Home-based Transcranial Direct Current Stimulation (tDCS) for Pain Management in Persons With Alzheimer's Disease and Related Dementias
Phase: NA
Conditions: Alzheimer's Disease and Related Dementias
Sponsor: Florida State University

 
Home-based Transcranial Direct Current 
Stimulation for Pain Management in 
Persons with Alzheimer’s Disease and 
Related Dementias 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCT 04457973 
March 1, 2022 
 
 

 
PROTOCOL TITLE: 
Home-based Transcranial Direct Current Stimulation for Pain Management 
in Persons with Alzheimer’s Disease and Related Dementias 
PRINCIPAL INVESTIGATOR:  
Name: Hyochol Ahn, PhD 
Department: Nursing 
Telephone Number: 850-644-2647 
Email Address: hahn@fsu.edu 
VERSION NUMBER/DATE: 
Version number: 1 
Date: January 6, 2022 
REVISION HISTORY 
 
Revision 
# 
Version Date 
Summary of Changes 
Consent 
Change? 
1 
3.1.2022 
Adding a telephone MoCA as an additional 
screening tool 
No 

 
Table of Contents 
1.0 
Study Summary ........................................................................................................ 3 
2.0 
Objectives* ............................................................................................................... 4 
3.0 
Background* ............................................................................................................ 4 
4.0 
Study Endpoints* ..................................................................................................... 4 
5.0 
Study Intervention/Investigational Agent .................................................................5 
6.0 
Procedures Involved* ............................................................................................... 5 
7.0 
Data and Specimen Banking* .................................................................................. 9 
8.0 
Sharing of Results with Subjects* .............................................................................9 
9.0 
Study Timelines* ...................................................................................................... 9 
10.0 Inclusion and Exclusion Criteria* ............................................................................ 9 
11.0 Vulnerable Populations* ......................................................................................... 10 
12.0 Local Number of Subjects ...................................................................................... 10 
13.0 Recruitment Methods ............................................................................................. 10 
14.0 Withdrawal of Subjects* ........................................................................................ 11 
15.0 Risks to Subjects* .................................................................................................. 11 
16.0 Potential Benefits to Subjects* ............................................................................... 12 
17.0 Data Management* and Confidentiality ..................................................................12 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 13 
19.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 14 
20.0 Compensation for Research-Related Injury ............................................................15 
21.0 Economic Burden to Subjects .................................................................................15 
22.0 Consent Process ..................................................................................................... 15 
23.0 Process to Document Consent in Writing .............................................................. 15 
24.0 Setting .................................................................................................................... 15 
25.0 Resources Available ............................................................................................... 16 
26.0 Multi-Site Research* .............................................................................................. 16 
 

 
1.0 
Study Summary 
 
Study Title 
Home-based Transcranial Direct Current Stimulation for 
Pain Management in Persons with Alzheimer’s Disease and 
Related Dementias 
Study Design 
Double-blind, randomized, sham-controlled, parallel group 
(1:1 for two groups) design. 
Primary Objective 
The purpose of this project is to assess the effect of the self- 
administered transcranial direct current stimulation (tDCS) 
in 40 older adults with ADRD 
Secondary 
Objective(s) 
The specific aims are the following: evaluate the 
preliminary effects of home-based M1-SO applied tDCS on 
clinical pain in persons with early-stage ADRD (specific aim 
1); evaluate the preliminary effects of home-based M1-SO 
applied tDCS on pain related cortical response in persons 
with early-stage ADRD (specific aim 2); and evaluate the 
feasibility and acceptability of home-based M1-SO–applied 
tDCS for pain management in persons with early stage 
ADRD (specific aim 3). 
Research 
Intervention(s)/ 
Investigational 
Agent(s) 
tDCS 
IND/IDE # 
N/A 
Study Population 
Older adults with early-stage Alzheimer’s Disease and 
Related Dementia (ADRD) 
Sample Size 
40 
Study Duration for 
individual 
participants 
3 months, including follow-up phone interviews 
Study Specific 
Abbreviations/ 
Definitions 
tDCS, transcranial direct current stimulation; ADRD, 
Alzheimer’s Disease and Related Dementia, SMC, Safety 
Monitoring Committee 

 
2.0 
Objectives 
The purpose of this project is to assess the feasibility, acceptability, and preliminary 
effects of this novel nonpharmacological treatment option in persons with ADRD. The 
specific aims are the following: evaluate the preliminary effects of home-based M1-SO 
applied tDCS on clinical pain in persons with early-stage ADRD (specific aim 1); 
evaluate the preliminary effects of home-based M1-SO applied tDCS on pain-related 
cortical response in persons with early-stage ADRD (specific aim 2); and evaluate the 
feasibility and acceptability of home-based M1-SO applied tDCS for pain management in 
persons with early-stage ADRD (specific aim 3). Outcome measures include clinical 
pain, pain-related cortical response using functional near-infrared spectroscopy, and 
participant experience and side effects using questionnaire. 
 
3.0 
Background* 
The World Health Organization has highlighted dementia care as one of its highest 
priorities. Alzheimer’s disease and Related Dementias (ADRD) is characterized by 
progressive and global deterioration in cognitive functions,15 and more than 5.5 million 
people in the United States have ADRD. Persons with ADRD are often elderly and have 
many age-related sources of pain (e.g., radiculopathy and arthritis), with approximately 
60% reporting chronic pain. Aside from behavioral and psychological symptoms of 
dementia (BPSD), pain is the most cited cause for decreased quality of life in persons 
with ADRD. Moreover, our group and others showed that pain in ADRD is associated 
with neuropsychiatric symptoms and a decline in cognitive functioning. Primary 
treatment options for pain management comprise mainly the prescription of analgesic 
medications; however, existing pharmacological approaches often produce significant 
adverse events (e.g., constipation, confusion, behavioral disorders, psychomotor 
retardation, and falls), and the treatment benefits may decrease over time (e.g., drug 
tolerance development). Furthermore, many studies suggest that alterations in pain 
related brain mechanisms may contribute to chronic pain. Indeed, neuroimaging studies 
have revealed increased pain-related brain activation in people with chronic pain, and 
alterations in pain related brain mechanisms have been associated with chronic pain and 
disability in older adults. Therefore, there is growing interest in nonpharmacological 
interventions targeting pain-related brain function in this population. Noninvasive brain 
stimulation, such as transcranial direct current stimulation (tDCS), has received 
significant attention as treatment of pain in chronic conditions owing to its 
neuromodulatory effects in the central nervous system. tDCS involves the application of 
low-amplitude direct electric current to the head in a noninvasive and painless manner, 
which modulates the resting membrane potentials of neurons, altering the excitability of 
the targeted cortical area. Hundreds of clinical trials have demonstrated that tDCS is safe 
and well tolerated within the established current intensities and durations. For pain 
treatment, stimulation is typically delivered multiple times with the anode electrode 
placed over the primary motor cortex of the left hemisphere and with the cathode 
electrode placed over the contralateral supraorbital region. A panel of experts of the 
International Federation of Clinical Neurophysiology published evidence-based 
guidelines in which they recommended 20-minute tDCS using 2 mA electrical current 
intensity for possible efficacy among populations with chronic pain. 

 
Therefore, we will examine the effect of tDCS in persons with ADRD. Our hypothesis is 
that remotely supervised tDCS at home will decrease clinical pain. 
 
4.0 
Study Endpoints* 
The study endpoint is 3 months, including monthly follow-up telephone 
assessments for 3 months after the completion of intervention. 
5.0 
Study Intervention/Investigational Agent 
tDCS with a constant current intensity of 2 mA will be applied for 20 minutes per 
session daily for 5 days via the Soterix 1x1 tDCS mini-CT Stimulator device 
(Soterix Medical Inc., NY; 6.5 inches long, 3 inches wide, 0.7 inches thick) with 
headgear and 5x7 cm saline-soaked surface sponge electrodes. The FDA has ruled 
that the aforementioned tDCS stimulator is a “non-significant risk” device, a 
requirement for Investigational Device Exceptions. The sponge electrodes snap 
into the custom headgear, which is secured to the participant’s head for simple 
and fail-safe electrode preparation. This single-position headgear with clearly 
labeled sponge markers eliminates room for user error and helps conserve the 
placement of the montage. Participants can only administer a stimulation session 
via the Soterix 1x1 tDCS mini-CT Stimulator device after being provided a 
single-use unlock code by the research staff once proper contact quality is 
achieved (only the on/off button will be adjustable by the study participants; they 
will not be able to adjust the device settings). After the participant enters the 
unlock code, the screen on the device will show a timer that counts down the 
minutes until the end of the session. At 20 minutes, the device will turn off 
automatically, and study staff will instruct the participant to remove the headset 
and discard the sponges and to safely store all materials for the next session. For 
sham stimulation, the electrodes will be placed in the same positions as for active 
stimulation, but the stimulator will only deliver 2 mA current for 30 seconds. This 
sham stimulation method has been shown to be reliable and indistinguishable 
from active treatment. 
6.0 
Procedures Involved* 
Alzheimer’s disease and Related Dementias (ADRD) affects more than 5.5 million 
individuals in the United States. Approximately 60% of persons with ADRD experience 
chronic pain, and pain is the second most commonly cited reason for decreased quality of 
life in persons with ADRD. Our group and others showed pain in ADRD is associated 
with behavioral and psychological symptoms of dementia. The current standard of care 
comprises mainly the prescription of analgesic medications, which often produce 
significant adverse effects. Moreover, recent evidence suggests that alterations in pain- 
related brain mechanisms may contribute to chronic pain. Therefore, there is growing 
interest in nonpharmacological interventions targeting pain-related brain function in this 
population. One promising treatment is tDCS with the anode over the primary motor 
cortex and the cathode over the contralateral supraorbital area (M1-SO applied tDCS), as 
it can change brain activity in a noninvasive, painless, and safe way. We will investigate 
the effects of home-based, remotely supervised, M1-SO applied tDCS on clinical pain in 
40 persons with early-stage ADRD using an experimenter- and participant-blinded, 

 
randomized, sham-controlled, parallel group (1:1 for two groups) pilot clinical trial. The 
central hypothesis is that home-based, remotely supervised tDCS will decrease pain. This 
hypothesis will be tested by pursuing the following specific aims: evaluate the 
preliminary effects of home-based M1-SO applied tDCS on clinical pain in persons with 
early-stage ADRD (specific aim 1); evaluate the preliminary effects of home-based M1- 
SO applied tDCS on pain related cortical response in persons with early-stage ADRD 
(specific aim 2); and evaluate the feasibility and acceptability of home based M1-SO– 
applied tDCS for pain management in persons with early stage ADRD (specific aim 3). 
We will also obtain data, as an exploratory aim, to investigate whether tDCS reduces 
behavioral and psychological symptoms of dementia. The proposed study will directly 
investigate the effects of home-based, remotely supervised tDCS in 40 persons with 
ADRD using an experimenter- and participant-blinded, randomized, sham-controlled, 
parallel group (1:1 for two groups) pilot clinical trial. Caregivers will set up and 
administer home-based tDCS for persons with ADRD and must be present at each home- 
based session, and participants will be remotely supervised by trained research staff at 
each stimulation to ensure the use of proper technique. Primary outcome (clinical pain 
assessed by the MOBID-2) will be performed by the caregivers. Caregivers will be 
trained at the in-person baseline visit to use tDCS devices and to perform outcome 
measures. tDCS session will be not performed if the caregiver is not available, and it 
needs to be the same caregiver throughout the trial. The proposed research is significant 
because it is expected to provide valuable insight into an exciting new modality of 
nonpharmacological pain management that is easy, safe, and noninvasive with minimal 
side effects. 
 
Participants will do remotely-supervised tDCS at their home or private room for 5 days 
under real time supervision by the research staff. Data will be collected by study staff 
across several points using equipment and resources available at Dr. Ahn’s (PI’s) 
laboratory at Florida State University (see Table below). The primary endpoint will be 
clinical pain (MOBID-2) collected after the final intervention session. Participants will 
visit Florida State University two times, and each visit will take approximately 2 hours. 
 
Research subjects/caregivers will be called one day prior to their scheduled study visit and 
asked a series of COVID-19 related questions covering topics such as isolation and 
quarantine, vaccination status, symptoms, test results, and exposure. And then subjects will 
be notified about the FSU COVID-19 precautions. Consent materials will be modified to 
include a statement to the effect that no in-person activity may involve any individual 
(human research participants (human subjects) or study staff—vaccinated or unvaccinated) 
who (1) tests positive for COVID-19 or (2) has been in close contact with someone who 
has COVID-19, within at least the past 10 days of the positive COVID-19 test or close 
contact; that prospective subjects will be screened for this purpose; and that for any in- 
person research activity the use of masks is strongly recommended (and may be required 
in certain locations) as is a full COVID-19 vaccination. 
 
 
Table 1. Timetable for Collection of Data 
Week 1 
F1 
F2 
F3 

 
Stimulation Session 
Baseline 
1 
2 
3 
4 
5 
MMSE 
X 
Medical History Questionnaire 
X 
Clinical Pain (MOBID-2): 
primary outcome 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Pain (NRS): secondary 
outcome 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BPSD (CMAI, NPI): secondary 
outcome 
X 
X 
X 
X 
X 
Pain-related cortical response 
(fNIRS): secondary outcome 
X 
X 
tDCS experience questionnaire: 
secondary outcome 
X 
Patient satisfaction (CSQ-8): 
secondary outcome 
X 
Side effects questionnaire: 
secondary outcome 
X 
X 
X 
X 
X 
Note: F, Weekly follow-up phone assessment after completion of tDCS treatment; MMSE, Mini- 
Mental Status Exam, MOBID, Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale; 
BPSD, behavioral and psychological symptoms of dementia; CMAI, Cohen-Mansfield Agitation 
Inventory; fNIRS, functional near-infrared spectroscopy; CSQ, Client Satisfaction Questionnaire. 
• MMSE. MMSE will be used to exclude people with severely diminished cognitive 
function (i.e., Mini-MentalStatus Exam score ≤ 15). 
• Medical History Questionnaire. All participants will complete a thorough questionnaire 
to collect demographic and medical history details, including age, sex, height, weight, 
duration of knee OA,current and past treatments for knee OA, comorbid conditions, and 
current medications. 
• Clinical pain will be measured to rate patients’ pain via the Mobilization-Observation- 
Behavior Intensity-Dementia (MOBID-2) scale from 0 to 10, which will be primary 
outcome measure for data analysis purposes. The MOBID-2 is a well-validated measure 
with good ability to detect painchange in persons with ADRD. We also measure clinical 
pain by asking participants to rate their average pain over the past 24 hours via NRS 
from 0 (no pain) to 100 (worst pain imaginable), following Initiative on Methods, 
Measurement, and Pain Assessment in Clinical Trials recommendations for clinical 
trials involving chronic pain. NRS is appropriate for use among older adults with mild 
to moderate dementia. 
• BPSD. NPI will be used to obtain information on behavioral and psychological 
symptoms of the patients. NPI comprises 12 items that are summed to yield an overall 
score of 0-144 (each item will be rated frequency X severity, totaling 0 – 12), with higher 
scores indicating greater symptoms. We also collect CMAI, which is comprised of 29 
items that are summed to yield an overall score of 29-203 (each item will be rated 7- 
point scale of frequency). Trained research staff will conduct the NPI interview. In terms 
of training, two raters (one primary and one back-up) conduct mock administrations to 
each other. Same rater will conduct the assessment with the subjects for fidelity. PI will 

 
review NPI and CMAI and will not refer subjects for clinical review based on the result. 
• A multichannel fNIRS imaging system (LIGHTNIRS, Shimadzu, Kyoto, Japan) will be 
used to determinechanges in regional cerebral blood flow in response to thermal stimuli 
applied to the right forearm of participants. The illumination and detection optodes will 
be arranged in a geometrical layout that will cover the prefrontal and somatosensory 
cortex regions bilaterally, consistent with locations investigated in previous studies. For 
evoked pain scans, low-intensity thermal stimuli at the thermal pain threshold level will 
be applied for a few seconds during multiple scanning runs, followed by an 
approximately equivalent interval of no stimulation, which is commonly used in pain 
related neuroimaging studies since thermal hyperalgesia is an important component of 
chronic pain. A temperature-controlled pain generator (Medoc TSA-II Neurosensory 
Analyzer) will be used to produce thermal stimulation through a 16 mm 
16 mm 
thermode. We expect to observe reduced pain-evoked activation in the active tDCS 
group in the prefrontal and somatosensory cortices. To minimize the inconvenience to 
participants, we will deliver thermal stimuli that are below the individual's pain 
tolerance level and set the cutoff temperature at 50°C. These procedures will ensure 
maximum patient safety and comfort while allowing successful and reliable imaging of 
the pain-related cortical response. 
• We will collect data on the tDCS experience via a questionnaire, adapted from Gillick 
et al. and Cha et al., at the conclusion of tDCS treatment on a 0 (strongly disagree) to 
10 (strongly agree) scale: 1) It was easy to prepare the device and accessories; 2) The 
device was unnecessarily complex; 3) The device was easy to use; 4) I felt the video 
conferences with a technical person were helpful; 5) I would imagine that most people 
would learn to use this device quickly; 6) The device was cumbersome to use; 7) I felt 
confident using the device; 8) I needed to learn a lot of things before I could get going 
with this device; 9) The effectiveness of the treatment increased over the course of 
treatment; and 10) Overall, I felt that transcranial electrical stimulation treatment 
benefited me. Participants/caregivers will also be encouraged to elaborate on their 
answers in free form. In addition, we will measure participant satisfaction with treatment 
using the Client Satisfaction Questionnaire (CSQ-8). The CSQ-8 comprises eight items 
that are summed to yield an overall score of 8-32, with higher scores indicating greater 
satisfaction. Moreover, we will evaluate the presence and severity of possible side 
effects of treatment at the end of each session on a 0 (not at all) to 10 (highest degree) 
scale. The participants will be asked in an open-ended manner whether they experienced 
any side effects, and they will then be asked specifically about tingling, itching 
sensation, burning sensation, pain at the stimulation site, fatigue, nervousness, 
headache, difficulty concentrating, mood change, and changes in vision or visual 
perception. If any side effects are reported, the degree of relatedness to the intervention 
will be assessed on a 5-point scale. This approach has been used in our previous study 
and frequently in other studies. 
 
7.0 
Data and Specimen Banking 
N/A 
 
8.0 
Sharing of Results with Subjects* 

 
We will publish research results at the peer-reviewed journal and/or scientific 
conferences. After completion of the study, results may be shared to research subjects if 
they want. 
 
9.0 
Study Timelines* 
The duration of an individual subject’s participation in the study is three months 
including follow-up phone assessments. The estimated date for the investigators 
to complete this study is 02/01/2023. 
 
10.0 Inclusion and Exclusion Criteria* 
A maximum of 40 persons with early-stage Alzheimer’s disease and related dementias 
(ADRD) will be enrolled. Participants who are 50 to 90 years old will be considered 
eligible if they (1) have early- stage ADRD, (2) have caregiver-reported chronic pain 
(average pain in the past 3 months ≥ 3 out of 10), (3) have a caregiver willing to 
participate in the study who sees the participant at least 10 hours/week, (4) can speak and 
read English, and (5) have no plans to change medication regimens during the trial. The 
diagnosis of early-stage ADRD will be verified by PI based on Mini-Mental Status Exam 
score (generally 16-23), the blind/telephone version of the Montreal Cognitive 
Assessment (MoCA, generally 16-26), or Clinical Dementia Rating scores (generally 0.5- 
1.0). We will assess the use of medications that can influence responses to tDCS (e.g., 
selective serotonin reuptake inhibitors, beta-blockers) and include them as covariates in 
our statistical models. Participants will be excluded if they have any concurrent medical 
conditions that could confound the interpretation of outcome measures, pose a safety risk 
for any of the assessment or tDCS procedures, or preclude the successful completion of 
the protocol. Specific exclusion criteria are: (1) history of brain surgery, brain tumor, 
seizure, stroke, or intracranial metal implantation, (2) alcohol/substance abuse, (3) 
severely diminished cognitive function (i.e., Mini-Mental Status Exam score ≤ 15), and 
(4) hospitalization within the preceding year for neuropsychiatric illness. Participants 
who do not have a device with internet access will be provided a smartphone to use 
during the study. 
 
11.0 Vulnerable Populations 
N/A 
 
12.0 Local Number of Subjects 
The number of subjects who are expected to be enrolled and screened is 24, and the 
number of subjects needed to complete the research procedures (i.e., numbers of subjects 
excluding screen failures.) is 20. The total number of subjects to be accrued locally is 20, 
since we completed data collection for 20 subjects at the University of Texas Health 
Science Center at Houston before PI (Dr. Ahn) moved to Florida State University. 
 
13.0 Recruitment Methods 
Participants will be recruited in Leon County under the direction of the PI. We will 
advertise around local institutions and communities by advertisement study flyers. PI will 

 
oversee participant screening and recruitment. We will share recruitment materials with 
potential study participants, and those patients who contact the study team for more 
information about the study will be approached by study investigators or trained study 
personnel for further determination of eligibility screening requirements and informed 
consent either in-person at a scheduled baseline visit. We will also recruit through the 
Institute for Successful Longevity participant registry, as well as contacting previous 
participants of Dr. Sheffler’s study who have consented to be contacted for future 
research studies. MMSE will be used to exclude people with severely diminished 
cognitive function (i.e., MMSE score ≤ 15), and we will get the consent from the subject 
whose MMSE score is above 15. In addition to the MMSE cutoff, to ensure participant 
understanding of the study procedures, participants will be required to accurately describe 
the purpose and requirements of their participation in the study following review of the 
informed consent form. 
 
Subjects will receive up to $240 in gift cards for completing the entire protocol, and they 
will receive partial payment if they do not complete the entire study. For each self-brain 
stimulation, subjects will receive $30 and an additional $30 for each visit to our testing 
center and $10 for each follow-up phone assessments. 
 
14.0 Withdrawal of Subjects 
Participation in this study is completely voluntary. All participants will be informed of 
the nature of the procedures and associated risks. Also, participants will be informed that 
they can withdraw from the study at any time by calling study team at 850-644-2647 and 
that this will have no adverse impact on the study or on their own future medical 
treatment. 
 
15.0 Risks to Subjects 
tDCS. The PI has extensive experience with tDCS interventions. Participants will be 
instructed to inform the experimenter of any discomfort during tDCS. To minimize risk 
associated with tDCS, participants will be asked to report any discomfort, and the 
examiner will monitor participants throughout the stimulation sessions. All tDCS 
sessions will be remotely supervised by a trained experimenter. Participants may stop at 
any time. tDCS has not been shown to cause seizures nor lower the seizure threshold in 
animals. There are no reports of seizure induced by tDCS in human participants in the 
literature. However, this may not be true for epilepsy patients, whose seizure threshold 
rates are likely abnormal. Thus, history of seizure is an exclusionary criterion for our 
study. 
 
Demographic and clinical survey questionnaires. The potential risk of the questionnaires 
involves participants’ feelings of discomfort or unease when reading or responding to 
survey questions that are personal. Throughout each questionnaire, participants will be 
reminded that participation is completely voluntary, they can refuse to answer any 
question, and they can stop at any time. Breaks will be given if needed. Research staff 
who collect data will have previous training in the conduct of all survey questionnaires. 

 
Functional near-infrared spectroscopy. Optical fibers will be secured to the participant’s 
scalp using the cap’s grommets. Although there is no designed measure that protects the 
participants from the risk of discomfort due to prolonged wearing of headgear, we will 
assess the participants’ level of discomfort through direct question immediately after 
wearing the headgear and periodically during the experiment. Participants will be 
instructed that they can discontinue the procedure if they experience any discomfort or 
unpleasant effects. 
 
Thermal stimulation. The primary potential risk of thermal stimulation involves burning 
of the skin; however, we will be using the Medoc TSA-II Neurosensory Analyzer to 
create thermal stimulation. The TSA-II is covered under FDA 510K #K922052, which 
mandated both hardware and software safety limits that prevent burning of the skin. The 
following precautions will be employed in the proposed study: 1) participants will be 
informed that they can withdraw their arm from the stimulator at any time; 2) the 
experimenter will continuously monitor stimulus temperature and can manually 
discontinue stimulation at any point; and 3) the stimulator has a built-in shut-down 
system to prevent the delivery of prolonged or high-intensity stimuli. Inconvenience to 
participants will be minimized by delivering brief stimuli that are below the individual's 
thermal pain tolerance level. These procedures will ensure maximum patient safety and 
comfort while allowing successful and reliable imaging of the brain. 
 
16.0 Potential Benefits to Subjects* 
Brain Stimulation have been shown to reduce pain in some older adults. We cannot 
promise any benefits to participants in this research. However, this study will help us to 
understand whether self-brain stimulation will reduce pain in older adults with 
Alzheimer’s Disease and Related Dementia, which might lead to better treatment for 
people with such condition. 
 
17.0 Data Management* and Confidentiality 
PI has substantial experience in the design and implementation of data management 
procedures that provide accurate recording and storage of data, participant 
confidentiality, and timely analysis. Based on our experience, we believe that the major 
data management and analysis needs for the proposed project can be met by using a high- 
end PC, equipped with SPSS and SAS for Windows and appropriate spreadsheet 
programs. All data files will be automatically backed up daily. 
The data entry system will require a login identification and password to gain access to 
the data. Where appropriate, validation and range rules will be applied to the actual entry 
fields. Only the PI and designated research staff will be able to view the data in its raw 
state. 
All data files will be automatically backed up daily. We will ensure data changes are 
documented and there is no deletion of entered data. Data will be accessible only by 
research team members via an encrypted and password-protected computer, and we will 
prevent unauthorized access to data. 

 
Confidentiality will be protected by assigning each participant a number, which will be 
used in all data tabulation and subsequent publications. The list linking this number to the 
participant’s identity will be maintained in a password-protected data file, accessible only 
by authorized research personnel associated with the human testing components of this 
project. The PI will oversee the compliance of the study, maintaining strict adherence to 
the requirements of the law, research protocols, and health information security. Only 
trained research team members designated in the IRB- approved study protocol will 
collect data. REDCap (http://www.project-redcap.org) will be used to capture and store 
participant data, accessible only by research team members via an encrypted and 
password-protected computer. All research data will be labeled using the participant’s 
unique identifier. No name or other identifying information will be used on research data. 
All paper data (e.g., participant contact information, consent forms) will be placed in a 
locked file cabinet within 24 hours of their acquisition. 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
Dr. Ahn, the PI, will have the primary responsibility for monitoring study research staff, 
who will receive training on the study design, recruitment, and protocol prior to study 
initiation. The research staff will attend weekly meetings with the PI and monthly team 
meetings during data collection with the PI and co-investigators to discuss any study- 
related issues regarding recruitment and follow-up data collection. These meetings will 
be used to discuss experiences with the intervention participants, provide consultation, 
ascertain whether the research staff are following study protocols, evaluate and reinforce 
cultural competence, and identify any potential adverse events. Dr. Miao, the study 
statistician, will coordinate data management and analysis. 
The Safety Monitoring Committee (SMC), which was approved by NIH, will be 
responsible for overseeing activities related to implementing the clinical trial to ensure 
patient safety, conformance to the clinical protocol, overall performance of the trial 
components, and integrity of the data being collected. The SMC will meet prior to the 
start of enrollment and then annually to review study progress (e.g., recruitment, 
retention, and safety procedures) and participant safety concerns and as needed to 
adjudicate any adverse events. All meeting materials will be considered privileged by 
SMC members. The SMC will comprise 3 members with expertise in neuromodulation, 
statistics, and geriatric clinical research: Ricardo Jorge, MD, professor of psychiatry and 
behavioral sciences at Baylor College of Medicine; Nikhil Padhye, PhD, associate 
professor and biostatistician at the UTHealth Cizik School of Nursing; and Jessica Lee, 
MD, Assistant Professor, Geriatric and Palliative Medicine, UTHealth McGovern 
Medical School. The SMC members are independent of the project. These members are 
appropriately qualified to review the scientific design and conduct of the study, to 
evaluate safety and risks to participants, to interpret data statistically, and to make 
recommendations concerning the continuation, modification, suspension, or termination 
of the study. 
 
19.0 Provisions to Protect the Privacy Interests of Subjects 

 
A number of data integrity procedures will be used to ensure the validity and integrity of 
the data and the safety of all participants involved in the study. All procedures involving 
human participants will be performed at the PI’s laboratory at FSU. Relevant data and 
safety information obtained from each study participant will be verified against the 
original source documents by the study coordinator, and any identified discrepancies will 
be reviewed at the weekly meetings. All identifying information will be archived on a 
password-protected server in password-protected folders and files. Only study staff will 
have access to these files. We will use the double data entry module in REDCap for self- 
report data (e.g., questionnaires). 
Computer-generated reports of variable frequencies and participant lists will be reviewed, 
leading to possible corrections to coding or entry. After data within a given group are 
checked for accuracy, the data will be stored in the password-protected folders. 
Adherence to the study protocol will be promoted throughout the trial. Of note, 
the research team will receive proper training using detailed manuals of 
procedures for all aspects of the proposed research, including treatment protocols 
and participant interaction, in a step-by-step fashion. All study personnel will be 
trained before study initiation, and the PI will carry out weekly supervision of the 
research team’s adherence to protocols. These procedures were successfully 
implemented in our previous studies. 
 
20.0 Compensation for Research-Related Injury 
This study poses minimal risks because (1) the discomfort is transient in nature 
and generally subsides immediately after the procedure; (2) participants are 
instructed that they may stop any procedure at any time with no adverse 
consequences; and (3) the level of discomfort experienced by participants is 
below their tolerance level. Also, risks will be minimized by adhering to our 
exclusion criteria, and the study physician will have full discretion to exclude 
participants who may be at excessive risk. There will be no compensation in the 
event of research related injury. 
 
21.0 Economic Burden to Subjects 
There will be no costs that subjects may be responsible for because of participation in the 
research. 
 
22.0 Consent Process 
Subjects will participate in the study only after they provide verbal and signed consent. 
MMSE will be used to exclude people with severely diminished cognitive function (i.e., 
MMSE score ≤ 15), and we will get the consent from the subject whose MMSE score is 
above 15. In addition to the MMSE cutoff, to ensure participant understanding of the 
study procedures, participants will be required to accurately describe the purpose and 

 
requirements of their participation in the study following review of the informed consent 
form. 
 
23.0 Process to Document Consent in Writing 
Trained research personnel will obtain consent in a private room where participants feel 
comfortable. Informed consent will be documented in writing via the participants’ and 
investigators’ signatures. 
 
24.0 Setting 
The research team will conduct the research at the PI’s research lab at the FSU. 
 
25.0 Resources Available 
This study, funded by NIH, was approved by the IRB at the University of Texas Health 
Science Center at Houston. On this R15 project, all the data will be collected at the Dr. 
Ahn’s laboratory at FSU. Adequate equipment and resources are available in the Ahn 
laboratory to carry out the procedures and accommodate the personnel described in this 
proposal. 
 
26.0 Multi-Site Research 
N/A