the name of the 
individual obtaining consent, will be thoroughly documented in the subject’s research record. 
Capacity to Consent 
Subject capacity to provide informed consent will be determined by trained team members or PI who will ask the 
participant open-ended questions regarding their understanding of key research information. All team members will 
be trained in GCP-ICH guidelines and will receive additional training by the PI or an experienced study team 
member. Global cognition will be assessed using resources accommodated for individuals with language 
impairment (WRAT-IV or PPVT-4, WAIS-IV Matrix Reasoning). These measures will be given prior to study 
enrollment with scores greater than 3.0 SD’s below age-normative scores being a cut-off for study inclusion.  
 
The results of the capacity assessment (WRAT-IV or PPVT-4, and WAIS-IV Matrix Reasoning) will not be placed 
in the subject’s medical record. This information will only be used for research purposes and will not be considered 
clinical data.  
 
Prospective subjects will be informed of the results of the capacity assessment after it’s conducted. If an individual 
is found not to have the capacity to consent, the assessor will explain this to the individual. The assessor will provide 
the necessary resources and referrals for further care and evaluation. 
 
Ongoing Assessment of Capacity 
At each study visit, subjects will have direct interaction with the licensed clinicians referenced above. If the licensed 
clinicians have any concerns about the subject’s capacity, a formal capacity assessment will be conducted as 
described above. 
 
Over the course of the study, it is possible that a subject who had capacity at enrollment may lose capacity or 
capacity may fluctuate. Subjects who lose capacity will be withdrawn. Subjects who appear to be unduly distressed 
will be withdrawn from the research in a manner consistent with good clinical practice. 
5.2 Duration of Study Participation 
Study participation will last approximately 1 month and will include: 
• 
Remote consent (20 minutes), with participant provided as much time as they need to review consent form. 
Once consented, participant will be scheduled for telehealth research screening. The screening will be 
scheduled based on participant and study/physician availability, which can occur on the same day as 
consent and anticipated to be within one week of consent. 
• 
Baseline speech and language assessment & tDCS Session 1 (approximately 3 hours: 20 minutes to orient 
to device, 1.5 hour assessments, 30 minute tDCS session, 15 additional minutes of word naming practice). 
• 
tDCS treatment sessions (20 x 30 min session over 4 weeks) 
• 
tDCS Session 20 & Treatment-end (2 hours) 
5.3 Total Number of Participants and Sites  
Recruitment will end when approximately 30 participants are enrolled (sign consent) through NYU Langone Health, 
Department of Neurology.  
5.4 Participant Withdrawal or Termination 
5.4.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request. An investigator may 
terminate participation in the study 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 participant 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation. 

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5.4.2 Handling of Participant Withdrawals or Termination 
If a participant wishes to withdraw from the study they may do so at any point without adverse effect on their 
standard-of-care treatment. Participants will be provided with study team e-mail and contact number and can 
withdraw at any time. 
5.5 Premature Termination or Suspension of Study 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. If the 
study is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) for 
the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping 
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and satisfy the 
sponsor, IRB and/or FDA. 
6 Study Device Intervention  
6.1 Study Device Description 
tDCS is a device that delivers weak electrical current (2.0 mA) through sponge electrodes placed on the scalp. The 
main components are: 
• 
1x1 Mini CT tDCS device: The device is powered by 9-volt (V) rechargeable batteries. The device can be 
easily operated, with a user-friendly large-button keypad interface. The device allows strict dose control 
and usage control, employing a one-time use code provided by the study technician to unlock the device 
for each stimulation session. The high sensitivity of the device to any changes allows us to monitor in real 
time the contact quality between the surface of the electrode and the skin ensuring safety and high quality 
of the delivered stimulation. 
• 
tDCS Headset: The headset will be used to standardize and simplify the electrode placement. The 
headset uses two electrodes: the anode electrode and the cathode electrode. An electrode 
montage targeting the left frontotemporal lobe (anode over F7 and cathode over O1) electrode 
montage will be used. The headset connects to the tDCS device with two wires (anode and 
cathode). 
• 
Sponge electrodes: The electrodes are square (5 x 5 cm2) pre-saturated saline sponge electrodes 
packaged for single use equipped with snaps to fasten the sponges to the headset. The participant will be 
only required to open the package and snap the sponge onto the headset. The use of pre-moistened, 
single-use electrodes avoids the possibility of over-saturating the sponge as this can saturate the hair, 
affecting the spread and the direction of the current flow. 
 
tDCS is a non-significant risk device because it is: 
1. not intended as an implant. 
2. it is not purported or represented to be for use supporting or sustaining human life. 
3. it is not for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise 
prevent impairment of human health and does not present a potential for serious risk to the health, safety, 
or welfare of a subject. tDCS has an established record of safety and tolerability for use from trials in a 
range of neurological and psychiatric condtions58 59, and including the specific remotely supervised and 
remote use as proposed for this study60 61. It has NSR designation for our trials specifically using the 
proposed procedures in participants with MS62 63 64 65 66 67 68 as well as for use as an NYU Langone Health 
approval as innovative care for our tDCS clinical service program69.  
4. it does not otherwise present a potential for serious risk to the health, safety, or welfare of a subject 

Study #: s22-01155 
 
 
 
 
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6.1.1 Acquisition 
The devices used in the NYU Langone RS-tDCS research program are manufactured by Soterix Medical Inc. and 
owned by NYULH.  
6.1.2 Product Storage and Stability 
Devices, when not allocated to participants, are stored in-house in a locked room. Device allocation notes including 
device serial number and device unlock codes will be stored for reference. 
6.1.3 Device Programming 
To ensure blinding, devices will be pre-programmed in advance by an independent staff member, who will not take 
part in the treatment and assessment70–72. The device is programmed to ramp up to 2.0 mA (for 30 seconds), 
provide constant current throughout session (29 minutes), and then ramp down (for 30 seconds) at the end.  
6.1.4 Dosing and Administration 
The tDCS device will deliver each session 2.0 mA for 30 minutes over the left frontotemporal lobe with focus on the 
inferior frontal gyrus (IFG). Participants will receive 20 intervention sessions over the course of this study on 
weekdays (M-F). 
 
 
Study technicians are always live with participants via Zoom when initiating and delivering the treatment and can 
address any issues that arise during treatment. Study technicians will direct headset placement remotely. The tDCS 
device can only operate if: 1) the headset is correctly placed for adequate connection, and 2) the study technician 
provides a session code that unlocks the device for a one-time only 30-minute period of use. 
 
If the device loses adequate electrode contact for any reason, the device will automatically discontinue the session. 
The session can only be reestablished if another unlock code is provided by the study technician. 
Specific stop criteria are outlined for treatment administration. Should any stop criteria be met at any point in 
administration of treatment, the participant will not undergo any further treatments and will be asked to return the 
study equipment. If the participant wishes to discontinue a session, they may press the "abort" key at any time, 
which ramps down and stops the stimulation current within 30 seconds. 
6.1.5 Route of Administration 
tDCS is administered through a paired of sponge electrodes placed on the scalp using the headset. The device 
allows strict usage control, employing a one-time use code provided by the study technician to unlock the device 
for each stimulation session. 
6.1.6 Duration of Intervention 
Participants will complete 20 sessions of active RS-tDCS over the course of approximately 4 weeks. The tDCS will 
be programmed to deliver 30 minutes of stimulation. 
6.1.7 Device Specific Considerations 
• 
Device size: Height 7.2 in; Width 3.6 in; Depth 1.2 in 
• 
Device model: Model 1601 
• 
Device settings and programming: Double-blind option: Sham (ON/OFF), Secure administrator mode to 
program sessions, storage of data and codes of 250 sessions; SMARTscan to provide continuous visual 
indication of electrode quality during stimulation 
6.2 Study Device Accountability Procedures 
The device accountability and inventory log will be used to log device-use including subject ID, date shipped, dates 
used, session technician, and date returned. 
7 Study Behavioral Intervention 
7.1.1 Word Naming Practice 
Each tDCS session will include simultaneous word naming practice via live video visit supervision with the trained 
tDCS clinician. tDCS clinicians for this study will be experienced psychometricians with master’s level training and 

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supervised by speech and language pathologist, Dr. Vogel-Eyny. Consistent with the protocol outlined by Flurie et 
al, 2020, study participants, with caregiver support, will select 100 treatment items of personal relevance (i.e., high 
familiarity and frequency) from a fixed list of 220 possible items representing everyday objects (nouns) and actions 
(verbs) (e.g., hat, toothbrush, book, supermarket, coffee, cooking, reading)33. Unselected items from the original list 
of 220 items served as the control word naming list. Baseline performance will dictate the number of words reviewed 
per treatment session to reduce the burden on participants.  
During each RS-tDCS session, once the stimulation has been activated the tDCS clinician will guide the participant 
in the word naming practice. Following the procedures of Henry et al. (2019), participants will be presented with 
photos of target items (via Zoom) and prompted to verbally produce the names of the pictures (common nouns and 
verbs) with the support of a word naming cueing hierarchy aimed at facilitating word retrieval through self-cueing35. 
Participants will be guided as needed through the prompting of semantic, orthographic, and phonological 
information about the target word. All cues within the hierarchy will be presented to the participant for each item 
whether they correctly identify the stimulus or not. This is in effort to reinforce lexical retrieval of the target stimuli. 
The word naming approach is consistent across all participants in the study and described in detail below and 
outlined in Table 1. 
• 
Semantic Self-Cue 
o 
When a target picture is presented for naming, the participant will first be instructed to generate 
semantic features/conceptual information using a fixed set of questions (e.g., “Where do you find 
it?” “What is it used for?”). At this stage, participants are also asked to provide any personal 
historical information about the target (e.g., “I drink this every morning”).  
 
• 
Orthographic Self-Cue 
o 
Next, participants are asked about any orthographic (written) information they might have about 
the word (i.e., whether they can write the word or the first letter of the word).  
 
• 
Phonemic Self-Cue 
o 
Participants are then asked to provide phonological or sound-based information about the word 
(e.g., the initial sound). If the participant cannot retrieve any aspect of the orthographic (written) or 
phonological (sound form) of the target, they are given the first letter of the target (e.g., for “coffee” 
they would be given the letter “c”) and will be asked to produce the corresponding sound of the 
letter. If the participant cannot produce the corresponding sound then the technician will provide it.  
 
• 
Oral Reading 
o 
Should the participant still be unable to name the word, the written form will be provided for oral 
reading. If the participant has difficulty reading the target word, then the spoken form will be given.  
 
• 
Written and Spoken Repetition 
o 
After these steps, the spoken and written forms for the target is named three times.  
 
• 
Yes/No Questions 
o 
Then yes/no questions are given to the participant (e.g., “Do you use this in your hair?”). 
 
• 
Recall 
o Finally, participants are asked to provide two semantic characteristics about the target (e.g., for 
coffee, participant might say, “you drink it”) and attempt to name and write the word.  
o 
Regardless of whether the participant is able to name the target at any step, they continued with 
the remaining steps (excluding the yes/no questions).  
Table 1. Word Naming Practice Cues 
Training Step 
Procedure 
Instructions 

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1. Semantic self-cue 
Picture 
presented; 
patient 
prompted 
for 
semantic 
information 
and/or 
autobiographical information  
What can you tell me about it? 
(Where do you find it? What is it 
used for? What is it made of?)  
2. Orthographic self-cue 
Prompt written form or first letter 
of word 
Can you write the word? Can you 
write the first letter?  
3. Phonemic self-cue 
Prompt initial phoneme 
What sound does that letter 
make? What is the first sound of 
the word?  
4. Oral reading 
If item not named, provide 
written form and participant 
reads aloud 
Here is the word. Can you read 
it? 
5. Written and spoken repetition 
Participant writes and says the 
word three times 
Now write and say the word 
(three times).  
6. Yes/no question 
Provide participants with yes/no 
questions. 
E.g., Is it sweet? Can you buy it 
at the supermarket? 
8. Recall 
Participant 
provides 
two 
semantic features and writes 
and says the word.  
Now tell me two important things 
about this item. What is this 
called? Can you write it? 
Adapted from Henry et al., 2019. 
7.1.2 Administration of Intervention 
Participants may receive a laptop computer with access to Zoom if they do not already have the necessary 
resources to virtually meet with a study technician. All study procedures requiring contact with a study clinician (RS-
tDCS, language assessment, and word naming practice) will be conducted using this laptop and Zoom connection.  
8 Study Procedures and Schedule 
8.1 Study Procedures 
 
• 
Pre-screening: 
o 
Diagnosis of PPA and tDCS eligibility will be confirmed via medical records. 
 
After subjects provide written informed consent, the following research procedures will take place over 
approximately 2 weeks: 
 
• 
Baseline Visit: 
o 
Following procedures for our validated protocol37–41,43–47, participants will first receive training on 
the use of the tDCS device and headset. 
 
o 
Participants will undergo a 90-second tDCS tolerability test to ensure the stimulation is tolerable. 
The participant will be given a one-time use code to initiate the stimulation, the tDCS device will 

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ramp up to its target stimulation intensity (2.0mA) and after 90 seconds, participants will be 
instructed to press “0” to stop the test. Participants are free to stop the test at any time before the 
90 seconds. Participants will then be instructed to remove the headset. Participants who cannot 
tolerate 2.0 mA will be considered a screen failure. 
 
o 
Participants will complete self-report questionnaires about their language use and daily functioning 
through REDCap survey function (see assessments section 8.2 below).  
 
o 
Participants will identify a list of high frequency common nouns and verbs that they use in their 
daily life. This list of words will then be utilized to make the trained and untrained stimuli lists. 
 
o 
For exploratory research, participants will complete cognitive measures (QAB, BNT, COWAT).  
 
• 
tDCS Session 1:  
 
o 
Participants will have their first 30-minute remote session of 2.0mA active tDCS combined with 
word naming practice. Participants will be presented with the list of common nouns and verbs 
previously identified and practice verbally identifying those words from pictures with the help of a 
lexica retrieval cuing hierarchy. At each treatment session, participants will complete brief adverse 
event reports before and after each session. Once the study technician visually confirms correct 
headset placement and participants confirms adequate contact quality (moderate or good), the 
technician will provide the participant with a one-time use unlock code to enter into their tDCS 
device. The participant enters the code when ready to initiate the stimulation. During each 
stimulation session participants will listen to a guided mindfulness meditation audio track on the 
study provided laptop computer.  
 
• 
Remotely-Supervised tDCS Sessions 2-20: 
o 
Over the next 4 weeks, participants will complete the remaining daily RS-tDCS + word naming 
practice as described above for session 1. 
 
o 
tDCS session 20 & Treatment-end: After completing the final tDCS session, participants will repeat 
the baseline self-report questionnaires and language assessment. Participants will be asked to 
return the equipment via Fedex using a prepaid return label. 
8.2 Study Assessments 
 
8.2.1 Self-Report Questionnaires 
• 
The Aphasia Communication Outcome Measure (ACOM): A measurement of patient-reported 
communicative functioning in aphasia73.  
• 
Stroke and Aphasia Quality of Life-39 Item (SAQOL-39): A measurement of quality of life among individuals 
with aphasia74.  
• 
Patient-Reported Outcomes Measurement Information System (PROMIS) – Social Roles and Activities: A 
measurement of the perceived ability to perform one’s usual social roles and activities75. 
• 
Patient-Reported Outcomes Measurement Information System (PROMIS) - Global Health: A measurement 
of symptoms, functioning, and healthcare-related quality of life75. 
 
8.2.2 
Cognitive and PPA symptoms Assessments (Exploratory) 
• 
Trained and Untrained Words: Participants will verbally name pictures of common nouns and verbs with 
the support of a lexical retrieval cueing hierarchy aimed at facilitating word retrieval through self-cueing35.  
• 
Quick Aphasia Battery- (QAB): This aim of the QAB is to provide a reliable and multidimensional 
assessment of language function in a shorter time period across 8 language subtests 76. QAB has been 
adapted for remote use. 
• 
Boston Naming Test (BNT)-Short form: Consists of 15 line-drawn pictures presented in order of difficulty 
from “easiest” (e.g., “house”) to “most difficult” (e.g., “palette”). Participants have 20 seconds to name each 
item correctly with a cueing hierarchy77.  

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• 
Controlled Oral Word Association Test (COWAT): A measure of verbal (phonemic and semantic) fluency 
where participants are given 60 seconds to name all of the words within a given category78. 
8.3 Study Schedule 
8.3.1 
Pre-Screening  
• 
Conduct eligibility phone screen to assess general eligibility. 
• 
PPA diagnosis and tDCS eligibility determined via medical records and tDCS safety questionnaire 
• 
Eligible participants will be scheduled for a baseline visit.  
8.3.2 
Consent & Telehealth medical screening 
• 
Remote consent through SendSafe (20 minutes) 
Once consented, study personnel will send tDCS and study materials to participant 
8.3.3 
Baseline Visit (visit 1) 
• 
Baseline language assessment (1.5 hours) 
• 
Self-report questionnaires (20 minutes) 
8.3.4 
tDCS Session 1 (Visit 2) 
• 
Train participant to use tDCS device (20 minutes) 
• 
Perform tDCS tolerability test (2 minutes) 
• 
Complete first remotely-supervised tDCS session + language skills practice (45 minutes) 
8.3.5 
Remotely-Supervised tDCS sessions 2-19 (Visits 3-20) 
• 
20x30 minutes of active tDCS with simultaneous language skills practice (45 minutes) 
• 
AE reporting 
8.3.6 
tDCS Session 20 & Treatment-end Visit (Visit 21) 
• 
Participants will complete tDCS and word naming practice session 20 (45 minutes) 
• 
Post-stimulation language assessment (1.5 hours) 
Equipment return 
9 Assessment of Safety 
9.1 Definition of Adverse Events (AE) 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the 
course of the study. Intercurrent illnesses or injuries should be regarded as adverse events. Abnormal results of 
diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
9.1.1 Definition of Serious Adverse Events (SAE) 
Serious Adverse Event 
Adverse events are classified as serious or non-serious. A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 
• an important medical event 

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Important medical events are those that may not be immediately life threatening, but are clearly of major clinical 
significance. They may jeopardize the subject, and may require intervention to prevent one of the other serious 
outcomes noted above. For example, drug overdose or abuse, a seizure that did not result in in-patient 
hospitalization, or intensive treatment of bronchospasm in an emergency department would typically be considered 
serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious adverse 
events. 
9.1.2 Definition of Unanticipated Problems (UP) 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as the IRB-
approved protocol or consent form) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a reasonable 
possibility that the incident experience, or outcome may have been caused by the procedures involved in 
the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
This definition could include an unanticipated adverse device effect, 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 (21 CFR 812.3(s)). 
9.1.3 Reporting of Pregnancy 
Women who are pregnant or breastfeeding as determined by participant self-report or medical record will not be 
included in this study. Women who cannot confirm their pregnancy status via self-report or medical record will be 
excluded. 
9.2 Classification of an Adverse Event 
9.2.1 Severity of Event 
For AEs not included in the protocol defined grading system, the following guidelines will be used to describe 
severity. 
• Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or other 
treatment. Severe events are usually potentially life-threatening or incapacitating. 
9.2.2 Relationship to Study Agent 
The clinician’s assessment of an AE's relationship to study device is part of the documentation process, but it is not 
a factor in determining what is or is not reported in the study. If there is any doubt as to whether a clinical observation 
is an AE, the event should be reported. All AEs must have their relationship to study agent assessed. In a clinical 
trial, the study product must always be suspect. To help assess, the following guidelines are used. 
• Related – The AE is known to occur with the study agent, there is a reasonable possibility that the study 
agent caused the AE, or there is a temporal relationship between the study agent and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between the study agent and the 
AE. 

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• Possibly Related – The AE may be related to the device. However, other factors may have contributed to 
the event (e.g., the participant’s clinical condition, other concomitant events). Although an AE may rate only 
as “possibly related” soon after discovery, it can be flagged as requiring more information and later be 
upgraded to “probably related” or “definitely related,” as appropriate. 
• Not Related – There is not a reasonable possibility that the administration of the study agent caused the 
event, there is no temporal relationship between the study agent and event onset, or an alternate etiology 
has been established. 
9.2.3 Expectedness 
Dr. Charvet will be responsible for determining whether an AE is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the risk information previously 
described for the study agent. 
9.3 Time Period and Frequency for Event Assessment and Follow-Up 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits or upon review 
by a study monitor. All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
on the appropriate RF. Information to be collected includes event description, date of onset, clinician’s assessment 
of severity, relationship to study product (assessed only by those with the training and authority to make a 
diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as baseline and 
not reported as an AE. However, if the study participant’s condition deteriorates at any time during the study, it will 
be recorded as an AE. UPs will be recorded in the data collection system throughout the study. 
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at each 
level of severity to be performed. AEs characterized as intermittent require documentation of onset and duration of 
each episode. 
 
The PI will record all reportable events with start dates occurring any time after informed consent is obtained until 
7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation. At each study visit, the 
investigator will inquire about the occurrence of AE/SAEs since the last visit. Events will be followed for outcome 
information until resolution or stabilization.  
 
All unresolved adverse events should be followed by the investigator until the events are resolved, the subject is 
lost to follow-up, or the adverse event is otherwise explained. At the last scheduled visit, the investigator should 
instruct each subject to report any subsequent event(s) that the subject, or the subject’s personal physician, believes 
might reasonably be related to participation in this study. The investigator should notify the study sponsor of any 
death or adverse event occurring at any time after a subject has discontinued or terminated study participation that 
may reasonably be related to this study. The sponsor should also be notified if the investigator should become 
aware of the development of cancer or of a congenital anomaly in a subsequently conceived offspring of a subject 
that has participated in this study.  
 
9.4 Reporting Procedures – Notifying the IRB  
9.4.1 Adverse Event Reporting 
Adverse event rates will be calculated and reviewed at DSMP meetings. Adverse event rates will be reported to the 
IRB as described previously. Should adverse event rates exceed the normal rates observed in the literature, the 
study PI will place the study on hold and review the safety of the study. 
9.4.2 Serious Adverse Event Reporting 
Serious adverse events that are related to the study device or interventions will be reported to the IRB within 24 
hours of becoming aware of the occurrence. 

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9.4.3 Unanticipated Problem Reporting 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of an UP report form. 
It is the site investigator’s responsibility to report UPs to their IRB and to the study sponsor. 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 or other corrective actions that have been taken or are proposed 
in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline: 
• UPs that are SAEs will be reported to the IRB and to the study sponsor within 5 business days of the 
investigator becoming aware of the event. 
• Any other UP will be reported to the IRB and to the study sponsor within 10 business days of the investigator 
becoming aware of the problem. 
• All UPs should be reported to appropriate institutional officials (as required by an institution’s written 
reporting procedures), the supporting agency head (or designee), and OHRP within 10 business days of the 
IR’s receipt of the report of the problem from the investigator. 
9.5 Reporting Procedures – Notifying the Study Sponsor 
The study clinician will complete a SAE Form within the following timelines: 
• All deaths and immediately life-threatening events, whether related or unrelated, will be recorded on the 
SAE Form and submitted to the study sponsor within 24 hours of site awareness. See Section 1, Key Roles 
for contact information. 
• Other SAEs regardless of relationship will be submitted to the study sponsor within 72 hours of site 
awareness. 
 
All SAEs will be followed until satisfactory resolution or until the site investigator deems the event to be chronic or 
the adherence to be stable. Other supporting documentation of the event may be requested by the study sponsor 
and should be provided as soon as possible.  
 
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the investigator shall 
provide further information, as applicable, on the unanticipated event or the unanticipated problem in the form of a 
written narrative. This should include a copy of the completed Unanticipated Problem form, and any other diagnostic 
information that will assist the understanding of the event. Significant new information on ongoing unanticipated 
adverse effects shall be provided promptly to the study sponsor. 
 
The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit to the study sponsor 
and to the reviewing IRB as soon as possible, but in no event later than 10 working days after the investigator first 
learns of the effect. The study sponsor contact information is provided in Section 1, Key Roles. 
 
As a follow-up to the initial report, within the following 48 hours of awareness of the event, the investigator shall 
provide further information, as applicable, on the unanticipated event or the unanticipated problem in the form of a 
written narrative. This should include a copy of the completed Unanticipated Problem form, and any other diagnostic 
information that will assist the understanding of the event. Significant new information on ongoing unanticipated 
adverse effects shall be provided promptly to the study sponsor. 
 
The study sponsor is responsible for conducting an evaluation of an unanticipated adverse device effect and shall 
report the results of such evaluation to FDA and to all reviewing IRBs and participating investigators within 10 
working days after the sponsor first receives notice of the effect. Thereafter the sponsor shall submit such additional 
reports concerning the effect as FDA requests. 
9.6 Study Halting Rules 
There are no predetermined stopping rules. 

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9.7 Safety Oversight 
9.7.1 Data Safety Monitoring  
It is the responsibility of the Principal Investigator to oversee the data safety monitoring of the study at his/her site. 
Data safety monitoring meetings will occur with every 10th subject enrolled (beginning when first participant is 
enrolled) and will include careful assessment of research procedures including protocol adherence, regulatory 
documentation, enrollment (e.g. rate of enrollment, screen fails, withdrawals), unanticipated problems (e.g. device 
malfunction, connection issues), and any issues that may arise during the course of research. There are no 
predefined stopping rules. 
 
Meetings will be documented in data safety monitoring reports (DSMR). An annual DSMR will be submitted to the 
IRB at the time of continuing review. This data safety monitoring will include careful assessment (e.g. frequency, 
relatedness, and expectancy) and appropriate reporting of adverse events (e.g. skin tingling, itching, warming, 
irritation) as noted above. Each tDCS administration will occur in the context of a live video visit through Zoom. With 
this real-time supervision of treatment, risk will be systematically monitored and minimized. 
9.7.2 Medical Monitoring 
Dr. Lauren Krupp, MD, Director of the NYU Langone MSCCC, will serve as medical monitor for this study and will 
be involved in data safety monitoring. Consistent with her ongoing role for the NYU Langone Health tDCS Program, 
Dr. Krupp will be responsible for resolving any clinical matters that may arise (e.g., unanticipated side effects of 
tDCS), including careful assessment of the number and type of serious adverse events, determining relatedness to 
the research, and resolution. This will be done through quarterly meetings with Dr. Krupp to review adverse events. 
Any adverse event that is judged to be treatment limiting or severe will be immediately addressed by Dr. Krupp per 
standard medical care and reported to IRB following guidelines. If these cases do occur, treatment will not resume 
until Dr. Krupp gives medical clearance to proceed. 
10 Statistical Considerations 
10.1 Statistical and Analytical Plans (SAP) 
Study data will be collected through REDCap survey function, and these records will be printed and stored in a 
locked cabinet only accessible to the research staff. While survey data is collected via REDCap, no data will be 
stored in REDCap. All data will be destroyed from REDCap after it is transferred for storage.  
10.2 Statistical Hypotheses 
This is a pilot test to assess the feasibility of RS-tDCS with word naming practice. The primary outcome measure 
will be percent compliance (e.g., at least 16/20 RS-tDCS sessions completed per participant). 
 
In exploratory analyses, pre- and post- language assessment outcomes (trained and untrained words, QAB, BNT, 
COWAT) will be compared to determine if the intervention led to improved scores. Descriptive analyses will be 
completed to identify any trends in predicting those participants who are most likely to have improvement in 
language function at study end (e.g., age, gender, baseline function). 
10.3 Sample Size Determination 
The primary objectives of this study are to: 1) establish feasibility of an RS-tDCS and word naming practice in an 
adult PPA population, and 2) collect preliminary efficacy data to inform a grant application and sample size 
calculations for a large controlled trial. 
A total of 30 adult PPA participants will be enrolled in the study based on the estimated number of eligible patient 
contacts across the study period. 
10.4 Description of Statistical Methods 
For Objective 1, feasibility, individuals will be categorized as “compliant” based on percentage of study completion. 
Compliance with the interventions will be assessed by summarizing the distributions of numbers and proportions of 

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completed sessions. Descriptive analyses will be completed to identify any trends in predicting those participants 
who are most likely to be compliant (e.g., age, gender, baseline function). 
 
For Objective 2, preliminary efficacy, we will convert performance at baseline and study end across study measures 
(QAB, BNT, COWAT, self-report questionnaires). Change in scores, indicating change following intervention, will 
be calculated for each compliant participant (defined as above). Descriptive analyses will be completed to identify 
any trends in predicting those participants who are most likely to have improvement in language function at study 
end (e.g., age, gender, baseline function) as well as corresponding degree of use of the RS-tDCS and word naming 
practice with magnitude of benefit. 
11 Source Documents and Access to Source Data/Documents 
Source data is all information, original records of clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents. 
Examples of these original documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ diaries or evaluation checklists, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and complete, and subject files. It is acceptable 
to use CRFs as source documents. If this is the case, it should be stated in this section what data will be collected 
on CRFs and what data will be collected from other sources. 
 
The study case report form (CRF) is the primary data collection instrument for the study. All data requested on the 
CRF must be recorded. All missing data must be explained. If a space on the CRF is left blank because the 
procedure was not done or the question was not asked, write “N/D”. If the item is not applicable to the individual 
case, write “N/A”. All entries should be printed legibly in black or blue ink. If any entry error has been made, to 
correct such an error, draw a single straight line through the incorrect entry and enter the correct data above it. All 
such changes must be initialed and dated. DO NOT ERASE OR WHITE OUT ERRORS. For clarification of illegible 
or uncertain entries, print the clarification above the item, then initial and date it. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator will permit 
study-related monitoring, audits, and inspections by the IRB, the sponsor, government regulatory bodies, and 
University compliance and quality assurance groups of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.). The investigator will ensure the capability for 
inspections of applicable study-related facilities. 
 
Participation as an investigator in this study implies acceptance of potential inspection by government regulatory 
authorities and applicable University compliance and quality assurance offices. 
 
12 Quality Assurance and Quality Control 
QC procedures will be implemented beginning with the data entry system and data QC checks that will be run on 
the database will be generated. Any missing data or data anomalies will be communicated to the site(s) for 
clarification/resolution. 
 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable NYU IRB regulatory 
requirements. 
 
The investigational site will provide direct access to all trial related sites, source data/documents, and reports for 
the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities. 
13 Ethics/Protection of Human Subjects 
13.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the Protection of 
Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, and/or the ICH E6. 

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13.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the 
IRB for review and approval. Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled. Any amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study. All changes to the consent form will be IRB approved; a determination will 
be made regarding whether previously consented participants need to be re-consented. 
13.3 Posting of Clinical Trial Consent Form 
N/A  
13.4 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed subject 
authorization informing the subject of the following:  
• What protected health information (PHI) will be collected from subjects in this study 
• Who will have access to that information and why 
• Who will use or disclose that information  
• The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the 
ability to use all information collected prior to the revocation of subject authorization. For subjects that have revoked 
authorization to collect or use PHI, attempts should be made to obtain permission to collect at least vital status (i.e. 
that the subject is alive) at the end of their scheduled study period. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the sponsor(s) and 
their agents. Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the IRB or pharmaceutical 
company supplying study product may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the 
participants in this study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use during the 
study. At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated 
by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at NYU Langone Medical Center. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems used by clinical sites and by NYU 
Langone Medical Center research staff will be secured and password protected. At the end of the study, all study 
databases will be de-identified and archived at the NYU Langone Medical Center. 
14 Data Handling and Record Keeping 
14.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of data. Black 
ink is required to ensure clarity of reproduced copies. When making changes or corrections, cross out the original 

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entry with a single line, and initial and date the change. DO NOT ERASE, OVERWRITE, OR USE CORRECTION 
FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for recording 
data for each participant enrolled in the study. Data reported in the eCRF derived from source documents should 
be consistent with the source documents or the discrepancies should be explained and captured in a progress note 
and maintained in the participant’s official electronic study record. 
 
The self-reported questionnaires will be administered through REDCap survey function providing access to secure 
online questionnaires that can be completed from any browser. All study data collected through REDCap will be 
printed and stored in locked cabinet only accessible to the research staff at 222 E 41st Street, 10th Floor.  
14.2 Study Records Retention 
Study documents will be retained for the longer of 3 years after close-out, 5 years after final reporting/publication, 
or 2 years after the last approval of a marketing application is approved for the drug for the indication for which it is 
being investigated or 2 years after the investigation is discontinued and FDA is notified if no application is to be filed 
or if the application has not been approved for such indication. No records will be destroyed without the written 
consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator when these 
documents no longer need to be retained. 
14.3 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Manual of Procedures (MOP) 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the study site 
staff. As a result of deviations, corrective actions are to be developed by the site and implemented promptly. 
 
These practices are consistent with ICH E6: 
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3 
• 5.1 Quality Assurance and Quality Control, section 5.1.1 
• 5.20 Noncompliance, sections 5.20.1, and 5.20.2. 
 
It is the responsibility of the site PI/study staff to use continuous vigilance to identify and report deviations within 10 
working days of identification of the protocol deviation, or within 10 working days of the scheduled protocol-required 
activity. 
 
All protocol deviations must be addressed in study source documents and reported to the local IRB per their 
guidelines. The site PI/study staff is responsible for knowing and adhering to their IRB requirements. Further details 
about the handling of protocol deviations will be included in the MOP. 
15 Study Finances 
15.1 Funding Source 
This study is not currently funded. 
15.2 Costs to the Participant 
Participants will not be responsible for any costs related to the research procedures involved in this study. 
15.3 Participant Reimbursements or Payments 
Participants will be compensated $300 for completing the study ($100 Baseline; $200 at treatment-end visit).  
16 Study Administration 
16.1 Study Leadership 
 

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Leigh Charvet, Ph.D.  
Dr. Charvet is a professor of neurology and the Director of MS Research for the NYU Langone Health’s MS 
Comprehensive Care Center, also directing the neuromodulation research program and clinical tDCS service. She 
has >25 years of clinical and research experience working with people living with MS. She has established a large 
research and clinical program using noninvasive brain stimulation with tDCS, and pioneered the development and 
validation of the remotely supervised, or RS-tDCS, tele-platform for interventions to be accessed by patients and 
research participants remotely. She has an extensive record of funding for investigator initiated clinical trials 
including those supported by the NIH, National MS Society, U.S. Department of Defense and other agencies. Dr. 
Charvet will be responsible for overseeing the completion of the research project, building on her extensive 
background in MS clinical trials, tDCS, and telerehabilitation. She will oversee all aspects of the study including 
procedures, recruitment, and tDCS intervention. She will coordinate the full study team with frequent contact and 
weekly meetings to successfully complete this trial. She will work with the study team to operationalize the study 
procedures and train all personnel in the procedures. She will lead participant recruitment, database creation, and 
data entry. She will monitor recruitment, and take the primary scientific responsibility for completing progress reports 
as well as presentation and publication of the study results.  
 
Amy Vogel-Eyny, Ph.D., CF-SLP 
Dr. Vogel-Eyny is a post-doctoral fellow in the NYU Langone MS Comprehensive Care Center with clinical and 
research experience with a variety of patient populations and with the use of tDCS as an adjuvant to behavioral 
treatment. Dr. Vogel-Eyny will serve as a consultant for the development and administration of the word naming 
practice and train study staff to administer and score this exercise. 
 
Eric McConathey, M.A. 
Eric McConathey is a Senior Research Coordinator in the NYU Langone MS Comprehensive Care Center with 
experience working with various clinical and research populations and various types of non-invasive brain 
stimulation. He will oversee the collection of data, and its recording and interpretation. Eric will be involved in the 
recruitment and consenting processes, administration of language assessments, daily RS-tDCS usage, and 
administration of word naming practice under the supervision and training of Dr. Vogel-Eyny. 
 
Giuseppina Pilloni, Ph.D. 
Dr. Pilloni is a biomedical engineer with the therapeutic applications of noninvasive brain stimulation and tDCS 
devices, with extensive and international experience working in MS rehabilitation. She will provide biomedical 
engineering expertise for all equipment use. Drs. Pilloni and Charvet will work with the vendors to ensure ongoing 
technical and equipment support and guidance for the study. 
 
Lauren Krupp, M.D.  
Dr. Krupp is the medical monitor for the NYU Langone tDCS program including all tDCS research studies and the 
clinical service program. She will participate in routine safety data monitoring and address issues related to 
tolerability as experienced during the trial. 
17 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical industry, is 
critical. Therefore, any actual conflict of interest of persons who have a role in the design, conduct, analysis, 
publication, or any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived 
conflict of interest will be required to have such conflicts managed in a way that is appropriate to their participation 
in the trial. The study leadership in conjunction with the NIH has established policies and procedures for all study 
group members to disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain greater 
than the minimum allowable by their institution, etc.) must have the conflict reviewed by the NYU Langone Conflict 
of Interest Management Unit (CIMU) with a Committee-sanctioned conflict management plan that has been 
reviewed and approved by the study sponsor prior to participation in this study. All NYULMC investigators will follow 
the applicable conflict of interest policies. 

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18 References 
1. 
Marshall CR, Hardy CJD, Volkmer A, et al. Primary progressive aphasia: a clinical approach. J Neurol. 
2018;265(6):1474-1490. doi:10.1007/s00415-018-8762-6 
2. 
Cotelli M, Manenti R, Ferrari C, Gobbi E, Macis A, Cappa SF. Effectiveness of language training and non-
invasive brain stimulation on oral and written naming performance in Primary Progressive Aphasia: A meta-analysis 
and 
systematic 
review. 
Neuroscience 
& 
Biobehavioral 
Reviews. 
2020;108:498-525. 
doi:10.1016/j.neubiorev.2019.12.003 
3. 
Macoir J, Martel-Sauvageau V, Bouvier L, Laforce R, Monetta L. Heterogeneity of repetition abilities in 
logopenic variant primary progressive aphasia. Dement Neuropsychol. 2021;15(3):405-412. doi:10.1590/1980-
57642021dn15-030014 
4. 
Henry ML, Rising K, DeMarco AT, Miller BL, Gorno-Tempini ML, Beeson PM. Examining the value of lexical 
retrieval treatment in primary progressive aphasia: two positive cases. Brain Lang. 2013;127(2):145-156. 
doi:10.1016/j.bandl.2013.05.018 
5. 
Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its 
variants. Neurology. 2011;76(11):1006-1014. doi:10.1212/WNL.0b013e31821103e6 
6. 
Henry ML, Grasso SM. Assessment of Individuals with Primary Progressive Aphasia. Semin Speech Lang. 
2018;39(3):231-241. doi:10.1055/s-0038-1660782 
7. 
Tippett DC, Hillis AE, Tsapkini K. Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol. 
2015;17(8):362. doi:10.1007/s11940-015-0362-5 
8. 
Galletta EE, Vogel-Eyny A. Translational treatment of aphasia combining neuromodulation and behavioral 
intervention for lexical retrieval: implications from a single case study. Front Hum Neurosci. 2015;9:447. 
doi:10.3389/fnhum.2015.00447 
9. 
Fregni F, El-Hagrassy MM, Pacheco-Barrios K, et al. Evidence-Based Guidelines and Secondary Meta-
Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders. Int J 
Neuropsychopharmacol. 2021;24(4):256-313. doi:10.1093/ijnp/pyaa051 
10. 
Pilloni G, Choi C, Shaw MT, et al. Walking in multiple sclerosis improves with tDCS: a randomized, double‐
blind, sham‐controlled study. Ann Clin Transl Neurol. 2020;7(11):2310-2319. doi:10.1002/acn3.51224 
11. 
tDCS for the Management of Multiple Sclerosis Related Fatigue. Published February 12, 2019. Accessed 
August 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03838770 
12. 
A Pilot Trial of Remotely-Supervised Transcranial Direct Current Stimulation (RS-tDCS) to Enhance Motor 
Learning in Progressive Multiple Sclerosis (MS). Published April 17, 2018. Accessed August 19, 2022. 
https://clinicaltrials.gov/ct2/show/NCT03499314 
13. 
Stagg CJ, Nitsche MA. Physiological Basis of Transcranial Direct Current Stimulation. Neuroscientist. 
2011;17(1):37-53. doi:10.1177/1073858410386614 
14. 
Chisari C, Fanciullacci C, Lamola G, Rossi B, Cohen LG. NIBS-driven brain plasticity. Arch Ital Biol. 
2014;152(4):247-258. doi:10.12871/00039829201445 
15. 
Fritsch B, Reis J, Martinowich K, et al. Direct current stimulation promotes BDNF-dependent synaptic 
plasticity: potential implications for motor learning. Neuron. 2010;66(2):198-204. doi:10.1016/j.neuron.2010.03.035 
16. 
Chervyakov AV, Chernyavsky AY, Sinitsyn DO, Piradov MA. Possible Mechanisms Underlying the 
Therapeutic 
Effects 
of 
Transcranial 
Magnetic 
Stimulation. 
Front 
Hum 
Neurosci. 
2015;9:303. 
doi:10.3389/fnhum.2015.00303 
17. 
Hoogendam JM, Ramakers GMJ, Di Lazzaro V. Physiology of repetitive transcranial magnetic stimulation 
of the human brain. Brain Stimul. 2010;3(2):95-118. doi:10.1016/j.brs.2009.10.005 
18. 
Kronberg G, Rahman A, Sharma M, Bikson M, Parra LC. Direct current stimulation boosts hebbian plasticity 
in vitro. Brain Stimul. 2020;13(2):287-301. doi:10.1016/j.brs.2019.10.014 
19. 
Kronberg G, Bridi M, Abel T, Bikson M, Parra LC. Direct Current Stimulation Modulates LTP and LTD: 
Activity Dependence and Dendritic Effects. Brain Stimul. 2017;10(1):51-58. doi:10.1016/j.brs.2016.10.001 
20. 
Huang YZ, Lu MK, Antal A, et al. Plasticity induced by non-invasive transcranial brain stimulation: A position 
paper. Clin Neurophysiol. 2017;128(11):2318-2329. doi:10.1016/j.clinph.2017.09.007 
21. 
Song S, Zilverstand A, Gui W, Li HJ, Zhou X. Effects of single-session versus multi-session non-invasive 
brain stimulation on craving and consumption in individuals with drug addiction, eating disorders or obesity: A meta-
analysis. Brain Stimul. 2019;12(3):606-618. doi:10.1016/j.brs.2018.12.975 
22. 
Pelletier SJ, Cicchetti F. Cellular and Molecular Mechanisms of Action of Transcranial Direct Current 
Stimulation: Evidence from In Vitro and In Vivo Models. Int J Neuropsychopharmacol. 2015;18(2). 
doi:10.1093/ijnp/pyu047 

Study #: s22-01155 
 
 
 
 
Page 34 of 37 
 
23. 
Pilloni G, Choi C, Shaw M, et al. Walking in Multiple Sclerosis Improves Following Aerobic Exercise Paired 
with Transcranial Direct Current Stimulation (tDCS): A Randomized, Double-Blind, Sham Controlled Trial. J 
NEUROL NEUROSUR PS. Published online 2020. 
24. 
Pilloni G, Choi C, Coghe G, et al. Gait and Functional Mobility in Multiple Sclerosis: Immediate Effects of 
Transcranial Direct Current Stimulation (tDCS) Paired With Aerobic Exercise. Front Neurol. 2020;11:310. 
doi:10.3389/fneur.2020.00310 
25. 
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 Stimulation. 2020;13(3):686-693. 
doi:10.1016/j.brs.2020.02.011 
26. 
Pilloni G, Vogel-Eyny A, Lustberg M, et al. Tolerability and feasibility of at-home remotely supervised 
transcranial direct current stimulation (RS-tDCS): Single-center evidence from 6,779 sessions. Brain Stimulation. 
2022;15(3):707-716. doi:10.1016/j.brs.2022.04.014 
27. 
NYU Clinical tDCS Service. Accessed August 19, 2022. https://nyulangone.org/locations/tdcs-program 
28. 
Ekert JO, Lorca-Puls DL, Gajardo-Vidal A, et al. A functional dissociation of the left frontal regions that 
contribute to single word production tasks. Neuroimage. 2021;245:118734. doi:10.1016/j.neuroimage.2021.118734 
29. 
Sharp DJ, Scott SK, Cutler A, Wise RJS. Lexical retrieval constrained by sound structure: the role of the 
left inferior frontal gyrus. Brain Lang. 2005;92(3):309-319. doi:10.1016/j.bandl.2004.07.002 
30. 
Xu Z, Shen B, Taji W, Sun P, Naya Y. Convergence of distinct functional networks supporting naming and 
semantic 
recognition 
in 
the 
left 
inferior 
frontal 
gyrus. 
Hum 
Brain 
Mapp. 
2020;41(9):2389-2405. 
doi:10.1002/hbm.24953 
31. 
Richardson JD, Galletta EE, Charvet L, Shaw M. Feasibility of Remotely Supervised Transcranial Direct 
Current Stimulation (RS-tDCS) for People with Stroke-Induced and Progressive Aphasia. Aphasiology. Published 
online May 23, 2022:1-25. doi:10.1080/02687038.2022.2076279 
32. 
Nissim NR, Moberg PJ, Hamilton RH. Efficacy of Noninvasive Brain Stimulation (tDCS or TMS) Paired with 
Language Therapy in the Treatment of Primary Progressive Aphasia: An Exploratory Meta-Analysis. Brain 
Sciences. 2020;10(9):597. doi:10.3390/brainsci10090597 
33. 
Flurie M, Ungrady M, Reilly J. Evaluating a Maintenance-Based Treatment Approach to Preventing Lexical 
Dropout in Progressive Anomia. J Speech Lang Hear Res. 2020;63(12):4082-4095. doi:10.1044/2020_JSLHR-20-
00059 
34. 
Reilly J. How to constrain and maintain a lexicon for the treatment of progressive semantic naming deficits: 
Principles of item selection for formal semantic therapy. Neuropsychological Rehabilitation. 2016;26(1):126-156. 
doi:10.1080/09602011.2014.1003947 
35. 
Henry ML, Hubbard HI, Grasso SM, et al. Treatment for Word Retrieval in Semantic and Logopenic Variants 
of Primary Progressive Aphasia: Immediate and Long-Term Outcomes. J Speech Lang Hear Res. 2019;62(8):2723-
2749. doi:10.1044/2018_JSLHR-L-18-0144 
36. 
Jokel R, Rochon E, Leonard C. Treating anomia in semantic dementia: Improvement, maintenance, or 
both? Neuropsychological Rehabilitation. 2006;16(3):241-256. doi:10.1080/09602010500176757 
37. 
Kasschau M, Sherman K, Haider L, et al. A Protocol for the Use of Remotely-Supervised Transcranial Direct 
Current Stimulation (tDCS) in Multiple Sclerosis (MS). J Vis Exp. 2015;(106):e53542. doi:10.3791/53542 
38. 
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 Stimulation. 2020;13(3):686-693. 
doi:10.1016/j.brs.2020.02.011 
39. 
Charvet LE, Dobbs B, Shaw MT, Bikson M, Datta A, Krupp LB. Remotely supervised transcranial direct 
current stimulation for the treatment of fatigue in multiple sclerosis: Results from a randomized, sham-controlled 
trial. Mult Scler. 2018;24(13):1760-1769. doi:10.1177/1352458517732842 
40. 
Charvet L, Shaw M, Dobbs B, et al. Remotely Supervised Transcranial Direct Current Stimulation Increases 
the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2018;21(4):383-389. 
doi:10.1111/ner.12583 
41. 
Shaw M, Pilloni G, Charvet L. Delivering Transcranial Direct Current Stimulation Away From Clinic: 
Remotely Supervised tDCS. Mil Med. 2020;185(Suppl 1):319-325. doi:10.1093/milmed/usz348 
42. 
Shaw MT, Best P, Frontario A, Charvet LE. Telerehabilitation benefits patients with multiple sclerosis in an 
urban 
setting. 
J 
Telemed 
Telecare. 
Published 
online 
July 
15, 
2019:1357633X19861830. 
doi:10.1177/1357633X19861830 
43. 
Dobbs B, Pawlak N, Biagioni M, et al. Generalizing remotely supervised transcranial direct current 
stimulation (tDCS): feasibility and benefit in Parkinson’s disease. J Neuroeng Rehabil. 2018;15(1):114. 
doi:10.1186/s12984-018-0457-9 

Study #: s22-01155 
 
 
 
 
Page 35 of 37 
 
44. 
Agarwal S, Pawlak N, Cucca A, et al. Remotely-supervised transcranial direct current stimulation paired 
with cognitive training in Parkinson’s disease: An open-label study. J Clin Neurosci. 2018;57:51-57. 
doi:10.1016/j.jocn.2018.08.037 
45. 
Pilloni G, Shaw M, Feinberg C, et al. Long term at-home treatment with transcranial direct current 
stimulation (tDCS) improves symptoms of cerebellar ataxia: a case report. J Neuroeng Rehabil. 2019;16(1):41. 
doi:10.1186/s12984-019-0514-z 
46. 
Clayton AM, Howard J, Dobbs B, Shaw MT, Charvet LE. Remotely Supervised Transcranial Direct Current 
Stimulation After ECT Improves Mood and Cognition in a Patient With Multiple Sclerosis: A Case Study. J ECT. 
2018;34(1):e15. doi:10.1097/YCT.0000000000000474 
47. 
Eilam-Stock T, George A, Charvet LE. Cognitive Telerehabilitation with Transcranial Direct Current 
Stimulation Improves Cognitive and Emotional Functioning Following a Traumatic Brain Injury: A Case Study. Arch 
Clin Neuropsychol. doi:10.1093/arclin/acaa059 
48. 
Vsee: world’s largest video telemedicine platform. Vsee. Published 2015. https://vsee.com/ 
49. 
NYU Langone Health. Assessment of TDCS-Induced Neuronal Responses in Multiple Sclerosis (MS) With 
Advanced 
MRI. 
clinicaltrials.gov; 
2020. 
Accessed 
September 
28, 
2020. 
https://clinicaltrials.gov/ct2/show/NCT03564496 
50. 
NYU Langone Health. A Pilot Trial of Remotely-Supervised Transcranial Direct Current Stimulation (RS-
TDCS) to Enhance Motor Learning in Progressive Multiple Sclerosis (MS). clinicaltrials.gov; 2020. Accessed 
September 28, 2020. https://clinicaltrials.gov/ct2/show/NCT03499314 
51. 
tDCS for the Management of Multiple Sclerosis Related Fatigue - Full Text View - ClinicalTrials.gov. 
Accessed September 29, 2020. https://clinicaltrials.gov/ct2/show/NCT03838770 
52. 
Remotely Supervised Transcranial Direct Current Stimulation for Persistent Post-traumatic Headache - Full 
Text View - ClinicalTrials.gov. Accessed September 30, 2020. https://clinicaltrials.gov/ct2/show/NCT04012853 
53. 
Ridner SH. Psychological distress: concept analysis. J Adv Nurs. 2004;45(5):536-545. doi:10.1046/j.1365-
2648.2003.02938.x 
54. 
Masters LW, Muccio M, He P, et al. Neuroimaging Indicates Response to Transcranial Direct Current 
Stimulation Treatments in Multiple Sclerosis (1892). AAN Enterprises; 2020. 
55. 
McConathey EM, White NC, Gervits F, et al. Baseline Performance Predicts tDCS-Mediated Improvements 
in 
Language 
Symptoms 
in 
Primary 
Progressive 
Aphasia. 
Front 
Hum 
Neurosci. 
2017;11:347. 
doi:10.3389/fnhum.2017.00347 
56. 
Sheppard SM, Goldberg EB, Sebastian R, Walker A, Meier EL, Hillis AE. Transcranial Direct Current 
Stimulation Paired With Verb Network Strengthening Treatment Improves Verb Naming in Primary Progressive 
Aphasia: A Case Series. Am J Speech Lang Pathol. 2022;31(4):1736-1754. doi:10.1044/2022_AJSLP-21-00272 
57. 
Hung J, Bauer A, Grossman M, Hamilton RH, Coslett HB, Reilly J. Semantic Feature Training in 
Combination with Transcranial Direct Current Stimulation (tDCS) for Progressive Anomia. Front Hum Neurosci. 
2017;11:253. doi:10.3389/fnhum.2017.00253 
58. 
Bikson M, Grossman P, Thomas C, et al. Safety of transcranial Direct Current Stimulation: Evidence Based 
Update 2016. Brain Stimul. 2016;9(5):641-661. doi:10.1016/j.brs.2016.06.004 
59. 
Antal A, Alekseichuk I, Bikson M, et al. Low intensity transcranial electric stimulation: Safety, ethical, legal 
regulatory and application guidelines. Clin Neurophysiol. 2017;128(9):1774-1809. doi:10.1016/j.clinph.2017.06.001 
60. 
Pilloni G, Woods AJ, Charvet L. No risk of skin lesion or burn with transcranial direct current stimulation 
(tDCS) using standardized protocols. Brain Stimul. 2021;14(3):511-512. doi:10.1016/j.brs.2021.03.006 
61. 
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. 2020;13(3):686-693. 
doi:10.1016/j.brs.2020.02.011 
62. 
Charvet LE, Dobbs B, Shaw MT, Bikson M, Datta A, Krupp LB. Remotely supervised transcranial direct 
current stimulation for the treatment of fatigue in multiple sclerosis: Results from a randomized, sham-controlled 
trial. Mult Scler. 2018;24(13):1760-1769. doi:10.1177/1352458517732842 
63. 
Charvet L, Shaw M, Dobbs B, et al. Remotely Supervised Transcranial Direct Current Stimulation Increases 
the Benefit of At-Home Cognitive Training in Multiple Sclerosis. Neuromodulation. 2018;21(4):383-389. 
doi:10.1111/ner.12583 
64. 
NYU Langone Health. Transcranial Direct Current Stimulation (TDCS) for the Management of Multiple 
Sclerosis 
Related 
Fatigue. 
clinicaltrials.gov; 
2020. 
Accessed 
August 
12, 
2021. 
https://clinicaltrials.gov/ct2/show/NCT03838770 
65. 
NYU Langone Health. Cognitive Remediation Augmented With Transcranial Direct Current Stimulation 
(TDCS). clinicaltrials.gov; 2021. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT03049969 

Study #: s22-01155 
 
 
 
 
Page 36 of 37 
 
66. 
NYU Langone Health. Study of the Combined Effect of Transcranial Direct Current Stimulation (TDCS) and 
Physical Activity on Gait and Functional Mobility in Participants With Multiple Sclerosis. clinicaltrials.gov; 2020. 
Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT03658668 
67. 
NYU Langone Health. Assessment of TDCS-Induced Neuronal Responses in Multiple Sclerosis (MS) With 
Advanced MRI. clinicaltrials.gov; 2021. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT03564496 
68. 
Soterix Medical. An Open Label Home-Administered Transcranial Direct Current Stimulation (TDCS) 
Clinical 
Trial 
of 
Unipolar 
Depression. 
clinicaltrials.gov; 
2021. 
Accessed 
August 
12, 
2021. 
https://clinicaltrials.gov/ct2/show/NCT04781127 
69. 
tDCS Program. Accessed August 14, 2021. https://nyulangone.org/locations/tdcs-program 
70. 
Wallace D, Cooper NR, Paulmann S, Fitzgerald PB, Russo R. Perceived Comfort and Blinding Efficacy in 
Randomised Sham-Controlled Transcranial Direct Current Stimulation (tDCS) Trials at 2 mA in Young and Older 
Healthy Adults. PLOS ONE. 2016;11(2):e0149703. doi:10.1371/journal.pone.0149703 
71. 
Dinn W, Göral F, Adigüzel S, Karamürsel S, Fregni F, Aycicegi-Dinn A. Effectiveness of tDCS blinding 
protocol in a sham-controlled study. Brain Stimulation: Basic, Translational, and Clinical Research in 
Neuromodulation. 2017;10(2):401. doi:10.1016/j.brs.2017.01.188 
72. 
Brunoni AR, Schestatsky P, Lotufo PA, Benseñor IM, Fregni F. Comparison of blinding effectiveness 
between sham tDCS and placebo sertraline in a 6-week major depression randomized clinical trial. Clin 
Neurophysiol. 2014;125(2):298-305. doi:10.1016/j.clinph.2013.07.020 
73. 
Hula WD, Doyle PJ, Stone CA, et al. Aphasia Communication Outcome Measure. Published online 
December 12, 2016. doi:10.1037/t56125-000 
74. 
Hliari K, Lamping DL, Smith SC, Northcott S, Lamb A, Marshall J. Stroke and Aphasia Quality of Life Scale-
39. Published online February 11, 2013. doi:10.1037/t17405-000 
75. 
Manual, P.G.S. GLOBAL HEALTH - A Brief Guide to the PROMIS Global Health Instruments. Patient-
Reported Outcomes Measurement Information System (PROMIS).; 2017:1-18. 
76. 
Wilson SM, Eriksson DK, Schneck SM, Lucanie JM. A quick aphasia battery for efficient, reliable, and 
multidimensional assessment of language function. Jäncke L, ed. PLoS ONE. 2018;13(2):e0192773. 
doi:10.1371/journal.pone.0192773 
77. 
Kaplan E, Goodglass H, Weintraub S. Boston Naming Test. Published online June 13, 2016. 
doi:10.1037/t27208-000 
78. 
Benton AL, Hamsher  de SK, Sivan AB. Controlled Oral Word Association Test. Published online March 
13, 2017. doi:10.1037/t10132-000 

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19 Schedule of Events 
 
 
 
Screening 
Baseline  
RS-tDCS sessions + word naming 
practice 
Treatment End 
1-20 
 
Study Team Procedures 
Obtain medical history  
X 
 
 
 
Obtain written informed 
consent  
X 
 
 
 
tDCS Device 
Training/tolerability test 
 
X 
 
 
Assessments 
Word naming practice 
 
 
X 
 
Exploratory cognitive and symptom measures 
Language Assessment 
 
X 
 
X 
Self-report 
Questionnaires 
 
X 
 
X 
Safety Reporting 
AE reporting  
 
 
X