Pilot Study of Transcranial Direct Current Stimulation (tDCS)
Phase: NA
Conditions: Multiple Sclerosis
Sponsor: NYU Langone Health

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A pilot study of remotely-delivered transcranial direct current stimulation (tDCS) in adults 
with multiple sclerosis (MS) (S15-01189)
Principal Investigator: Leigh Charvet
Version: November 20, 2017
I.
PURPOSE OF PROTOCOL
The proposed study will test the tolerability and preliminary efficacy of transcranial direct current 
stimulation (tDCS) combined with a cognitive training program, remotely-delivered using a telemedicine 
protocol in n=85 adults with multiple sclerosis (MS) and in n=30 adults with Parkinson’s Disease. Overall, 
the enrollment goal for this study shall be n=115. The objective of this study is to establish a study 
protocol to use in clinical trials to evaluate the efficacy of tDCS to ameliorate two of the most debilitating 
symptoms of MS that remain without effective treatment: cognitive impairment and fatigue.
We developed the protocol to be used for this study at our former institution, Stony Brook Medicine, and 
have published the results1. As described below, it has been tested in n=20 adults with MS with over 192 
active sessions. The tDCS administered in our protocol has been very well-tolerated (all sessions 
successfully completed, no side effects reported to be more than moderate level).
II.
BACKGROUND
MS is a common disorder associated with major costs. MS is characterized by demyelination, 
immune-mediated inflammation, and neurodegeneration within the central nervous system2, 3. The most 
common subtype is relapsing-remitting and over half of these individuals transition to a progressive 
course; the remainder have a progressive course from the onset4. MS is the most common progressive 
neurologic disorder in adults of working-age5. It is estimated to affect more than 2.3 million people 
worldwide including over 400,000 individuals in the US costing up to ~$52,000 per patient per year 5, 6.
tDCS is a novel, safe, well-tolerated and low-cost treatment approach that strongly warrants 
investigation in MS. The application of tDCS is a relatively recent therapeutic development that utilizes 
low amplitude direct currents to induce changes in cortical excitability7, 8. tDCS is expected to produce 
neuronal polarization of less than one mV 9. tDCS produces relatively diffuse current flow, as 
demonstrated by imaging studies and computational models10, 11. Most of the studies in healthy and 
clinical populations have used electrode montages that produce some current flow across the frontal lobe 
(including any montage with a supra-orbital “return”). A broad neuromodulation of the frontal pole may 
be consistent with a general mechanism of action for its activating effects, along with a general increase  
in large-scale network connectivity12.
tDCS produces current intensities in the brain orders of magnitude below other stimulation techniques 
such as transcranial magnetic stimulation (TMS) or electroconvulsive therapy (ECT) 13; tDCS has none of 
the significant side-effects reported with these much more intensive interventions.  Many subjects feel 
nothing or only mild sensation during the main course of tDCS. Across studies, the most common side 
effect reported from this technique is a mild tingling sensation 8, 14.
Though various non-invasive neuromodulation technologies are available (e.g., transcranial magnetic 
stimulation), tDCS has many advantages compared to other stimulation methods including ease of use, 
lower cost, and better tolerability (e.g., it has not been associated with development of seizures15, 16). 
With an extensive record of safety and tolerability, the most common side effects are specific to the
NCT02746705

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electrode site and include itching, tingling, and burning17. Initial studies have found tDCS to be effective 
in a variety of uses in healthy participants as well as in a range of clinical conditions18,8, 19, 20,21, 22 and may 
be preferred to drug treatment in special populations (such as pregnant women18) due to its safety 
advantages.
tDCS is considered especially promising for symptomatic treatment in MS both for its tolerability, 
deployability (based on our innovative remotely-supervised approach), and presumed 
mechanism of action. While there is emerging study the cellular mechanisms of tDCS23, what is 
established is that sustained (minutes) of tDCS can produce lasting changes in brain excitability24 and 
that these changes are plastic and cumulative with repeated sessions 25. One of the largest and more 
reproducible effects in healthy volunteers is enhanced vigilance with an increased ability to engage 
selective attention23, 26-28, a finding which may indirectly underpin the cognitive benefits of tDCS29, 30. In 
clinical populations, one of the most replicated measures is elevated mood and has been considered an 
effective treatment for depression.
We have developed a telemedicine tDCS protocol that will facilitate recruitment, increase 
compliance, and enable designs with multiple sessions to evaluate benefits of a cumulative effect. 
tDCS urgently requires further study to fully leverage this treatment modality for maximal clinical benefit 
in MS. Repetitive sessions are necessary to produce cumulative effects as shown in neurophysiology 
studies and clinical trials for neuropsychiatric disorders and rehabilitation8, 31-33. For the treatment of 
depression, a clinical application that has received extensive study, some patients have required 20 to 30 
sessions or more for optimal improvement 33,20, 29, 30, 34.
We believe that studies of tDCS in MS have been limited by sample size and number of treatment sessions 
due to the barrier of access for most MS patients to participate in studies requiring multiple consecutive 
clinic visits for treatment. Daily travel to a treatment facility is a real-world limitation because it is not 
feasible for those with a full work and family schedule (requiring time taken from meeting these other 
obligations), or limited mobility and/or restricted transportation options (which can be especially 
burdensome for caregivers). For example, all but one study of tDCS in MS to date (treating symptoms of 
pain, fatigue, sensory and motor functioning 31, 35-40) has included more than five sessions, and none have 
enrolled more than 31 participants (and, in this largest sample size, participants only completed one tDCS 
session31). To study multiple applications of tDCS in MS, participants must be able to access these 
treatments from home.
To address this need, we have developed a remotely-supervised telemedicine protocol to provide access 
to tDCS treatment to participants in their homes. Our protocol was developed following our group’s 
extensive experience with a remotely-supervised cognitive remediation program 41, and meets 
collaborative guidelines and standards that we established working with a diverse group of tDCS clinical 
investigators42. As detailed below, our protocol is opposed to self-directed home use, where a patient is 
given a device without parameters and real-time supervision, which is not advisable due to both safety 
concerns as well as problems with uniformity and reproducibility of results. Instead, we maintain clinical 
trial standards for safety and consistency with a specially-designed tDCS device (that “unlocks” one  
“dose” per code, controlled by a study technician) with extensive checkpoints and built-in safety features 
for study using remote supervision through a telemedicine videoconferencing platform.
Feasibility and safety study for our telemedicine tDCS protocol Consistent with the demonstrated 
safety and tolerability across hundreds of clinical trials in tDCS58,59, including a total of eight published 
trials in MS43,35, 37, 38, 44, we found very high tolerability in our feasibility study. In less than five months

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we administered 192 active tDCS sessions in n=20 MS patients receiving 10 open-label sessions over 
two weeks (approaching the combined published experience of tDCS in MS fatigue). Participants have 
ranged in age from 30 to 69 years and included individuals with all subtypes (n=6 relapsing remitting, 
n=12 secondary progressive, n=2 primary progressive), and a range of disability from mild to severe or 
wheelchair dependent disability (EDSS scores of 1.0 to 8.0). No adverse effects or side effects of severe 
intensity have been reported in any session, and no session has been discontinued. As seen in Figure 1, 
the most common adverse event reported was skin tingling, and this did not exceed an intensity of 
“moderate.”
Due to both the novelty of tDCS and the option to participate remotely, we have met great interest in our 
MS patient community with rapid enrollment, limited only by device and staff availability (53 patients on 
a waitlist over a three-month period). Compliance has been near-universal and all but one participant 
(95%) completed at least 8 of the 10 study sessions (this study discontinuation was due to personal 
family events unrelated to tDCS or the study). Further, the majority of participants have reported benefit 
from tDCS and requested to continue past the study’s 10 sessions.
Figure 1: Frequency of side effects reported across 192 tDCS sessions with remotely-supervised 
protocol
III.
SIGNIFICANCE AND BACKGROUND FOR THE STUDY
The objective of this study is to establish a study protocol to use in clinical trials to evaluate the 
efficacy of tDCS to ameliorate two of the most debilitating symptoms of MS that remain without 
effective treatment: cognitive impairment and fatigue.
Cognitive impairment:
Cognitive impairment occurs frequently in MS and is without an effective treatment option: Cognitive 
impairment occurs in up to 70% of all patients45-47 and, in this younger adult population, is a major cause 
of disability leading to unemployment, social isolation, and increasing dependence on caregivers48, 49. The 
most common deficits are in the area of working memory (WM), measured by tests of information 
processing, attention, and new learning50-52. Impairment can occur independently from other disease 
features47 and is linked to cerebral atrophy, and, in particular, regional grey matter volume loss53. 
Unfortunately, medications have not been effective47, 54, 55. Disease-modifying medication possibly slows 
the progression of deficits, but does not improve functioning55-59. Symptomatic medications such as the

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cholinesterase inhibitor donepezil (trials completed at our center)60-62 and L-amphetamine are not 
effective as standard treatment63, 64 and can include safety concerns (e.g., potential for abuse65).
•Neural plasticity-based computerized cognitive training (CT) programs are promising: There has been 
limited study of CT in MS. Traditional approaches (e.g., clinician-delivered compensatory strategies and 
drill-and-practice training) are costly and difficult to uniformly implement, with inconsistent benefit66-69. 
Recent technological advances have led to computer-based CT approaches70-73. Rather than focusing on 
compensation, intensive repetitive targeted exercise may actually improve cognitive ability at the 
processing level, possibly through mechanisms of neural plasticity71-76. This plasticity-based approach 
aims to drive change with exercise components including trials that are rapidly adapted to the individual 
user in real-time to maintain a consistent level of challenge71, 73. Initial studies in MS have linked cognitive 
reorganization with training77, 78.
We have completed two controlled trials in MS demonstrating the superiority of this type of CT compared 
to ordinary computer games. Our group has developed a protocol to allow participants to access CT from 
home, targeting 60 sessions over 12 weeks 41. The remote access has resulted in rapid enrollment of >160 
patients in two years; in comparison, in the largest published CT trial in MS, an outpatient memory 
training program with10 sessions in five weeks, required >7 years to enroll n=86 participants68. Using 
our protocol we have found very high compliance, with no loss of study equipment, weekly participant 
phone interviews, and all but two completing the program through the study end visit. These results 
emphasize the tremendous unmet treatment need for people living with MS, and have led to the 
established procedures to be used in this study to deliver remotely-supervised cognitive remediation.
•tDCS can increase the benefit of CT: While many questions remain, pairing tDCS with CT has increased 
learning and performance particularly in tasks depending on WM27-30, 79-81.  Preliminary data from our 
recently-completed randomized double-blind active-placebo controlled trials show that CT leads to leads 
to greater gains in a neuropsychological testing composite z score when compared to playing ordinary 
computer games (n=135, program by Posit Science82, p=0.02, report in preparation; and n=20, program 
by Lumos Lab, 0.46 ± 0.59 improvement vs.−0.14 ± 0.48 decline, p = 0.02 41). However, the difference in 
average improvement of the composite z-score is relatively modest, z-score 0.20±0.36 vs. 0.05±0.31, 
p=0.02, Cohen’s d =0.43. The proposed research will take the first step towards determining whether the 
benefit of CT can ultimately be improved when combined with tDCS.
Fatigue:
Fatigue is the most frequent debilitating symptom of MS and remains without an effective treatment: 
75% or more of patients report it is among their most disabling MS problem83, 84, and 55% indicate it to 
be the worst85, 86. Defined by the subjective sense of overwhelming tiredness and exhaustion, there are 
serious adverse health care consequences linked to fatigue in general, and MS fatigue in particular. 
Fatigued MS patients leave the work force early, have increased health care utilization, and are at risk for 
depression87. However, despite careful description (initially with the Fatigue Severity Scale or FSS, 
developed by study Co-I Dr. Lauren Krupp), the etiology of MS fatigue remains poorly understood88. MS 
fatigue is neither consistently linked to disease severity as measured by the Expanded Disability Status 
Scale or EDSS89 nor disease duration90, although it is generally found to be worse with individuals with 
the secondary progressive subtype83, 90-92. Fatigue is distinct from sleepiness and fails to improve with 
adequate sleep93. Multiple factors contribute to fatigue, including CNS demyelination and axonal loss94, 
immunological changes, MS-related problems (trigeminal neuralgia, spasms), psychological and chronic 
illness factors (depression, pain, poor sleep), and medications95, 96.

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A wide variety of therapies have been attempted for fatigue in MS but there remains no accepted or 
standardized treatment88. Fatigue may improve with disease modifying therapy but there is no evidence of 
consistent benefit97-99. No symptomatic medication, including large trials of modafinil100, amantadine and 
pemoline 101, has been found to be reliably effective86, 102, 103. Behaviorally-based management programs (e.g. 
cognitive behavioral therapy, mindfulness-based interventions), exercise programs103 and comprehensive 
strategies to manage MS fatigue directly104 have also been studied. While these  treatment efforts have had 
somewhat more success than medications, they are costly in terms of clinician and patient time, usually require 
weekly or more frequent clinic visits for therapy, and are not widely available. Overall, fatigue in MS has 
remained frustratingly treatment-resistant. A consistently effective, reliable and accessible fatigue treatment 
option is greatly needed.
Of the eight published trials of tDCS to date, three have directly targeted fatigue35, 37, 38. As shown in Table 1, 
all three have used sham-controlled crossover designs, and found significant improvement in fatigue 
following active treatment in either the full group or subset analyses35, 37, 38. Each of the three studies varied 
in their montage with similar results.
Table 1. tDCS studies of fatigue in MS to date, including our feasibility study and proposed study
Author (Year)
Sample Design
#Sessions, Treatment Montage
n
Ferrucci et al. (2014) 38
25
Sham-controlled
5 sessions x 1.5 mA motor cortex x 15
crossover
minutes
Saiote et al. (2014 )37
13
Sham-controlled
5 sessions x 1.0 mA DLPC x 20 minutes
crossover
Tecchio et al. (2014)35
10
Sham-controlled
5 sessions x 1.5 mA x 15 minutes;
crossover
sensorimotor cortex
Protocol feasibility
17
Open-label (remote
10 sessions x 1.5 mA DLPFC x 20 minutes
study
protocol)
Two of the three studies included analyses to link to the mechanism of benefit, with unclear results. Saiote et 
al.37 included MRI and found a correlation between lesion load in left frontal cortex and reduced fatigue 
following tDCS treatment. In a follow-up second analyses, Tecchio et al.35 found tDCS treatment was more 
effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area 
(but changes in S1 and M1 excitability did not correspond to treatment benefit).
IV.
SPECIFIC AIMS
Specific Aim 1: To test the feasibility of a randomized, controlled remotely-supervised tDCS clinical 
trial protocol developed specifically for use in MS. Participants (n=85) will be randomly assigned to 
receive 40 x 20-minute sessions of either active (up to 2.5 mA) paired with cognitive remediation, to 
two separate control conditions. The first is an active tDCS condition paired with non-adaptive, 
traditional puzzle and board games and will act as this study’s negative control. The second control will 
act as the study’s positive control and will be sham tDCS paired with cognitive remediation. Each study 
session, regardless of study arm, will be followed by an additional 10 minute computerized training 
sessions post-stimulation. Each study arm will complete 40 sessions over eight weeks.
The primary outcome for feasibility will be the number of participants completing at least 80% or n=32of the 
targeted 40 sessions. Secondary outcomes will be comparison of tolerability and participant- reported side 
effects between the two treatment arms.

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Specific Aim 2: To test the preliminary efficacy of tDCS to treat fatigue and to enhance outcomes of 
cognitive training. These data will inform the design of a large, controlled clinical trial.
The primary outcome will be comparisons between the active and control conditions on measures of 
fatigue and cognitive functioning.
V.
DESCRIPTION OF THE PROTOCOL
The goal of this pilot study is to establish a structured protocol for safe remotely-supervised delivery 
of 40 consecutive tDCS sessions (active and control conditions) to be used in a randomized, 
controlled double-blind clinical studies in participants with MS.
a) Study Design: Participants will complete a total of 40 sessions across eight weeks: training at baseline 
with a study technician and then monitoring (through secure online video) by the study technician for  
the remaining thirty-nine sessions. We will use the most common montage of bilateral dorsolateral 
prefrontal cortex (DLFPC) placement, with the anodal electrode placed on the left side. This offers ease of 
reliable electrode placement and wide therapeutic applications. Dose will be up to the target of 2.5 mA 
with reduction to 2.0, 1.5, or 1.0 mA based on tolerability testing at baseline. At study end, participants in 
the sham condition will be offered 10 open label active sessions.
x
b)
Study Equipment: For the remotely-supervised sessions, participants will be given the specially- 
designed tDCS device and headset, study laptop computer for secure video monitoring with study 
technician (must have internet access), a detailed reference manual, and a training video. The Soterix 
mini-CT is uniquely designed for remotely-supervised delivery and requires a one-time use code 
provided by the study technician to unlock the device for one stimulation session. The device will not 
operate without correct headset placement and has a single-button option to abort the session. The 
device will also automatically abort the session if optimal conditions are not maintained. It reports and 
records a completion code for each session.
c) Randomization: Participants will be assigned to each condition in a 1:1:1 Stratified randomization 
procedure. Participants will be matched according to the degree of cognitive impairment (Symbol Digit 
Modalities test or SDMT105 score) and neurologic (motor) impairment (Expanded Disability Status Scale 
or EDSS89 score). Participants will be randomized to either the active tDCS condition paired with 
cognitive remediation or one of the two control conditions. The positive control condition will consist of 
cognitive remediation paired with sham tDCS and the negative control condition will consist of  active 
tDCS with non-adaptive puzzle and board games using block randomization of permuted block sizes 3 and 
6, based on our experience in cognitive remediation trials. SDMT performance will be categorized 
compared to published age-normative means (>0.99 SD, 1 to 2 SD and 2 to 3 SD below mean) and EDSS 
score will be categorized as mildly or moderately impaired (0 to 3.0 vs. 3.5 to 8.0).
d)Outcome Measures: Before and after each session, participants will complete brief measures to 
monitor for any stimulation-related events as well as mood and fatigue. In addition a pain scale will be 
administered during the session. Participants will also complete baseline and study-end inventories of 
mood and fatigue and complete a brief battery of cognitive tests including the Brief International 
Assessment of Cognition in MS or BICAMS106, to help guide power estimates for the future trials. A 
summary of outcome measures can be found in Table 2.
Table 2. Study Outcome Measures

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Test
Screen
ing
Baseline
Daily 
Study 
Session
s (1-20)
Mid-
study
Daily 
Study 
Sessions 
(21-40)
Study 
End 
(Follow-
up)
Online/ 
Telephone 
Survey 
(Study end 
date + 1 
month)
Medical Clearance
X
Expanded Disability 
Status Scale 
X
Wide Range Achievement 
Test (WRAT-4)
X
X
X
Symbol Digit Modalities 
Test (SDMT)
X
X
X
X
Beck Depression 
Inventory-Fast Screen*
X
X
tDCS Aptitude Test
X
X
tDCS Tolerance Test (2.0 
mA, will possibility to 
repeat at 1.5 mA)
X
X
Multiple 
Sclerosis 
Neuropsychological 
Questionnaire (MSNQ)*
X
X
X
X
PROMIS Measure of 
Fatigue, Mood and Health-
Related Quality of Life*
X
X
X
X
Neuro-Quality of Life*
X
X
X
X
Fatigue Impact Scale*
X
X
X
X
Fatigue Severity Scale*
X
X
X
X
Pittsburgh Fatigability 
Scale*
X
X
X
Attention Network Test- 
Interaction*
X
X
X
Cogstate Brief Battery*
X
X
X
ERTSLab Processing 
Battery*
X
X
X
Controlled 
Oral Word 
Association*
X
X
X
Rey Auditory Verbal 
Learning Test*
X
X
X
X (delayed 
recall only)
Brief Visuospatial Memory 
Test- Revised*
X
X
X
King Devick Test*
X
X
X
Test of Everyday 
Cognitive Ability*
X
X
X
Grip Strength*
X
X
X
Grooved Pegboard*
X
X
X
Positive and Negative 
Affect Scale (PANAS)*
X
X
X
X
X
Visual analog scale for 
X
X
X
X
X

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fatigue (pre- and post-
session)
Visual analog scale for 
pain (pre-, early-, mid- 
and post-session)
X
X
X
X
X
Tolerability 
questionnaire - 
administered by 
study staff
(pre- and post-session)
X
X
Safety and tolerability 
questionnaire –self-report 
(pre- and post-session)
X
X
Score for Computerized 
cognitive games (daily)*
X
X
Daily assessment of 
sleep 
X
X
Patient and Caregiver 
Questionnaires*
X
Participant Evaluation of 
Study Procedures*
X
X
X
X
Count of successful tDCS 
sessions (confirmation 
code by session days)
X
X
X
X
Optional measures that may be excluded based on study personnel judgement are indicated by an asterisk.

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e)Analytic Plan:
Specific Aim 1 is to determine feasibility; to be measured by the number of participants successfully 
completed using the proposed protocol for training and monitored administration. As would be 
expected, there is a high rate of compliance for in-clinic tDCS administration and therefore remotely- 
supervised administration should be designed to be similarly compliant. Study success will be defined by 
80% participants having completed 80% sessions, shown to be the target compliance for previous tDCS 
studies107 . We will also determine the effectiveness of our sham procedures to ensure blinding, as tested 
by comparing those who accurately identified the sham condition. We will assess whether the frequency 
or type of side effects differ between the active and control conditions and whether they occur at the 
same rate as reported from studies of in-clinic administration. Secondary outcomes will be tolerability, 
participant-reported adverse events, and comparisons of active and control conditions on these 
measures.
Specific Aim 2 will be to determine preliminary signals for efficacy, and to have pilot findings to 
determine necessary sample sizes for an adequately-powered clinical trial. For each participant, change 
scores will be calculated between baseline and study end scores on measures of fatigue and cognitive 
functioning. These difference scores will then be described and compared between groups (t-tests and 
ANOVA related analyses) to determine signals of efficacy for active tDCS paired with cognitive 
remediation vs. active tDCS paired with non-adaptive puzzle and board games vs. sham tDCS paired 
with cognitive remediation.
VI.
METHODS AND PROCEDURES
All remotely-supervised sessions will be completed while connected to a video session with the study 
technician. The protocol is designed to have a decision-tree series of checkpoints that must be met in 
order to proceed at each step (Figure 2). These checkpoints address compliance (attendance, ability to 
complete the procedures as instructed, following the study guidelines) and tolerability (at any time, if any 
predefined events are reported). Following state of the art in tDCS research, devices will be programmed 
in advance by the PI to provide either active or sham sessions following current standards for blinding33, 
108. During a sham session, the device is programmed to ramp up to the desired intensity (target 2.5 mA) 
and ramp down for the initial 60 seconds, with no current delivery during the following 18 minutes of the 
session, and then current is ramped up and down for 60 seconds at the end of the session. These brief 
periods of stimulation serve to mimic the effects of a true stimulation session. Both participants and 
study coordinator (who administers study outcome measures) will be blinded, and will be asked to guess 
the assigned condition at study end.
The PI will not be blinded to study condition. The PI or an un-blinded study technician will 
preprogram devices according to randomization and then provide to the study coordinator for each 
participant. That is, the study coordinator and participant will be blinded to which condition 
programmed to the assigned device. All procedures will be the same for all three conditions.  Adverse 
events will be addressed in either condition, and the study PI will always know the assigned condition 
for each participant.

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Figure 2. Study stop criteria
Screening:
Participants for all groups will be recruited from the NYU Langone Medical Center Multiple 
Comprehensive Care Center. Once a potential participant is identified, a screening phone call will take 
place to determine general eligibility (See section IX. Consent Process). Once a participant is deemed 
generally eligible, the individual will be scheduled for a visit at NYU to review and sign consent and 
complete screening procedures, including a medical clearance. For those interested in study 
participation, once eligibility is confirmed by a NYU MS Center clinician, their baseline appointment will 
be scheduled.
Baseline Visit:
*Note clinician assessment for medical clearance may occur either before or at the baseline visit
All women who are of child-bearing age will complete a pregnancy test (human chorionic gonadotrophin 
urine assay) to assure they are eligible for all study procedures. Women who receive a result denoting 
heightened hCG levels will be considered study screen failures. 
Prior to tDCS training, the tests and evaluations detailed in Table 2 will be administered.
tDCS aptitude screen and tolerability test:

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●
tDCS Aptitude: Participants will first complete an aptitude test to confirm that they have 
the cognitive and motor skills required for headset placement. With instruction of the study technician, 
they will be asked to insert the sponges onto the headset and place the electrodes into the sponges. The 
technician will determine whether or not the participant is qualified to proceed. Participants will not be 
allowed to proceed if they are not able to correctly either 1) attach sponges to headset or 2) place 
electrodes into the sponges.
tDCS Tolerability: The study technician will next directly place the headset and then initiate a one-minute 
test session, with 30 seconds of ramp-up to target, followed by a 30-second ramp down. The tolerability test 
will first take place using 2.5 mA stimulation. If the participant tolerates and agrees, 2.5 mA will be used for 
all following stimulation sessions. Alternatively, if the participant cannot tolerate 2.5 mA, stimulation will be 
based on highest amplitude tolerated, following 0.5 mA decrements (2.0, 1.5., and 1.0 mA.) till finally a base 
1.0 mA stimulation is offered. Once the tolerable dose is established, it will remain constant throughout the 
study. If the participant cannot tolerate any of the offered stimulation levels, they are excluded from the 
study.
Remotely Monitored Study Sessions 2 to 40: 
These sessions will be completed from home with remote monitoring by the study technician. For 
participants in the sham condition who elect 10 additional sessions of the open-label, active tDCS, these 
same procedures will be repeated.
Participants will schedule times during which they are certain they can self-administer the tDCS while 
they are being remotely monitored by study staff. They will be observed using a secure internet-based 
video chat program that will be installed in the laptop they will use for the study. To start their session, 
the participant will connect to study staff via a secure internet-based video program.
They will put on the tDCS headgear while being monitored, and tell study staff if the device feedback 
indicates that the electrodes are acceptably placed. The participant will then receive the activation code 
from the tDCS device. If the study staff observes the participant making any errors that may cause the latter 
discomfort they can intervene with instructions for correction.
Safety notes:

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 20 
minute period of use.

If the device loses adequate 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.

If the participant wishes to discontinue the session at any time, they will be instructed to press the 
“abort” key which ramps down the current within 30 seconds to allow for headset removal.
Study End Visit:
Within three days of their last session (including same day), participants will have their final study end 
visit in clinic. The tests and evaluations administered at baseline will be given to the participant again 
(Table 1).  The equipment that had been provided to the participant for this study will be returned on this 
visit.

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Online/Telephone Survey:
One month following the study end visit, participants will receive an online survey to complete through 
REDcap. This survey will consist of a text box to enter delayed recall words from the RAVLT task 
completed at follow-up, as well as the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), 
PROMIS Measure of Fatigue, Mood and Health-Related Quality of Life, Neuro-Quality of Life measures, the 
Fatigue Impact Scale, the Fatigue Severity Scale, and the Positive and Negative Affect Scale (PANAS). In 
addition to these 7 measures, participants will be asked to assess their experience with the study:
“Overall, did you feel a benefit from participating in this trial? If so, how? If so, has the benefit 
lasted?” 
All data will be entered into REDcap, either directly by participants if they select to complete the measures 
online, or by research assistants if the participants select to complete the measures in an interview format 
via phone.
Open label tDCS Sessions:
Following the study end visit, individuals in the sham condition will be offered 10 open-label active tDCS 
sessions.
VII.
SUBJECT SELECTION
Characteristics of the Research Population
We will enroll a total of n=85 adults (ages 18 and over) with confirmed MS. Participation will be open to 
those with all subtypes and levels of disability who meet the eligibility criteria as below.
Eligibility Criteria
Enrolled participants must have a diagnosis of MS (any subtype) with stable disease status and expanded 
disability status scale (EDSS) 89 scores of less than 6.5 or above with proxy. Individuals with a Symbol 
Digit Modalities Test or SDMT 105 score ≥3.0 SD below published norms will be excluded as will those 
with any health condition contraindicated with the use of a tDCS device (including history of seizures, 
abnormal EKG, skin disorders, head trauma or medical device in the head or neck). Baseline screening 
evaluation will include a neurological exam and medical clearance by the study physician and brief 
screening evaluations for ability to operate the study equipment.
Inclusion Criteria
Exclusion Criteria

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●
Ages 18-79 
●
Definite MS diagnosis, all subtypes [95]
●
MS-related changes in cognitive 
functioning*
●
A score of 6.5 or lesson the Expanded 
Disability Status Scale (EDSS) OR more 
than 6.5 with proxy
●
Has stable and continuous access to 
internet service at home compatible with 
the study laptop (Wi-Fi or ethernet cable)
●
Adequate internet capacity for remote 
monitoring, as tested by 
http://www.speedtest.net/)
●
Adequate home facilities (enough space, 
access to quiet and distraction free area)
●
Visual, auditory and motor deficits that would 
prevent full ability to understand study 
instructions or operate the tDCS device or 
study laptop, as judged by treating neurologist 
or study staff
●
Relapse or steroid use in previous month
●
History of mental retardation, pervasive 
developmental disorder or other neurological 
condition associated with cognitive 
impairment
●
Primary psychiatric disorder that would 
influence ability to participate
●
History of seizures or seizure disorder

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
Able to commit to the two-week 
period of training sessions with 
baseline and follow-up visits.
●
Able to understand the informed consent 
process and provide consent to 
participate in the study
●
History of head trauma (e.g., head injury, brain 
surgery) in the past year or medical device 
implanted in the head (such as Deep Brain 
Stimulator) or in the neck (such as a Vagus 
Nerve Stimulator)
●
Any skin disorder/sensitive skin (e.g., eczema, 
severe rashes), blisters, open wounds, burn 
including sunburns, cuts or irritation, or other 
skin defects which compromise the integrity of 
the skin at or near stimulation locations 
(where electrodes are placed)
●
Treatment for a communicable skin disorder 
currently or over the past 12 months
●
History of uncontrolled or labile hypertension.
●
Other serious uncontrolled medical condition 
(e.g., cancer or acute myocardial infarction)
●
History of clinically significant abnormalities 
on electrocardiogram (EKG)
●
Alcohol or other substance use disorder
●
Learned English language after 12 years of age
●
Pregnant or breastfeeding
●
Symbol Digit Modalities Test ≥3.0 SD below 
published norms
Gender and Minority Inclusion of Subjects
Gender and minority inclusion for this project will be promoted in several ways. Enrollment will 
primarily be through the NYU MS Comprehensive Care Center, with a diverse patient The Health 
Initiative for Underserved Communities and members of its Community Health Advisory Board will be 
informed of the project and asked to make their members aware of eligibility.
Vulnerable Subjects
Participants with MS may be considered as vulnerable subjects due to cognitive impairment; however, 
those who lack capacity to consent will not be enrolled in this study. For all participants, we will confirm 
capacity to consent with their care provided at the visit. We will also screen those with estimated overall 
cognitive impairment and reading ability by administering a reading measure Wide Range Achievement 
Test 4 (WRAT-4). It will be clearly explained and written for all potential participants that the study is 
entirely optional and there will be no negative consequences to their decision not to participate.
VIII.
STUDY LOCATION
Participants screening, baseline and study end visits will be completed at the NYU MS Langone MS 
Comprehensive Care Center, 240 East 38th Street, 18th Floor, NY NY 10016, or the satellite location for the

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MS Center, NYU Langone Huntington Medical Center, 180 E Pulaski Rd, Huntington Station, NY 11746. 
For participants with limited mobility, visits can be completed from the participant’s home.
IX.
DATA ANALYSES AND DATA MONITORING
Database and Patient Information
Data will be entered in the HIPAA- compliant NYU REDCap database designed specifically for this study. 
An anonymous database number will be assigned to each participant and will be used for both the Data 
Entry Sheet and the Patient Follow-up Sheets. The original front sheet, which includes the patient name 
and ID number, will be stored separately in a locked filing cabinet in a locked office. Access to this data 
will be restricted to study personnel only. Research data will be entered online through the secure NYU 
database software REDCap and source documents will be kept in a locked filing cabinet in a locked office. 
Patient clinical data will be entered directly into the Patient Registry (on-line entry). Participant data will 
be coded by the assigned ID and identifying information will not be presented or published to maintain 
participant privacy and confidentiality.
Additional Quality Assurance Measures

Development of standard protocols to perform all data collection and follow-up activities.

Use of standardized forms.

Uniform criteria for patient recruitment.

Standardized data processing.

Regular communications between study staff and study investigators to resolve questions.

Performance monitoring of data collection and data processing activities, as well as preparation of 
periodic reports and analyses on performance monitoring.

Monthly monitoring of recruitment statistics.
Monitoring
We will utilize operating procedures for reviewing patient safety data and source data generated from 
this study. This will include weekly meetings between the PI. Co-investigators, and study coordinator. At 
these meetings, the entire research team will review the clinical ratings, assessments, clinical course, and 
medical records for each subject. Consideration of dropping any patient from the study for any reason will 
be discussed. If after the completion of the first 10 subjects the compliance is significantly less in one or 
more arm of the study relative to our previously observed compliance rates, the study will be put on hold 
and reviewed. Based on the extensive body of literature using tDCS across a range of conditions, and our initial 
participants studied to date (completed at Stony Brook Medicine, we have had >94% compliance in the active 
condition. Therefore, this discrepancy in compliance is not expected. We would define discrepancy in compliance 
as >50% difference in mean number of visits completed and/or 50% difference in number of “completers” in each 
condition (defined by completing at least 50% of n=5/10 sessions) 109.   If there is significantly poor compliance in 
the active session, we will be able to identify reasons including tolerability as well as symptom experiences.  
Tolerability is measured before, during and after each session and all participants will be monitored for all 
sessions. Safety is carefully addressed in our protocol with a series of stop criteria and clearly defined action items.
Specific attention will be given to data quality and timeliness, HIPAA-complaint, safe storage of data, and 
data backup of electronic source data. Attention will also be given to participant recruitment, accrual and 
retention, participant risk versus benefit, adverse events, and other factors that can affect study outcome, 
including scientific or therapeutic developments that may have an impact on the safety of the participants 
or the ethics of the study.

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An adverse event is defined as any rating (at any time) of pain of greater than “moderate” or side 
effects or sensations that arise preceding, during, or following stimulation. Pain and tolerability are 
measured before, during and after each session. As noted, there is an extensive body of literature 
demonstrating the safety and tolerability of tDCS both in MS and in a range of clinical disorders. Our 
lab at Stony Brook Medicine administered >200 active tDCS sessions to MS participants with no pain 
ratings of severe or greater and no discontinued session (for any reason, safety or tolerability)109. 
Figure 3 below demonstrates these results.
Figure 3. Self-applied tDCS sessions across n=20 participants109
We will submit study data safety monitoring reports to the IRB after 10 participants are enrolled in the active 
condition, and follow with reports for each further increment of 10 active enrollees.
Statistical Analyses
Analyses will be completed with IBM SPSS v. 23. Means, medians, standard deviations (SD) will be 
compared between subgroups on the measures using conventional cut-off points for each of the 
symptoms will be compared.
Specific Aim 1 will be tested by comparing the number of participants in each condition meeting the 
study definition of compliance (having completed 80% sessions). We will also determine the 
effectiveness of our sham procedures to ensure blinding, as tested by comparing those who accurately 
identified the sham condition. We will assess whether the frequency or type of side effects differ 
between the three conditions and whether they occur at the same rate as reported from studies of in-
clinic administration.

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Specific Aim 2 will be to determine preliminary signals for efficacy, and to have pilot findings to 
determine necessary sample sizes for an adequately-powered clinical trial. For each participant, change 
scores will be calculated between baseline and study end scores on measures of fatigue and cognitive 
functioning. These difference scores will then be described and compared between groups (t-tests and 
ANOVA related analyses) to determine signals of efficacy.
Cognitive performance will be evaluated for those who completed at least 18 sessions. We conservatively 
plan for comparison of 15 participants in each group, allowing for up to 33% dropout. While both 
cognitive remediation groups are expected to improve with cognitive training, we hypothesize that the 
active tDCS condition will gain one standard deviation (of the published normative mean) or more in 
score than the sham condition and that the group with active tDCS paired with non-adaptive puzzle and 
board games will neither improve nor decline.
Secondary outcomes will be used to compare the groups in change in performance on the additional 
measures listed in Table 2. These are the most commonly-used outcome measures in MS trials52, 106, 112,
113. While important to include, they will not be the primary outcome due to strong susceptibility of 
improvement with practice effects over repeated administrations in MS samples52, 113-116. In addition, 
performance on the WM CT will be analyzed across training sessions, including time to advance to a new 
level and overall levels achieved, parameters shown to improve with tDCS44. Similar analysis as what 
have been planned for the primary outcome will be performed for comparing the change in these 
secondary outcomes between two groups.
MS clinical features (age, gender, MS subtype, treatment type, disease duration) will be compared by 
correlational analysis.
X.
SUBJECT RECRUITMENT AND CONSENT/ASSENT
Subject Identification, Recruitment and Consent/Assent 
Method of Subject Identification and Recruitment
The MS Comprehensive Care Center of NYU Langone Medical Center has an extensive recruitment base. 
Patients will be recruited to participate in studies from all over New York and the other continental 
United States. Patients who are seen by medical staff at NYU Langone Medical Center, who fit the 
eligibility criteria, will be referred for the study by the study PI and sub-investigators. All physicians and 
medical staff at the MS Care Center will be presented with the study description. A patient who is seeing 
one of these medical staff members as their treating physician will be introduced to the study by that 
medical staff member. If the patient is interested and agrees, then a member of the study staff will contact 
them. Once a patient is identified, study staff will meet with the patient or call them to provide additional 
information

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regarding study participation. After the patient has reviewed the consent form and asked all questions, 
and provides consent to participate, the patient will be enrolled in the study.
Advertisements
An IRB approved flyer will be posted in local physician offices and waiting rooms and throughout NYU, 
the surrounding community, and on Long Island. A description of the study will be posted on MS related 
websites.
Process of Consent
All potential participants will complete a screening interview to ensure general eligibility. The study staff 
member speaking to the subject will provide the subject with an overview of the study and verbally 
receive their permission, under a waiver of documentation of consent, to complete the general eligibility 
screening. This phone screen is minimal risk to the participant and collected information will be 
maintained in secured, locked files. De-identified information (assigned a study screening code) will be 
entered into a secure, NYU approved online screening database. If a participant is not eligible, they will be 
considered a screen fail. No additional information will be collected. PHI will be destroyed immediately if 
a participant is not eligible or does not return to sign written consent/authorization to participate. Only 
study staff will have access to these records.
Once the participant is generally eligible, the PI, or one of the trained study team members will review 
the consent form with the subject and explain the purpose of the study, the procedures, as well as risks 
and benefits. All questions will be addressed before acquiring the participant’s signed consent.
Dr. Lauren Krupp will be responsible for assessing the capacity to consent. An independent assessor will 
not be utilized. There is a large body of literature indicating no known safety or tolerability risk for use of 
tDCS. Further, tDCS is currently being studied as an alternative to relatively higher risk treatments (such 
as medication) in special populations such as pregnant women and developmentally disabled children. 
Published studies in MS, including the work in our lab at Stony Brook Medicine, show tDCS to be a 
tolerable and safe treatment approach. Dr. Krupp and team at the MS Center are MS specialists with 
extensive experience in the assessment of patients with MS, including cognitive capacity, and including 
capacity to consent for numerous clinical drug trials where there is a substantially greater potential risk 
posed than what are the known risks for tDCS. Therefore, taken together, we do not believe that the use 
of tDCS represents a situation where an independent party would be needed.
Dr. Krupp is an internationally renowned expert of cognition in MS. She has the expertise in MS and 
cognitive related symptoms of MS to specifically be capable of determining cognitive capacity of potential 
participants. She is a professor of neurology and the director of the NYU MS Center. She has over 30 years 
of experience with direct clinical care of MS patients, and is an internationally-recognized expert in the 
area of MS symptomatic management. She has served as PI for numerous investigator-initiated federally- 
funded clinical trials in MS as well as industry-sponsored treatment trials. She has authored over 150 
articles on topics directly related to the current project. Dr. Krupp also served in the same medical 
monitoring role for the pilot study at Stony Brook Medicine, where n=23 patients have successfully 
completed our study protocol that has included over 200 active tDCS sessions.
Participants will be informed of the assessment and consequences of the assessment – those who refuse 
the capacity assessment will not be enrolled. The assessment involves a MS Neurological Examination 
including EDSS, Physical Examination summary to address General, HEENT, Lungs, COR, Abdomen, 
Extremities, and Skin. Additionally, Dr. Krupp will base capacity to consent on the participants 
understanding of the following 4 items a) that the activity described in this consent document constitutes 
research, not standard treatment, b) the risks and benefits of this study c) the alternatives that are 
available if s/he chooses not to participate, and d) that the decision to not participate will be accepted 
without penalty, i.e., without jeopardizing his/her clinical care.

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Process to Document Consent in Writing
After review of the consent form and prior to the start of the first session, the PI or one of the co- 
investigators will obtain written consent with a signature of the patient on the consent form. All original 
signed consent forms will be maintained in the study file, separate from the participant data.
Subject Capacity
All participants will be confirmed to have the capacity to provide consent by Dr. Lauren Krupp as 
described above.  Further, those participants with estimated premorbid intellectual functioning and/or 
impaired reading ability (as determined by the WRAT-4 Reading Subtest), and those with severely 
impaired information processing speed (as determined by the SDMT) will be excluded.
Debriefing Procedures
No information will be purposely withheld from the subjects. A clinical neuropsychologist (PI) and the 
treatment team will be available to answer any questions concerning the tests and results, and provide 
initial feedback as warranted, including referral for clinical neuropsychological assessment.
Consent Forms
Participants will receive a NYU consent form to review and sign prior to participating in the study.
Documentation of Consent
The PI is responsible for ensuring that valid consent is obtained and documented for all subjects. An 
enrollment log will be maintained and consent forms will be kept in secure location separate from the 
participant’s data.
Costs to the Subject
There will be no cost to the participants.
Risk to Participants
As described above, tDCS poses low risks to participants and our protocol is well-tolerated. To our 
knowledge, hundreds of tDCS studies in the US have all been designated Non-Significant-Risk (NSR) the 
lowest risk level (devices that are not: intended as an implant with potential for serious risk to health, 
safety, or welfare of subject; purported or represented to be for use in supporting or sustaining human 
life with a potential for serious risks; for use of substantial importance in diagnosing curing, mitigating, 
treating disease or otherwise preventing impairment of human health with potential for significant risk; 
otherwise presents significant risk to the health, safety, or welfare of a subject). For these reasons, the 
Soterix Mini CT, as used in this study, also qualifies as a NSR device. While tDCS remains an 
investigational technique (simply because no company has applied to the FDA for approval to market 
tDCS for any given indication), tDCS is a broadly reproduced and tested techniques that is considered 
effective in modulating brain excitability in a manner that may support learning and with adverse events 
(different than sham) limited to tingling, itching, and redness that dispel after stimulation stops. In a 
prior study of use in a vulnerable population (developmentally disabled children), the FDA issued a NSR 
for tDCS device (see attached letter). The letter provided as an example of the FDA’s designation of tDCS 
devices as IDE. Because of its prior designation of tDCS devices as IDE, trials do not typically seek further 
declaration. In the letter provided, Dr. Wasserman specifically sought FDA review of the trial due to the 
use of tDCS in a vulnerable population (developmentally disabled children). To date, hundreds of trials 
have been designated as non-signficant-risk by IRB review which provide its IDE status. Results of 
completed trials, including our own work in MS using this protocol, have supported the risk designation 
provided by IRBs. The Stony Brook Medicine IRB confirmed the NSR and IDE status of tDCS for our study

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and others at the institution. We have learned that the NYU IRB has also confirmed tDCS devices 
(including those manufactured by Soterix) as IDE for current ongoing studies at this institution.
The safety of this technique has been addressed and tested by multiple researchers (e.g., Hummel, et 
al.117; Fregni, et. al.19, 118; Nitsche, et al. 13, 24, 119; Priori, et al.120) who have concluded that tDCS, as applied 
in a manner similar to our proposed protocol, induces only temporary mood, cognitive / motor effects, 
and no negative side effects.  For example, researchers at the National Institute of Neurological 
Disorders and Stroke (NINDS), Iyer et al.19 conducted a safety study on tDCS, investigating 20-minute 
sessions of 1 mA and 2 mA current stimulation with healthy controls (n=103). No negative effects were 
identified. Nitsche and colleagues found no measurable structural changes in brain tissue due to tDCS121. 
In a meta-analysis of over 200 tDCS studies conducted from 1998 to 2010, 56% of studies mentioned 
adverse events, which were generally minor. The most commonly reported side effects included itching, 
tingling, headache, burning sensation and discomfort limited to the scalp site where the tDCS electrodes 
were applied. To date, there have been no reports of seizures induced by tDCS14. Importantly this is the 
case in normal volunteers, but also in different populations of patients, including patients with disorders 
where there might be an increased risk of seizures (e.g. Alzheimer’s disease, recent stroke, epilepsy). A 
study from NYU on the use of tDCS in patients with epilepsy122 encountered no increase in complications 
of tDCS in the patients as compared with controls. Specifically, there were no instances of seizures 
induced by tDCS.
Participants in all groups may find the questionnaires time consuming and potentially bothersome. 
Neuropsychological testing and the computer training sessions may, in some individuals, be stressful or 
anxiety producing. There is a small risk of loss of confidentiality. Participants will be assigned a study ID 
and their name will not be used on any of the information collected. The program used for brain training 
games will not collect any personally identifiable information. The results of these data collected may be 
used for publication but will not include the participants’ names. Hardcopies of the data files will be kept 
in secure, locked files and data will be entered in a secure, NYU approved database
Benefits to Participants
Participants may have some benefit from this study. The cognitive training sessions (brain training 
games) may enhance cognitive functioning for all groups. Additionally, participants in the active tDCS 
condition, as well as those in the sham condition who elect for 10 open label sessions at study end, may 
have an increase in cognitive functioning through the use of the tDCS device. We hope the knowledge 
gained from this study will help others with MS in the future.
Payment for Participation
Participant will receive up to $100 in total compensation. They will be compensated $50 for the initial 
screening and baseline visit, and $50 for the follow-up visit. Attempted completion of a study session will 
be defined by signing in to the secure internet-based video for contact with study technician within 15 
minutes of scheduled time for all days of remote contact. If the participant is unable to establish video 
contact with the study technician due to technical difficulties, they must contact the study technician by 
phone by the scheduled time to receive credit for effort.
XI. EXPLORATORY AIM: FEASIBILITY IN PARKINSON’S DISEASE
Purpose
We have established the feasibility and safety of the current protocol in MS and now plan to extend its 
use to other neurological disorders. The purpose of this additional aim is to test the feasibility of the

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established remotely supervised in-home self-administered tDCS combined with computerized cognitive 
activities in Parkinson’s disease (PD) patients.
Background
Parkinson’s disease is the second leading neurodegenerative disease and affects near 5.1 million 
Americans. Clinical trials in PD have relatively low rates of success. Investigators face major challenges, 
mostly in recruitment and retention of participants, largely due to the difficulty maintaining compliance 
from a patient suffering from PD. Common symptoms in PD that potentially interfere with compliance 
include poor mobility, impaired equilibrium, fatigue, mood disorder, lack of motivation (apathy) and fear 
of the potential adverse consequences/side effects of taking part in clinical trials.
The safety profile, tolerability, and ease of applicability of conventional tDCS are very well established 
and are promising technical strengths that could lead to a complementary therapy in PD. Conventional 
tDCS therapy in PD has yielded promising results improving executive function22, gait 123-125, motor 
impairment126-128, and cognitive impairment129, 130
However, similar to protocols with MS, sample sizes are limited, as are the number of tDCS sessions due 
to the requirement to make repeated visits to clinic, with some studies including just eight participants 
124 and the largest including just 25 participants128. Adequately powered, sham-controlled clinical trials 
are needed to ascertain real therapeutic applications and we hope to establish a remotely-supervised 
protocol to guide future studies using tDCS in PD
For this Exploratory Aim, remote tDCS feasibility in Parkinson’s disease, the protocol will be open label 
and mirrored for the active tDCS condition. We initially plan enrolling 30 participants with PD
Exploratory Aim
Exploratory Aim: We will test the feasibility of remotely-supervised in-home 
self-administered tDCS combined with computerized cognitive activities in 
Parkinson’s Disease (PD). Participants (n=30) will be trained to administer active 
tDCS and complete a cognitive training activity in their home under remote 
supervision by study staff.
Hypothesis 1: Remotely-supervised in-home delivery of the tDCS combined with 
computerized cognitive activity is a safe and feasible treatment for impairment 
in Parkinson’s disease.
Primary outcome will be number of days of successful tDCS delivery. Secondary 
outcomes will be tolerability and participant-reported adverse events, fatigue and 
mood.
Description of the protocol
Will mirror the exact protocol detailed in section V, however this study will be an open 
label feasibility study, with all participants receiving active, open-label tDCS. There will be no 
sham condition for the PD aim.

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Methods and Procedures
Will mirror the exact methods detailed in section VI, with the exception that this study will 
be an open label feasibility study, with all participants receiving active, open-label tDCS. The 
exploratory aim to test the methods in a PD population will also run for a shorter duration. The 
treatment will occur over the course of 10 days rather than 40 to test initial feasibility of the 
methods in PD. Participants will attend the initial baseline visit in clinic, with the remaining 9 
sessions occurring from home with remote supervision.
PD Specific Outcome Measures: Before and after each session, participants will complete brief 
measures to monitor for any stimulation-related events as well as mood and fatigue. In addition, a 
pain scale will be administered during the session. Participants will also complete baseline and 
study-end inventories of mood and fatigue and complete a brief battery of cognitive tests, to help 
guide power estimates for the future trials. A summary of outcome measures can be found in Table 3.
Table 3
Test
Screening
Baseline
Daily Study 
Sessions (2-
10)
End of 
Study 
Session
Online/ 
Telephone 
Survey 
(Study end 
date + 1 
month)
Medical Clearance
X
Expanded Disability 
Status Scale 
X
X
Wide Range 
Achievement Test 
(WRAT-4)
X
X
Symbol Digit Modalities 
Test (SDMT)
X
X
X
Beck Depression 
Inventory-Fast Screen
X
X
tDCS Aptitude Test
X
tDCS Tolerance Test 
(2.0 mA, will possibility 
to repeat at 1.5 mA)
X
Multiple 
Sclerosis 
Neuropsychological 
Questionnaire (MSNQ)
X
X
X
PROMIS Measure of 
Fatigue, Mood and 
Health-Related Quality 
of Life
X
X
X
Neuro-Quality of Life
X
X
X
Fatigue Impact Scale
X
X
X
Fatigue Severity Scale
X
X
X
Pittsburgh Fatigability 
Scale
X
X

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Attention Network Test- 
Interaction
X
X
Cogstate Brief Battery
X
X
ERTSLab Processing 
Battery
X
X
X
Controlled 
Oral Word 
Association
X
X
Rey Auditory Verbal 
Learning Test
X
X
X (delayed 
recall only)
Brief Visuospatial 
Memory Test- Revised
X
X
King Devick Test
X
X
Test of Everyday 
Cognitive Ability
X
X
Grip Strength
X
X
Grooved Pegboard
X
X
Positive and Negative 
Affect Scale (PANAS)
X
X
X
Visual analog scale for 
fatigue (pre- and post-
session)
X
X
X
Visual analog scale for 
pain (pre-, early-, mid- 
and post-session)
X
X
X
Tolerability 
questionnaire - 
administered by 
study staff
(pre- and post-session)
X
Safety and tolerability 
questionnaire –self-
report (pre- and post-
session)
X
Score for Computerized 
cognitive games (daily)
X
UPDRS
X
X
X*
CG S/I
X
X
X
PDQ-39
X
X
X
Parkinson’s Fatigue 
Scale (PFS-16)
X
X
Daily assessment of 
sleep 
X

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Patient and Caregiver 
Questionnaires
X
Participant Evaluation 
of Study Procedures
X
X
Count of successful 
tDCS sessions 
(confirmation code by 
session days)
X
X
* Only UPDRS Part 2: Self-assessment of activities of daily living.
Subject Selection
Characteristics of the Research Population
We will enroll a total of n=30 adults (30-89) with confirmed Parkinson’s disease. Participation will 
be open to those with all levels of disability who meet the eligibility criteria as below.
Eligibility Criteria
Enrolled participants must have a diagnosis of Parkinson’s disease confirmed by a neurologist 
with expertise in Movement Disorders.
Patients with a Symbol Digit Modalities Test or SDMT105 score ≥3.0 SD below published norms 
will be excluded as will those with any health condition contraindicated with the use of a tDCS 
device (including history of seizures, abnormal EKG, skin disorders, head trauma or medical 
device in the head or neck). Baseline screening evaluation will include a neurological exam and 
medical clearance by the study physician and brief screening evaluations for ability to operate the 
study equipment.
Parkinson’s Inclusion Exclusion table here:
Inclusion
Exclusion

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●Ages 30-89
●PD diagnosis confirmed by Movement 
Disorder specialist
●Has stable and continuous access to 
internet service at home compatible with
the study laptop (Wi-Fi or ethernet cable)
●Adequate internet capacity for remote 
monitoring, as tested by
http://www.speedtest.net/)
●Adequate home facilities (enough space, 
access to quiet and distraction free area)
●Able to commit to the two-week period of 
training sessions with baseline and
follow-up visits.
●Able to understand the informed consent 
process and provide consent to
●Visual, auditory and motor deficits that 
would prevent full ability to understand 
study instructions or operate the tDCS device 
or study laptop, as judged by treating 
neurologist or study staff 
● History of seizures or seizure disorder
●Current uncontrolled chronic headaches 
or migraines. In addition, if a subject has 
had a change in the rate or severity of head 
pressure, headache, or migraine in the 
past two weeks, they are excluded.
●History of head trauma (e.g., head injury, 
brain surgery) in the past year or medical 
device implanted in the head (such as Deep 
Brain Stimulator) or in the neck (such as a 
Vagus Nerve Stimulator)
●Any skin disorder/sensitive skin (e.g., 
eczema, severe rashes), blisters, open 
wounds, burn including sunburns, cuts or 
irritation, or other skin defects which

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participate in the study
compromise the integrity of the skin at or 
near stimulation locations (where 
electrodes are placed)
●Treatment for a communicable skin 
disorder currently or over the past 12 
months
●History of uncontrolled or labile 
hypertension.
●Other serious uncontrolled medical 
condition (e.g., cancer or acute myocardial 
infarction)
●History of clinically significant 
abnormalities on electrocardiogram (EKG)
●Alcohol or other substance use disorder
●Learned English language after 12 years of 
age
●Pregnant or breastfeeding
●Symbol Digit Modalities Test ≥3.0 SD 
below published norms
Study Location
Participants screening, baseline and study end visits will be completed at the Fresco Institute for 
Parkinson’s Disease and Movement Disorders at NYU Langone Medical Center, 240 East 38th 
Street, 20th Floor, NY, NY 10016; or alternatively at the 18th floor, the NYU Langone MS 
Comprehensive Care Center (240 East 38th Street, 18th Floor, NY NY 10016). For participants with 
limited mobility, visits can be completed from the participant’s home.
Data Analyses and Data Monitoring
These items will mirror exactly the procedures detailed in section IX, with the exception of the Statistical 
Analyses (detailed below)
Statistical Analyses
Data analyses will be descriptive to inform protocol development for a larger controlled clinical 
trial. To determine feasibility of number of days of successful administration will be calculated. 
Any participants who fail either an aptitude or tolerability test at baseline will be characterized 
with clinical and cognitive factors.
Subject Identification, Recruitment and Consent/Assent 
Method of Subject Identification and Recruitment
The Fresco Institute for Parkinson’s Disease and Movement Disorders of NYU Langone Medical 
Center has an extensive recruitment base. Patients will be recruited to participate in studies from

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all over New York and the other continental United States. Patients who are seen by medical staff 
at NYU Langone Medical Center, who fit the eligibility criteria, will be referred for the study by the 
study PI and sub-investigators. All physicians and medical staff at Fresco Institute will be 
presented with the study description. A patient who is seeing one of these medical staff members 
as their treating physician will be introduced to the study by that medical staff member. If the 
patient is interested and agrees, then a member of the study staff will contact them. Once a patient 
is identified, study staff will meet with the patient or call them to provide additional information 
regarding study participation. After the patient has reviewed the consent form and asked all 
questions, and provides consent to participate, the patient will be enrolled in the study and 
medically cleared.
Advertisements
An IRB approved flyer will be posted in local physician offices and waiting rooms and throughout 
NYU, the surrounding community, and on Long Island. A description of the study will be posted on 
Fresco Institute related websites.
Process of Consent
All potential participants will complete a screening interview to ensure general eligibility. The 
study staff member speaking to the subject will provide the subject with an overview of the study 
and verbally receive their permission, under a waiver of documentation of consent, to complete 
the general eligibility screening. This phone screen is minimal risk to the participant and collected 
information will be maintained in secured, locked files. De-identified information (assigned a 
study screening code) will be entered into a secure, NYU approved online screening database. If a 
participant is not eligible, they will be considered a screen fail. No additional information will be 
collected. PHI will be destroyed immediately if a participant is not eligible or does not return to 
sign written consent/authorization to participate. Only study staff will have access to these 
records. . Once the participant is generally eligible, the PI, or one of the trained study team 
members will review the consent form with the subject and explain the purpose of the study, the 
procedures, as well as risks and benefits. All questions will be addressed before acquiring the 
participant’s signed consent.
Dr. Agarwal will be responsible for assessing the capacity to consent. An independent assessor will 
not be utilized. There is a large body of literature indicating no known safety or tolerability risk for 
use of tDCS. Further, tDCS is currently being studied as an alternative to relatively higher risk 
treatments (such as medication) in special populations such as pregnant women and 
developmentally disabled children. Published studies in MS and other neurological diseases, 
including the work in our lab at Stony Brook Medicine, show tDCS to be a tolerable and safe 
treatment approach. Dr. DiRocco and team at the Fresco Institute for Parkinson’s and Movement 
Disorders in the Department of Neurology at NYU are movement disorder specialists with 
extensive experience in the assessment of patients with Parkinson’s disease, including cognitive 
capacity, and including capacity to consent for numerous clinical drug trials where there is a 
substantially greater potential risk posed than what are the known risks for tDCS. Therefore, taken 
together, we do not believe that the use of tDCS represents a situation where an independent party 
would be needed. Additionally, Drs. Biagioni and Shashank will base capacity to consent on the 
participants understanding of the following 4 items a) that the activity described in this consent 
document constitutes research, not standard treatment, b) the risks and benefits of

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this study c) the alternatives that are available if s/he chooses not to participate, and d) that the 
decision to not participate will be accepted without penalty, i.e., without jeopardizing his/her 
clinical care.
Process to Document Consent in Writing, Subject Capacity, Debriefing Procedures, Consent 
Forms, Documentation of Consent, Costs to the Subject, Risk to Participants, Benefits to 
Participants, and Payment for Participation
These items will mirror exactly the procedures detailed in section X.
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