Development of Memesto Wearable Repetitive Message/Music Therapy Device That Senses and Reduces Agitation in Alzheimer's Disease and Alzheimer's Disease Related Dementia (AD/ADRD) Individuals
Phase: PHASE1
Conditions: Alzheimer Disease
Sponsor: Edgewater Safety Systems, Inc.

 
 
 
 
 
Does an Audio Wearable lead to Agitation Reduction in 
Dementia: The Memesto AWARD Proof-of-Principle 
Clinical Research Study  
Protocol Number: ESS-MEM-001 
Principal Investigator: Raj C. Shah, MD 
Sponsor: Edgewater Safety Systems, Inc. 
Grant Title: Development of Memesto, a wearable repetitive message and 
music therapy device that senses and reduces agitation in persons with 
AD/ADRD 
Grant Number: 1R43AG074725 
Funded by: National Institute on Aging 
Version Number:  1.0 
01 December 2021 
 
 
 
 
 
 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

 
 
 
 
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................ 1 
INVESTIGATOR’S SIGNATURE ............................................................................................................................. 2 
1 
PROTOCOL SUMMARY .............................................................................................................................. 3 
1.1 
Synopsis ............................................................................................................................................... 3 
1.2 
Schema ................................................................................................................................................ 4 
1.3 
Schedule of Activities ......................................................................................................................... 4 
2 
INTRODUCTION ........................................................................................................................................... 5 
2.1 
Study Rationale ................................................................................................................................... 5 
2.2 
Background .......................................................................................................................................... 5 
2.3 
Risk/Benefit Assessment ................................................................................................................... 6 
2.3.1 
Known Potential Risks .................................................................................................... 6 
2.3.2 
Known Potential Benefits ............................................................................................... 6 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 6 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................................... 6 
4 
STUDY DESIGN ............................................................................................................................................ 7 
4.1 
Overall Design ..................................................................................................................................... 7 
4.2 
Scientific Rationale for Study Design ............................................................................................... 7 
4.3 
Justification for Intervention ............................................................................................................... 8 
4.4 
End-of-Study Definition ...................................................................................................................... 8 
5 
STUDY POPULATION .................................................................................................................................. 8 
5.1 
Inclusion Criteria ................................................................................................................................. 8 
5.2 
Exclusion Criteria ................................................................................................................................ 8 
5.3 
Lifestyle Considerations ..................................................................................................................... 9 
5.4 
Screen Failures ................................................................................................................................... 9 
5.5 
Strategies for Recruitment and Retention ....................................................................................... 9 
6 
STUDY INTERVENTION .............................................................................................................................. 9 
6.1 
Study Intervention Administration ..................................................................................................... 9 
6.1.1 
Study Intervention Description ...................................................................................... 9 
6.1.2 
Administration and/or Dosing ...................................................................................... 10 
6.2 
Fidelity ................................................................................................................................................ 10 
6.2.1 
Interventionist Training and Tracking ......................................................................... 10 
6.3 
Measures to Minimize Bias: Randomization and Blinding .......................................................... 10 
6.4 
Study Intervention Adherence ......................................................................................................... 10 
6.5 
Concomitant Therapy ....................................................................................................................... 10 
6.5.1 
Rescue Therapy ............................................................................................................ 10 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................................................................... 10 
7.1 
Discontinuation of Study Intervention ............................................................................................ 10 
7.2 
Participant Discontinuation/Withdrawal from the Study .............................................................. 11 
7.3 
Lost to Follow-Up .............................................................................................................................. 11 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 11 
8.1 
Endpoint and Other Non-Safety Assessments ............................................................................. 11 
8.1.1 
Neuropscyhiatric Inventory .......................................................................................... 11 
8.1.2 
Clinical Global Impressions Scale - Severity ............................................................. 11 
8.2 
Safety Assessments ......................................................................................................................... 11 
8.3 
Adverse Events and Serious Adverse Events .............................................................................. 12 

 
 
 
 
8.3.1 
Definition of Adverse Events ........................................................................................ 12 
8.3.2 
Definition of Serious Adverse Events ......................................................................... 12 
8.3.3 
Classification of an Adverse Event ............................................................................. 12 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 13 
8.3.5 
Adverse Event Reporting ............................................................................................. 13 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 14 
8.3.7 
Reporting Events to Participants ................................................................................. 14 
8.3.8 
Events of Special Interest ............................................................................................ 14 
8.3.9 
Reporting of Pregnancy ................................................................................................ 14 
8.4 
Unanticipated Problems ................................................................................................................... 14 
8.4.1 
Definition of Unanticipated Problems ......................................................................... 14 
8.4.2 
Unanticipated Problems Reporting ............................................................................. 14 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 14 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 14 
9.1 
Statistical Hypotheses ...................................................................................................................... 15 
9.2 
Sample Size Determination ............................................................................................................. 15 
9.3 
Populations for Analyses ................................................................................................................. 15 
9.4 
Statistical Analyses ........................................................................................................................... 15 
9.4.1 
General Approach ......................................................................................................... 15 
9.4.2 
Analysis of the Primary Endpoint(s) ........................................................................... 15 
9.4.3 
Analysis of the Secondary Endpoint(s) ...................................................................... 15 
9.4.4 
Safety Analyses ............................................................................................................. 16 
9.4.5 
Baseline Descriptive Statistics .................................................................................... 16 
9.4.6 
Planned Interim Analyses ............................................................................................ 16 
9.4.7 
Sub-Group Analyses ..................................................................................................... 16 
9.4.8 
Tabulation of Individual Participant Data ................................................................... 16 
9.4.9 
Exploratory Analyses .................................................................................................... 16 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 16 
10.1 
Regulatory, Ethical, and Study Oversight Considerations .......................................................... 16 
10.1.1 
Informed Consent Process .......................................................................................... 16 
10.1.2 
Study Discontinuation and Closure ............................................................................. 17 
10.1.3 
Confidentiality and Privacy ........................................................................................... 17 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 18 
10.1.5 
Key Roles and Study Governance .............................................................................. 18 
10.1.6 
Safety Oversight ............................................................................................................ 18 
10.1.7 
Clinical Monitoring ......................................................................................................... 18 
10.1.8 
Quality Assurance and Quality Control ...................................................................... 18 
10.1.9 
Data Handling and Record Keeping ........................................................................... 19 
10.1.10 
Protocol Deviations ....................................................................................................... 19 
10.1.11 
Publication and Data Sharing Policy .......................................................................... 19 
10.1.12 
Conflict of Interest Policy .............................................................................................. 20 
10.2 
Additional Considerations ................................................................................................................ 20 
10.3 
Abbreviations and Special Terms ................................................................................................... 20 
10.4 
Protocol Amendment History ........................................................................................................... 22 
11 
REFERENCES ............................................................................................................................................. 23 
 

Protocol ESS-MEM-001 
 
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STATEMENT OF COMPLIANCE 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 
21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for 
the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to an Institutional Review Board (IRB) for review and approval. Approval of both the protocol 
and the consent form(s) must be obtained before any participant is consented. Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the study. 
All changes to the consent form(s) will be IRB-approved; a determination will be made regarding whether 
a new consent needs to be obtained from participants who provided consent, using a previously approved 
consent form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator: 
Signed: 
 
Date: 
 
 
Name:   Raj C. Shah, MD  
 
Title:   Associate Professor, Family Medicine and Rush Alzheimer’s Disease Center                 
Rush University Medical Center 
Principal Investigator Contact Information: 
 
Affiliation: 
Rush Alzheimer’s Disease Center, Rush University Medical Center 
Address: 
1653 West Congress Parkway, Chicago, IL 60612 
Telephone: 
1-312-563-2902 
Email:  
Raj_C_Shah@rush.edu  
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Does an Audio Wearable lead to Agitation Reduction in Dementia: The 
Memesto AWARD Proof-of-Principle Clinical Research Study 
 
Grant Number: 
 
1R43AG074725-01 
 
 
Study Description: 
 
This is a 12-week proof-of-concept study to evaluate the efficacy of 
Memesto in reducing agitation in persons with Alzheimer’s disease and 
Alzheimer’s disease related dementias (AD/ADRD) currently living in a 
residential care facility. It is hypothesized that Memesto use will result 
in a reduction in agitation. 
 
Study Objectives and 
Endpoints: 
 
Primary Objective 
Primary Endpoint 
To evaluate the efficacy of 
Memesto in reducing agitation 
Change in average score on the 
Neuropsychiatric Inventory (NPI) 
agitation domain subscale from 
baseline to Week 10 
 
Secondary Objective 
Secondary Endpoint 
To evaluate the clinical benefit of 
Memesto in reducing agitation 
Change in average score on the 
Clinical Global Impressions – 
Severity (CGI-S) scale from 
baseline to Week 10 
 
 
 
Study Population: 
Participants will include 20 persons with AD/ADRD living in a 
residential care facility. Each participant will have two study partners: 
(1) a spouse, sibling, or adult child, and (2) a professional caregiver 
from the care facility (e.g., nurse, activity director, certified assistant). 
 
 
Phase or Stage: 
 
Proof-of-Concept  
 
 
Description of 
Sites/Facilities Enrolling 
Participants: 
 
This study is to be conducted in one or more residential care facilities in 
the United States. 
 
 
Description of Study 
Intervention/Experimental 
Manipulation: 
 
After informed consent is obtained and preliminary eligibility 
established, participants will be trained and issued the Memesto device 
for use over a 2-week screening/training phase. Participants 
successfully completing this phase will proceed into a 10-week open-
label treatment phase (via telephone and/or in-person data collection). 
 
 
Study Duration: 
 
The entire study (opening of enrollment through completion of data 
collection) is anticipated to last approximately 7 months. 
 

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Participant Duration: 
 
Study participation will consist of a 2-week screening/training phase 
followed by a 10-week data collection phase. 
 
1.2 
SCHEMA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Screening 
 
Open-Label Treatment 
 
        
       Baseline/Day 1 
 
 
 
 
Week 10 
 
 
 
1.3 
SCHEDULE OF ACTIVITIES 
 
*ET = Early Termination 
 
 
Screening 
Treatment 
Visit 
1 
2 
3 
4 
5 
6 
7/ET 
Study Activity                   
Week -2 to 0 
Baseline 
Week 2 
Week 4 
Week 6 
Week 8 
Week 10/ET* 
 
Day 1 
(±3 days) 
(±3 days) 
(±3 days) 
(±3 days) 
(±3 days) 
Informed Consent 
X 
 
 
 
 
 
 
Personal/Demographic 
Information 
X 
 
 
 
 
 
 
Brief Medical History 
X 
 
 
 
 
 
 
Device Allocation/Training 
X 
 
 
 
 
 
 
Device Use Accountability 
 
X 
X 
X 
X 
X 
X 
Device Return 
 
 
 
 
 
 
X 
CGI-S 
X 
X 
X 
X 
X 
X 
X 
NPI agitation domain 
 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Memesto Intervention 
(biweekly in-person or remote data collection) 
Screening/Training 
(2 weeks) 

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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) represent the most common 
forms of dementia, with an estimated 7.2+ million Americans living with Alzheimer’s disease or Lewy body 
dementia.1-2 As many as 70% of persons with AD/ADRD experience reduced quality of life due to 
agitation,3 with behavioral disruptions such as aggression, combativeness, shouting, exit-seeking, and 
disinhibition. Agitated individuals with dementia make up a significant portion of those living in residential 
care facilities, because family/home caregivers can no longer manage the burden alone.  
Based on studies on the effectiveness of simulated presence therapy, repetitive messaging, and 
reminiscence therapy,4-5 Edgewater Safety Systems developed a smart media player (Memesto) worn by 
the AD/ADRD patient that delivers personalized music and pre-recorded messages to reduce agitation.  
The current study will confirm proof-of-concept by generating quantitative data that audio therapy of 
family/caregiver voice and music delivered by the Memesto reduces agitation in AD/ADRD persons living 
in a residential care facility. 
2.2 
BACKGROUND  
An unprecedented need exists for rigorous, transformative solutions to improve health outcomes for the 
7.2+ million people in the United States (US) who suffer with AD/ADRD. 1-2 AD/ADRD are age-related 
neurodegenerative diseases characterized by losses in memory, orientation, independent decision-
making capacity, and self-care. Lack of effective care approaches and technologies leads to premature 
institutionalization for AD/ADRD sufferers and poor quality of life for themselves and their caregivers.6-7 
Up to 70% of AD/ADRD sufferers experience acute agitation,3 which worsens as the disease advances. To 
reduce agitation, caregivers regularly administer anti-psychotic drugs, which can have serious side effects 
that include risk of fall, heart problems, stroke, and possibly even death. A 2018 Human Rights Watch 
report states that every week, US care facilities provide anti-psychotic drugs to over 179,000 people who 
do not have diagnoses for the drug’s intended use, using them instead to ‘mentally subdue’ distressed 
patients.8 AD/ADRD patients displaying agitation, especially once it has reached crisis level, require 
significant stressful intervention from caregivers, contributing to caregiver burn-out. 
Typically, caregivers detect building agitation in AD/ADRD persons from experience. Two key problems 
with this approach are that: 1) caregivers are often overwhelmed with direct patient care and 
intervention, reducing patient monitoring time; and 2) rising agitation isn’t always obvious until it reaches 
crisis mode and severe behavioral problems arise. Therapies (Behavior-Based Ergonomic Therapy, for 
example) are used which aim to calm patients by keeping them busy with activities they like and hoping 
for the best. Such therapies work some of the time, but require staff resources, and can neither predict 
nor stop rising agitation.  
A means of detecting agitation in patients as it increases and automatically delivering an effective, calming 
intervention would have benefit. Edgewater Safety Systems created the Memesto, a wearable smart 
audio player that delivers time-settable and/or repeating voice/music therapy to reduce patient agitation. 
The device was informally piloted on AD/ADRD persons in care facilities, with 11 of 11 caregivers rating 
the unit 4.5 of 5 for “usefulness in lowering agitation”. Caregiver feedback indicated patients were calmer, 

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quality of life increased, and less anxiety medication was required. Positive testimonials from caregivers 
on the effectiveness of the device spawned the idea that an automated wearable device with sensors that 
could detect rising agitation and proactively intervene would substantially aid patient and caregiver. 
There are two key knowledge gaps to close in proving feasibility of an automated, agitation-sensing next-
generation Memesto device. First, quantitative evidence must be used to demonstrate that Memesto-
delivered audio therapy reduces agitation. Second, the feasibility of an automated agitation-sensing and 
audio intervention system must be established by building a prototype and testing it to validate real-time 
operation. This study aims to generate the quantitative data needed to show Memesto-delivered audio 
therapy reduces agitation. 
2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
Risks to study participation are minimal. The Memesto exists in the form of an off-the-shelf, commercially 
available wi-fi enabled cellular phone coupled with a mobile operating system- and web-based application 
that enables recording and loading of audio media via the internet. The device will not be used as a cellular 
phone nor will it have cellular service. Per guidance issued by the US Food and Drug Administration (FDA) 
on software device functions and mobile medical applications,9 the Memesto is not considered a medical 
device and is therefore not regulated by the FDA.  
There is potential that using the device (e.g., wearing the device, listening to repeated music/voice 
messages) as well as answering study-related questions about the participant’s mood and behavior may 
become upsetting, frustrating, and/or tiring to either the participant and/or study partners. 
2.3.2 KNOWN POTENTIAL BENEFITS  
Participants with AD/ADRD may see modest benefit if agitation is improved. Study partners also may find 
some relief and/or feel more engaged in caring for a person living with AD/ADRD experiencing agitation 
through use of the device. Finally, study-related questions may serve to help study partners recognize 
agitation symptoms more reliably and with greater precision. 
In contrast, societal benefits may be substantial. Problems associated with dementia and agitation are 
common and create significant distress for persons living with AD/ADRD and their family and professional 
caregivers. Knowledge gained from the study has direct implications for efforts to advance a non-
pharmacological approach to reducing the morbidity associated with agitation in persons living with 
AD/ADRD. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
This is a minimal risk study. While it could not otherwise be carried out without the involvement of persons 
with AD/ADRD and their caregivers, study-related questions may be refused and further participation may 
be declined at any time. Potential study benefits, while modest to the participant, may be of critical 
importance to providing family and professional caregivers with more tools for improving agitation in 
persons living with AD/ADRD. Thus, the anticipated benefit-risk profile of this study is favorable. 
3 
OBJECTIVES AND ENDPOINTS  

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OBJECTIVES 
ENDPOINTS 
Primary 
 
To evaluate the efficacy of 
Memesto in reducing agitation 
Change in average score on the Neuropsychiatric Inventory 
(NPI) agitation domain subscale from baseline to Week 10 
 
Secondary 
 
To evaluate the clinical benefit of 
Memesto in reducing agitation 
 
Change in average score on the Clinical Global Impressions – 
Severity (CGI-S) scale from baseline to Week 10 
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
This is an open-label, proof-of-concept study evaluating the efficacy of Memesto in reducing agitation in 
persons with AD/ADRD currently living in a residential care facility. Approximately 20 persons with 
AD/ADRD will take part in the study. Each participant will have two study partners: a family caregiver and 
a professional caregiver (from the residential care facility) willing to participate in the study along with 
the person with AD/ADRD. 
Participants will be adults with a dementia diagnosis who have clinically significant agitation, defined as a 
state of poorly organized and purposeless psychomotor activity characterized by at least one of the 
following: aggressive verbal (screaming, cursing), aggressive physical (destroying objects, grabbing, 
fighting), or non-aggressive physical (restlessness, pacing) behaviors.  
After informed consent is obtained from both the participant and respective study partners, participants 
will complete a preliminary screening for eligibility and trained on the Memesto to use over a two-week 
screening/training phase. Once satisfactorily completing this phase, participants will be followed for 10 
weeks of data collection with visits (either in-person or via telephone) occurring at baseline and at Weeks 
2, 4, 6, 8, and 10. 
The primary study endpoint is the NPI agitation domain subscale with a secondary study endpoint of the 
CGI-S scale; both assessed as the average change from baseline to the end of treatment (Week 10). 
The study will be approved and overseen by an Institutional Review Board (IRB). Safety will be monitored 
by the principal investigator (PI) and study staff via adverse event reporting in accordance with all IRB and 
funding agency requirements. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
As this is a proof-of-concept study designed to provide initial data to determine whether Memesto use 
quantitatively reduces agitation in persons with AD/ADRD, study design consists of a single open-label 
treatment arm. While the open-label design has some risk for reporting bias, it is expected that 
“triangulation” with ratings from two separate study partners will reduce some of the bias while still 
enabling a clear signal for further device development in the form of a future randomized trial involving a 
sham device.  

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4.3 
JUSTIFICATION FOR INTERVENTION 
This study is designed to demonstrate the efficacy of Memesto in reducing agitation in persons with 
AD/ADRD. Data collected across the 10-week treatment phase is intended to establish device feasibility 
for further development.  
4.4 
END-OF-STUDY DEFINITION 
The end of the study is defined as completion of Visit 7 (Week 10) or Early Termination (ET) as shown in 
Section 1.3, Schedule of Activities. 
5 
STUDY POPULATION 
Approximately 20 participants will be enrolled in the study. Each participant will have two study partners: 
(1) a spouse, sibling, or adult child; and (2) a professional caregiver from the care facility (e.g., nurse, 
activity director, certified assistant). 
All participants must meet all the inclusion criteria and none of the exclusion criteria. 
In order to provide a broader understanding of the Memesto’s use in diverse populations of persons living 
with AD/ADRD, we plan on 50% of the participants living with AD/ADRD being non-White and anticipate 
20% being Latino. Additionally, approximately 67% of the participant cohort will be women and 33% will 
be men. 
5.1 
INCLUSION CRITERIA 
1. Age 18 years or older at time of informed consent. 
2. Diagnosis of AD/ADRD as confirmed by study partner. 
3. Significant agitation characterized by at least one of the following behaviors that are severe 
enough to warrant pharmacological treatment: 
a. Verbal aggression (e.g., screaming, cursing); 
b. Physical aggression (e.g., destroying objects, grabbing, fighting); or 
c. Non-aggressive physical behavior (e.g., restlessness, pacing). 
4. CGI-S score ≥ 4 at Screening. 
5. Availability of (1) a spouse, sibling, or adult child AND (2) a professional caregiver from the care 
facility (e.g., nurse, activity director, certified assistant) willing to serve as study partners who 
can: 
a. Provide study staff accurate information regarding the participant’s personal and health 
information, mood, behavior, medications, and device use throughout the course of the 
study; and 
b. Record personalized messages and/or help identify music for audio therapy and 
program the Memesto’s therapy schedule. 
6. Signed informed consent obtained from (a) the participant or the participant’s legally authorized 
representative (if the participant is incapable of providing consent for him or herself), and (b) 
both study partners. 
5.2 
EXCLUSION CRITERIA 

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1. Inability to demonstrate compliance using the Memesto during the screening/training phase as 
evidenced by continued inability to schedule audio therapies within the application or 
inconsistent use (i.e., wearing) of the device as reported by study partner(s). 
5.3 
LIFESTYLE CONSIDERATIONS 
N/A 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in this study but do not proceed 
into the 10-week treatment phase. 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of meeting 
the exclusionary criteria may be rescreened. Rescreened participants will be assigned the same participant 
number as for the initial screening. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
Working with dementia unit directors, nurse managers, and activity directors at given residential care 
facility (i.e., formal study partner), family caregivers of persons with AD/ADRD and agitation will be 
identified and approached. The recruitment process involves a presentation about AD/ADRD and 
agitation, the need for the study, and what is involved in study participation. Written materials on 
dementia, agitation, and the Memesto will be made available. Study staff will then engage individually 
with each potential participant and family caregiver (i.e., informal study partner) who expresses interest 
in the study. All study procedures, risks and benefits, and the option to withdraw without penalty will be 
reviewed. 
Since this study is most likely to involve persons with moderate to severe dementia based on who typically 
have agitation with AD/ADRD in residential care facilities, most if not all participants will likely not have 
capacity to consent at the time of enrollment. Therefore, the power of attorney/authorized decision 
maker for the person living with AD/ADRD will be approached to provide consent for participation. After 
all parties have had as much time as needed to consider participation and all their questions answered, 
signed consents will be obtained with copies provided for their records.  
Study retention is supported by having a two-week training period built into the protocol. Also, close 
follow-up with the participant triad (person with AD/ADRD, family caregiver, professional caregiver) will 
be maintained by study staff. 
6 
STUDY INTERVENTION 
6.1 
STUDY INTERVENTION ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
Study intervention is 10-week use of the Memesto. The device exists in the form of an off-the-shelf, 
commercially available wi-fi enabled cellular phone coupled with a mobile operating system- and web-

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based application that enables recording and loading of audio media via the internet. The device will not 
be used as a cellular phone nor will it have cellular phone service. 
A neck lanyard with waterproof case will be provided with the device to facilitate use and accountability. 
6.1.2 ADMINISTRATION AND/OR DOSING 
Participants will be provided the Memesto at Screening for a two-week screening/training phase of use. 
Participants successfully completing this phase will continue use for 10 weeks of bi-weekly data collection.  
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
All study staff responsible for providing device training will be instructed on device use by Edgewater 
Safety Systems. Training will be documented and filed in the Investigator Site File (ISF). Further, 
representatives from Edgewater Safety Systems will be available throughout the duration of the study for 
device- or application-related questions or troubleshooting. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
N/A 
6.4 
STUDY INTERVENTION ADHERENCE 
Adherence to study treatment will be recorded in the form of a device accountability log completed by 
the formal study partner in-between study visits as well as review of scheduled voice/music therapies 
within the Memesto application. 
6.5 
CONCOMITANT THERAPY 
Use of prescription and non-prescription medications will be reviewed at each study visit and documented 
in the relevant electronic case report form (eCRF). 
6.5.1 RESCUE THERAPY 
N/A 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
All participants who permanently discontinue study treatment and do not agree to continued data 
collection through study completion (Week 10), for whatever reason, will be withdrawn from the study. 
Refer to Section 0, Schedule of Activities for data to be collected at the time of discontinuation (i.e., ET). 

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7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. The PI may 
discontinue a participant from the study for any of the following reasons: 
 
• 
Significant study intervention non-compliance; 
• 
Inability to replace a study partner should a study partner’s participation end early; 
• 
Lost-to-follow up; unable to contact participant (see Section 7.3, Lost to Follow-Up); 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up 
study data would not be in the best interest of the participant; or 
• 
The study is cancelled. 
 
The reason for participant discontinuation or withdrawal from the study will be documented in the 
relevant eCRF.  
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she repeatedly fails to participate in scheduled 
visits and is unable to be contacted by study staff after at least 3 documented attempts.  
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
8.1.1 NEUROPSCYHIATRIC INVENTORY 
The Neuropsychiatric Inventory (NPI) is a widely used, well-established instrument that assesses 
behavioral changes in neurologic illnesses through a structured interview with a caregiver.10 Behavioral 
domains are scored based on frequency and severity. The nursing home version of the inventory will be 
utilized in this study and administered (in-person or via telephone) to both the formal and informal study 
partners by qualified and trained study staff. Only the agitation domain of the NPI will be administered as 
part of this study. 
8.1.2 CLINICAL GLOBAL IMPRESSIONS SCALE - SEVERITY 
The Clinical Global Impressions Scale – Severity (CGI-S) is a brief observer-rated instrument that 
establishes a global rating of illness severity.11 The scale responses range from 1 (normal) to 7 (amongst 
the most extremely ill). The CGI-S in relation to agitation will be administered (in-person or via telephone) 
to both the formal and informal study partners by qualified and trained study staff. 
8.2 
SAFETY ASSESSMENTS 
Adverse event (AE) reporting will begin at Screening and will continue until the end of the study. The 
occurrence of AEs will be sought by non-directive questioning of the participant and/or study partners 
during each study visit. AEs may also be detected when volunteered through unsolicited contact by the 
participant and/or study partners between study visits. Refer to Section 8.3, Adverse Events and Serious 

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Adverse Events and Section 8.4, Unanticipated Problems for further details regarding collection, 
documentation, and reporting requirements.  
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
This protocol uses the National Institute on Aging (NIA) guidelines for reviewing and reporting adverse 
events (AEs) and serious adverse events (SAEs). Definitions are from the January 2007 Office of Human 
Research Protections (OHRP) Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects 
or Others and Adverse Events: OHRP Guidance.12 
8.3.1 DEFINITION OF ADVERSE EVENTS 
An AE is defined as any untoward or unfavorable medical occurrence in a human study participant, 
including any abnormal sign (e.g., abnormal physical exam or laboratory finding), symptom, or disease, 
temporally associated with the participants’ involvement in the research, whether or not considered 
related to participation in the research.  
Given this is a minimal risk study, only AEs associated with use of the Memesto device or with study-
related questioning will be recorded. 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
An SAE is defined as any AE that: 
• 
Results in death 
• 
Is life threatening, or places the participant at immediate risk of death from the event as it 
occurred 
• 
Requires or prolongs hospitalization 
• 
Causes persistent or significant disability or incapacity 
• 
Results in congenital anomalies or birth defects 
• 
Is another condition which investigators judge to represent significant hazards 
Hospitalizations/emergency room visits for worsening of agitation associated with the underlying 
AD/ADRD will not be considered SAEs.  
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
All recorded AEs will have their severity classified by an appropriately-trained clinician as follows:  
• 
Mild – Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing 
no loss of time from normal activities. Symptoms do not require therapy or a medical evaluation; 
signs and symptoms are transient. 
• 
Moderate – Events introduce a low level of inconvenience or concern to the participant and may 
interfere with daily activities, but are usually improved by simple therapeutic measures; moderate 
experiences may cause some interference with functioning. 
• 
Severe – Events interrupt the participant’s normal daily activities and generally require systemic 
drug therapy or other treatment; they are usually incapacitating. 

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Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed.  
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All recorded AEs will have their relationship to study procedures, including the intervention, assessed by 
an appropriately-trained clinician based on temporal relationship and his/her clinical judgment. The 
degree of certainty about causality will be graded using the following categories:  
• 
Definitely Related – The AE is clearly related to the investigational agent/procedure – i.e., an 
event that follows a reasonable temporal sequence from administration of the study intervention, 
follows a known or expected response pattern to the suspected intervention, that is confirmed 
by improvement on stopping and reappearance of the event on repeated exposure and that could 
not be reasonably explained by the known characteristics of the subject’s clinical state. 
• 
Possibly Related – An adverse event that follows a reasonable temporal sequence from 
administration of the study intervention follows a known or expected response pattern to the 
suspected intervention, but that could readily have been produced by a number of other factors.  
• 
Not Related – The adverse event is clearly not related to the investigational agent/procedure - 
i.e. another cause of the event is most plausible; and/or a clinically plausible temporal sequence 
is inconsistent with the onset of the event and the study intervention and/or a causal relationship 
is considered biologically implausible. 
8.3.3.3 EXPECTEDNESS  
All recorded AEs will be assessed by an appropriately-trained clinician as to whether they were expected 
to occur or unexpected as follows: 
• 
Unexpected – Nature or severity of the event is not consistent with information about the 
condition under study or intervention in the protocol or consent form. 
• 
Expected – Event is known to be associated with the intervention or condition under study. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an event may come to the attention of study staff during study visits or through 
unsolicited reporting by the participant and/or study partner outside of a study visit. All AEs occurring 
while on study, not otherwise precluded per the protocol, will be documented appropriately regardless 
of relationship. Events will be followed for outcome information until resolution or stabilization. 
8.3.5 ADVERSE EVENT REPORTING  
All events will be recorded on the relevant eCRF. Information to be collected includes event description, 
time of onset, clinician’s assessment of severity, relationship to study procedures, whether it was 
expected, and time of resolution/stabilization of the event. This study will utilize the NIA-approved flow 
sheets and forms to identify and track events. 
Events will be assessed to determine if they meet criteria for an AE, SAE, or unanticipated problem (UP).  
Events meeting criteria for an AE will be reported, as necessary, in accordance with IRB and funding agency 
requirements. Further details regarding AE reporting are outlined in the Data and Safety Monitoring Plan 
(DSMP). 

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8.3.6 SERIOUS ADVERSE EVENT REPORTING  
Events meeting criteria for an SAE will be assessed by the PI or delegated designee to determine if the 
event is unexpected, related to study procedures, or places participants or others at a greater risk of 
physical or psychological harm than was previously known or recognized. SAEs that are unanticipated in 
nature and deemed related to study procedures will be reported to the sponsor within 48 hours of 
knowledge of the SAE and to the IRB, when appropriate, in accordance with IRB requirements. Further 
details regarding SAE reporting are outlined in the DSMP. 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
8.3.9 REPORTING OF PREGNANCY  
N/A 
8.4 
UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
As defined by DHHS 45 CFR part 46, an unanticipated problem (UP) is any incident, experience, or outcome 
that meets all of the following criteria: 
• 
Unexpected, in terms of nature, severity, or frequency, given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the study population; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
8.4.2  UNANTICIPATED PROBLEMS REPORTING  
Events meeting criteria for a UP will be reported to the sponsor within 48 hours of knowledge of the UP 
and to the IRB, when appropriate, in accordance with IRB requirements. Further details regarding UP 
reporting are outlined in the DSMP. 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
9 
STATISTICAL CONSIDERATIONS  

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9.1 
STATISTICAL HYPOTHESES 
The primary hypothesis is that treatment with Memesto will result in a reduction in the average 10-week 
NPI agitation domain score compared to the average baseline score. The secondary hypothesis is that 
treatment with Memesto will result in a reduction in the average 10-week CGI-S score compared to the 
average baseline score. 
Alternatively, the null hypotheses for both primary and secondary endpoints is that no change will be 
observed. 
9.2 
SAMPLE SIZE DETERMINATION 
As a proof-of-concept study, no formal power calculation was utilized. 
9.3 
POPULATIONS FOR ANALYSES 
The population for treatment and safety analyses will be participants who consented and successfully 
completed a baseline visit after going through a two-week training on the use of Memesto.   
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
The general analytic approach is to compare outcome scores at 10 weeks of exposure to Memesto as 
compared to the baseline scores after the 2-week training period with Memesto. Missing data would be 
handled by the last observation carried forward method. 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
The pre-specified quantitative end point will be change from baseline in the NPI agitation domain score. 
The NPI agitation domain will be rated by each study partner (professional and family caregiver, 
respectively) for symptom frequency and severity. The domain score is a composite (frequency x severity) 
score of 1 to 12. 
The average 10-week NPI agitation domain score from the reports of the two study partners will be 
compared to the baseline average agitation score. A positive finding would be that at least half of the 
participants would have a 30% reduction in the agitation domain score. The NPI manual 
(http://npitest.net/faqs.html) suggests that a 30% decrease in scores is generally clinically meaningful.  
Therefore, a positive finding would be that at least half of the study participants would have a 30% 
improvement after 10 weeks of treatment. 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
A secondary endpoint will be a validated agitation measure (change in the average CGI-S score over the 
10-weeks of data collection). The CGI-S is measured based on a 7-point Likert scale. The number of persons 
with a CGI-S score showing improvement will be calculated, defined as achieving a final Week 10 score (or 
if missing last observation, carried forward score) of 3 or less. A clinically meaningful signal will be if 
improvement is noted on 30% of the participants. 

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9.4.4 SAFETY ANALYSES 
Safety outcomes will include adverse events as related to the device or with study procedures.  A table of 
safety outcomes by frequency will be generated, if applicable. 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Participant baseline demographic (such as age, gender, race/ethnicity) and health characteristics (such 
as baseline scores on agitation measures) will be summarized using numbers and percentages for 
categorical variables and by means, medians, standard deviations, and ranges for continuous variables. 
 
9.4.6 PLANNED INTERIM ANALYSES  
N/A 
9.4.7 SUB-GROUP ANALYSES 
N/A 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
N/A 
9.4.9 EXPLORATORY ANALYSES 
An exploratory analysis will be the number of participants with a change in psychotropic medications (i.e., 
decrease) at 10-weeks of Memesto treatment as compared to baseline.   
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
Written documentation of informed consent will be obtained from the participant (or power of 
attorney/authorized decision maker, when necessary) and both study partners prior to the start of the 
study. Informed consent forms and informational documents utilized in the conduct of this study will meet 
the requirements of 21 CFR 50, local regulations, ICH GCP guidelines, Health Insurance Portability and 
Accountability Act (HIPAA), and the IRB. All documents will be submitted and approved by the IRB prior 
to use; any revisions to the documents will be submitted and re-approved by the IRB prior to 
implementation. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 

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Since this study is most likely to involve persons with moderate to severe dementia based on who typically 
have agitation with AD/ADRD in residential care facilities, most if not all participants will likely not have 
capacity to consent at the time of enrollment. Therefore, the power of attorney/authorized decision 
maker for the person living with AD/ADRD will most often be approached to provide consent for 
participation.  
Before written consent is obtained, an appropriately trained and delegated study staff member will 
explain the purpose and requirements of the study, procedures involved, risks and benefits to 
participation, and the option to withdraw at any time without penalty. Ample opportunity will be given to 
consider study participation and to ask questions. After all parties have had as much time as needed to 
consider participation and all their questions answered, signed consents will be obtained with copies 
provided for their records.  
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. 
Circumstances that may warrant termination or suspension by the PI, sponsor, and/or funding agency 
include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance of study staff to the protocol (i.e., significant protocol violations) 
The study may resume once concerns about safety and protocol compliance are addressed, and satisfy 
the funding agency, sponsor, and IRB requirements. 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the PI, study staff, the sponsor, and 
funding agency. This confidentiality is extended to the data being collected as part of this study. Data that 
could be used to identify a specific participant will be held in strict confidence within the research team. 
No personally-identifiable information from the study will be released to any unauthorized third party 
without prior written approval of the sponsor/funding agency.  
All research activities will be conducted in as private a setting as possible. 
The authorized representatives of the sponsor or funding agency and representatives of the IRB may 
inspect all source documentation collected as part of this study. The study site will permit access to such 
records. 
The participant’s and study partners’ contact information will be securely stored for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure location for as long a 
period as dictated by IRB, institutional, and sponsor/funding agency requirements. 
Participants and their research data will be identified by a unique study identification number. The study 
data entry and study management systems used by the site will be secured and password protected.  
It is NIH policy that the results and accomplishments of the activities that it funds should be made available 
to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms used to 
share data will include proper plans and safeguards for the protection of privacy, confidentiality, and 
security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be 

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traceable to a specific study participant). Plans for archiving and long-term preservation of the data will 
be implemented, as appropriate.  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has 
issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical 
or other human subjects research funded wholly or in part by the federal government. Recipients of NIH 
funding for human subjects research are required to protect identifiable research information from forced 
disclosure per the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth 
in 45 CFR Part 75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered 
by this Policy are required to establish and maintain effective internal controls (e.g., policies and 
procedures) that provide reasonable assurance that the award is managed in compliance with Federal 
statutes, regulations, and the terms and conditions of award. It is the NIH policy that investigators and 
others who have access to research records will not disclose identifying information except when the 
participant consents or in certain instances when federal, state, or local law or regulation requires 
disclosure. NIH expects investigators to inform research participants of the protections and the limits to 
protections provided by a Certificate issued by this Policy. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
N/A 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator: 
Raj C. Shah, MD 
Institution: 
Rush Alzheimer’s Disease Center, Rush University Medical Center 
Address: 
1653 West Congress Parkway, Chicago, IL 60612 
Telephone: 
1-312-563-2902 (o); 1-630-217-9959 (c) 
Email: 
Raj_C_Shah@rush.edu  
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be under the direction of the PI. 
10.1.7 CLINICAL MONITORING 
N/A 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Quality control (QC) procedures will be implemented as follows: 
Informed Consent: Study staff will review both the documentation of the consenting process as well as 
the completed consent documents. This review will evaluate compliance with GCP, accuracy, and 
completeness.  Feedback will be provided to the study team to ensure proper consenting procedures are 
followed.  
Source Documents and the Electronic Data: Data will be initially captured on source documents (see 
Section 10.1.9, Data Handling and Record Keeping) and will ultimately be entered into the study 

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database. To ensure accuracy, study staff will compare a representative sample of source data against the 
database, targeting key data points in that review. 
Intervention Fidelity: Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
Protocol Deviations: Study staff will review protocol deviations on an ongoing basis and will implement 
corrective actions when the quantity or nature of deviations are deemed to be at a level of concern. 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection will be the responsibility of study staff under the supervision of the PI. The investigator 
will be responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data reported. 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data.  
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant consented/enrolled in the study.  Data recorded in the eCRF derived 
from source documents will be consistent with the data recorded on the source documents.  
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) will be entered into REDCap, a 21 CFR Part 11-compliant data capture system. Data will be entered 
directly from the source documents. 
10.1.9.2 STUDY RECORDS RETENTION  
Study documents will be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Council on Harmonisation (ICH) region and until there are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor/funding agency, if applicable. It is the responsibility of the 
sponsor/funding agency to inform the PI when these documents no longer need to be retained. 
10.1.10 
PROTOCOL DEVIATIONS   
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol or 
International Council on Harmonisation Good Clinical Practice (ICH GCP) requirements. The 
noncompliance may be either on the part of the participant, the PI, or study staff. As a result of deviations, 
corrective actions will be developed by the site and implemented promptly.  
It will be the responsibility of the PI to use continuous vigilance to identify and report deviations in 
accordance with all IRB and funding agency requirements. All deviations will be addressed in study source 
documents.  
10.1.11 
PUBLICATION AND DATA SHARING POLICY  

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This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
• 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access 
to the published results of NIH funded research. It requires scientists to submit final peer-
reviewed journal manuscripts that arise from NIH funds to the digital archive PubMed Central 
upon acceptance for publication. 
• 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-
Funded Clinical Trial Information and the Clinical Trials Registration and Results Information 
Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information 
from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to 
publish results in peer-reviewed journals. Data collected by Rush University will be accessible in a 
de-identified manner at the conclusion of the study, after the primary results are published in one 
or more peer-reviewed journals and otherwise as per NIH guidelines. In the meantime, data will 
be stored on secure Rush University servers and contact regarding data acquisition by interested 
parties can be made through ClinicalTrials.gov. Considerations for ensuring confidentiality of 
these shared data are described in Section 10.1.3, Confidentiality and Privacy. 
10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial. This study will be conducted in accordance with all IRB and NIA policies, 
procedures, and guidelines for the disclosure and management of conflicts of interest. 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AE 
Adverse Event 
AD/ADRD 
Alzheimer’s Disease and Alzheimer’s Disease Related Dementias 
CFR 
Code of Federal Regulations 
CGI-S 
Clinical Global Impression - Severity 
CoC 
Certificate of Confidentiality 
DHHS 
Department of Health and Human Services 
DSMP 
Data and Safety Monitoring Plan 
eCRF 
Electronic Case Report Form 
ET 
Early Termination 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HHS 
Health and Human Services 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
NIA 
National Institute on Aging 

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NIH  
National Institutes of Health 
NIHGPS 
National Institutes of Health Grants Policy Statement 
NPI 
Neuropsychiatric Inventory 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
SAE 
Serious Adverse Event 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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10.1002/alz.120668. Epub ahead of print. PMID: 32157811 
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2021 Nov 24. Available from: https://medlineplus.gov/genetics/condition/dementia-with-lewy-
bodies/. 
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behavior problems in persons with advanced dementia? Psychiatry Res. 2015 Jul 30; 228(1): 59-64. 
doi: 10.1016/j.psychres.2015.03.043. Epub 2015 Apr 14. PMID: 25933478; PMCID: PMC4451402.  
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https://www.nia.nih.gov/approved-concepts#disparities. 
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[Internet]. Washington, DC: The National Academies Press (US). 2016. Available from: 
https://doi.org/10.17226/23606. 
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https://www.hrw.org/report/2018/02/05/they-want-docile/how-nursing-homes-united-states-
overmedicate-people-dementia. 
9. U.S. Food and Drug Administration. Policy for device software functions and mobile medical 
applications: guidance for industry and Food and Drug Administration staff [Internet]. Silver Spring 
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Food 
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10. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric 
Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994 Dec; 44(12): 
2308-14. doi: 10.1212/wnl.44.12.2308. PMID: 7991117.  
11. Guy, W. ECDEU assessment manual for psychopharmacology, revised. Rockville (MD): U.S. Dept. of 
Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health 
Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division 
of Extramural Research Programs; 1976.  
12. U.S. Department of Health and Human Services. Reviewing and reporting unanticipated problems 
involving risks to subjects or others and adverse events: OHRP guidance [Internet]. Rockville (MD): 
Office 
for 
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Protections 
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2007 
Jan 
15. 
Available 
from: 

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https://www.hhs.gov/ohrp/regulations-and-policy/guidance/reviewing-unanticipated-
problems/index.html.