Indiana Palliative Excellence in Alzheimer's Care Efforts- Randomized Control Trial
Phase: NA
Conditions: Dementia
Sponsor: Indiana University

Revision Date: 4/10/2020 
 
 
 
 
 
 
 
 
Indiana Palliative Excellence in Alzheimer’s Care Efforts- 
Randomized Control Trial 
Protocol 
 
 
Greg A. Sachs 
720 Eskenazi Avenue  
Indianapolis, IN 46202  
Ph: (317) 630-2564 
Sachsg@iu.edu 
 
NCT#03773757 
Protocol dated: 4/10/2020 
 
 
Co-Investigators: 
 
Sujuan Gao, PhD 
Indiana University Department of Biostatistics 
 
Susan Hickman, PhD 
Indiana University School of Nursing 
 
Kurt Kroenke, MD 
Indiana University School of Medicine 
 
Alexia Torke, MD 
Indiana University School of Medicine 
 
 
 
 
 
 
 
 
 
 

Revision Date: 4/10/2020 
Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Inclusion/Exclusion Criteria 
4.0 
Enrollment/Randomization 
5.0 
Study Procedures 
6.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants or 
Others 
7.0 
Study Withdrawal/Discontinuation 
8.0 
Statistical Considerations 
9.0 
Privacy/Confidentiality Issues 
10.0 Follow-up and Record Retention 
 
 

Revision Date: 4/10/2020 
1.0 
Background 
Dementia is an increasingly prevalent, costly and burdensome condition. The dramatic aging of the US 
population is creating a dementia “epidemic” that our health care system is poorly prepared to handle.  More 
than 5 million people are affected by Alzheimer’s disease (AD) and related dementias in 2016, with that 
number estimated to nearly triple to 13.8 million by 2050. The direct health care costs alone for dementia care 
are projected to increase from $236 billion in 2016 to more than $1 trillion in 2050. In addition to cognitive and 
functional deterioration, patients with dementia experience behavioral and psychological complications such as 
agitation and depression. Family caregivers of patients with dementia experience higher levels of anxiety, 
depression, chronic fatigue, and an increased mortality risk.  
 
Dementia and palliative care are national research priorities. Both dementia and palliative care 
have been identified as priority conditions for research and quality improvement by numerous 
organizations such as the Institute of Medicine, National Quality Forum, the Centers for Medicare and 
Medicaid Services, and Agency for Healthcare Research and Quality and NIA.  In addition, a 
workgroup developing milestones for care and support under the U.S. National Alzheimer’s Plan has 
explicitly stated that palliative care needs to be incorporated throughout the course of caring for 
patients and families affected by dementia.  
 
 
2.0 
Rationale and Specific Aims 
 
Aim 1:  To test the effect of the IN-PEACE intervention on patients’ neuropsychiatric 
symptoms (e.g., agitation/aggression, anxiety, repetitive behaviors).  Mixed effects models will 
be used to compare repeated NPI-Q scores obtained at 3, 6, 9, 12, 15, 18, 21, and 24 months. 
Repeatedly measured NPI-Q scores will be the dependent variable in the model.  
  
Aim 2: To test the effect of the IN-PEACE intervention on patients’ overall symptom outcomes.  
Analyses in this aim will use repeatedly measured SM-EOLD scores over 24 months of follow-up as 
the dependent variable in the mixed effects model, similarly to the approach described for Aim 1. 
  
Aim 3: To test the effect of the IN-PEACE intervention on caregivers’ distress and mood. Aim 3 
analyses will use repeatedly measured caregiver NPI-Q distress scores and caregiver PHQ-9 over 24 
months of follow-up as the dependent variables in separate mixed effects models, similar to the 
approach for Aim 1. 
  
Aim 4: Evaluate the effect of the IN-PEACE intervention on ER/hospital use.  ER/hospitalization 
events will be obtained from accessing electronic medical records maintained by the Indiana Health 
Information Exchange (IHIE) and the Indiana Network for Patient Care (INPC).  Poisson regression 
models will be used to compare rates of any ER/hospitalization event between the two groups while 
adjusting for dementia severity and significant baseline variables that differ between the two groups.  
 
3.0 
Inclusion/Exclusion Criteria 
 
We will recruit a total of 225 patient-caregiver dyads, randomizing 112 dyads each to the intervention and 
control (usual care) arms. 
 
Eligibility criteria for patients include:  
• 
age 65 or older 
• 
community-dwelling in the Indianapolis metropolitan area (assisted living facility acceptable; 
long stay NH residents excluded);  
• 
have an established diagnosis of dementia of any etiology as determined by memory care 
practice and confirmed by research team review of medical record;  

Revision Date: 4/10/2020 
• 
dementia in the moderate (FAST stage 5) to severe stage (FAST 6-7); and  
• 
have a primary caregiver available and willing to serve as both an informant on the patient’s 
status and as a subject him or herself.  
 
Exclusion criteria for patients include: 
• 
resident living in a nursing facility, Skilled Nursing Facility, Long Term Acute Care (LTC), 
Personal Care Home 
• 
patient expressing dissent 
• 
being diagnosed with a serious mental illness such as bipolar or schizophrenia 
• 
Hospice enrollment (Addition IRB Approved: 5/13/2019) 
 
Eligibility criteria for caregivers include:  
 
• 
reside locally;  
• 
English-speaking;  
• 
live with patient or have at least 2 contacts per week on average with the patient (1 face-to-
face); 
• 
designation as the patient’s primary caregiver; and 
• 
has not been diagnosed with a serious mental illness such as bipolar or schizophrenia.   
 
Recruitment 
Dyads will be recruited from Indiana Discovery Network for Dementia (http://indydiscoverynetwork.org/) 
memory care practices in the Indianapolis area. Utilizing established memory care practices allows us to rely 
on their diagnostic assessment (confirmed by record review by research team) and to efficiently recruit eligible 
subjects.  Our customary and successful recruitment methods utilize the Indiana Network for Patient Care 
(INPC) and the Indiana Health Information Exchange (IHIE) to identify potentially eligible patients with 
dementia based on ICD-9 and ICD-10 diagnostic codes and prescriptions for anti-dementia drugs in medical 
records. Memory care providers then help narrow the list of potential dyads to be approached and allow access 
to clinic schedules.  Research assistants then arrange to meet dyads at a clinic appointment or offer a home 
visit to discuss the study.  
 
Research staff will ask caregivers a series of questions to assess the patient’s cognitive and functional status. 
This information will be used to determine the severity of the patient’s dementia using the FAST.   Only 
patients meeting criteria for FAST stage 5 (moderately severe) or stage 6-7 (severe) will continue in the 
enrollment process.  
 
An IN-PEACE research assistant, with approval from the practitioner, will obtain informed consent of the 
patient’s legally authorized representative (LAR) for study participation. (The LAR and caregiver will be two 
individuals in a few cases. For example, one adult child may hold power of attorney for the patient and 
another adult child may be the primary caregiver. In those cases, the LAR gives proxy consent for the patient 
and the caregiver gives informed consent for their own participation.)  Because the severity of the patient’s 
dementia is advanced, while decision making capacity of the patient will be assessed using the teach-back 
method, we expect most patients will lack decisions making capacity to provide informed consent If the patient 
expresses meaningful dissent, patient will not be enrolled, even if the LAR is willing to consent.  
 
Potential subjects can self-refer for this study. Approved study brochures will be distributed at community 
events, such as conferences, meetings, or other contacts with the public. Interested subjects will be asked to 
provide their name, email address, telephone number and mailing address.  A Research Assistant will contact 
potential subjects with the contact information provided to screen for inclusion/ exclusion criteria to determine 
eligibility.   We may email/ direct mail consent statement to interested participants, upon request.  The 
mail/email template will include the scripted language previously approved with the screening/ enrollment 
script, and approved IN-PEACE brochure.  An Email/Direct mail template has been approved by the IRB. 
 

Revision Date: 4/10/2020 
4.0 
Enrollment/Randomization 
 
After enrollment and baseline assessments are completed, subjects will be classified according to disease 
severity (moderately severe (FAST = 5) or severe (FAST = 6-7).  
 
Stratified randomization based upon dementia severity will be used to assign patient-caregiver dyads to either 
the intervention or usual care arm.   
 
5.0 
Study Procedures 
 
Timeline 
The study will take place over five years with a six month start-up time period.  It will take 24 months to 
accrue the target sample size utilizing a rolling enrollment and intervention delivery process.  Subjects receive 
the intervention for 24 months and the last outcome assessment is also at 24 months. In the final year of the 
study, in addition to completing analyses and preparation of manuscripts, we would plan a competitive 
renewal proposal to continue following the subjects in order to address aims relating to care in the last 
days/weeks of life, hospice referral, and resource utilization.   
 
YEAR 01 
YEAR 02 
YEAR 03 
YEAR 04 
YEAR 05 
Start-up activities 
 
 
 
 
 
 
Subject accrual 
 
rolling enrollment over 24 
months 
 
 
 
Intervention 
Delivery 
 
each dyad receives 24 months of the intervention 
 
Outcome 
assessments 
 
each dyad assessed at baseline, 3, 6, 9,12, 15, 18, 21, 
and 24 months 
 
Analysis; 
manuscripts 
 
 
 
 
 
 
 
 
Assessments: Measures and Schedule of Administration 
 
Domain 
Measure 
Items 
Schedule (months) 
0 
3 
6 
9 
12 
15 
18 
21 
24 
EOL 
Patient  (PT) measures 
Patient related measures assessed directly by research assistant 
Cognition 
MOQA 
30 
X 
 
 
 
X 
 
 
 
X 
 
Patient related measures obtained via caregiver (CG) interview (proxy report) 
Neuropsychiatric 
Symptoms 
Neuropsychiatric Inventory 
Questionnaire (NPI-Q)91 
12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Symptom 
Management 
Symptom Management at the End of 
Life in Dementia (SM-EOLD)92 
9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Comfort Assessment 
Comfort Assessment in Dying with 
Dementia (CAD-EOLD)92 
15 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Activities of Daily 
Living 
Physical Self-Maintenance Scale106 
13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Functional status 
FAST staging80 (caregiver report, 
ADLs) 
 
X 
 
 
 
 
 
 
 
 
 
Medical comorbidity 
Checklist of conditions11 
10 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Caregiver measures from CG interview 
CG Distress from 
Neuropsychiatric 
Symptoms 
Neuropsychiatric Inventory 
Questionnaire (NPI-Q)91  (CG reaction 
portion of instrument) 
12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Depression (CG) 
Patient Health Questionnaire (PHQ-
8)65 
9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Caregiver Strain 
Caregiver Strain Index107 
13 
X 
 
 
 
X 
 
 
 
X 
 
Satisfaction with Care 
Satisfaction with Care at the End of 
Life in Dementia (SWC-EOLD)92 
10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

Revision Date: 4/10/2020 
 
Intervention 
Intervention arm. Multi-disciplinary clinical team meetings with PI, co-investigators (MA, KK, SH, 
AMT), and care coordinators will be held weekly throughout the study.  During these meetings, the 
team will review data from the baseline assessments to 
• identify triggers for interventions,  
• make protocol and other treatment recommendations, and  
• communicate these to the care coordinator for dyads randomized to the intervention arm. 
Caregivers will be contacted by the care coordinator within one week following the clinical team 
meeting or within ten days of the baseline assessment.   
 
Care coordinators will initiate caregiver protocols to address unmet needs and individualized areas of 
focused care, overcoming barriers to provision of excellent palliative care.  The assigned care 
coordinator will be the primary contact and will follow the dyad throughout the study with backup 
support and cross-coverage (i.e. social worker may call in RN for help with nursing issues and vice 
versa). 
 
The coordinator will direct the caregiver to the INPEACE manual (provided at enrollment that contains 
PREVENT materials relating basic dementia care needs, caring for the caregiver, management of 
neuropsychiatric symptoms, and the IN-PEACE materials on goal setting and advance care planning, 
pain evaluation and management, navigating the hospital, feeding difficulties, and hospice transitions, 
including appropriate industry materials).  Specific tools to aid in the evaluation and management of 
pain include a list of nonverbal indicators of pain77 and a card with the Iowa Pain Thermometer78 on 
one side and Faces Pain Scale81 on the other. These will aid in rating pain and in communicating 
about it with the care coordinators and physicians.  Caregivers will be instructed that they can refer to 
the management techniques in the manual on their own and should have it available when speaking 
with the care coordinator on the phone. Caregivers will be asked to contact the IN-PEACE care 
coordinators throughout the study at times of acute events or symptom changes, hospitalization, or 
with questions, concerns, and referral/resource requests.   
 
Care coordinators will record information on all contacts and interventions in templated notes in the 
web-based tracking system, both to provide information for follow up, as well as to provide descriptive 
information on numbers and types of contacts, protocols triggered, and interventions carried out.   
 
Care coordinators will initiate contact with caregivers at 1, 2, and 4 weeks after enrollment and then 
monthly thereafter.  At each contact, the DCC will use, open-ended questions about the patient’s 
most bothersome symptoms, and the caregiver’s assessment of the patient’s level of 
pain.  Responses indicating symptoms that are frequent or causing distress in the patient or caregiver 
trigger the appropriate protocols for managing those symptoms. Non-pharmacological and behavioral 
strategies have an early and important role in the protocols.  Several of the protocols have the 
equivalent of laboratory “panic values,” findings that would trigger a more intensive response from the 
care coordinator.  For example, new onset pain that is severe would result in a call to the patient’s 
primary care physician and discussion about whether the patient should be seen in the office or even 
the emergency room.  Some of the protocols may trigger follow up sooner than the next scheduled 
Respondent Burden 
Benefit and Burden Scale108 
4 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Other data from CG interview 
Advance Care 
Planning (ACP) 
Questions on specific directives 
10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hospice 
Hospice utilization 
4 
 
 
 
 
 
 
 
 
 
X 
Socio-demographics 
(PT/CG) 
age, race, sex, education, marital, job 
status, income 
10 
X 
 
 
 
 
 
 
 
 
 
Medical Record Review and INPC/IHIE Data Stream 
Etiology of Dementia 
Chart review 
n/a 
X 
 
 
 
 
 
 
 
 
 
ER/Hospitalizations 
Health information exchange data 
n/a 
 
 
 
 
X 
 
 
 
X 
X 

Revision Date: 4/10/2020 
monthly contact.  Using pain as the example again, the care coordinator will contact the caregiver 
within 72 hours and continue to intervene if there has not been at least a 50% reduction in the rating 
of pain.   
 
Some protocols, such as feeding/weight loss and planning for hospice, may be triggered either by a 
decline in functional status or a hospital admission, rather than a symptom.  Goal setting and advance 
care planning will be addressed repeatedly, first at enrollment and then as major changes in clinical 
status occur.  The clinical team will meet weekly with the care coordinators to discuss scheduled 
contact reports, caregiver initiated contacts and questions, and review and revise plans of care. 
Recommendations of the clinical team will be tracked in the care coordinator’s contact database with 
follow up appointments set.  For more urgent medical issues, care coordinators can contact the 
clinical team representative between meetings for advice or recommendations to the caregiver to 
seek care from the primary care provider or emergency room. 
 
Table 2 outlines barriers to palliative care in dementia, possible solutions, and the aligned 
protocols developed for IN-PEACE to address the barriers.  
 
Table 2: Palliative Care in Dementia: Barriers and Solutions 
Barrier to excellent palliative care 
in dementia82  
Potential Solution(s) 
IN-PEACE Protocols/Interventions 
“Dementia not a terminal illness” 
Reframing advanced stages as terminal 
Prognostic Information 
Lack of advance care planning 
Ongoing care planning with caregivers 
Goals of Care / Advance Care Planning 
Poor symptom management 
Proactive assessment and attentive 
management 
Proactive Assessment (behaviors/psychological; 
pain; other symptoms; caregiver mood/distress) 
Symptom Protocols 
Caregiver Support Protocols 
Difficult decisions: antibiotics and 
tube feeding 
Information about benefits & burdens; 
context of goals of care, alternatives 
Goals of care / Advance Care Planning 
Feeding / Weight Loss 
Navigating Hospital 
Avoidable hospital use 
Burdensome treatments/transitions 
Underutilization of hospice 
Support care at home 
Increase discussion of benefits of 
palliative care and hospice options 
Symptom Protocols 
Goals of Care / Advance Care Planning 
Transition to Hospice 
 
The information collected by the care coordinators via telephone that are either scheduled or 
initiated by caregiver concerns at any time will be reviewed at weekly interdisciplinary team meetings. 
This information will consist primarily of reports of behavioral problems, pain and other bothersome 
symptoms, and caregiver well-being. This “clinical data” is used solely to help manage care of the 
patient and caregiver and are not part of the separately scheduled research outcome assessments. 
The team also will review any interventions carried out or ordered by the care coordinator, additional 
services recommended, and assess initial responses to these actions, if already available. The team 
may further modify the care plan.   
 
The two Research Assistants will be blinded to the randomization assignment and will not be involved 
in any meetings or discussions about intervention subjects. The research manager (LH) will review 
outcomes measures  and if there are any values that exceed pre-specified levels, she will bring those 
to the attention of the PI. These are similar in nature to “urgent” or “panic” values in laboratory blood 
test reports or X-ray reports requiring attention of a clinician and represent a safety feature for all 
dyads, control and intervention, and not a part of the IN-PEACE intervention.  For example, any 
severe pain or pain associated with a fall or other trauma will result in a call to a physician and either 
scheduling of an appointment or instructions to go to the emergency room.   
 
The revised plans of care generated by the care coordinators and the supportive care clinical team 
are intended to affect the study outcomes and should be thought of as integral components of the 

Revision Date: 4/10/2020 
intervention.  Tailoring protocolized treatment actions to the particular patient’s needs is the standard 
for multi-component trials of collaborative care interventions. 
 
The care coordinators will send periodic updates, in the mode and frequency as requested, to the 
patient’s primary care provider. Most participating providers in the Indianapolis area will be familiar 
with electing secure email, fax, phone, or text pager for their preferred modes of communication 
because of the INPC, IHIE, and other ongoing, innovative efforts, such as those sending pending lab 
results from hospital and emergency room visits to physicians’ offices. The team will communicate 
with the primary care provider to request referrals to other specialists and when initiating protocols 
such as pain and hospice conversations.  
 
Additionally, up to 25 caregivers, randomized to the intervention arm, will be asked to participate in a 
one-time qualitative interview aimed to explore the attitudes toward and experience with decisions to 
deprescribe medications of caregivers for community dwelling patients with moderate-severe AD with 
a focus on learning from the caregivers the ethical considerations that they take into account. The 
study will employ semi-structured interviews (in-person or by telephone) and qualitative methods for 
analyzing transcriptions of the recorded interviews.   
 
 
Usual care arm.   
Dyads randomized to “usual care,” will be receiving care that is likely of a higher quality than 
the typical patient with dementia in the community setting given the involvement of IDND memory 
care practitioners.  However, control dyads will not have access to the dementia care coordinator 
proactively making contact, assessing needs, and implementing IN-PEACE management protocols 
as the intervention subjects will have.  Caregivers in the usual care group will have access to 
educational and informational materials from the local chapter of the Alzheimer’s Association and 
other community resources and will be reminded of their availability.  Protocols will be in place for 
appropriate referral when research assistants’ assessments elicit information about severe symptoms 
or distress. 
 
Data Collection 
Baseline and final outcome assessments will be done in person at the subjects’ home or the memory 
care practice site. Other outcome assessments will be done by phone or in the home, based on 
caregiver preference.  The outcome measures for both intervention and usual care groups will be 
collected at baseline and months 3, 6, 9, 12, 15, 18, 21, and 24 post-enrollment. Caregivers also will 
be interviewed 6 to 8 weeks after the patient’s death if that occurs during the course of the study. 
Data will be collected by research assistants who have not been involved in the ongoing management 
of the patients and are blinded to dyad assignment to intervention or usual care arm.  
 
Data obtained from the one-time qualitative interview will be audio-record and transcriptions will be 
used for data analysis using grounded theory. 
 
6.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants 
or Others 
 
The safety monitoring for this study will be the responsibility of the Principal Investigator (Sachs), 
study biostatistician (Gao), and Safety Officer, who is external to Indiana University, and  who are 
knowledgeable about dementia and older adults.  Specifically, the Safety Officer will be selected 
based on the knowledge and experience in dementia, caregiving, palliative care, and clinical research 
studies.  The Safety Officer, PI, Program Officer, and study biostatistician will meet by phone semi-

Revision Date: 4/10/2020 
annually during active recruitment, data collection and analysis.  Topics the group will review include: 
inclusion/exclusion criteria; participant accrual; and adherence and modifications to research 
protocols and procedures. Preliminary data trends on the primary and secondary outcomes will be 
discussed.  In addition, the group will review procedures for protection of human subjects, including 
study withdrawals and adverse events reports and devise stopping rules, as applicable, based on 
potential harms and adverse events.    
 
7.0 
Study Withdrawal/Discontinuation 
 
Subject withdraws, and adverse events will be reviewed by the Safety Officer, PI, Program Officer 
and study team members  at the semi-annual meeting, or as prescribed in the Data Safety and 
Monitoring plan. 
 
8.0 
Statistical Considerations 
 
The proposed study is a RCT comparing the multi-component, supportive care intervention (IN-
PEACE) to usual care. Primary and secondary outcomes will be collected at baseline, 3, 6, 9, 12, 15, 
18, 21, and 24 months. A patient reaches study endpoint by either completing 24 months of follow-up 
or other conditions described in Subject tracking. We will compare baseline characteristics between 
the intervention group and the control group using two sample t-tests for continuous normally 
distributed variables, Wilcoxon test for continuous non-normal variables, or chi-square tests for 
categorical variables. Variables found to be significantly different at the α=0.05 level will be adjusted 
in the comparisons of all outcome variables. 
 
Table 4: Power estimates for significant interactions between group and time in the mixed effect 
models with 85 patients per group. 
Outcome 
Measures 
Expected Change in 
Outcome 
(3-month interval) 
Power 
Intervention 
Usual Care 
Aim 1: NPI-Q Severity 
-0.45 
0.2 
80% 
Aim 2: SM-EOLD 
1.31 
0* 
85% 
Aim 3a: Caregiver NPI-Q 
distress 
-0.39 
0.08 
80% 
Aim 3b: Caregiver PHQ-9 
-0.22 
0.16 
81% 
 
 
9.0 
Privacy/Confidentiality Issues 
 
We will also take great care in assuring data security.  Perhaps the most important element of 
data security is proper training of the scientists and their staff in research involving human subjects 
and in privacy and confidentiality.  Data are handled only by research staff with specific training in 
data privacy and confidentiality.  Data are stored on a secured workstation that is in a locked office 
within a locked suite of offices and the workstation and files are password protected.  On rare 
occasions when data are to be transferred from secured workstations to one of the investigators’ 
workstations for further analyses, the transferred dataset will be stripped of unique identifiers (de-
identified dataset) including SSN, name, address, dates, and any personal identifiers.  This is 
standard operating procedures for our work with research data.  In addition, Regenstrief Institute 
databases and individual workstations are protected from unauthorized remote access by a 
sophisticated firewall which is tested on a regular basis.  Data presented in reports are always 
reported in aggregate and never contain personally identifiable health information. 
 

Revision Date: 4/10/2020 
10.0 Follow-up and Record Retention 
 
The study is scheduled for 24 months.  Records will be maintained in secure location and will be 
retained as required per regulations.