Modulating Brain Activity to Improve Goal-directed Physical Activity in Older Adult
Phase: NA
Conditions: Aging
Sponsor: Hebrew SeniorLife

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Title: Modulating brain activity to improve goal-directed physical activity in older adults 
 
Date: 10-11-2022 
Principal Investigator: Bradley Manor, Ph.D. BradManor@hsl.harvard.edu  
Organization: Institute for Aging Research Address: 1200 Centre Street, Boston, MA 02131-1101  
Phone: 617-971-5332 
 
Sponsor: National Institute on Aging - NIA/NIH: 31 Center Drive, MSC 2292, Bethesda, MD 20892 
 
Advarra Protocol #Pro00044372 
HSL IRB #: IRB-2019-26 
 
Research Site: Institute for Aging Research Address: 1200 Centre Street, Boston, MA 02131-1101  
Phone: 617-971-5332 
 
 
 
 
 
 
 
Study Team: 
Amy Lo, Ph.D 
Lewis Lipsitz, M.D. 
Andrea Ross, Ph.D. at University of Pittsburgh  
 
 
 
 
 
This protocol was prepared to meet the IRB requirements for a protocol.  A prior application from Cayuse was submitted to 
transfer the study to Advarra for initial approval.  
 

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Purpose 
Although the majority of older adults are aware of the compelling evidence that regular exercise is critical to the 
maintenance of health into old age, most do not meet recommendations for daily exercise. This lack of 
engagement in ‘goal-directed’ physical activity stems from numerous interrelated factors including lack of 
motivation, depressed mood, and cognitive “executive” impairments that diminish one’s ability to regulate 
behavior over time. Intriguingly, each of these factors has been linked to the function of brain networks that 
include the left dorsolateral prefrontal cortex (dlPFC). Transcranial direct current stimulation (tDCS) is a 
noninvasive and safe means of modulating the excitability of specific brain regions and their connected neural 
networks. tDCS designed to facilitate the excitability of the left dlPFC has been shown to improve motivation, 
mood, and multiple aspects of executive function in healthy adults. We thus hypothesize that tDCS holds 
promise to increase goal-directed physical activity in older adults. 
We aim to conduct a pilot randomized controlled trial on the feasibility and effects of a 2-week, 10-session tDCS 
intervention targeting the left dlPFC on physical activity and community mobility, over a two-month period 
following the setting of a personalized physical activity goal, in relatively physically-inactive older adults without 
overt illness or disease. 
 
 

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Background 
 
Regular physical activity is an extremely effective, safe, and modifiable means of health promotion, especially in 
old age. Yet, nearly 60% of older adults do not reach recommended amounts of daily physical activity.1  Although 
there are many factors contributing to physical inactivity in older age, three main barriers are lack of motivation,2 
depressed mood,3,4 and poor executive function.5,6  Recent neuroimaging studies have linked each of these 
barriers to functional integrity and/or activation of the left dorsal lateral prefrontal cortex (dlPFC) and its 
connected neural networks.7-13  As such, strategies designed to facilitate activation of the left dlPFC hold promise 
to reduce barriers to physical activity and thus, increase such goal-directed behavior in older adults. 
 
Transcranial direct current stimulation (tDCS) is a non-invasive device to modulate cortical excitability (i.e. the 
likelihood of neuronal firing) by inducing current flow between two or more electrodes placed upon the scalp.14,48  
tDCS enables selective facilitation of brain tissue excitability by using electrodes placed on the scalp to deliver 
low-amplitude electrical currents that polarize populations of cortical neurons. The electric fields generated by 
tDCS and their effects on brain tissue depend upon electrode size, polarity, and placement, as well as current 
amplitude and duration.14 A single 20-minute session of tDCS with the positive electrode over the F3 region of 
the 10-20 EEG placement system and the negative electrode over the contralateral supra-orbital margin 
facilitates left dlPFC excitability and its connected neural networks for at least one hour following stimulation.15  
Such effects on excitability have been observed in younger and older adults of varying cognitive status.16,17  
Moreover, multiple exposures to tDCS over a relatively short time period (e.g., 10 once-daily sessions within two 
weeks) induces longer-lasting increases in both cortical excitability18,19 and cerebral perfusion.20 
 
tDCS designed to facilitate the excitability of the left dlPFC, improves motivation, mood, and even executive 
function in numerous populations including older adults. In particular, studies have suggested that single- and or 
multi-session interventions of this form of tDCS:  
- 
Increases the willingness of healthy adults to exert physical and cognitive efforts for rewards,21 Induces 
lasting improvements in mood, even in older adults with moderate-to-severe depression,22,23  
- 
Enhances multiple aspects of executive function relevant to goal-directed behavior, including working 
memory,24 selective attention,25 task switching,26 multitasking,27 problem solving,27 and decision making.29 
Our team has demonstrated that this form of tDCS improves gait and balance—abilities critical to 
exercise and falls self-efficacy30—in older adults (details below).  
 
We have demonstrated through a series of studies that tDCS improves executive function, as well as the 
executive control of gait and balance, in older adults.31-34 Most recently, we reported that in a small sample 
(n=20) of non-demented ambulatory older adults without overt illness or disease, yet who presented with mild-to-

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moderate executive dysfunction at baseline, that a two-week tDCS intervention targeting the left dlPFC, as 
compared to sham stimulation induced clinically-meaningful improvements in the Montreal Cognitive Assessment 
(MoCA), and particularly within the executive function sub-score of this exam.31 Moreover, tDCS, as compared to 
sham, improved the ability to stand and walk, especially while engaging in an additional cognitive task (i.e., 
verbalized serial subtractions of 3 from a random 3-digit number). This ability to “dual task” is a sensitive 
predictor of both falls and cognitive decline in the future38-42 and is critical to safe mobility during physical activity. 
Furthermore, dual tasking requires multiple higher-level cognitive executive functions,42-47 including working 
memory, mental flexibility, and self-control, that are together needed to initiate and ultimately sustain physical 
activity in the presence of distractors. These results, combined with the aforementioned reports that this form of 
tDCS may also improve motivation and mood, gives us confidence that 1) a 2-week tDCS intervention is safe 
and feasible for older adults of varying functional status, and that 2) such an intervention will likely induce 
numerous functional benefits that will together translate into improved effectiveness of a goal-directed physical 
activity behavioral intervention. 
 
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24. Fregni F, Boggio PS, Nitsche M, et al. Anodal transcranial direct current stimulation of prefrontal cortex 
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Participant Selection 
Number of Subjects: 32 participants in total (16 participants per group, two groups: counseling+ real stimulation, 
counseling + sham stimulation) 
 
Inclusion criteria 
 
Men and women aged 65 – 85 years 
 
Live in subsidized housing in Boston area communities 
 
Meet at least one the following: 1) self-report of exercising, on average, less than 150 minutes of at least 
moderate-intensity exercise per week, as determined by phone-screen completion of the International 
Physical Activity Questionnaire-Short Form (IPAQ short), or 2) self-report ‘room to improve’ and the 
motivation to increase their current physical activity levels. 
 
Exclusion criteria 
 
An inability to ambulate without the assistance of another person (canes or walkers allowed) 
 
Self-report of falls for more than twice over the past six months.  
 
Self-report of physician-diagnosed dementia, more than moderate cognitive impairment defined as a 
Montreal Cognitive Assessment (MoCA) score <18, or an inability to understand the study protocol as 
determined by study staff 
 
A clinical history of stroke, Parkinson’s disease or parkinsonian syndromes, multiple sclerosis, normal 
pressure hydrocephalus or other movement disorder affecting gait 
 
Any report of severe lower-extremity arthritis or physician-diagnosis of peripheral 
 
neuropathy 
 
Use of antipsychotics, anti-seizure, benzodiazepines, or other neuroactive medications Severe 
depression defined by a Geriatric Depression Scale score greater than 11 
 
Any report or physician-diagnosis of schizophrenia, bipolar disorder or other psychiatric illness 
 
Any unstable medical condition 
 
Contraindications for tDCS, including reported seizure within the past two years, use of neuro-active 
drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, 
medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active 
dermatological condition, such as eczema, on the scalp 
 
Participant recruitment 
We will leverage our established relationships within the Boston area subsidized housing providers to recruit 
older individuals living in low income senior housing. We will meet with housing site administrators, and post 
flyers within these communities. We will also attend community meetings to raise awareness and meet with 
resident council members to discuss the study. We will hold informational gatherings to allow housing site 

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residents to attend and obtain one-on one information about the study.  We will also place flyers (attached) within 
local senior living communities and/or advertise in local media outlets targeting senior citizens (e.g., 50+ 
Advocate). 
 
Those displaying interest in participation will complete an initial phone screening which will provide an overview 
of the study and a series of questions related to initial inclusion and exclusion criteria (attached). Participants 
who are potentially eligible based upon the phone screen will be scheduled for the first study visit, which will 
begin with a formal consent process and further in-person screening procedures. 
 
Consent Process 
Individuals will contact the study team at the number provided on the study advertisement. A research assistant 
will give an overview of the study to the individual. At this point, the individual will be asked if they are interested 
in participating. They will then be asked if they have time to complete a 10-minute over-the-phone screening 
questionnaire based on the inclusion and exclusion criteria. If so, the research assistant will continue the 
screening (see attached phone screening form). If the potential subject does not have time, the PI will obtain 
their contact information and a more convenient time to call the potential subject back. If the participant meets all 
criteria of the study, the formal in-person study visit will be scheduled. For these individuals, we will send a copy 
of the informed consent in the mail or via email (based on the participant's preference). This will allow the 
participant time to review the consent form prior to their study visit. 
 
On the day of the scheduled visit, the Research Assistant will review the informed consent with the participant 
and answer any remaining questions. If the participant would like to continue, the participant and the research 
assistant will sign the consent form. The PI and/or the Research Assistant will provide a copy of the signed 
consent form for the participant to keep for their records. 
 
 
 

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Methods and Procedures 
 
Screening Procedures 
Phone screen: 
Interested individuals will first complete a phone screen, which will include the International Physical Activity 
Questionnaires (IPAQ)-short to determine their physical activity level. 
 
Visit 1: In-person screen and introduction (1 hour); Participant's Housing Site 
Those potentially eligible will complete an in-person visit (Visit 1). This visit will take place in the participant's 
housing site, in a comfortable and private location that will be arranged in advance by the research team. Written 
informed consent will be obtained at this time. A medical history questionnaire will be completed, medications, 
blood pressure, height, body mass and years of education will be recorded, and the MoCA will be administered. 
Eligible individuals will then be enrolled in the study. 
 
Physical Activity Monitoring: At the end of Visit 1, participants will be provided with a FitBit™ activity tracker and 
familiarized with its functionality. The FitBit Alta wireless and waterproof activity tracker wristband 
(https://www.fitbit.com) will be used to record physical activity, including step counts and minutes of moderate-to-
vigorous activity. Participants will be asked to wear theFitBit™ every day, removing it only at night to recharge 
the battery. Participants will wear the FitBit™ for 2 weeks. Baseline physical activity will then be recorded over 
this two-week period as participants go about their normal daily lives. 
 
Community Mobility Monitoring: At the end of Visit 1, participants will be also provided a global positioning 
system (GPS) device (Columbus V990) to wear for the entire study period. They will be asked to take it with 
them whenever they leave their home and keep it on their person. Devices will be returned at the end of the 
study. Data will be downloaded to a secure computed and saved with only the study ID number. No personally 
identifying information will be included in the GPS data files.  
 
Baseline Procedure 
Visit 2: Baseline Assessment Visit (~ 1.5 hour); Participant's Housing site 
 
Baseline Assessments: (90 minutes) The assessments described below have been designed to capture 
information on motivation, barriers, and self-efficacy related to physical activity, mood, cognition, and mobility. 
 
A 20-minute battery of validated questionnaires will be used to assess motivation for physical activity (Exercise 
Self-Regulation Questionnaire, SRQ-E), self-efficacy for exercise (SCI Exercise Self-Efficacy Scale, SES-E), 
self-efficacy for walking (Self Efficacy for Walking Scale, SES-W), barriers to exercise (Barriers Self-Efficacy 

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Scale, BARSE), mood (15-item Geriatric Depression Scale), cognitive reserve (Cognitive Reserve 
Questionnaire) 
 
A 40-minute battery of tests will assess global cognitive function (MoCA), executive function (Trail Making Test A 
and B), working memory (WAIS-IV Digit Span Forwards and Backwards), sustained attention and motor speed 
(gradCPT and WAIS-IV Coding test), verbal learning (Category and Phonemic Fluency tests), and episodic 
memory (Hopkins Verbal Learning Test.Revised, HVLT-R). These tests were selected because they are 
sensitive to cognitive status and/or self-regulation in older adults, are suitable for repeat testing as they have 
alternate forms or are resistant to practice effects, have excellent psychometric properties and normative data, 
and have minimal ceiling and floor effects. 
 
A 30-minute battery of functional tests will be completed. Dual task standing and walking will be assessed 
following recommendations that produce excellent test-retest reliability in older adults. Participants will complete 
two, 60-second trials in each of six conditions: 1) Single task—seated cognitive task (see below for description); 
2) Single task—standing; 3) Single task—walking; 4) Single task-fast walking; 5) Dual task—standing with 
cognitive task; 6) Dual task—walking with cognitive task. The cognitive task will be verbalized serial subtractions 
of 3’s from a random three-digit number between 200 and 999. Participant responses will be recorded. We have 
chosen this task because it activates a distributed cortical network including the left dlPFC,67 induces 
meaningful dual task costs to both gait and posture in older adults, and is reliable and minimally influenced by 
learning in older adults. All trials will be completed using the portable Mobility Lab™ motion capture system 
(APDM, Seattle WA). Walking trials will be completed in a long hallway. Participants will be reminded to walk at 
their preferred, comfortable pace. During the fast walking trials, participants will be reminded to walk as fast as 
they can walk safely. Assistive devices will be allowed for trials of walking (but not standing). Finally, functional 
mobility will be assessed by the Timed Up-and-Go (TUG) test, which correlates with mobility disability73 and has 
excellent inter- and intra-rater reliability. Participants will be randomized to tDCS intervention arm (to begin at 
Visit 3) at this time and the behavioral intervention will be initiated at the end of Visit 2.  
 
Visit 3: First Personalized Counseling Session (~0.5 hour); Participant’s housing Site  
Behavioral intervention to promote physical activity (~30 min): We will utilize a modified version of a 
personalized, goal-based counseling approach to promote physical activity in older adults. Briefly, a physical 
therapist (Dr. Amy Lo) or a nurse (Peggy Gagnon) will complete a face-to-face counseling session with each 
participant, tailored to their state of readiness to increase physical activity levels. Dr. Lo or Peggy will provide the 
participant with a goal to increase their average daily step count by 20% from baseline, review their stated 
barriers to exercise and provide them with a list of strategies they may use to augment their step counts 
throughout each day. The participant will also be encouraged to spend time each day to plan their walking 
activities for the next day. Dr. Lo and the research staff will conduct both in-person and telephone counseling 

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sessions, as noted above in Figure 1, over the eight week follow-up period to discuss challenges and provide 
additional tips for increasing physical activity. Regular calls will be scheduled once a week for alternate weeks 
(i.e., weeks 3,5,7 and between assessment visits and in-person counseling visits (i.e., weeks 2,4,6,8, and 10). 
The goals of these regular telephone calls will be to check in, review and discuss activity performance, and 
answer any questions the participant may have regarding their efforts to increase physical activity 
 
Physical Activity Monitoring: All participants will continue to use the FitBit™ to track their activity during the entire 
eight week follow-up period. At the end of visit 2, they will be instructed how to synchronize the FitBit™ to their 
computer or smartphone, and will be instructed to do this each day. If participants do not have access to a 
computer or smartphone, the research team will synchronize the participant's FitBit™ during scheduled in-person 
sessions. Research staff will confirm compliance and data uploads by pre-registering each FitBit and monitoring 
its activity via the company’s website. 
 
Participants will receive regular behavioral intervention calls from the study staff throughout their study 
enrollment, until the final study visit, Visit 15. Participants will be given contact information for the study team 
members, so that they may reach the study team if needed at anytime between scheduled study activities. 
 
Experimental Procedures 
Visits 4-13: tDCS Brain Stimulation visits (30 minutes); Participant's Housing site 
Participants will complete 10 twenty minute brain stimulation sessions (Monday-Friday) over the next two weeks. 
 
tDCS intervention: Similar to our preliminary study, this intervention will consist of 10, 20-minute sessions 
delivered on Monday-Friday over two weeks. Stimulation will be delivered using the Startim-8™ device and 
software (Neuroelectrics Corp, Cambridge MA), which enables custom amounts of current to be delivered 
through an array of up to eight Pi™ gel Ag/AgCl electrodes placed on the scalp according to 10-20 EEG 
convention. This system also enables the blinding of study staff and participants to stimulation type. At the end of 
the first session and every other session thereafter, participants will complete a side effects questionnaire.51 A 
blinding efficacy questionnaire will also be completed after the final session, on which participants state whether 
they believe they received tDCS or sham and their confidence in this belief. 
 
Real tDCS: Similar to our preliminary studies, tDCS will be delivered via six gel electrodes with placement and 
current parameters optimized based on a standard brain to maximize the average normal component of the 
generated electric field over the left dlPFC. Current delivered by anyone electrode will never exceed 2.0 mA; the 
total amount of current from all electrodes will not exceed 4 mA. Each 20-minute session will begin and end with 
a 60-second ramp up/down of current amplitude to maximize comfort. 
 

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Sham stimulation: An ‘active’ sham will be used in which very low-level currents are transferred between the 
same electrodes used in the active condition throughout the 20-minute session. However, currents will be 
designed to mimic the cutaneous sensations induced by tDCS yet not significantly influence cortical tissue. This 
approach effectively blinds participants and operators to stimulation condition and does not affect functional 
outcomes.52 
 
Visit 14: Follow-Up Assessment (1.5 hours); Participant's Housing site 
Follow-up assessment, as described above in Visit 2, will be completed immediately after and 2 weeks after the 
tDCS intervention. 
 
Visit 15, 16 and 17: Follow-up Personalized Counseling visits (30 minutes); Participant's Housing site 
Three bi-weekly in-person counseling sessions will be completed after the tDCS intervention. 
 
Visit 18: Final Assessment visit (1.5 hours); Participant's Housing site 
Final follow-up assessments, as described above in Visit 2, will be completed after 6 weeks of the tDCS 
intervention. 
 
At the end of visit 18, we will provide the opportunity for participants to continue tracking their FitBit information 
for up to additional 3 months. If the participant agrees, we will keep the tracking option available for the study 
team to track the retention of the intervention. The study team will terminate this tracking service by the end of 
the retention phase.  
 
Materials for recruitment and study conduct 
StimFit_Recruitment_Flier_20200108_clean.pptx 
StimFit_Recruitment_Flier_notabs_20200108_clean.pptx 
StimFit_Recruitment_letter_20200205_tracked IRB edits_clean.doc 
Assessment of Protocol Understanding Form.docx 
International Physical activity Questionnaire IPAQ short procedure Q by Q and questions.docx 
MOCA.pdf 
Stim-Fit_Phone_Screen_2020205_clean.docx 
Stim-Fit_tDCS_Eligibility_Questionnaire.docx 
The PAR Q.docx 
gradCPT Instructions_FrailAdults.docx 
N-Back_Instruction.docx 
TRAILS_V1.pdf 
TRAILS_V2.pdf 

Page 14 of 25                                                   Version 26March2021 
Trails_v3_corrected.docx 
Digit Span.pdf 
Blood Pressure Form_42219.docx 
DT Balance Assessment 42219.docx 
DT familiarization and sitting assessment 42219.docx 
DT gait assessment 42219_AlipgEdit.docx 
GDS15.pdf 
Height and Weight Form 42219.docx 
Medical History Questionnaire_1 71318.docx 
Medication Review Form_1 42219.docx 
Sociodemographic Form 42219.docx 
TUG form 42219.doc 
BARSE.pdf 
ESES worksheet_exercise_self-efficacy_scale_eses_0.docx 
SEW_DUR.pdf 
SRQ-Exercise_short.pdf 
WHAS Pain Questions.docx 
tDCS Blinding Efficacy.docx 
tDCS Side Effects Questionnaire.docx 
Cognitive Reserve Questionnaire.pdf 
 
 
 

Page 15 of 25                                                   Version 26March2021 
Data Analysis and Data Monitoring 
Data Analysis 
This study will enroll 32 participants. We have conservatively planned for approximately 20% attrition and have 
thus based our statistical plan on complete datasets of n = 26. 
 
Assessment of feasibility endpoints will be based on sample computations, including the screened to enrolled 
ratio, retention rate, assurance of blinding, and safety assessment (see above). Adverse events (AE) will be 
organized according to the MedDRA classification system and reported in each DSMB communication both by 
MedDRA System Organ Class (SOC) and overall. Both the number of individuals with one or more of AEs within 
each SOC, as well as the total count of all AEs within each SOC, will be reported. These will be accompanied by 
point and 95% confidence interval estimates of the proportion of individuals who would experience AEs and the 
total count of AEs per person-time within each SOC, respectively. The latter computation will acknowledge 
clustering at the level of the participant by using generalized estimating equations (GEE) in estimation with 
robust variance estimates used for computing confidence intervals. 
 
We will use variance decomposition to generate estimates of within and between-individual variation in functional 
outcomes that would potentially be used in a subsequent trial (see above), along with confidence interval 
estimates for said variance measures, in order to assist in planning of the subsequent study. We will also 
conduct an exploratory analysis of the of mean change in these endpoints using mixed-effects linear regression 
of all time points, with a random effect included at the participant level in acknowledgement of serial correlation 
of repeated measures. Dependent variables will be the change in outcomes related to average daily activity from 
baseline to the six-week post-tDCS follow-up period, as well as the change in laboratory-based functional 
outcomes from baseline to each planned follow-up visit. 
 
Feasibility outcomes: 
The proposed sample size was motivated by our experience in similar pilot studies, the need to develop a 
sufficiently detailed profile of the background population and convincing demonstration of the feasibility of our 
protocols, the anticipated drop-out rate, and the need to make resource and sample size estimations for the 
subsequent trial. We anticipate, based on prior work, that we will screen between 5 and 15 individuals for each 
participant enrolled. Enrollment of 32 individuals will allow us to determine to within 1 individual the expected 
number of participants screened to enrolled in the subsequent trial using an 80% confidence interval; similarly, 
we will be able by the same method to estimate the probability a given participant will complete intervention to 
within 0.10. 
 
Functional outcomes:  
Assuming type-I error probability = 0.05 and cumulative attrition and missingness approximately = 20% (i.e. 

Page 16 of 25                                                   Version 26March2021 
evaluable data on 26 participants with complete data, the design will obtain 90% power to detect standardized 
differences [ratio of mean within–participant difference on endpoints to the standard deviation (SD) of same] of at 
least 0.41, and 80% power to detect effects of 0.36 or greater. 
 
Our primary functional endpoint is habitual physical activity defined as average daily step counts derived from a 
FitBit wristband. As no prior study has investigated the change in total steps per week as a result of this type of 
intervention, we estimate the SD of the intervention-attributable change based on prior data on changes in 
weekly step counts in other conditions. Given that a prior study of pulmonary rehabilitation demonstrated a SD of 
150 steps per week,84 we will have 90% power to detect changes as small as 62 steps per week, and 80% 
power to detect 54 steps per week. 
 
The GPS data will be analyzed by the team at the University of Pittsburgh. The GPS data were downloaded to a 
secure computer and saved with only the study ID number. Our team will upload the GPS data to the secure 
server at the University of Pittsburgh. No other identifiable information will be provided to the team at the 
University of Pittsburgh.  
 

Page 17 of 25                                                   Version 26March2021 
 
Data Storage and Confidentiality 
 
Data Storage 
All data collected for analysis will be de-identified and assigned a unique study number. Data collection forms will 
be kept in a locked file cabinet in the office of the PI at Hebrew SeniorLife. Data will be entered and stored on a 
password-protected secure server at HebrewSeniorLife. 
 
The Institute for Aging Research primarily employs the REDCap system to facilitate data management 
operations. REDCap is a full-featured clinical trials data management system (DMS) accessible to data entry and 
data analysis workstations using secure Web technologies. The REDCap product is developed and maintained 
by Vanderbilt University in cooperation with REDCap Consortium members, including Hebrew SeniorLife. HSL 
hosts and maintains a dedicated instance of REDCap for use across our research enterprise. Each research 
study is provided separate project workspace in which all of the study data are stored in a MySQL relational 
database on the private corporate network behind several firewalls and located physically within the HSL data 
center. 
 
Data will be kept on a secure, password protected Hebrew SeniorLife server in a REDCap Database. Only study 
members at the Hebrew SeniorLife site will have access to the REDCap database. All hard copy forms will be 
kept in a locked filing cabinet that only study members will be able to access. 
Data security measures 
 
Only those listed on the approved IRB protocol will have access to subject data. Subject data will be coded and 
locked in a file cabinet in a locked office. Identifying information will not be used during discussion, presentation 
or research publication. All data are password protected and only the principal investigator or the study staff with 
a direct role in data collection or data management will have access to the data files and codes. 
 
We will follow the current Hebrew SeniorLife Record Management, Retention, Disposition and Destruction 
Guidelines for this study. Identifiers will be kept for 7 years following the completion of the study. At this time 
destruction of materials containing identifiers and keys will be completed. 
 
Confidentiality  
The following are the planned procedures for effectively protecting against and minimizing loss of participant 
privacy: 
 
Phone screening will be conducted in a private office space. 
 
Study visits will be conducted in private rooms located within the participant's housing site. 

Page 18 of 25                                                   Version 26March2021 
 
Each participant will be given a unique study identification number and data will not include any of the 
participant's PHI. 
 
All participant- identifying information will be stored and managed on a secured database server. The 
information will be password protected. 
 
Participant confidentiality will be maintained in accordance with HIPAA regulations. 
 
Only the PI and study personnel approved by the IRB and authorized to view PHI will have access to the 
information 
 
PHI will not be used during discussion, presentation or publication of any research data. 
 
Files containing PHI data collected for recruitment and screening purposes will be kept in locked, secured 
file cabinets accessible only to designated study personnel (research assistants and investigators. 
 
 

Page 19 of 25                                                   Version 26March2021 
  
 
Risks/ Benefit Assessment 
 
Risks 
Possible risks associated with physical activity:  
Participants will be provided with a personalized goal to increase their average daily physical activity (i.e., step 
counts) during the study period. Participants are thus expected to increase their physical activity during this 
period. This activity is expected to be of low to moderate intensity. Potential risks are minimal and most likely 
transient, including strains, sprains, muscle soreness, light-headedness and physical fatigue. In rare instances, 
more serious side effects such as an injurious fall may occur. 
 
Tests of walking and physical function: 
The proposed walking tests have been adapted from the large-scale, population-based MOBILIZE Boston study 
(PI: L. Lipsitz) and multiple completed and ongoing clinical studies within the Clinical Research Laboratory at 
IFAR. They have been designed to be safe for individuals of varying risk and conditioning levels including older 
adult fallers. The physical activity associated with these tests is of low to moderate intensity. Potential risks 
include strains, sprains, muscle soreness, and light-headedness. In rare instances, more serious side effects 
such as an injurious fall may occur. For all functional tests, a trained "spotter" will stand behind or close to the 
subject to provide stabilizing assistance if necessary. Subjects will be instructed to stop performing or skip any 
test that makes them feel uncomfortable. Adequate rest will be given in between each test, and any reusable 
equipment will be cleaned with disinfectant after each use. 
 
Transcranial direct current stimulation (tDCS): 
 
tDCS has been widely used during the last decade demonstrating non-significant risk to participants. Expected 
side effects include: 
1) Sensations reported by subjects under the electrodes: (These sensations can sometimes continue 
throughout and for a brief period following completion of the tDCS but usually resolve shortly after the 
initiation of tDCS) 
Mild tingling (20-70%) 
Light itching (30-40%) 
Slight burning (10-22%) Discomfort or mild pain (10-18%) 
 
2) Other effects that can occur both during and after tDCS include:  
Mild fatigue (15%) 

Page 20 of 25                                                   Version 26March2021 
Skin redness (20%) 
Headache (10-15%) 
Difficulties in concentration (11%) 
 
3) Additionally, the following rare side effects have been described:  
Nausea (<1%) 
Nervousness (<1%) 
Although it has never been reported in tDCS, seizures are a theoretical risk. Individuals with a history of 
seizures and/or a diagnosis of epilepsy will therefore be excluded from this study. 
 
Tests of mental function: 
Risks associated with answering the cognitive test questions are minimal, but participants may experience 
mental fatigue and/or anxiety during this form of testing. 
 
Minimizing Inconvenience 
We will minimize the risk to subjects in this study by excluding those with conditions listed in the exclusion 
criteria. The proposed protocol requires multiple visits and therefore considerable participant burden with respect 
to time and effort. Our study team has a strong track record of successful clinical research requiring similar 
participation, and retention has been high in these projects. The Clinical Research Laboratory at IFAR is located 
next to a cafeteria and equipped with comfortable seating, a TV, movies, books and magazines to keep 
individuals occupied during resting periods. Several additional strategies will be employed to minimize participant 
burden and maximize adherence to the protocol. We will: Develop a personal relationship between participants 
and members of the staff by matching research assistants with individual participants. Schedule appointments at 
convenient times with familiar staff. Explain to participants all aspects of their participation and follow up. We will 
demonstrate and practice study procedures before beginning data collection. Provide reminders of all 
appointments and follow-up phone calls. Include personal notes in the participant’s data file to remember events 
in the life of the participant; these can be commented on at the next visit (e.g., birthday, birth of a grandchild). 
Provide snacks during all visits. Provide transportation for all visits, if required. Provide valet or dedicated, on-site 
parking spaces. Compensate participants for visits. 
  
COVID-19: 
During the COVID 19 quarantine and social distancing procedures, precautions will be taken to minimize contact 
when possible by performing teleconferencing and frequent check ins with participants on a remote basis.   
 
Potential Benefits 
Participants may not receive any significant health benefit from participation, although some may benefit from 

Page 21 of 25                                                   Version 26March2021 
knowledge of their health status, as well as potential therapeutic effects of completing a behavioral intervention 
to increase physical activity. Participants will be provided a $160 stipend to help cover the costs of their time 
spent completing study procedures. They will also have the option to keep the Fitbit device that they use in the 
study. 
 
We believe that the potential benefits of establishing tDCS as a noninvasive intervention to improve goal-directed 
physical activity in physical inactive older adults significantly outweigh the above-outlined potential risks to 
participants, which are expected to be minor, transient and relatively rare. 
 
The observations from these studies are expected to provide important information regarding the effects of 
noninvasive electrical brain stimulation on goal-directed physical activity in older adults. Results are also 
expected to provide insights into the feasibility and effectiveness of such intervention within this population, thus 
increasing the potential for deployment of tDCS interventions to larger numbers of older adults. 
 
Costs incurred during the study for medical care/injury 
Any subject who suffers an adverse event during the conduct of study protocols will receive the medical care 
necessary to treat the adverse event. If we cannot provide the care directly, we will arrange for the medical care 
to be provided to the subject. If the event meets the definition of a serious adverse event, the participant will be 
removed from the study, and will be referred to their primary care physician for ongoing care. The treating 
provider will bill the insurance company or other third parties, if appropriate, for the care a participant receives for 
any injury. We will try to have these costs paid for, but the participant may be responsible for some of them. For 
example, they may be responsible for payment of any deductibles and co-payments required by the insurer. 
There are no plans to provide any compensation for an injury beyond what is described above, should one occur. 
If the event does not meet the criteria of a serious adverse event, and the participant is willing and able to 
continue, he/she will be able to continue and complete the study 
 
Payment to Participants 
Describe the type remuneration and the timing of remuneration to study procedures e.g. participants will be 
provided with $50 per study visit, to be distributed as visits are completed, etc. 
Participants receive up to $160 for taking part in this study. Participants will also receive a FitBit and will be able 
to keep it when the study has ended if they wish. Specifically, participants will receive the following amounts for 
each visit completed: 
 
Visit 1 - In-person screening visit - $10 Visit 2 – Baseline visit - $10 
Visits 3- 12: Brain stimulation– 10 visits over two weeks; $10 for each visit= total of $100 
Visits 13-14: Follow-up assessment visits - $10 for each visit = $30 total for completion of all 3 follow-up visits. 

Page 22 of 25                                                   Version 26March2021 
Visit 15: Final in-person counseling session - $10 Visit 16: Final follow-up study assessment - $10 
Participants will receive a check in the mail within eight weeks of study participation. 
 
Participant Withdrawal 
Participation may be terminated at the discretion of the PI, if the PI feels that study discontinuation is necessary 
to protect the participant, or that there are unmanageable factors which will interfere significantly with the study 
procedures and/or interpretation of results. The study participant will be informed of this and withdrawn from the 
study. The participant can, at any time, request the study be terminated and to be withdrawn. Any previously 
collected data prior to termination/withdrawal will be maintained in the study data set. 
 
Adverse Event Reporting 
An adverse event is any untoward medical occurrence in a participant, whether or not it is causally related to the 
study. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom or disease temporally associated with the study. Adverse events will 
be recorded on the appropriate case report forms and source documents. The investigator and/or trained staff 
member will evaluate all adverse events as to their severity and relation to the test article. The severity of 
adverse events will be graded as follows: 
 
Serious adverse events will be reported to the IRB, as well as the identified Safety Monitor, within 24hrs by fax or 
email. A related written report will be submitted within 5 business days of learning of the event, and a submission 
of the incident to the IRB system will be completed within one week of learning of the event. This form will record 
any adverse symptoms and/or study protocol deviations. 
 
All other adverse events/study incidents will be reported to the HSL IRB and identified Safety Monitor, according 
to policy, within 5 business days of learning of the event. A related submission of the incident will be completed 
via the eIRB system within one week of learning of the event. 
 
Safety Monitoring 
Safety monitoring procedures will be implemented and reviewed by a Safety Monitor (to be determined upon 
Notice of Grant Award), in accordance with NIA safety policies for human intervention studies. 
 
The criteria for discontinuing a participant's participation include the participant's request, as well as any 
unexpected life-threatening or potentially disabling event, including syncope, an injurious non-accidental fall, 
hemodynamic collapse, stroke, transient ischemic attack, dysrhythmia, renal insufficiency, angina, myocardial 
infarction, anaphylaxis, acute hemorrhage, or hospitalization for acute illness. These adverse events will be 
recorded in accordance with IRB requirements and included in the study database. If a determination about 

Page 23 of 25                                                   Version 26March2021 
continued participation cannot be made according to these criteria, the adverse event report will be faxed to the 
un-blinded Safety Monitor, who will make the final decision. 
 
Prior to the start of the study the Safety Monitor will review the IRB approved protocol, procedure manual and 
informed consent documents, with regard to participant safety, recruitment, randomization, intervention, data 
management, quality control, and confidentiality. The Safety Monitor will recommend any necessary changes of 
the protocol to the PIs and will review and approve revisions. The Safety Monitor will identify relevant data 
parameters and the format of the information to be regularly reported. 
 
The Safety Monitor will then meet biannually with the investigators to review standardized reports. He/She will 
review the progress of recruitment and retention of participants, compliance with the protocol, and operating 
procedures. If they raise concerns about safety issues, they may request additional data and propose specific 
analyses. They will make recommendations to the PIs regarding recruitment, retention, compliance, and safety 
issues, and will  
 
The investigator and/or trained staff member will evaluate all adverse events as to their severity and relation to 
the test article. The severity of adverse events will be graded as follows: 
- 
Mild: Awareness of a sign or symptom but easily tolerated. 
- 
Moderate: Discomfort sufficient to cause interference with usual activity or to affect clinical status. 
- 
Severe: Incapacitating with inability to do usual activity or to significantly affect clinical status. 
- 
Life Threatening: The participant was at immediate risk of death from the adverse event as it occurred. 
 
The Investigator will also assess the relationship of any adverse event to study, based upon available 
information, using the following guidelines: 
- 
0 = Unlikely: No temporal association, or the cause of the event has been identified.  
- 
1 = Possible: Temporal association, but other etiologies are likely to be the cause; however, involvement 
of the study procedures cannot be excluded. 
- 
2 = Probable: Temporal association, other etiologies are possible, but not likely. 
 
A serious adverse event is any experience that results in any of the following outcomes: death, is life threatening, 
inpatient hospitalization or prolongation of hospitalization, a persistent or significant disability/incapacity. 
Important medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the 
patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. 
 

Page 24 of 25                                                   Version 26March2021 
 
Unanticipated and adverse event reporting 
Unanticipated problems and adverse events will be reported according to the IRB written guidelines for 
interventional studies. Serious adverse events will be reported to the Hebrew SeniorLife’s IRB, as well as the 
identified Safety Monitor, within 24hrs by fax or email. A related written report will be submitted within 5 business 
days of learning of the event, and a submission of the incident via the eIRB system will be completed within one 
week of learning of the event. This form will record any adverse symptoms and/or study protocol deviations. 
 
All other adverse events/study incidents will be reported to the IRB and Safety Monitor, according to policy, 
within 5 business days of learning of the event. A related submission of the incident will be completed via the 
eIRB system within one week of learning of the event. Safety monitoring procedures will be implemented and 
reviewed by a Safety Monitor (to be determined upon Notice of Grant Award), in accordance with NIA safety 
policies for human intervention studies. 
 
Prior to the start of the study the Safety Monitor will review the IRB approved protocol, procedure manual and 
informed consent documents, with regard to participant safety, recruitment, randomization, intervention, data 
management, quality control, and confidentiality. The Safety Monitor will recommend any necessary changes of 
the protocol to the PIs and will review and approve revisions. The Safety Monitor will identify relevant data 
parameters and the format of the information to be regularly reported. 
 
The Safety Monitor will then meet biannually with the investigators to review standardized reports. He/She will 
review the progress of recruitment and retention of participants, compliance with the protocol, and operating 
procedures. If they raise concerns about safety issues, they may request additional data and propose specific 
analyses. They will make recommendations to the PIs regarding recruitment, retention, compliance, and safety 
issues, and will send a written report to the Program Administrator following each meeting. The Safety Monitor 
will be sent reports of research activity and summaries of safety monitoring information before each meeting. 
 
Participant discontinuation 
The criteria for discontinuing a participant's participation include the participant's request, as well as any 
unexpected life-threatening or potentially disabling event, including syncope, an injurious non-accidental fall, 
hemodynamic collapse, stroke, transient ischemic attack, dysrhythmia, renal insufficiency, angina, myocardial 
infarction, anaphylaxis, acute hemorrhage, or hospitalization for acute illness. These adverse events will be 
recorded in accordance with IRB requirements and included in the study database. If a determination about 
continued participation cannot be made according to these criteria, the adverse event report will be faxed to the 
un-blinded Safety Monitor, who will make the final decision. 
 

Page 25 of 25                                                   Version 26March2021 
Publication Plan 
We will register this clinical trial at ClinicalTrials.gov. We also will ensure that informed consent documents for 
this clinical trial will include a specific statement relating to posting of clinical trial information at ClinicalTrials.gov. 
Hebrew SeniorLife’s Institute for Aging Research has an internal policy in place to ensure that clinical trials 
registration and results reporting occur in compliance with policy requirements. Results will be disseminated 
through publications in peer-reviewed medical journals, presentations at national meetings, and announcements 
on the HSL website and other public media.