The Role of Palliative Care Interventions to Reduce Circadian Rhythm Disorders in Persons With Dementia: The Healthy Patterns Study
Phase: PHASE3
Conditions: Dementia, Alzheimer Disease, Circadian Rhythm Disorders, Circadian Rhythm Sleep Disorder, Insomnia, Hypersomnia, Cognitive Impairment, Cognitive Decline, Mild Cognitive Impairment, Frontotemporal Dementia, Neurocognitive Disorders, Vascular Dementia, Sleep Disorder, Memory Impairment
Sponsor: University of Pennsylvania

Official Title of the Study: The Role of Palliative Care Interventions to Reduce Circadian Rhythm 
Disorders in Persons With Dementia: The Healthy Patterns Study 
NCT Number: NCT03682185 
Date of the Document: November 2, 2020 
 

Page 1 of 23
Modiﬁcation
Basic Info
Conﬁrmation Number:
dbjiagia
Protocol Number:
825000
Created By:
HODGSON, NANCY A
Principal Investigator:
HODGSON, NANCY A
Protocol Title:
The Role of Palliative Care Interventions to Reduce Circadian Rhythm Disorders in Persons with Dementia
Healthy Patterns Study
Short Title:
Healthy Patterns Sleep Study
Protocol Description:
This Phase III efﬁcacy trial of the Healthy Patterns intervention, a home-based activity 
intervention, is designed to improve symptoms of circadian rhythm disorders (CRD) and quality 
of life (QOL) in home dwelling person with dementia. We will use a randomized two-group 
parallel design of 200 people with dementia and their caregivers assigned to intervention or 
attention control intervention. Outcomes include measures of QOL as well as actigraphic and 
proxy reported measures of CRDs
Submission Type:
Social and Biological Sciences
Application Type:
EXPEDITED Category 7 and Category 3
PennERA Protocol Status
Approved
Resubmission*
No
Are you submitting a Modiﬁcation to this protocol?*
Yes
Current Status of Study
Study Status
Currently in Progress
If study is currently in progress, please enter the following
Number of subjects enrolled at Penn since the study was initiated
170
Actual enrollment at participating centers
170
If study is closed to further enrollment, please enter the following
Number of subjects in therapy or intervention
0

Page 2 of 23
Number of subjects in long-term follow-up only
35
IRB Determination
If the change represents more than minimal risk to subjects, it must be reviewed and approved by the 
IRB at a convened meeting. For a modiﬁcation to be considered more than minimal risk, the proposed 
change would increase the risk of discomfort or decrease beneﬁt. The IRB must review and approve the 
proposed change at a convened meeting before the change can be implemented unless the change is 
necessary to eliminate an immediate hazard to the research participants. In the case of a change 
implemented to eliminate an immediate hazard to participants, the IRB will review the change to 
determine that it is consistent with ensuring the participant&prime;s continued welfare. Examples: 
Convened Board Increase in target enrollment for investigator initiated research or potential Phase I 
research Expanding inclusion or removing exclusion criteria where the new population may be at 
increased risk Revised risk information with active participants Minor risk revisions that may affect a 
subject&prime;s willingness to continue to participate Expedited Review Increase in target enrollment 
at Penn where overall enrollment target is not exceeded or potentially sponsored research Expanding 
inclusion or removing exclusion where the new population has the same expected risk as the previous, 
based on similarities of condition Revised risk information with subjects in long-term follow-up Minor 
risk revisions with no subjects enrolled to date 
Expedited Review
Modiﬁcation Summary
Please describe any required modiﬁcation to the protocol. If you are using this form to submit an 
exception or report a deviation, enter 'N/A' in the box below.
We are adding a questionnaire to our three-month follow-up calls with our participants. This 
questionnaire is called the University of Pittsburgh COVID Caregiving Questionnaire and is attached. It 
seeks to ask persons with dementia and their caregivers about their experiences with the COVID-19 
pandemic. We are also hoping to make the following personnel changes. Removing Personnel Remove 
Laurel Caffeé as Study Contact Adding Personnel Add Sarah Bujno as Study Contact o Department: 
602, Biobehavioral Health Sciences o Role: Research Project Manager o Email: sbujno@upenn.edu  o 
Address: Claire M. Fagin Hall 418 Curie Boulevard Philadelphia, PA 19104-4217 Add Yeji Hwang as 
Key Study Personnel o Department: School of Nursing o Role: Research Assistant o Email: 
yejih@nursing.upenn.edu  Add Fanghong Dong as Key Study Personnel o Department: School of 
Nursing o Role: Research Assistant o Email: dofa@nursing.upenn.edu
Risk / Beneﬁt
Does this amendment alter the Risk/Beneﬁt proﬁle of the study?
No
Change in Consent
Has there been a change in the consent documents?
No
If YES, please choose from the options below regarding re-consenting
Deviations
Are you reporting a deviation to this protocol?*
No

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Exceptions
Are you reporting an exception to this protocol?*
No

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Protocol Details
Resubmission*
Yes
Hospital Sites
Will any research activities and/or services be conducted at a Penn Medicine afﬁliated hospital site?
No
Study Personnel
Principal Investigator
Name:
HODGSON, NANCY A
Dept / School / Div:
602 - Biobehavioral and Health Sciences
Campus Address
Mail Code
Address:
418 Curie Blvd.
City State Zip:
Philadelphia PA 19104-4217
Phone:
215-898-8413
Fax:
-
Pager:
Email:
hodgsonn@nursing.upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
04/26/2019
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
Study Contacts
Name:
TALWAR, SONIA
Dept / School / Div:
602 - Biobehavioral and Health Sciences
Campus Address
Mail Code
4217
Address:
CLAIRE M. FAGAN NURSING 
418 CURIE BLVD 
City State Zip:
PHILADELPHIA PA 19104-4217
Phone:
Fax:
4217
Pager:
Email:
talwars@nursing.upenn.edu
HS Training Completed:
No
Training Expiration Date:
Name of course completed :

Page 5 of 23
Name:
BUJNO, SARAH J
Dept / School / Div:
602 - Biobehavioral and Health Sciences
Campus Address
Mail Code
6035454597
Address:
3859 MELON STREET 
APT 1 
City State Zip:
PHILADELPHIA PA 19104-0000
Phone:
603-545-4597
Fax:
Pager:
Email:
sbujno@upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
Other Investigator
Name:
PEREZ, GLORIA A
Dept / School / Div:
603 - Family and Community Health
Campus Address
Mail Code
4217
Address:
CLAIRE M. FAGAN NURSING 
418 CURIE BLVD 
City State Zip:
PHILADELPHIA PA 19104-4217
Phone:
602-410-5905
Fax:
-
Pager:
Email:
adrianag@nursing.upenn.edu
HS Training Completed:
Yes
Training Expiration Date:
01/13/2022
Name of course completed :
CITI Protection of Human Subjects Research Training - ORA
Responsible Org (Department/School/Division):
600 - School of Nursing
Key Study Personnel
Name:
PETROVSKY, DARINA
Department/School/Division:
Family and Community Health
HS Training Completed:
Yes
Training Expiration Date:
01/14/2019
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA

Page 6 of 23
Name:
NATHANSON, GRACE A
Department/School/Division:
DM-Geriatrics
HS Training Completed:
Yes
Training Expiration Date:
06/27/2018
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
RAJPARA, ANJALI
Department/School/Division:
Health System
HS Training Completed:
No
Training Expiration Date:
Name of course completed:
Name:
CONNELL, LASHAUNA M
Department/School/Division:
Nursing Ofﬁce of Diversity Affairs
HS Training Completed:
Yes
Training Expiration Date:
12/11/2020
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
DUBINER, BENJAMIN
Department/School/Division:
Health System
HS Training Completed:
No
Training Expiration Date:
Name of course completed:
Name:
MCPHILLIPS, MIRANDA V
Department/School/Division:
Biobehavioral and Health Sciences
HS Training Completed:
Yes
Training Expiration Date:
02/09/2018
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
PEREZ, GLORIA A
Department/School/Division:
Family and Community Health
HS Training Completed:
Yes
Training Expiration Date:
01/10/2019
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
HWANG, YEJI
Department/School/Division:
School of Nursing
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA

Page 7 of 23
Name:
BOATENG, AUGUSTINE C
Department/School/Division:
School of Nursing
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
FOLEY, KIERRA A
Department/School/Division:
School of Nursing
HS Training Completed:
Yes
Training Expiration Date:
11/17/2019
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
GOONERATNE, NALAKA
Department/School/Division:
DM-Geriatrics
HS Training Completed:
Yes
Training Expiration Date:
08/19/2019
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
RAMIREZ, KATIE A
Department/School/Division:
Biobehavioral and Health Sciences
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Name:
DONG, FANGHONG
Department/School/Division:
Biobehavioral and Health Sciences
HS Training Completed:
Yes
Training Expiration Date:
Name of course completed:
CITI Protection of Human Subjects Research Training - ORA
Disclosure of Signiﬁcant Financial Interests*
Does any person who is responsible for the design, conduct, or reporting of this research protocol have 
a FINANCIAL INTEREST?
No
Penn Intellectual Property*
To the best of the Principal Investigator's knowledge, does this protocol involve the testing, 
development or evaluation of a drug, device, product, or other type of intellectual property (IP) that is 
owned by or assigned to the University of Pennsylvania?
No
Certiﬁcation
I have reviewed the Financial Disclosure and Presumptively Prohibited Conﬂicts for Faculty 
Participating in Clinical Trials and the Financial Disclosure Policy for Research and Sponsored 
Projects  with all persons who are responsible for the design, conduct, or reporting of this research; and 
all required Disclosures have been attached to this application.
Yes

Page 8 of 23
Social and Biological Sciences
Study Instruments
Discuss the particulars of the research instruments, questionnaires and other evaluation instruments in 
detail. Provide validation documentation and or procedures to be used to validate instruments. For well 
know and generally accepted test instruments the detail here can be brief. More detail may be required 
for a novel or new instrument. For ethnographic studies identify any study instruments to be used (i.e. 
for deception studies) and describe in detail where, when and how the study will be conducted and who 
or what are the subjects of study. Note: For more information on how to conduct ethical and valid 
ethnographic research, follow the link For oral histories or interviews provide the general framework 
for questioning and means of data collection. If interviews or groups settings are to be audio taped or 
video taped describe in detail the conditions under which it will take place. Include a copy of any novel 
or new test instruments with the IRB submission. 
All measures to be used in the study are established indexes. No new or novel instruments will be used. 
Quality of life in persons with dementia will be assessed using two well established measures the QOL-
AD and the PHQ-9. The dementia-speciﬁc 13-item Quality of Life in Alzheimer's Disease scale reﬂects 
multiple dimensions (physical, social, emotional, and functional well-being) with each rated as 1=poor, 
2=fair, 3=good, or 4=excellent. A total score representing the sum of items ranging from 13 to 52 will 
be derived separately for persons with dementia and the family caregivers (CG). In addition, CG will be 
asked to complete the PHQ-9. Persons with dementia will be administered the MMSE. Other 
instruments include the MMSE, the Barthel Index,  Cognitive status will be measured at baseline using 
the Mini Mental State Exam (MMSE) Physical function will be measured at baseline using the Barthel 
Index Neuropsychiatric symptoms will measured using the Neuropsychiatric Inventory (NPI) Sleep 
disturbance will be assessed using the PROMIS Sleep Related Impairment index. Neuroendocrine 
activity in persons with dementia will be assessed using the biological signature of the HPA response 
via salivary cortisol. CG will be instructed to collect assays at the awakening challenge and at 3 
additional intervals (30 minutes after waking, mid day, and at bedtime one hour after dim light 
exposure) . Caregivers will be provided all materials and marked plastic bags to freeze samples until 
pick up by the trained data collector. Caregivers will be asked to collect saliva for 2 consecutive days 
prior to the ﬁrst study visit, and again after the last intervention visit. Sleep-wake activity will be 
measured using an actigraphy bracelet worn by the person with dementia. The Motionlogger actigraph, 
which is manufactured by AMI and utilize the same algorithm as used in earlier studies of community 
dwelling persons with dementia, will be placed on the non-dominant wrist at baselineand will be worn 
for consecutive 24 h-periods until removal at 1 month (T2) data collection. Actigraphs will be set to 
collect data in 60-second epochs via tri directional accelerometer using a validated algorhythm. The 
primary measure of interest will be number of minutes of wake after sleep onset (WASO). Other 
parameters that will also be subject to analysis include total sleep time (TST), day/night sleep ratio, and 
number of night awakening. There will NOT be any remove monitoring or data transfer with the 
actigraph through a wireless connection.
Group Modiﬁcations
Describe necessary changes that will or have been made to the study instruments for different groups.
None
Method for Assigning Subjects to Groups
Describe how subjects will be randomized to groups.
After completing all baseline measurement subjects will be randomly assigned to intervention or 
control conditions. The project manager will prepare sealed envelopes and enact randomization. These 
envelopes will indicate on the outside the sequential recruitment number. Inside will be the subjects 
group assignment, determined using a random number generator. The project manager will open the 
envelopes and contact respective interventionists within 48 hours of randomization. Maintaining 
blindness to group assignment is assured at baseline since randomization occurs only after completion 
of that visit. Randomization procedures will be the responsibility of the project manager, who will not 
disclose subject assignment to data collectors.
Administration of Surveys and/or Process
Describe the approximate time and frequency for administering surveys and/or evaluations. For surveys, 
questionnaires and evaluations presented to groups and in settings such as high schools, focus group 
sessions or community treatment centers explain how the process will be administered and who will 
oversee the process. For instance, discuss the potential issues of having teachers and other school 

Page 9 of 23
personnel administer instruments to minors who are students especially if the content is sensitive in 
nature. Describe the procedure for audio and videotaping individual interviews and/or focus groups and 
the storage of the tapes. For instance, if audio tape recording is to be used in a classroom setting, 
describe how this will be managed if individuals in the class are not participating in the study. Explain 
if the research involves the review of records (including public databases or registries) with identiﬁable 
private information. If so, describe the type of information gathered from the records and if identiﬁers 
will be collected and retained with the data after it is retrieved. Describe the kinds of identiﬁers to be 
obtained, (i.e. names, social security numbers) and how long the identiﬁers will be retained and 
justiﬁcation for use. 
Once eligibility is determined and consent is signed, dyads of persons with dementia and their 
caregivers will receive a baseline home interview (T1). Following the baseline interview, participants 
will be randomly assigned to experimental or attention-control group conditions. Experimental dyads 
will receive up to 8 contacts with a interventionist over 1-month. The attention-control group dyads will 
receive comparable attention in a structured program involving the same number and mix of in-home 
and telephone contact as the treatment group. All dyads will be retested at 1-month from baseline (T2) 
to evaluate proximal outcomes of neuropsychiatric symptoms, QOL, and sleep quality and at 4 months 
(T3) to evaluate sustained uptake and distal outcomes of QOL and other measures of satisfaction with 
the study procedures. Outcome measures will be assessed by interviewers masked to treatment 
assignment. In addition, participants will be asked about their experience with the COVID-19 pandemic 
(using the University of Pittsburgh COVID Caregiving Questionnaire) at T3. This data will be collected 
via telephone only. The only information collected will include their answers to the questions on the 
survey and their de-identiﬁed participant number.
Data Management
Describe how and who manages conﬁdential data, including how and where it will be stored and 
analyzed. For instance, describe if paper or electronic report forms will be used, how corrections to the 
report form will be made, how data will be entered into any database, and the person(s) responsible for 
creating and maintaining the research database. Describe the use of pseudonyms, code numbers and 
how listing of such identiﬁers will be kept separate from the research data. 
Written personal identifying information concerning study participants will to be kept to a minimum. A 
master list of study participants that includes the assigned ID#, the ﬁrst and last names, and any project-
necessary grouping designations (e.g., control vs. experimental group) maintained for tracking purposes 
is stored in password-protected administrative databases only on the PI's server and kept in locked ﬁling 
cabinets in her ofﬁce. Screening forms and interview cover sheets only include identifying information 
this is necessary. All of this information is conﬁdential and kept in a locked ﬁle cabinet separate from 
study data. Any information with subject identiﬁcation that is not needed must be shredded. Computer 
ﬁles used for the purpose of tracking study participants are set up with password protection. Access to 
these ﬁles is restricted to deﬁned key personnel.
Radiation Exposure*
Are research subjects receiving any radiation exposure (e.g. X-rays, CT, Fluoroscopy, DEXA, pQCT, 
FDG, Tc-99m, etc.) that they would not receive if they were not enrolled in this protocol?
No
Human Source Material*
Does this research include collection or use of human source material (i.e., human blood, blood 
products, tissues or body ﬂuids)?
Yes
CACTIS and CT Studies*
Does the research involve Center for Advanced Computed Tomography Imaging Services (CACTIS) 
and CT studies that research subjects would not receive if they were not part of this protocol?
No
CAMRIS and MRI Studies*
Does the research involve Center for Advanced Magnetic Resonance Imaging and Spectroscopy 
(CAMRIS) and MRI studies that research subjects would not receive if they were not part of this 
protocol?
No

Page 10 of 23
Cancer Related research not being conducted by an NCI cooperative group*
Does this protocol involve cancer-related studies in any of the following categories?
No
Medical Information Disclosure*
Does the research proposal involve the use and disclosure of research subject's medical information for 
research purposes?
No
CTRC Resources*
Does the research involve CTRC resources?
No
If the answer is YES, indicate which items is is provided with this submission:
Use of UPHS services*
Does your study require the use of University of Pennsylvania Health System (UPHS) services, tests or 
procedures*, whether considered routine care or strictly for research purposes?
No
Primary Focus*
Sociobehavioral (i.e. observational or interventional)
Protocol Interventions
x Sociobehavioral (i.e. cognitive or behavioral therapy)
Drug
Device - therapeutic
Device - diagnostic (assessing a device for sensitivity or speciﬁcity in disease diagnosis)
Surgical
Diagnostic test/procedure (research-related diagnostic test or procedure)
Obtaining human tissue for basic research or biospecimen bank
Survey instrument
None of the above
The following documents are currently attached to this item:
There are no documents attached for this item.
Sponsors
Business Administrator
none
Department budget code
000 - 000 - 0 - 000000 - 0000 - 0000 - 0000
Funding Sponsors
Name:
NATIONAL INSTITUTE OF NURSING RESEARCH/NIH/DHHS
Type:
UPENN Federal

Page 11 of 23
Funding sponsors billing address
If you have selected a commercial or industry sponsor, please provide the appropriate address and 
contact information for the Sponsor for the purposes of billing for IRB review fees (initial review, 
continuing review and convened modiﬁcation fees apply here). If the Sponsor is not industry/
commercial, this information is not necessary to provide with your application.
Funding sponsors gift
Is this research being funded by a philanthropic gift?
No
Regulatory Sponsor
IND Sponsor
none
000 - 000 - 0 - 000000 - 0000 - 0000 - 0000
Industry Sponsor
None
Project Funding*
Is this project funded by or associated with a grant or contract?
Yes
Selected Proposals
Proposal No
Title
10057075-01
The Role of Palliative Care Interventions to Reduce Circadian Rhythm Disorders in Persons with Deme
Sponsor Funding
Is this study funded by an industry sponsor?
No
Status of contract
The following documents are currently attached to this item:
There are no documents attached for this item.
Multi-Center Research
Penn as lead
1. Is this a multi-center study where Penn is serving as the Lead Site or the Penn PI is serving as the 
Lead Investigator?
No
Management of Information for Multi-Center Research
Penn irb of record
2. Is this a multi-center study where the Penn IRB will be asked to serve as the IRB of Record for other 
external study sites?
No
Other Sites
No other sites

Page 12 of 23
Protocol
Abstract
Over 5 million Americans have Alzheimer's disease or a related dementia, a progressive and fatal 
neurodegenerative condition, affecting close to 15 million family caregivers (CG). Circadian rhythm 
disorders (CRDs) occur in the majority of persons with dementia and include late afternoon/evening 
agitation and irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, 
and poor sleep efﬁciency. CRD symptoms pose a great burden to CG, and are the principal causes of 
distress, poor QOL, and institutionalization. Regulating the circadian system through the use of light 
and activity has been shown to alter core clock processes that drive CRD symptoms and suggests that a 
combination of cognitive, physical and sensory-based activities, delivered at strategic times, may be an 
effective mechanism through which to reduce CRD symptoms. To date, there are no trials linking the 
nature and timing of activities with key palliative and biobehavioral outcomes. We propose a deﬁnitive 
Phase III efﬁcacy trial of the Healthy Patterns intervention, a home-based activity intervention designed 
to improve CRDs and QOL that builds on our pilot work. We will use a randomized two-group parallel 
design of 200 people with dementia and their CGs (dyads) assigned to the Healthy Patterns intervention 
or a control intervention of equivalent in-home attention and social contact. The success of the 
intervention will be determined by its impact on palliative outcomes including measures of QOL as 
well as actigraphic and proxy reported measures of CRD symptoms. CG outcomes of interest will be 
burden, subjective sleep quality, and QOL.
Objectives
Overall objectives
We propose a deﬁnitive Phase III efﬁcacy trial of the Healthy Patterns intervention, designed to improve 
sleep disturbance symptoms and QOL, that systematically builds on our pilot work demonstrating 
feasibility, safety and potential beneﬁts. We will use a randomized, two-group, parallel design of 200 
persons with dementia (PWD) and their family caregivers (dyads) assigned to the Healthy Patterns 
intervention or an attention control intervention of equivalent in-home attention and social contact. 
Speciﬁc components of this brief, one-month, eight session, home-based intervention include: 1) 
assessing PWD health/functional status and preferences/interests; 2) educating caregivers on 
environmental cues to promote activity and sleep; and 3) training of CG in using timed morning, 
afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes 
of interest are QOL, and indices of sleep as measured by objective and subjective indictors including 
actigraphy, subjective sleep quality, and assessment of neuropsychiatric symptoms. Caregiver outcomes 
of interest are QOL, burden, conﬁdence using activities, and sleep disruption. The speciﬁc aims for this 
study are to test: 1. The immediate (at 1 month) and sustained (at 4 months) effect of the Healthy 
Patterns activity intervention on PWD quality of life and CRD symptoms. Hypothesis 1a. Compared to 
control group participants, PWD receiving the intervention will demonstrate quality of life, total sleep 
time, nocturnal wake after sleep onset, day/night sleep ratio, and neuropsychiatric symptoms at 1 
month. Hypothesis 1b. Compared to control group participants, PWD subjects receiving the 
intervention will demonstrate quality of life, total sleep time, and neuropsychiatric symptoms at 4 
months. 2. The immediate (1 month) and sustained (4 months) effect of the Health Patterns activity 
intervention on caregiver outcomes. Hypothesis 2a. Compared to control group participants, caregivers 
who have received the intervention training will demonstrate quality of life, burden, conﬁdence in using 
activities, and sleep disruption at 1 month. Hypothesis 2b. Compared to control group participants, 
caregivers who have received the intervention training will demonstrate quality of life, burden, 
conﬁdence in using activities, and sleep disruption at 4 months. 3. The mediating effect of 
neuroendocrine activity on changes in CRD symptoms. Hypothesis 3. CRD symptoms will be mediated 
by changes in diurnal cortisol from baseline to 1 month.
Primary outcome variable(s)
Symptoms of sleep disruption as measued by actigraphy Neuropsychiatric symptoms

Page 13 of 23
Secondary outcome variable(s)
Quality of life
Background
Circadian rhythm disorders (CRDs) are a speciﬁc cluster of neuropsychiatric symptoms that occur in 
over 60 percent of patients with dementia and are associated with increased morbidity and mortality and 
poor quality of life.(1,2) CRD symptoms include late afternoon/evening agitation (e.g., sundowning) 
and irregular sleep-wake rhythms such as daytime hypersomnia, frequent night wakenings and poor 
sleep efﬁciency (3,4) CRD symptoms place a tremendous burden on family caregivers, and are the 
leading causes of distress, poor quality of life (QOL), and institutionalization in this growing 
population.(5) Most nonpharmacologic trials for CRD symptoms to date have focused on the 
administration of artiﬁcial indoor light because bright light is the strongest entraining agent for the 
circadian clock.. While these studies have demonstrated modest improvements in CRD symptoms in 
otherwise healthy adults(6), they are poorly tolerated in persons with dementia (PWD) (7). Scheduled 
activity for PWD is shown to be important in reducing neuropsychiatric behaviors and improving QOL 
but its optimal therapeutic use including the timing and structure of various types of activities remains 
unknown.. A growing body of research supports the importance of activity-based interventions as a 
palliative approach to reduce the frequency and intensity of CRD symptoms, enhance personhood and 
dignity, and improve QOL (8). To date, there are no trials linking the nature and timing of activities 
with key palliative and biobehavioral outcomes. Scheduling activities based on shifting diurnal patterns 
across the day such as using cognitively stimulating activities in the mid-morning hours, physically 
stimulating activities in the afternoon hours and relaxing activities in the evening hours may help to 
reduce CRD symptoms. In this R01 application we describe a palliative approach that will address these 
gaps and systematically expand upon our pilot ﬁndings. We plan to test the efﬁcacy of a timed and 
planned activity intervention (Healthy Patterns) designed to improve CRDs symptoms and QOL, and to 
determine the underlying mechanisms by which the intervention achieves its beneﬁts. 1 Ancoli-Israel S, 
Klauber MR, Jones DW, Kripke DF, Martin J, Mason W, Pat-Horenczyk R, Fell R. (1997). Variations in 
circadian rhythms of activity, sleep, and light exposure related to dementia in nursing-home 
patients.Sleep. Jan; 20(1):18-23. 2 Peters ME, Schwartz S, Han D, Rabins PV, Steinberg M, Tschanz 
JT, Lyketsos CG. (2015) Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's 
dementia and death: The Cache County Dementia Progression Study. American Journal of Psychiatry. 
Jan 13:appiajp201414040480. 3 Zee, P.C., Vitiello, M. (2009). Circadian Rhythm Sleep Disorder: 
Irregular sleep wake rhythm type. Sleep Med Clin. 4(2): 213218. 4 Sack RL, Auckley D, Auger RR, 
Carskadon MA, Wright KP Jr, Vitiello MV, Zhdanova IV (2007) Circadian rhythm sleep disorders: part 
II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder, and irregular 
sleep-wake rhythm. An American Academy of Sleep Medicine review. Sleep. 30(11):1484-501. 5 Rose 
KM, Beck C, Tsai PF, Liem PH, Davila DG, Kleban M, Gooneratne NS, Kalra G, Richards KC.(2011). 
Sleep disturbances and nocturnal agitation behaviors in older adults with dementia. Sleep.Jun 1;34
(6):779-86. 6 Mishima, K., Okawa, M., Hozumi, S., Hishikawa, Y. (2000). Supplemental administration 
of artiﬁcialbright light and melatonin as potent treatment for disorganized circadian rest-activity and 
dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly 
persons.Chronobiology International 17(3);419-432. 7 Riemersma-van der Lek RF, Swaab DF, Twisk J, 
Hol EM, Hoogendijk WJ, Van Someren EJ.(2008).Effect of bright light and melatonin on cognitive and 
noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 
;299 (22): 264255. 8 Gitlin, L.N., Hodgson, N.A., & Choi, S. (2016, In press). Home-based 
interventions targeting persons with dementia: What is the evidence and where do we go from here?
Study Design
Phase*
Phase III
Design
We propose a prospective, single blind, two group, randomized trial to test whether the Healthy Patterns 
intervention improves symptoms of sleep (CRD symptoms) and QOL compared to an attention control 
condition and to investigate the mechanisms by which CRD symptoms are inﬂuenced by the 
intervention.

Page 14 of 23
Study duration
The study is estimated to begin in June 2016 and end in May 2021. Each participant will be enrolled in 
the study for 4 months.
Resources necessary for human research protection
Describe research staff and justify that the staff are adequate in number and qualiﬁcations to conduct 
the research. Describe how you will ensure that all staff assisting with the research are adequately 
informed about the protocol and their research related duties. Please allow adequate time for the 
researchers to conduct and complete the research. Please conﬁrm that there are adequate facilities for 
the research.
Characteristics of the Study Population
Target population
Participants will be 200 male and female individuals 60 years of age or older who have been diagnosed 
with probable dementia (PWD) and their primary caregiver (CG). All will live in the Philadelphia, PA, 
metropolitan area. We estimate that 51% of participants will be women and approximately one ﬁfth will 
be African-American.
Subjects enrolled by Penn Researchers
200
Subjects enrolled by Collaborating Researchers
0
Accrual
Our primary recruitment strategy involves identifying potential study participants from three possible 
sources: 1) A subject registry, which contains names of over 1000 individuals with dementia and their 
caregivers who participated in the study teams previous studies and have indicated a willingness to be 
contacted for future studies via Penn Seek; 2) the Penn Memory Center, and 3) mailings to families 
through over 50 community-based programs and clinical services in the Philadelphia region serving 
cognitively frail individuals and with whom the study team has a recruitment partnership, 4) utilization 
of social media, for example, Facebook and Twitter, and 5) iConnect to increase low recruitment 
numbers.
Key inclusion criteria
Inclusion criteria for PWD: (1) be over age 60; (2) English speaking; (3) be able to tolerate wrist 
actigraphy; (4) diagnosed with dementia using standard assessments and diagnostic criteria; (5) has CG 
reporting the presence of CRD symptoms (e.g. symptoms on). If the PWD is on any of four classes of 
psychotropic medications (antidepressant, benzodiazepines, antipsychotic, or anti-convulsant) or an 
anti-dementia medication (memantine or a cholinesterase inhibitor), we will require that he/she have 
been on a stable dose for 90 days prior to enrollment (typical time frame in clinical trials) to minimize 
possible confounding effects of concomitant medications
Key exclusion criteria
Exclusion criteria for PWD: (1) deemed to be in a crisis/unsafe situation at baseline, (2) reported 
planned transition to another residential or care setting in less than 6 months, (3) at end-stage disease 
(deﬁned as bed-bound and non-communicative, or on hospice at baseline), (4) currently enrolled in a 
interventional clinical trial for dementia or associated symptoms (5) regular use of medications with 
substantial known effects on the measurement of HPA activity (e.g. corticosteroids, interferons, beta-
blockers, cytotoxic chemotherapy); major surgery in the past 3 months; history of major psychiatric 
and/or personality disorder; history of heavy cigarette smoking (e.g. than 50 pack years); loss of a loved 
one in the past 3 months. (6) conditions known to affect measurement of circadian rhythm such as use 
of sedatives/ hypnotics, Huntingtons disease, Cushings disease, Addisons disease, normal pressure 
hydrocephalus, Parkinsons disease, advanced heart failure (New York Heart Stage 3-4), morbid obesity 
(BMI 35)

Page 15 of 23
Vulnerable Populations
Children Form
Pregnant women (if the study procedures may affect the condition of the pregnant woman or 
fetus) Form
Fetuses and/or Neonates Form
Prisoners Form
Other
x None of the above populations are included in the research study
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Populations vulnerable to undue inﬂuence or coercion
Primary participants and their study partners will receive an explicit assessment of capacity consisting 
of questions related to their understanding of the purpose of the study, the beneﬁts, the risks of the 
study, and if they are able to withdraw at any time. Due to the progressive nature of dementia and 
Alzheimer's disease, it is not expected that participants will regain capacity for informed consent over 
the course of the study if they lack capacity at the initial visit. It's possible that participants may lose 
consent capacity. At the beginning of each followup visit, the study team will remind the primary 
participant and study partner/caregiver of the goals of the study, the procedures, beneﬁts, risks, and that 
they are able to withdraw at any time. If consent capacity has changed, the consent designee will delay 
further data collection until the appropriate consent procedures have been done. The consent /assent 
procedures will follow the same steps as described below (In CONSENT SECTION) and the LAR will 
be asked to consent on behalf of the persons with dementia.
Subject recruitment
Our primary recruitment strategy involves identifying potential study participants from three possible 
sources: 1) A subject registry, which contains names of over 1000 individuals with dementia and their 
caregivers who participated in the study teams previous studies and have indicated a willingness to be 
contacted for future studies; 2) the Penn Memory Center, and 3) mailings to families through over 50 
community-based programs and clinical services in the Philadelphia region serving cognitively frail 
individuals including PennSeek and with whom the study team has a recruitment partnership, and 4) 
utilization of social media, for example, Facebook and Twitter, to increase low recruitment numbers. 
The ﬂyers/letters will have contact information for interested patients to contact the research staff. 
Flyers/letters will not refer to any disease or condition. Once an interested patient contacts the research 
staff, the research staff will call interested potential participants. Research staff will not obtain names of 
potential participants or their contact information until they have expressed a willingness to participate. 
Research staff will NOT mail or recruit patients who have opted out of research.The penndatastore 
excludes all patients that have chosen to make use of the opt out ﬂag for research recruitment so study 
team will not be able to access anyone who has opted out in the reports that are run.  Persons screened 
potentially eligible by telephone and willing to participate will then be scheduled to receive a home 
assessment and consent visit by Dr. Hodgson or study nurse within a 10 day window and who will 
conduct a structured and standard clinical examination to: 1) obtain history of cognitive function and 
cognitive decline, pattern of losses, behavioral changes, and current functioning; 2) substantiate 
dementia diagnosis and disease stage using standardized mental, general physical, and neurological 
examinations including the Clinical Dementia Rating Scale (CDR-0.5=very mild dementia; 
CDR-1=mild; CDR-2=moderate;CDR-3=severe), 3) obtain medical history, co-morbidities, and 
medication use; and 4) established presence of sleep disturbance.
Will the recruitment plan propose to use any Penn media services (communications, marketing, etc.) for 
outreach via social media avenues (examples include: Facebook, Twitter, blogging, texting, etc.) or does 
the study team plan to directly use social media to recruit for the research?
No
The following documents are currently attached to this item:

Page 16 of 23
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Subject compensation*
Will subjects be ﬁnancially compensated for their participation?
Yes
The following documents are currently attached to this item:
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If there is subject compensation, provide the schedule for compensation per study visit or session 
and total amount for entire participation, either as text or separate document
Subjects will receive $100 gift card at the completion of the study.
Study Procedures
Suicidal Ideation and Behavior
Does this research qualify as a clinical investigation that will utilize a test article (ie- drug or biological) 
which may carry a potential for central nervous system (CNS) effect(s)?
No
Procedures
The proposed study is a prospective, single blind, two group randomized trial to test whether a timed 
activity intervention improves symptoms of CRD compared to an attention control condition and to 
investigate the mechanisms by which CRDs are inﬂuenced by a timed activity intervention. Interested 
CGs who contact the research team will be screened for eligibility by telephone. Those initially eligible 
and willing, will receive a clinician assessment to obtain written informed consent and to rule out 
primary sleep disorders requiring specialty care. Once eligibility is determined dyads will receive a 
baseline home interview (T1). Following the baseline interview, participants will be randomly assigned 
to experimental or attention-control group conditions and will be contacted to be informed of their 
respective group assignment within 48 hours of randomization. Experimental dyads will receive up to 8 
contacts with a trained nurse interventionist over 1-month. The attention-control group dyads will 
receive comparable attention in a structured program involving the same number and mix of in-home 
and telephone contact as the treatment group. All dyads will be retested at 1-month from baseline (T2) 
to evaluate proximal outcomes of CRD symptoms, QoL, and CG sleep quality; and at 4 months to 
evaluate distal outcomes including QoL and other measures of satisfaction with the study procedures. 
Outcome measures will be assessed by interviewers masked to treatment assignment. Timed Activity 
Intervention Protocol: The timed activity group will involve 4 in-home visits in the mid morning and up 
to 4 brief telephone education sessions in the evening provided over 4 weeks The timed activity 
intervention provides activities delivered at speciﬁc times in the daily cycle; it is theory-based, its 
components have been tested in pilot work; and it is portable and replicable (e..g, protocols are 
manualized). As in the pilot studies, the in-home sessions are spaced weekly so that the participants can 
have the opportunity to practice the activity with the interventionist and then on their own. During each 
session the interventionist will reinforce activity use, review problem solving approaches and provide 
education. In Session 1 (home visit), the interventionist will explain the nature of the visit and assess 
the health and functional status and preferences/interests of the PwAD. The interventionist will then 
provide a suggested morning activity that will match the functional capabilities and interests of the 
PwAD i.e., based on repetitive motion (e.g., folding towels; sorting objects) and integrating multi-
sensory stimulation (photos of interest, objects pleasant to touch). Activities selected are simpliﬁed (1 to 
2 steps vs. multiple, complex steps), to minimize errors. In Session 2 a follow up phone call will be 
provided on the following evening to provide coaching in the morning activity. In Session 3 (home 
visit) the interventionist will review the implementation of morning activities and provide training 
materials for the evening relaxation protocol. The evening relaxation protocol is a brief 10-step 
reﬂexology intervention in which pressure is applied to each of the reﬂex points on the feet for 30 
seconds at a time for a total of 10 minutes. The protocol sequence is based on best practice guidelines. 
CG are provided a ﬂip book and a CD-ROM demonstrating the procedure and developed in our pilot 
stud. In Sessions 4-5 (one home visit and one phone call), the interventionist will review integration of 

Page 17 of 23
morning and evening activities into daily schedule and will provide written instruction on 
environmental cues to promote activity and sleep. Session 6 (home visit) is a ﬁnal review session and 
wrap up. Attention-Control Condition: The attention control group protocol will be delivered by trained 
RAs who will provide social attention, empathy and engagement similar in duration to that provided to 
the Timed Activity Intervention group. The length of time spent will be comparable to the length of 
time spent in the treatment arm, however this condition will contain no active elements beyond its 
nonspeciﬁc components, and no theoretical basis to support an effect on CRDs. The attention-control 
group will also involve 4 in-home visits in mid morning and up to 4 brief telephone education sessions 
in the evening. Each session is prescriptive and designed to maximize attention; yet, sessions will not 
involve any of the components of the timed planned activity (e.g. meaningful activities or relaxation). 
The attention control group will receive printed Alzheimers Association and NIH materials on home 
modiﬁcation, health promotion/ talking to your doctor and advanced care planning that coincide with 
session content. In Session 1 (home visit), the attention control interventionist will explain the nature of 
the visit and provides information on home safety. In Sessions 2-3 (one home visit and one phone call) 
the interventionist will work together with CG to answer questions about home safety and review health 
promotion material. In Sessions 4-5 (one home visit and one phone call), the interventionist will 
provide and review information on advanced care planning. Session 6 is a wrap up and review provided 
in the home. Time with the attention-control RA will be documented on a tracking sheet for each 
session and signed by the CG. Bi-monthly supervisory sessions with attention-control RAs will involve 
case presentations to track content of the attention-control sessions. In our previous studies, we found 
that the attention-control intervention is well received and that participants fully participated in 
sessions.  Treatment Implementation Monitoring: We have a well-deﬁned oversight plan of treatment 
implementation in both treatment and attention control group arms using the NIH Behavior Change 
Consortium. To enhance ﬁdelity, we incorporate their recommended strategies including use of 
treatment manuals, regular contact of PI with interventionists who present cases and discuss protocol 
issues, and on-going monitoring through direct observation of randomly selected sessions. We will 
address ﬁdelity through training (using intervention manuals and separate interventionists for each 
condition), delivery (reminder calls to CGs the night before the intervention sessions, records of home 
sessions by date and duration, receipt (checklist completed by study team regarding intervention 
engagement) and enactment (demonstration by CG to interventionists). Feedback will be provided to 
each interventionist throughout the study period. We will quantitatively evaluate treatment delivery, 
including dose, intensity; and treatment receipt. Biweekly supervisory sessions will be held with 
treatment interventionists and control group interventionists separately. All project staff will undergo 
extensive training before they have contact with subjects. We will audiotape 10% of treatment and 10% 
of control group sessions. Audiotapes will be reviewed by the research team using monitoring 
checklists that evaluate quality of the session. Table 1 (uploaded) describes the variables to be measured 
their respective testing occasions and sources.
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Deception
Does your project use deception?
No
International Research
Are you conducting research outside of the United States?
No
Analysis Plan
Sample Size: Sample size calculations are based on our ability to detect a medium effect size (d) of 
0.45; and d) a type I error rate of .05. Our projected effect size is justiﬁed for two reasons. First, clinical 
trials on symptoms of CRD use this effect size as an indication of clinical signiﬁcance. Second we were 
able to achieve large treatment effects across outcomes in the pilot phase- although we acknowledge 
that effect sizes may be overly optimistic in pilot studies. To attain 80% power for a two-sided 
comparison of the two treatment groups at 1 month will require 78 dyads per group (Aim 1 and 2). We 
plan to recruit an additional 22 per group or 100 dyads for a total of 200 allowing for 22% attrition by 4 
months (Aim 3). The statistical power for secondary analyses at 3 months will be the same as for the 
primary; 80% for a 0.45 effect size with 5% two-tailed tests.  Analysis of aims: First, we will conduct 

Page 18 of 23
descriptive analyses and univariate comparisons of the experimental and control intervention group 
conditions. We will use Chi-square, Wilcoxon rank-sum tests, and independent groups t-tests as 
appropriate to identify any differences between experimental and control group participants at baseline. 
In addition to serving as a ﬁnal data quality check, these analyses will be used to characterize our study 
population, assess the success of randomization in balancing the two groups and determine the impact 
of any dropouts on group balance. Aim 1: to test the timed activity intervention on patient CRD 
symptoms and QOL. Our primary analysis will examine the effect of the timed intervention compared 
to the attention control condition based on "intention to treat" (ITT). Data from all dyads randomized to 
the experimental group will be part of analyses regardless of actual number of completed intervention 
sessions. We will test the normality assumption for the primary CRD outcome measure (WASO) and for 
the other dependent measures (TST, neuropsychiatric symptoms; QoL) by examining the distribution of 
residuals after standard parametric comparisons. If the residual distribution is markedly skewed, we will 
examine whether data transformations are sufﬁcient for improving the ﬁt of the data to the normality 
assumption. Aim 1: To analyze the effects of the timed intervention on our primary outcomes difference 
scores (T2 T1) will be calculated for each participant and these change scores will be analyzed as a 
function of the treatment group, with the baseline observation (T1) serving as a covariate. Other 
potential covariates measured at baseline (e.g., age, education) will also be evaluated as potential 
predictors of change in outcome, and included as additional covariates of the intervention effect as 
indicated.  Aim 2: To test the effect of the timed activity intervention on caregiver outcomes. For Aim 2, 
we follow the approach for Aim 1 by examining group differences in the baseline-adjusted change 
scores (T2-T1; T3-T1) for CG outcome measures of burden and intent to institutionalize. Aim 3: To test 
the mediating effect of patient HPA axis activity on symptoms of CRD. We will test mediation by 
modeling the measures of baseline-adjusted changes in CRD symptoms (WASO, TST, neuropsychiatric 
symptoms) in nested analytic models that either do or do not included the proposed mediator (T2 T1 
change in saliva cortisol). Using nested regression models, estimates will be obtained of 1) the effect of 
the intervention on baseline-adjusted change in cortisol, 2) the effect of the change in cortisol on 
baseline-adjusted change in WASO (or other outcomes), 3) the effect of the intervention on baseline-
adjusted WASO before adding change in cortisol to the model, and 4) the effect of the intervention on 
baseline-adjusted WASO after adding change in cortisol to the model. These path estimates are often 
referred to by the letters a, b, c, and c in the mediation literature70. The product of the a and b estimates 
(a*b) represents the mediated effect, and this will be tested for statistical signiﬁcance using the standard 
Sobel method or with bootstrapping techniques.The proportion of the total effect (c) that is explained by 
mediation (a*b) will also be calculated and tested for signiﬁcance. Mediation models for data from two-
wave randomized trials can provide substantially different results depending on whether change scores 
are used and whether baseline covariate adjustments are implemented. Our approach will capitalize on 
this recent methodological work and provide sensitive analyses that determine whether the interventions 
impact on 1-month change in CRD symptoms is partly due to its effect on 1-month change in cortisol 
secretion.
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Page 19 of 23
Data conﬁdentiality
x Paper-based records will be kept in a secure location and only be accessible to personnel involved 
in the study.
x Computer-based ﬁles will only be made available to personnel involved in the study through the 
use of access privileges and passwords.
x Prior to access to any study-related information, personnel will be required to sign statements 
agreeing to protect the security and conﬁdentiality of identiﬁable information.
x Wherever feasible, identiﬁers will be removed from study-related information.
A Certiﬁcate of Conﬁdentiality will be obtained, because the research could place the subject at 
risk of criminal or civil liability or cause damage to the subject's ﬁnancial standing, 
employability, or liability.
A waiver of documentation of consent is being requested, because the only link between the 
subject and the study would be the consent document and the primary risk is a breach of 
conﬁdentiality. (This is not an option for FDA-regulated research.)
Precautions are in place to ensure the data is secure by using passwords and encryption, because 
the research involves web-based surveys.
Audio and/or video recordings will be transcribed and then destroyed to eliminate audible 
identiﬁcation of subjects.
Subject Conﬁdentiality
All research information will be kept in locked cabinets, in secure locked ofﬁces at the School of 
Nursing. Access to identifying information will be limited to research staff assigned to the project. 
Subjects will be advised of the precautions we will take to preserve conﬁdentiality during the consent 
process. Data with identiﬁers will not be permitted outside of the PI ofﬁce space. All discussions 
between the research staff members will be held in a private area. Pre-coded data collection instruments 
will be prepared for use with study participants at each testing occasion. Identiﬁcation numbers to 
assure participant conﬁdentiality will be used. Only one master log of subject name, address and 
telephone number and study identiﬁcation assignment will be maintained. This log, in both hard copy 
and disk, will be stored in a locked ﬁling cabinet separate from other identifying information All de-
identiﬁed data abstracted from study tools will be entered into a password protected and encrypted 
internet-based data management system known as REDCap (Research Electronic Data Capture). We 
will store all paper-based records in the PI's secure ofﬁce space for 7 years, per requirements, and only 
de-identiﬁed data (without names or medical record numbers of patients enrolled) will be entered into 
REDCap system.
Sensitive Research Information*
Does this research involve collection of sensitive information about the subjects that should be excluded 
from the electronic medical record?
No
Subject Privacy
Privacy refers to the person's desire to control access of others to themselves. Privacy concerns people, 
whereas conﬁdentiality concerns data. Describe the strategies to protect privacy giving consideration to 
the following: The degree to which privacy can be expected in the proposed research and the safeguards 
that will be put into place to respect those boundaries. The methods used to identify and contact 
potential participants. The settings in which an individual will be interacting with an investigator. The 
privacy guidelines developed by relevant professions, professional associations and scholarly 
disciplines (e.g., psychiatry, genetic counseling, oral history, anthropology, psychology). 
We will only contact individuals who have given previous permission to be contacted for research, or 
who call or contact the research team to express interest in the study. Those individuals who express 
interest in the study will receive a telephone call to describe the study, and conduct a telephone screen. 
Once an individual is screened, a copy of the consent form will be mailed, and a home visit will be 
scheduled to conduct the consent and baseline visit.

Page 20 of 23
Data Disclosure
Will the data be disclosed to anyone who is not listed under Personnel?
No
Data Protection*
x Name
x Street address, city, county, precinct, zip code, and equivalent geocodes
All elements of dates (except year) for dates directly related to an individual and all ages over 89
x Telephone and fax number
Electronic mail addresses
Social security numbers
Medical record numbers
Health plan ID numbers
Account numbers
Certiﬁcate/license numbers
Vehicle identiﬁers and serial numbers, including license plate numbers
Device identiﬁers/serial numbers
Web addresses (URLs)
Internet IP addresses
Biometric identiﬁers, incl. ﬁnger and voice prints
Full face photographic images and any comparable images
Any other unique identifying number, characteristic, or code
None
Does your research request both a waiver of HIPAA authorization for collection of patient information 
and involve providing Protected Health Information ("PHI") that is classiﬁed as a "limited data set" 
(city/town/state/zip code, dates except year, ages less than 90 or aggregate report for over 90) to a 
recipient outside of the University of Pennsylvania covered entity?
No
Tissue Specimens Obtained as Part of Research*
Are Tissue Specimens being obtained for research?
No
Tissue Specimens - Collected during regular care*
Will tissue specimens be collected during regulator clinical care (for treatment or diagnosis)?
No
Tissue Specimens - otherwise discarded*
Would specimens otherwise be discarded?
No
Tissue Specimens - publicly available*
Will tissue specimens be publicly available?
No
Tissue Specimens - Collected as part of research protocol*
Will tissue specimens be collected as part of the research protocol?
No
Tissue Specimens - Banking of blood, tissue etc. for future use*
Does research involve banking of blood, tissue, etc. for future use?
No

Page 21 of 23
Genetic testing
If genetic testing is involved, describe the nature of the tests, including if the testing is predicative or 
exploratory in nature. If predictive, please describe plan for disclosing results to subjects and provision 
of genetic counseling. Describe how subject conﬁdentiality will be protected Note: If no genetic testing 
is to be obtained, write: "Not applicable."
Not applicable
Consent
1. Consent Process
Overview
Two groups of individuals will be participants in this research study i.e. primary participants--Persons 
with Dementia (PWD), their informal caregivers (CG). We will recruit participants through ﬂyers. The 
ﬂyers will have contact information for interested patients to contact the research staff. The research 
staff will call interested potential participants. Research staff will not obtain names of potential 
participants or their contact information until they have expressed a willingness to participate  
Enrollment involves a 2-step screening process; an initial telephone screen with CGs followed by a 
clinical home assessment to conﬁrm PWD diagnosis, and inclusion criteria.  TELEPHONE 
SCREENING ASSENT: First, CGs contacting the research team are screened to determine initial 
potential eligibility using a 10 minute telephone screen tested in our pilot phase. Also, CGs will be 
asked about symptoms of CRD. The presence of one or more symptoms occurring in the PWD several 
times a week over the past month will be used as the cut off for potential eligibility. These criteria will 
maximize the number of individuals who are eligible in the clinical home screening stage. Assent for 
telephone screen (based on an IRB approved telephone screening form and interviewer script) will be 
obtained from PWD during the initial phone screen by a trained study coordinator or research assistant. 
If PWDs cognitive impairment prevents him/her from accurately recounting the purpose of the screen 
immediately following the description, the interviewer will ask to speak with the legal authorized 
representative (LAR), usually the CG, to obtain proxy phone screening assent. PWD and CGs will be 
informed that their participation in the telephone interview is conﬁdential and completely voluntary. 
The objectives, procedures, and a clear statement explaining risks and beneﬁts of this study will be 
presented at the telephone screen (see uploaded telephone screen). WRITTEN CONSENT: CGs 
screened potentially eligible by telephone and willing to participate will then be scheduled to receive a 
home assessment and consent visit by Dr. Hodgson or study nurse within a 10 day window and who 
will conduct a structured and standard clinical examination to: 1) obtain history of cognitive function 
and cognitive decline, pattern of losses, behavioral changes, and current functioning; 2) substantiate 
dementia diagnosis and disease stage using standardized mental, general physical, and neurological 
examinations including the Clinical Dementia Rating Scale (CDR-0.5=very mild dementia; 
CDR-1=mild; CDR-2=moderate;CDR-3=severe), 3) obtain medical history, co-morbidities, and 
medication use; and 4) establish presence of CRD. We will mail consent forms out to PWD and CGs 
immediately following a positive telephone screen so they have some time to review the form prior to 
the in-person written consent procedures. Written consent will be obtained for both the PWD and their 
CG at the beginning of the in-home visit. The consent form, written in large print, will assure 
participants that their participation is voluntary. The consent will explain to them in laymans terms that 
they will wear an activity monitoring device on their wrist. The consent form will inform them that we 
will be collecting a small amount of saliva and ask them to complete a brief questionnaires to provide 
information about their medical conditions. The consent form will also inform them that they will be 
randomly assigned to one of two groups. It will inform them of all aspects of the study and their right to 
withdraw at any time.  We will follow similar procedures as used in the pilot study for the consenting 
process Every reasonable effort will be made to ensure that participants with sensory deﬁcits have 
access to any and all medical devices and aides (e.g. reading glasses, hearing aides with functioning 
battery) during the consent procedure and during study visits. For those with language deﬁcits, every 
reasonable attempt will be made ensure adequate communication. The consent designee will have the 
discretion to terminate the interview if he/she believes that communication is too impaired to ensure 
proper consent procedures. If the PWD is too impaired to provide consent, proxy consent will be 
obtained from the legally authorized representative (LAR), and oral assent will be obtained from the 
PWD. PWD and their CGs will receive an explicit assessment of capacity and the consent procedure 

Page 22 of 23
will be documented by the study's consent designee. Dr. Hodgson will train and very closely supervise 
the study team in conducting the consent procedures and capacity assessment and ensure that all ethical 
procedures are followed and are documented. She has extensive experience performing the consent 
procedures in vulnerable participants who suffer from cognitive impairment. For primary participants 
and caregiver, who may be at risk for diminished decision making capacity, consent designees will 
conduct an explicit assessment of capacity to consent.
Children and Adolescents
N/A
Adult Subjects Not Competent to Give Consent
Individuals with dementia in this study are expected to have progressive decisional impairment. As 
such, the subject will be asked to involve an individual of his/her choice at the beginning of the study 
who may later serve as an LAR. Capacity to provide informed consent will be determined by asking 
standard reﬂective questions thoughout the consent process. 1) What is the main purpose of the study? 
2) What are the beneﬁts of the study? 3) What are the risks of the study? 4) Are you able to withdraw 
from the study at any time? If a person with suspected dementia is unable to answer the question the 
ﬁrst time the research team member will review the section of the consent and ask the question a second 
time. If at any point the person with demenita is unable to answer the question correctly after reviewing 
the section then proxy consent will be sought. If the person with demenita is unable to provide informed 
consent then his/her signed or verbal assent will be sought. The subject's assent will be obtained after 
informing the subject of the following: 1. The fact that he/she is being asked to participate in research 2. 
That he/she has been determined to lack capacity to self-consent to research participation 3. The name 
of the LAR who has been identiﬁed, that he or she has granted permission for the subject's participation 
in the research and the extent to which the LAR will be involved in the subject's research participation 
4. That the subject may choose freely to undergo study procedures or may withdraw from participation 
at any time without penaltiy or loss of beneﬁts. At each study visit the study tem member will fresh the 
subjects of the major objectives of the study, the scope of his/her participation, and the fact that 
participation is voluntary.
2. Waiver of Consent
Waiver or Alteration of Informed Consent*
No Waiver Requested
Minimal Risk*
Impact on Subject Rights and Welfare*
Waiver Essential to Research*
Additional Information to Subjects
Written Statement of Research*
No
If no written statement will be provided, please provide justiﬁciation
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Risk / Beneﬁt
Potential Study Risks
The risks of participation should be no more than minimal with effective conﬁdentiality safeguards. 
Should conﬁdentiality safeguards fail, there is potentially signiﬁcant harm in the form of social risks 
and disclosure of private information. The safeguards to prevent inadvertent disclosure of study data are 
described in the section below. Some participants might ﬁnd it somewhat uncomfortable to wear an 

Page 23 of 23
actigraph for multiple 24-hour periods.
Potential Study Beneﬁts
Caregivers in the experimental group will potentially beneﬁt from the intervention by learning speciﬁc 
techniques for tailoring and timing activities that engage PWD and utilize their preserved capabilities. 
PWD will potentially beneﬁt from the intervention since it is designed to reduce their sleep disruption 
and symptoms of CRD and enhance their quality of life by introducing activities that they are able to 
participate in and which they ﬁnd meaningful. They should also beneﬁt from the potential of reducing 
caregiver stress and improving their skills in managing difﬁcult behaviors. Participants in the control 
intervention group may potentially beneﬁt from obtaining important education to address various 
concerns associated with managing the disease including safety risk. PWD in this group may also 
beneﬁt by interacting with a staff member trained to engage the person in conversation
Alternatives to Participation (optional)
Data and Safety Monitoring
The PI will serve as the primary monitor for this study.  Plan for reporting unanticipated problems or 
study deviations. The entire study team will be trained on immediately reporting any adverse events, 
alerts (e.g., hazardous or emergency situations), or study deviations to the PI. See Chart A (uploaded) 
for types of possible alerts that may be encountered and types of actions to be taken. If any serious 
possible or potentially study-related adverse events arise, the PI will notify to the IRB within 48 hours 
of learning of the events and will provide a safety report describing the adverse event and actions taken 
by the study. Additionally the PI will keep a log of adverse events in compliance with IRB policies and 
whether the event is unrelated, possibly related, or probably related to the study or intervention. Study 
deviations will be reported to the IRB when discovered along with any corrective actions taken by the 
study. Routine adverse events (such as non-intervention related events such as death) will be 
summarized for the IRB during the annual reviews. At the start of the study, participants and study 
partners will be instructed to report serious adverse events to the Coordinator who in turn will notify the 
PI. Serious adverse events, discovered either by the clinical team in routine activities or ones which the 
family report, will be presented to the PI together with the available data, and they will make a 
determination as to whether the event is unrelated, possibly related, or probably related to the study 
intervention. Because this is an evidence-based psychosocial intervention which seeks to provide care 
to meet the care needs of individuals with dementia living in the community, we do not anticipate 
adverse events beyond the background rate for this elderly population. Additionally, the aforementioned 
terms will be acknowledged if funding is received for a diversity supplement.
The following documents are currently attached to this item:
There are no documents attached for this item.
Risk / Beneﬁt Assessment
This is a minimal risk study with potential beneﬁt to subject and society.
General Attachments
The following documents are currently attached to this item:
Cover Letter (summaryofchanges.pdf)
Questionnaires (covid-19questionnaire.pdf)