Efficacy of a Virtual Intervention for Informal Caregivers of Adults With Frontotemporal Dementia
Phase: NA
Conditions: Behavioral Variant of Frontotemporal Dementia, Caregiver Stress Syndrome
Sponsor: University of Pennsylvania

 
 
 
 
 
 
 
 
Protocol with Statistical Analysis Plan 
 
Protocol Title: Efficacy of a Virtual Intervention for Informal Caregivers of Adults with Frontotemporal Dementia 
 
NCT Number: NCT04686266 
 
Document Date: Version 8.25.2020  

 
 
 
 
 
 
Efficacy of a Virtual Intervention for Informal Caregivers of Adults with 
Frontotemporal Dementia 
8/25/2020 
PRINCIPAL INVESTIGATOR:  
Riegel, Barbara J 
Penn School of Nursing 
Behavioral and Health Sciences 
Claire M. Fagin Hall 
418 Curie Blvd/Room 335 Fagin Hall 
Philadelphia, PA 19104 
215-898-9927 
briegel@nursing.upenn.edu 
Co-Investigator: 
Massimo, Lauren 
Department of Neurology/School of Nursing 
Penn FTD Center 
6 Richards Medical Research Laboratories 
3700 Hamilton Walk 
Philadelphia, PA 19104 
215-349-8463 
lmassimo@upenn.edu 
Study Contacts: 
Gladys Thomas 
Penn School of Nursing 
Behavioral and Health Sciences 
Claire M. Fagin Hall 
418 Curie Blvd/Room 335 Fagin Hall 
Philadelphia, PA 19104 
215-898-5089 
glthomas@nursing.upenn.edu 
 
Laira Lucas 
Department of Neurology 
Penn FTD Center 
6 Richards Medical Research Laboratories 
3700 Hamilton Walk 
Philadelphia, PA 19104 
215-349-5863 
LairaL@Pennmedicine.upenn.edu 
 
Sean Lydon 
Department of Neurology 
Penn FTD Center 
Ralston House 
3615 Chestnut st. 
Philadelphia PA, 19104 
215-349-8857 
slydon@pennmedicine.upenn.edu 

 
 
 
 
 
Table of Contents 
INTRODUCTION AND PURPOSE: ................................................................................................................................................. 4 
OBJECTIVES: ................................................................................................................................................................................ 4 
BACKGROUND: ........................................................................................................................................................................... 4 
CHARACTERISTICS OF THE STUDY POPULATION: ....................................................................................................................... 5 
1. 
Target Population and Accrual: ...................................................................................................................... 5 
2. 
Key Inclusion Criteria: ..................................................................................................................................... 6 
3. 
Key Exclusion Criteria: .................................................................................................................................... 6 
4. 
Subject Recruitment and Screening: .............................................................................................................. 6 
5. 
Early Withdrawal of Subjects: ......................................................................................................................... 7 
6. 
Vulnerable Populations: .................................................................................................................................. 7 
7. 
Populations vulnerable to undue influence or coercion: ................................................................................. 7 
STUDY DESIGN: ........................................................................................................................................................................... 7 
METHODS: .................................................................................................................................................................................. 8 
1. 
Study Instruments: .......................................................................................................................................... 8 
2. 
Group Modifications: ....................................................................................................................................... 9 
3. 
Method for Assigning Subjects to Groups: ..................................................................................................... 9 
4. 
Administration of Surveys and/or Process: ..................................................................................................... 9 
5. 
Data Management: ....................................................................................................................................... 10 
6. 
Subject Follow-up: ........................................................................................................................................ 10 
STUDY PROCEDURES: ................................................................................................................................................................ 10 
1. 
Detailed Description: ..................................................................................................................................... 10 
2. 
Data Collection: ............................................................................................................................................ 11 
3. 
Genetic Testing: ............................................................................................................................................ 11 
4. 
Use of Deception: ......................................................................................................................................... 11 
5. 
Statistical Analysis: ....................................................................................................................................... 11 
RISK/BENEFIT ASSESSMENT: ..................................................................................................................................................... 12 
1. 
Risks: ............................................................................................................................................................ 12 
2. 
Benefits: ........................................................................................................................................................ 12 
3. 
Subject Privacy: ............................................................................................................................................ 12 
4. 
Subject Confidentiality: ................................................................................................................................. 13 
5. 
Protected Health Information ........................................................................................................................ 14 
6. 
Compensation: .............................................................................................................................................. 14 
7. 
Data and Safety Monitoring: ......................................................................................................................... 14 
8. 
Investigator’s Risk/Benefit Assessment: ....................................................................................................... 14 
INFORMED CONSENT: ............................................................................................................................................................... 14 
1. 
Consent Process: ......................................................................................................................................... 14 
2. 
Waiver of Informed Consent: ........................................................................................................................ 15 
RESOURCES NECESSARY FOR HUMAN RESEARCH PROTECTION: ............................................................................................. 15 
 

 
 
 
PROTOCOL TITLE: Efficacy of a Virtual Intervention for Informal Caregivers of Adults with Frontotemporal Dementia 
 
INTRODUCTION AND PURPOSE:  
 
Caregivers of adults with dementia report significant stress and poor self-care. Virtual Caregiver Coach for You (ViCCY 
[“Vicky”]), a virtual support intervention, may relieve stress and promote self-care in dementia caregivers. Even less is known 
about the effect of caregiver support interventions on dementia patient outcomes. Thus, we propose to extend the novel self-
care support intervention ViCCY (“Vicky”) to caregivers of persons with behavioral variant frontotemporal dementia (bvFTD) 
and we will explore the effect of caregiver outcomes on bvFTD patient outcomes. This work will allow us to develop a new 
and innovative way to increase support that is urgently needed to reduce poor outcomes in this distressed and underserved 
caregiver population. 
 
 
OBJECTIVES: 
 
Aim 1: Compare the preliminary efficacy of ViCCY vs. Health Information (HI) alone in improving self-care in FTD caregivers. 
We hypothesize that, at 6 months after enrollment, caregivers randomized to ViCCY vs. HI alone will have H1a: Improved 
self-care measured  with the Self-Care Inventory (primary outcome); H1b: Reduced self-reported stress measured with the 
Perceived Stress Scale (secondary outcome); H1c: Reduced depression measured with Center for Epidemiologic Studies 
Depression Scale (CES-D; secondary outcome); H1d: Improved coping measured with the Ways of Coping Questionnaire, 
short form (secondary outcome); H1e: Reduced burden measured with Zarit Burden Interview (ZBI; secondary outcome); and 
H1f: improved perceived mental and physical health status measured with the SF-36 (secondary outcome). 
 
Aim 2: Explore the effect of caregiver outcomes on FTD patient outcomes. We hypothesize that, at 6 months after enrollment, 
FTD patients whose caregivers improve vs. not improve in self-care – regardless of group – will demonstrate H2a: Fewer 
behavioral symptoms measured with the Frontotemporal Dementia Rating Scale (primary outcome) and Neuropsychiatric 
Inventory (secondary outcome).  
 
BACKGROUND: 
 
Informal caregivers are stressed and their self-care is poor. The number of people living with Alzheimer’s disease (AD) and 
related disorders (ADRD) will continue to grow exponentially, with most being cared for by informal caregivers, the majority of 
whom are spouses. As a group, informal caregivers have more stress, worse self-care, poorer health status,  and higher 
mortality than non-caregivers. Caregivers often feel left alone to cope with problems, which exacerbates their stress.  When 
stressed, caregivers are less vigilant and less motivated to engage in self-care behaviors that are important for maintaining 
physical and emotional health.  As a consequence, high levels of poor outcomes such as depression and anxiety and poor 
physical health have been observed in dementia caregivers. Together, these studies illustrate the risk that informal care 
providers face when they defer self-care in response to the stress of caregiving and highlight the urgent need to develop 
innovative strategies to promote self-care activities.  
 
 
Informal caregivers of persons with Frontotemporal degeneration (FTD) are an understudied population with unique needs. 
FTD is a common cause of young-onset dementia with no known cure. Behavioral variant FTD (bvFTD) is the most common 
of the FTD syndromes and involves a progressive disorder of emotional regulation and personality, and significant 
impairment in executive function. bvFTD caregivers face unique challenges which are particularly stressful, including young 
age at which the disorder appears, behavioral symptoms like apathy and disinhibition that are severe and appear early in 
bvFTD, and the lack of appropriate supportive services. Indeed, numerous studies have demonstrated that stress, 
depression and burden are higher in FTD caregivers than in any of the other ADRDs, yet caregiver interventions tested in 
specifically in the FTD population have been limited to a few small studies that focus on education around patient behavior 
management, not caregiver self-care. Recent evidence suggests that the personal and societal costs of FTD substantially 
exceed those of dementia in the elderly, yet supportive services that are available are for older persons and thus, rarely meet 
the needs of this particular groups of caregivers.  
        
 
                   
Effective interventions are needed for FTD caregivers. Given the challenges outlined above, there is an urgent need to 
develop supportive interventions for FTD caregivers that are flexible in nature. A recent scoping review found only five 
intervention studies targeting FTD caregiver stress, but these were mainly limited to small pilot studies exploring the use of 
support groups. While support groups are an important resource for FTD caregivers, geographical barriers as well as 
caregiving and life demands severely limit attendance. Web-based interventions may be an effective solution to overcome 
these accessibility barriers as the home environment may be the best place to deliver an intervention, where distractions are 
predictable and privacy can be optimized. Home interventions are perceived as convenient, requiring less time commitment, 
travel costs, financial costs, and waiting times; duration and timing of sessions can be flexible and accommodate caregiver 
preferences. Indeed, web-based interventions for dementia caregivers have been reported to be convenient and beneficial in 
reducing caregiver depression and stress, yet these studies have been limited to forms of dementia like Alzheimer’s disease 

 
 
 
where the caregiving experience significantly differs from that of FTD. Therefore, we propose to extend the intervention, 
ViCCY, to address these gaps by offering: 1) a psychosocial rather than purely educational approach; 2) flexibility; 3) 
multidimensionality including information and support tailored for the specific needs of FTD caregivers.  
Dyadic processes influence patient behavioral symptoms. Caring for a person with bvFTD is extremely challenging. Caregivers 
often misinterpret patient behavioral symptoms such as apathy or disinhibition as a sign of volitional opposition and poor 
cooperation, leading to high level of stress and dissatisfaction with caregiving. Studies have demonstrated that caregivers 
must adjust their own affect and demeanor to meet the needs of the patient with behavioral symptoms and negative emotional-
behavioral responses and altered interactions may therefore increase behavioral and psychological symptoms of dementia 
(BPSD). We hypothesize that improving caregiver affect through self-care may also reduce BPSD in the care recipient.                        
Theoretical Framework. The proposed study is based on the Transactional Model of Stress and Coping. Stressful 
experiences such as caregiving demand – circumstances that give rise to real or perceived stress – are construed as person-
environment transactions. Primary appraisal of demand involves assessment of its significance, which results in perceived 
burden. Secondary appraisal involves assessment of the resources available to cope with it. These appraisals lead to the 
coping effort.  
Without successful coping, self-care is poor, which decreases health status in caregivers. Our virtual support intervention 
[ViCCY (“Vicky”) – Virtual Caregiver Coach for You] addresses both appraisal and coping. Because stress does not affect all 
people equally, the intervention is tailored to individual appraisals and the factors most likely to influence demand and 
perceived burden. A key strength of the Transactional Model of Stress and Coping is its recognition that both individual and 
environmental variables respond to coping.  
Scientific premise. This study builds on a strong body of evidence that describes stress and poor self-care in FTD caregivers. 
Health coaching has been shown to decrease perceived stress and improve self-care and health status in Alzheimer’s 
dementia caregivers, however FTD caregivers are a unique group who are most at-risk for poor self-care, stress and 
depression. Furthermore, in addition to our primary aims, we will explore the impact of caregiver mood on patient behavioral 
outcomes. Although a growing body of research illustrates the influence of caregivers on patients and vice versa, (i.e., dyadic 
processes), we are not aware of intervention studies that have explored the influence of the FTD caregiver mood on 
behavioral and psychological symptoms (BPSD) in the patient.  
 
CHARACTERISTICS OF THE STUDY POPULATION: 
 
1. Target Population and Accrual: 
 
In the proposed randomized clinical trial, we will enroll adults who are informal caregivers of adults with bvFTD and the 
bvFTD patients they care for. The study focuses on the caregivers, but we will also enroll bvFTD patients because we will be 
collecting patient demographic and disease severity (i.e., modified Clinical Dementia Rating Scale) information.  
 
The informal caregivers and the bvFTD patients are anticipated to be adults because bvFTD is a condition affecting adults. 
The mean age of bvFTD patient participants in the Penn FTD Center is 64 years and most of their caregivers are spouses of 
a similar age.   
 
The sampling plan involves enrolling a consecutive sample of adult caregivers and patients with bvFTD. We will focus 
enrollment on caregivers. We have a large referral source from the Penn FTD Center and we will initially draw from this pool 
of caregivers by contacting those we know are willing to participate in research. Caregivers must be informal caregivers of 
patients with a confirmed diagnosis of bvFTD. They will be screened with the 10-item Health Self-Care Neglect scale. We will 
enroll only those who are poor in self-care using a cut-point of ≥2 based on our pilot study. Caregivers must be able to 
provide informed consent (speak English, see, hear, cognitively intact) and complete the protocol. We will exclude caregivers 
with cognitive impairment because we anticipate that they would have difficulty completing the intervention. We will exclude 
anyone with untreated major psychiatric illness such as psychosis. Caregivers in a competing trial testing a support 
intervention also will be excluded. In this way, we anticipate enrolling only caregivers who are able to provide true informed 
consent and those who will potentially benefit from the intervention. Any bvFTD patient cared for by an enrolled caregiver will 
be consented (see consent procedures). 
 
Most caregivers will be spouses but some will be adult children. We expect to enroll slightly more female than male 
caregivers because most caregivers are female and support interventions are more appealing to women. We will monitor 
enrollment weekly to ensure that it is appropriately balanced. We will enroll 30 caregivers and patients (15 caregivers per 
study arm) to achieve over 90% power to detect significant overall differences in longitudinal profiles between the groups on 
the primary outcome of Self-Care Inventory. We estimate enrolling 10 caregivers per month over 3-4 months. We will require 
a minimum of 12 months for enrollment. We have conservatively allowed 6 months for enrollment and 6 months to complete 
the study. Duration of study participation is 6 months. 
 

 
 
 
Dr. Riegel (PI) and Dr. Massimo (Co-I) will oversee the recruitment and enrollment. Participants will be primarily recruited 
from the Penn FTD Center located in Philadelphia, PA. The Penn FTD Center draws patients from other parts of 
Pennsylvania, New Jersey, and Delaware. Patient recruitment reflects the average of the population characteristics of these 
areas as provided by the U.S. Census Bureau (https://www.census.gov/quickfacts/table/). Recruitment, selection and 
enrollment into the parent study are non-discriminatory regarding race and sex. However, research suggests that members of 
the minority populations are less likely to participate in dementia research because, relative to their Caucasian counterparts, 
they are often diagnosed later and, thus do not receive specialized dementia care. We will make every effort to ensure that 
the subject populations conform to the NIH policy guidelines on Gender and Minority Inclusion in Research Studies, and we 
make special efforts to recruit women and minorities. On-going efforts to increase minority population include educational 
series at community centers in Philadelphia and surrounding areas to engage a community of minorities and an annual FTD 
Caregiver conference sponsored by the Penn FTD Center. All of these efforts will be used to aggressively increase and retain 
minority group representation. 
 
We expect to enroll women more easily than men because most caregivers are women and this type of intervention is more 
appealing to women. Recruitment efforts will focus on enrolling a sufficient number of men so that we can analyze sex-based 
differences in response to the intervention. No caregivers who are < 18 years of age will be included because their stresses 
may be unique. The randomization sequence will be generated a priori by a statistician unassociated with the study. 
Caregiver participants will be notified of their group assignment by the Project Manager. Both groups will receive Health 
Information (HI) delivered by the Internet in addition to standard care. The intervention group will receive virtual health 
coaching (ViCCY) by video conferencing, with 10 front-loaded health coaching contacts over six months. This dose is based 
on published data demonstrating that six months of health coaching is needed to be effective. No other collaborating sites are 
involved. 
 
2. Key Inclusion Criteria: 
 
1. Informal caregiver providing care at least 8 hours/week 
2. Reporting poor self-care on screening (Health Self-Care Neglect Scale, score ≥ 2) 
3. Able to complete the protocol, e.g., adequate vision and hearing, English speaking 
4. Caregiver of a patient diagnosed bvFTD 
 
 
3. Key Exclusion Criteria: 
 
1. Participation in another support RCT 
2. Untreated major psychiatric illness (Use of anti-anxiety/anti-depressant medicines is acceptable and will be adjusted 
in analysis if group imbalance is identified.) 
3. Caregiver with Cognitive Impairment based on Telephone Interview for Cognitive Status (TICS) score <25 
 
 
4. Subject Recruitment and Screening: 
 
We will enroll a consecutive sample of informal bvFTD caregivers identified from the Penn Frontotemporal Degeneration 
Center (https://ftd.med.upenn.edu), one of the largest NIH-funded centers dedicated to the study of young-onset dementias in 
the United States and a site where Dr. Massimo is PI of other FTD-related studies. The Penn FTD Center is actively studying 
110 bvTD patients, all of whom have caregivers and we see approximately 20 bvFTD patients a year. If recruitment is slower 
than expected, we will identify caregivers through the Association for Frontotemporal Degeneration, a national caregiver 
organization, with whom Dr. Massimo works closely.  
 
To obtain a consecutive sample we will seek a HIPAA waiver to screen the FTD Center clinic daily appointment schedule to 
identify every patient with a potentially eligible caregiver. FTD Center clinic providers and staff will identify potential caregiver 
participants (e.g., speak English) and determine their interest in speaking with research staff about the study. If caregivers 
agree to speak with research staff, the RA will explain the study and screen the caregiver for inclusion and exclusion criteria 
with standardized testing (e.g., Health Self-Care Neglect scale) and interview (e.g., hearing). Fully eligible caregivers who 
provide informed consent (see Human Subjects) will complete the virtual baseline assessment before being randomized to 
study arm. After all baseline data are collected, the caregiver will be randomized to study arm. At that time, participants will 
be trained in tablet use and how to access the Health Information website.  
 
 
 
 
 

 
 
 
To safeguard confidentiality and privacy we have planned a 2 step screening process: 
 
1. The RA will obtain Verbal Consent from interested caregivers to conduct preliminary screening for eligibility using study 
inclusion and exclusion criteria: 
- 
Caregiver is providing care at least 8 hours /week 
- 
Able to see, hear, speak and read English 
- 
Not planning to move out of the area soon 
- 
Not participating in another support study 
 
2. If appropriate, RA will continue with the full screening process by assessing the following: 
- 
Reporting poor self-care on screening (Health Self-Care Neglect scale score greater than or equal to 2) 
- 
Telephone Interview for Cognitive Status (TICS) score <25 
 
After screening, the RA will obtain informed consent from caregivers to continue with study procedures. Those who agree to 
participate will be asked to read and sign the consent form with integrated HIPAA authorization information (i.e., specifics 
about data elements to be collected and use of the private information). Fully eligible caregivers who provide informed 
consent will complete the baseline assessment before being randomized to study arm. After all baseline data is collected the 
caregiver will be randomized to study arm. At that time, participants will be trained in tablet use and how to access the Health 
Information website. We will seek bvFTD patient consent to review their medical records and to complete the modified 
Clinical Dementia Rating Scale (mCDR).  
 
Remote enrollment. In the event that written consent cannot be obtained in person due to safety or practical reasons we will 
telephone caregivers who have expressed a willingness to speak with us about the study or were referred to us by clinical or 
other research staff. We will explain the study and screen those who are interested in participating. The screening will be 
done by telephone. Those who are eligible to participate will be pushed an electronic link that begins with the consent form. 
Staff will talk through the consent in detail. If the caregiver wishes to think about the study but not commit at this time, we will 
contact him/her at a later date. If the caregiver immediately decides to participate, the consent can be signed electronically. 
Once signed, the full enrollment survey will be available for completion. Staff will offer to stay connected and support survey 
completion for those who wish support. 
 
5. Early Withdrawal of Subjects: 
 
Participants may withdraw from the study at any time without impact to their care.  They may also be discontinued from the 
study at the discretion of the Investigator for lack of adherence to intervention or study procedures or visit schedules or AEs.  
The Investigator may also withdraw subjects who violate the study plan, to protect the subject for reasons related to safety or 
for administrative reasons. It will be documented whether or not each subject completes the study. Participants who withdraw 
early will not be compensated for research activities they did not yet complete. 
 
6. Vulnerable Populations:  
 
Children, pregnant women, fetuses, neonates, or prisoners are not included in this research study. 
 
7. Populations vulnerable to undue influence or coercion: 
 
The following populations will not be included in the study: children, prisoners, pregnant women, mentally disabled persons, 
or economically or educationally disadvantaged persons. 
 
STUDY DESIGN: 
 
This study is funded by NIH Grant # 3R01NR018196 - 02W1. In the proposed RCT we will enroll adults who are informal 
caregivers of adults with behavioral variant frontotemporal degeneration (bvFTD) and the bvFTD patients they care for. The 
study focuses on the caregivers, but we will also enroll the bvFTD patients to address our exploratory aim. We will seek 
bvFTD patient consent to review their medical records for factors anticipated to add to the demand of caregiving (e.g., 
dementia severity on mCDR).   
 
Caregivers must be informal caregivers of patients with a confirmed diagnosis of bvFTD. They will be screened with the 10-
item Health Self-Care Neglect scale; we will enroll only those who are poor in selfcare using a cut-point of 2 based on our 
pilot study. Caregivers must be able to provide informed consent (speak English, see, hear, cognitively intact) and complete 
the protocol. We will exclude caregivers with cognitive impairment because we anticipate that they would have difficulty 
completing the intervention. We will exclude anyone with untreated major psychiatric illness such as psychosis. Anyone who 

 
 
 
is planning to move out of the area will not be enrolled. Anyone in a competing trial testing a support intervention also will be 
excluded. In this way, we anticipate enrolling only caregivers who are able to provide true informed consent and those who 
will potentially benefit from the intervention.  
 
Caregivers in both the intervention and control arms will receive augmented standard care content (Health Information [HI]) 
through the Internet. In addition, caregivers randomized to the intervention [ViCCY ("Vicky") - Virtual Caregiver Coach for 
You] will receive 10 front-loaded sessions of virtual health coaching by trained Health Coaches over 6 months with content 
based on the theoretical framework our prior research. Sessions are provided using tablets. Initially, sessions are weekly to 
build the relationship, but the frequency of sessions decreases over time. A document of the detailed description of the health 
coaching intervention content is attached. 
 
We help caregivers gain the knowledge and skills needed to achieve self-identified health goals through self-care using 
motivational interviewing. We focus on identifying personal values, solving problems, and transforming goals into action using 
a combination of psychological and behavioral interventions. ViCCY is standardized in a treatment manual. Because stress 
does not affect all people equally, the intervention is tailored to individual appraisals and the factors most likely to influence 
demand and perceived burden.  
     
METHODS: 
 
1. Study Instruments: 
 
Self-care refers to those behaviors undertaken to maintain health. In this study we will measure self-care using the Health 
Self-Care Neglect (HSCN) scale, a 10-item dichotomous scale. This scale has been demonstrated to be reliable (alpha 0.76) 
have content validity. This will be augmented with the Self-care Inventory (SCI), a 5-point likert scale assessment consisting 
of 20 items.  
 
Self-reported stress will be measured with the Perceived Stress Scale, a 14-item instrument that provides a global rating of 
an individual’s belief in the severity and frequency of stressful experiences during the last month. The Perceived Stress Scale 
includes 14 items designed to assess symptoms of stress and global measures of the degree of stress experienced in the 
past month. Each item is scored from 0 (never) to 4 (very often), with total sum scores ranging from 0 to 56; higher scores 
indicate higher perceived stress. Cronbachs alpha of the scale ranges from 0.84 to 0.86 and was 0.91 for older African 
American and European American females.  
 
Coping will be measured using the Ways of Coping Questionnaire, short form. This 42-item questionnaire measures the use 
of five different coping styles: avoidance, problem-focused, seeking social support, self-blame, and wishful thinking. The 
original scale has been used widely since developed by Lazarus in 1985. The short version (30 items) uses a 4-point Likert-
scale response format (0 = not used to 3 = used a great deal); higher scores indicate greater coping. It is reliable (alpha 0.95) 
and has construct validity. This instrument has been used numerous times in studies with older adult caregivers. 
 
Health status (physical and mental health). Medical Outcomes Study Short form (SF)-36. The SF-36 has 36 items formatted 
in scales of varied format (3-, 5- and 6-pt scales and dichotomous [yes/no] scales). each component score is standardized a 
0-100 point scale. Reliability is varied samples is typically 0.80. Convergent and divergent validity have been demonstrated in 
various populations, including caregivers. A benefit of using the SF-36 is that it is one of the common data elements.  
 
Depression will be assessed with the Center for Epidemiological Studies – Depression (CES-D). The CES-D is a valid and 
reliable scale for detecting caregiver depression in dementia. It has added utility, beyond that of a caregiver burden scale, in 
identifying a subgroup of caregivers with depression but not burden. This measure uses 20, 3-point Likert scale response 
items and is reliable (alpha = 0.90).  
 
Burden will be measured with the Zarit-Burden-Interview (ZBI). The ZBI has been used in numerous informal dementia 
caregiver studies to capture burden associated with providing care to a loved one. Total scores are summed and a range is 
provided for little to no burden (0-21) to severe burden (61-88). This is a reliable scale (alpha = 0.86) consisting of 22 items 
rated on a 5-point likert scale (0=never to 4=nearly always). 
 
Quality of caregiver-patient relationship will be measured with the Mutuality scale. The Mutuality Scale is a valid and reliable 
scale that captures the quality of the relationship between the patient and caregiver regarding dimensions of love and 
affection, shared pleasurable activities, shared values, and reciprocity. This measures uses 15 item scored on a 5 point Likert 
scale and is reliable and valid in patient-caregiver dyads.   
 

 
 
 
Evaluation of perceived efficacy of the intervention at 1 month will be evaluated with the Credibility-
Expectancy scale to measure intervention credibility and treatment expectancy early on in the study. The 
Credibility-Expectancy scale is reliable (alpha=0.84) and consists of 6 items scored on a 9 point Likert scale.  
 
 
 
 
 
 
Caregiving characteristics will be collected at baseline in a sociodemographic survey interview format to assess work 
performance with the 7-day work performance questionnaire. This measure has 13 items of 10-pt scale, dichotomous 
assessment, and a record of number hours spent performing paid and unpaid work; alpha = 0.73. 
 
The Protocol for Responding to and Assessing Patients Risk and Experiences (PRAPARE) is a tool kit developed by the 
National Coalition on Community Health Centers to standardize the collection of data on social determinants of health (SDH) 
and facilitate its integration into health records, as a response to recommendations from the National Academy of Medicine. 
The PRAPARE has 16 core domains (Race, Ethnicity, Education, Employment, Insurance, Income, Material Security, 
Transportation, Stress, Housing stability, Housing status, Language, Veteran status, Address/Neighborhood, 
Migrant/seasonal farm work and Social integration/support) and four optional domains (Incarceration history, Safety, Refugee 
status and Domestic Violence) that align with Healthy People 2020 and the Center for Disease Control and Preventions 
agenda for prioritizing SDH in health centers.  
 
Patient characteristics and outcomes will be assessed at baseline with the modified Clinical Dementia Rating Scale (mCDR) 
which includes behavior and language domains. We will also use the Frontotemporal Dementia Functional Rating Scale 
(FTD-FRS) and the Neuropsychiatric Inventory (NPI) to measure behavioral and psychological symptoms of dementia 
 
2. Group Modifications: 
 
No modifications have been made for the study instruments described above. 
 
3. Method for Assigning Subjects to Groups: 
 
Fully eligible caregivers who provide informed consent will complete the baseline assessment before being randomized to 
study arm. The Project Manager will open a numbered sealed envelope, prepared by the team in advance, which assigns 
caregivers to their study arm. The Project Manager will then notify the study staff and participants of their group assignment 
(ViCCY or HI only) by telephone, email or message. The Project Manager will notify the study staff and participants of their 
group assignment (ViCCY or HI only) by telephone, email or message, as preferred by the individual. Although balance in 
sample size can be achieved with block randomization, the groups may not be fully comparable on other factors. Initial 
comparison of the groups will allow us to control for important covariates in the analyses. Investigators and all staff involved 
in collecting assessment data will be blinded to group assignment until after the data are locked. The Health Coaches 
providing the intervention and the caregiver participants will not be blinded. All baseline data will be collected prior to 
randomizing. Timing of follow-up assessments will be based on day of randomization 
 
4. Administration of Surveys and/or Process: 
  
We will enroll 30 informal bvFTD caregivers and the bvFTD patients for whom they care. After collecting baseline data, we 
will block randomize the caregivers 1:1 to the intervention or control group, stratifying randomization by caregiver sex and 
relationship to the patient (e.g., spouse, adult child) factors known to influence caregiving burden, perceived stress, and 
receptivity to the intervention. 
 
We will provide tablet devices with wireless network access and connect caregivers in both conditions to the Internet so they 
can access the Internet site providing Health Information (HI) content for 6 months of the study. A data plan will be provided 
and is included on the tablets. Research staff will provide instruction on how to use the tablet and how to access the HI 
website. A research diary will also be provided to aid tracking of healthcare resources used and costs. Participating 
caregivers in both study arms will be encouraged to spend at least 30 minutes weekly using the Internet modules or books for 
six months.  Those who choose to use books rather than the website will be asked to keep track of the number of book 
chapters reviewed each month. Use of the website or book chapters will be used as a measure of fidelity in both arms. After 
six months, we will collect all tablet devices (both groups) to minimize bleeding of the intervention into the follow-up period, 
and we will continue to track use of the website to identify if bleeding occurs. 
 

 
 
 
In addition to augmented standard care HI, caregivers randomized to ViCCY will receive 10 front-loaded sessions of virtual 
health coaching by trained RNs over the first 6 months with content based on the theoretical framework and our prior 
research. Health coaching sessions will be provided though the tablets via Zoom conferencing software. Sessions are weekly 
initially and decrease in frequency over time. Because maintaining contact is important to the success of stress reduction 
interventions, the assigned Health Coaches will check in with caregivers between intervention sessions. We will offer booster 
sessions to any caregiver in the ViCCY arm who wishes to receive additional support during the 6-month intervention interval. 
We will track the number of sessions and test for differential effectiveness based on the dose received. If a brief check-in call 
becomes an intervention session, it will be tracked for use in analysis. We will mail monthly newsletters to maximize 
retention. 
 
 
5. Data Management: 
 
The research team at the University of Pennsylvania will create and maintain a Redcap research database for all participant 
and adherence data collected during the trial. The database will be stored electronically in the School of Nursing, on a 
Nursing institutionally secured and managed network drive. Please note that all data entered into the research database will 
be password-protected with several levels of protection: first, a password will be required to access the computer of the user 
who has access to the database; second, a password will be required to access the database. 
 
The research team at the University of Pennsylvania will identify potential participants and assign a unique participant 
identification number. This information will be stored in a password-protected document that is only accessible to research 
team members. A member of the University of Pennsylvania research team will approach each potential participant and 
administer informed consent via a paper document. These consent forms will be stored at the University of Pennsylvania in a 
locked file cabinet. 
 
Paper forms will be used to collect participant information during the initial interview and all subsequent interviews, and from 
the medical chart extraction process. These forms will also be kept in a locked file cabinet and the information entered into 
the research database by a member of the University of Pennsylvania research team. We will use standard operating 
procedures to guide all data management activities, such as the naming of variables, data cleaning and handling of missing 
data. Missing fields will not be allowed except in certain pre-specified cases (e.g., income). 
 
6. Subject Follow-up: 
 
Assessments of self-care, perceived stress, depression, burden, coping, relationship quality, and health status will be 
conducted at baseline (after enrollment but prior to randomization) and by phone at 3 and 6 months. We will also collect the 
credibility-expectancy scale at 1 month to evaluate treatment expectancy.  Using contrasts within a mixed-effect modeling 
framework, we will assess intervention efficacy at 6 months using intention-to-treat analysis. We provide 10 health coaching 
sessions based on pilot data and literature demonstrating that a shorter duration of health coaching is not routinely effective. 
We chose to assess the primary aim at 6 months based on prior psychosocial intervention studies, but we will also assess 
outcomes at 3-months based on this rationale: baseline (enrollment), to generate consistent profiles of all enrollees at a 
consistent point in time and prior to implementation of the intervention; at 3-months to evaluate very early effects; and at 6-
months to demonstrate efficacy of the intervention. Our goal is to establish preliminary efficacy and in a future study we will 
evaluate longer terms effects of ViCCY vs. HI at 6-months. 
 
If a subject can no longer participate in the study safely or due to changes in circumstance that prevents participation (e.g., 
imprisonment, long term hospitalization, etc.) they will be withdrawn from the study. Data collection will not continue for 
participants who are withdrawn from the study. If applicable, research staff will arrange to collect study equipment from the 
participants who are withdrawing. 
 
STUDY PROCEDURES: 
 
1. Detailed Description: 
 
We will use a RCT design to achieve robust and unbiased results, as detailed below. We will enroll 30 informal bvFTD 
caregivers and the bvFTD patients for whom they care. After collecting baseline data, we will block randomize the caregivers 
1:1 to the intervention or control group, stratifying randomization by caregiver sex and relationship to the patient (e.g., 
spouse, adult child) factors known to influence caregiving burden, perceived stress, and receptivity to the intervention. We 
will provide tablet devices with wireless network access and connect caregivers in both conditions to the Internet so they can 
access the Internet site providing Health Information (HI) content, which will be the only content provided to caregivers in the 
control group. In addition to HI, the intervention group will receive 10 front-loaded sessions of ViCCY over 6 months. To 
safeguard confidentiality, tablets provided to caregivers can only be used for the study. Assessments of self-care, perceived 

 
 
 
stress, coping, and health status will be conducted at baseline (after enrollment but prior to randomization) and by phone at 3 
and 6 months. Using contrasts within a mixed-effect modeling framework, we will assess intervention efficacy at 6 months 
using intention-to-treat analysis. We chose to provide 10 health coaching sessions based on our pilot data and literature 
demonstrating that a shorter duration of health coaching is not routinely effective. We chose to assess the primary aim at 6 
months based on prior psychosocial intervention studies, but we will assess outcomes at 3-months based on this rationale: 
baseline (enrollment), to generate consistent profiles of all enrollees at a consistent point in time and prior to implementation 
of the new intervention; at 3-months, very early effects, at 6-months longer-term effects of ViCCY. We will pull resource use 
data from the electronic medical record (EMR) in 30-day increments and validated these data during routine follow-up calls 
with caregivers. We expect the proposed study to require 5 years for completion.  
 
2. Data Collection: 
 
A separate database will contain PHI and the link to the assigned patient identifier. Only the PI and the research staff will be 
able to access the PHI data. This information will be maintained by the PI upon the completion of this study; however, this 
data will not be shared or identified for secondary use without IRB approval. Data from the participating subjects will be 
stored in a password protected limited access human subject research database.  Original source records will be maintained 
in locked offices. 
 
3. Genetic Testing: 
 
Not applicable 
 
4. Use of Deception: 
 
None 
 
5. Statistical Analysis: 
 
All analyses will use an intent-to-treat approach. Descriptive statistics will be used to characterize the sample, with measures 
of central tendency and variation for continuous measures, and frequencies and percentages for categorical variables. 
Distributional properties will be examined to determine if variance stabilizing or normalizing transformations should be 
applied. Non-inferential interim analyses will be performed to ensure data collection and archiving procedures are operating 
correctly. Outliers will be assessed by visual inspection and checked for accuracy. Once the database is locked, comparisons 
by group will assess for balance and identify multi-collinearity and areas requiring statistical adjustment. For comparisons 
involving continuous variables, homoscedasticity will be evaluated using Levines tests. Normality will be assessed using 
Shapiro-Wilk tests. Should violations emerge, transformations will be applied, or nonparametric tests used.  
 
While every effort will be made to obtain complete data on every participant, some missing data are inevitable. The 
underlying mechanism missing completely at random (MCAR), nonignorable or not missing at random (NMAR)will be 
evaluated prior to adjusting to minimize bias from missing data. We expect most missing data to be MCAR (e.g., finding data 
collection burdensome). However, systematic bias may exist for those who withdraw so baseline characteristics will be 
compared among those with and without complete follow-up data. To assess potential biases, we will compare withdrawal 
rates and time to withdrawal. If the number lost to follow-up is small (5%) and the missing observations can be considered 
MCAR, then the primary hypotheses will be tested using the complete observed data. If missing observations cannot be 
assumed to be MCAR, more complex approaches will be considered such as shared parameter models or random pattern-
mixture models. Sensitivity analyses for these models will be performed. These approaches assume that participants 
dropped out for either informative (e.g., illness exacerbation) or non-informative reasons (e.g., withdrawing consent). If 
dropouts are informative, we will adjust for this potential bias by introducing a covariate(s) into the analysis to help to explain 
why participants dropped out early.  
 
To assess changes in each of the primary and secondary outcomes over time, separate mixed effects regression models will 
be generated with SAS Proc Mixed. We are not powered for secondary outcomes (e.g., stress, coping, health status), but we 
will examine effect sizes and confidence intervals (CIs) to determine if lack of power is driving nonsignificant results. Mixed 
models can account for correlation between repeated measures and handle non-excessive MAR or MCAR data better than 
traditional models and allow for use of time-independent and time-dependent covariates. Both random slopes and random 
intercepts will be modeled to represent deviations from the average, or fixed-effect, slope over time and intercept, 
respectively. REML will be used for parameter estimation and the most appropriate covariance structure will be examined. 
Scores will be analyzed as repeated observations, with mean-centered baseline outcome scores serving as a covariate. 
Other predictor variables will include group, assessment time, and the interaction of group time (primary effect of interest). 
Baseline measures and group will be analyzed as time-independent covariates. The evaluation of differences in outcome 
profiles over time according to group will rely on the group x time interaction terms, while differences by the balancing 

 
 
 
variables will rely on the mixed-effects modeling of higher order interaction terms. Statistical significance for individual 
intervention contrasts will be evaluated for each outcome, applying the Benjamini & Hochberg method to control for the type I 
error rate at 5%. The Akaike information criterion (AIC) will be used to evaluate overall model fit and to select the best-fitting 
longitudinal change pattern. We expect the groups to be balanced on baseline characteristics due to randomization; however, 
imbalances that occur by chance will be adjusted for in all analyses. To evaluate patient outcomes (Aim 2) over time we will 
use mixed effects regression modeling. As described above, scores will be analyzed as repeated observations, with mean-
centered baseline outcome scores serving as a covariate. Other predictor variables will include time-dependent caregiver 
variables, assessment time, and the corresponding two-way interaction term (primary effect of interest).                                         
 
RISK/BENEFIT ASSESSMENT: 
 
1. Risks:  
 
Protection Against Risk: 
 
Fatigue- To minimize the most likely risk of fatigue during data collection, we selected surveys that are as short as possible. 
Completion of the self-report survey packet requires less than one hour. Testing will be scheduled at a time that is convenient 
for subjects. If participants are too fatigued to complete all measures, sociodemographic and clinical data will be administered 
at enrollment and the baseline surveys will be gathered in a subsequent telephone call (but before randomization). All 
delayed data collection will occur within a two-week interval. The RAs will be trained to be sensitive to signals from 
participants that a break is needed during testing. All participants will be informed that they can stop their participation in the 
study at any time. For subjects who find data collection too fatiguing, we will offer the option of providing only the most 
essential data reflecting the key outcome variables (e.g., health self-care neglect). 
 
Stress- To minimize the risk of stress during data collection the RAs will be trained to be supportive and helpful to participants 
with questions about data collection. If a participant becomes stressed during data collection because of the questions asked, 
the burden of data collection, or for other personal reasons, data collection will be terminated, delayed, or abbreviated to only 
the most essential items (e.g. primary outcome variable). Significant stress will be reported to the Project Manager who will 
contact the caregiver to discuss the issue if indicated (the PI is blinded). The RAs will be trained to detect any signals that the 
participant is becoming upset before stress escalates. In a prior study, we hired nursing and psychology students as RAs, 
which facilitated the assessment and management of participant stress during data collection. RAs will be required to have 
sufficient maturity and background to interact appropriately with ill, aging, stressed individuals. The protocol for the training of 
RAs, detailed in our operations manual, addresses enrollment methods and the collection of data in a uniform manner. 
Training for RAs in data collection will occur during a two-day period prior to beginning subject enrollment. Training will begin 
with classroom instruction, including the purpose and background on each measure, importance of strict adherence to the 
standardized protocol, step-by-step instruction for survey administration, criteria for aborting testing and the procedure for 
audiotaping sessions and transmitting data. RAs will be trained to ensure that they do not prompt subjects with verbal or 
nonverbal cues. Training will include practice administering all tests. Consistency in data collection procedures will be 
assessed and reinforced during routine staff meetings. Retraining and retesting will be done immediately if a new RA is hired 
and annually thereafter. The PI and the Project Manager will meet weekly or bi-weekly with staff (in-person or by video) to 
discuss issues of enrollment and data collection. All decisions will be logged and filed for future reference. All issues will be 
reported immediately to the IRB and the Data Safety Monitoring Board, as discussed in that plan. 
 
We will be enrolling a sample of stressed individuals and it is possible that we will identify someone with severe distress. Dr. 
Riegel (PI) has previously tested  a detailed safety plan, which has been refined for use in this study. This safety plan 
addresses the concerns associated with severe stress that need to be handled in order to ensure that the research 
participants needs are addressed. This plan includes the requirement that research staff undergo training in this safety 
protocol and participate in ongoing regular supervision by Dr. Massimo (Co-I) on these procedures. In addition, for 
participants randomized to the ViCCY group, specific rules to ensure privacy and safety will be discussed in the first session, 
such as being in a private place during sessions and not engaging in discussions while driving. 
 
2. Benefits: 
 
We cannot guarantee that any participant will benefit by participating in this study, although all of the caregivers will receive 
health information. We acknowledge that subject burden may be an issue for these already-burdened caregivers. However, 
we believe that the benefits of the knowledge gained will outweigh the burden and the risks to participants. A Data and Safety 
Monitoring Board will be used to ensure the validity and integrity of the data. We anticipate that the results of this study will 
benefit society most, by helping to improve the support provided to caregivers of bvFTD patients. 
 
3. Subject Privacy: 
 

 
 
 
Data will be compiled from all of the subjects in the study and aggregated for analysis and publication. All identifying data will 
be eliminated from files before data are electronically transferred to the biostatistician. As a result of aggregation, no 
individual subjects will be identifiable from the written materials. Audiotaped interviews will be assigned a unique identifier; 
any identifiable information in the interviews will be deleted during the transcription process. All videoconferencing sessions 
will be conducted using secure encrypted platforms. All companies providing third-party platforms used for this study 
completed the Vendor Security Technical Assessment of Risk (V-STAR) forms and have been vetted by SONs IT 
Department. And tablets provided to caregivers can only be used for the study. 
 
4. Subject Confidentiality: 
 
A trained research assistant will review the electronic medical record to make sure that the caregivers approached qualify to 
be participants before we invite them to join the study (eg. the patient has bvFTD). Accessing the EMR means that we will 
see PHI but we will limit our review to only those elements essential to establish eligibility. If the record review indicates that a 
caregiver is not eligible, we will note this on our paper-and-pencil log so that we do not need to repeat the review the next 
time the patient comes into the clinic. That paper log will be transported back to the School of Nursing and locked in a drawer 
until the next scheduled day of enrollment. We will not disclose the information on the log to anyone not directly involved in 
the study. 
 
To protect against any risk to subject confidentiality, all printed data forms will be coded with unique identifiers. The unique 
identification number will be kept separate from the files with protected health information (PHI) to protect subject 
confidentiality. Every effort will be made to prevent anyone who is not on the research team from knowing what information 
was collected from a particular subject. As part of the consent process, subjects will be made aware of the fact that there are 
some circumstances where the research team may have to provide subject information to other people (regulatory or legal 
circumstances). In addition, as we are unable to ensure total Internet security, this limitation of privacy will be noted in the 
informed consent. In this manner caregivers will be informed that although it is highly unlikely that anyone would access an 
audiotaped session, the prevention of such intrusions cannot be guaranteed. The content of the intervention sessions is not 
anticipated to be confidential in nature. 
 
Since this data storage system is behind multiple firewalls, is monitored regularly, and is accessible only to key personnel 
who receive private network/firewall, server/password, and data directory access rights, the risk of unlawful penetration is not 
a significant data safeguard concern. Individually identifiable or deducible data will not be transmitted by unsecured 
telecommunications, which include the Internet, email, and electronic File Transfer Protocol (FTP). Further, the data will not 
be physically moved or transmitted in any way from the server without written approval from the project manager. All output 
containing individual identifiable information is treated as confidential data. This information is never transferred electronically 
via email or other protocols. 
 
All data will be backed up daily and system backups will be done weekly. Batch validity checks will be run on the database at 
periodic intervals to identify data that violate predefined rules. Data will be de-identified and stored on the database server 
with strong access controls, software firewall, secure file transfer protocols, network-wide virus protection software, and daily 
back-ups. The computers will be password-protected and maintained in a secure, locked location at the School of Nursing. 
Interim checks will be conducted regularly to ensure that data collection and archiving procedures are operating correctly and 
security and confidentiality are not compromised. All information obtained on paper (e.g., consent forms) will be numerically 
coded and locked in a secure location, as described further below. 
 
Signed consent forms and other subject-specific information containing names will be kept separate from the subject 
identification numbers. The master list and subject information will be stored in different locked file cabinets in the PIs 
research offices at the University of Pennsylvania, School of Nursing. Access to these master files will be limited to those 
directly involved in the study. 
 
Regarding internet access and video-conferencing sessions, study tablet devices, which are versatile for allowing privacy, will 
be provided to all participants and can only be used for the study. Health coaching sessions will be provided through the 
tablets via Secure VidyoConferencing software. Sessions are weekly initially and decrease in frequency over time. The tablet 
uses an embedded computer camera capable of full 2-way duplex video and audio transmissions for real-time 
communication. Existing broadband Internet connection is not required because we supply devices with mobile connectivity. 
Technology experts (Caryl Technologies, with whom we have worked in the past) will train research staff to set up Internet 
service. 
 
How will confidentiality of data be maintained?  Check all that apply. 
 
 Paper-based records will be kept in a secure location and only be accessible to personnel involved in 
the study. 

 
 
 
 Computer-based files will only be made available to personnel involved in the study through the use of 
access privileges and passwords. 
 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. 
 Whenever 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.  
 Other (specify):     
 
 
5. Protected Health Information 
 
Name 
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 
Telephone and fax number 
Electronic mail addresses 
Medical record numbers 
 
 
 
6. Compensation:  
 
As data collection is anticipated to require significant commitment and effort on the part of subjects, remuneration will be 
provided. We carefully considered the amount to pay participants using the guidelines from Dickert and Grady. Because 
of the potential burden of data collection, we chose a market model of payment where the amount serves as an incentive 
rather than a reward. The advantage is more rapid recruitment and avoidance of subject financial sacrifice. Further, a 
completion bonus encourages subject retention. Using this model, caregivers will receive $25 at enrollment, $25 at 3 
months and $75 when they complete the study for a total remuneration of $125 for a 6-month commitment. This amount 
is not anticipated to be undue inducement, considering the effort and commitment required of participants. 
 
This study is funded by NIH Grant # 3R01NR018196 - 02W1. 
 
7. Data and Safety Monitoring: 
 
We will use a Data Monitoring Committee as described in the attached document. 
 
8. Investigator’s Risk/Benefit Assessment: 
 
It is our judgment that benefits outweigh the risk to study participants. 
 
INFORMED CONSENT: 
 
1. Consent Process: 
 
After approval by the Institutional Review Board (IRB) at Penn, the research staff will work with clinical staff to identify eligible 
caregivers for referral to us. To obtain a consecutive sample we will seek a HIPAA waiver to screen the clinics daily 
appointment schedule to identify every patient with a confirmed diagnosis of bvFTD and a potentially eligible caregiver. If 
enrollment from the clinic is slow we will also look for bvFTD patients participating in research at the Penn Frontotemporal 

 
 
 
Degeneration center. Once identified, clinic or research staff will ask potential caregiver participants (e.g., those who speak 
English) and determine their willingness to speak with research staff about the study. Those agreeing to speak with us will 
have the study carefully explained to them by the research staff. Potential participants will be fully informed regarding the 
interventions and the schedule of the data collection. Those willing to be screened will provide verbal consent to undergo 
screening to assess inclusion and exclusion criteria.  
 
After screening, the RA will obtain written informed consent from caregivers and bvFTD patients. Those who agree to 
participate will be asked to read and sign the consent form with integrated HIPAA authorization information (i.e., specifics 
about data elements to be collected and use of the private information). The consent form will specify that some intervention 
sessions will be audiotaped to ensure the quality of the intervention and judge treatment fidelity. We will explain that these 
audiotapes will be transcribed for analysis and then destroyed. We will use SameDay transcription for our audio recordings. 
They are a HIPAA-compliant company that has been vetted by SON's IT Department. The RAs will answer questions and 
make sure that the procedures that are to be used are fully understood. 
 
The study will provide tablet devices with wireless network access and active antivirus to all participants. The tablets will only 
be able to be used for the study. Caregivers in both conditions will be able to access the Internet site providing Health 
Information (HI) content for 6 months of the study. A data plan will be provided and is included on the tablets. Research staff 
will provide instruction on how to use the tablet and how to access the HI website and assist participants to access the HI site 
if necessary. A research diary will also be provided to aid tracking of health care resources used. 
 
In the case that participants cannot be consented in-person, participants may be consented remotely at the PI’s discretion. 
Screening will be done by telephone and those who are eligible to participate will be pushed an electronic link that begins 
with the consent form. Staff will talk through the consent in detail. If the caregiver wishes to think about the study but not 
commit at this time, we will contact him/her at a later date. If the caregiver immediately decides to participate, the consent 
can be signed electronically.  
 
2. Waiver of Informed Consent: 
 
No waiver requested. 
 
RESOURCES NECESSARY FOR HUMAN RESEARCH PROTECTION: 
 
OVERALL STRUCTURE OF THE STUDY TEAM 
This is a single site clinical trial with a Clinical Coordinating Center (CCC) with direct oversight by Dr. Massimo and Dr. Reigel 
and a Data Coordinating Center (DCC) with oversight by Co-Investigator Dr. Aryal. Enrollment will take place primarily at the 
Penn Frontotemporal Degeneration Center. Oversight of the clinical intervention will be done by Dr. Reigel and Dr. Massimo. 
 
The Project Manager will identify training requirements relevant to the study activities and develop a training plan and 
process for providing and documenting training activities. This includes developing training materials (checklists, manuals, 
slides, and FAQs) and implementing a process for tracking. She will oversee participant enrollment, data collection, data 
entry and cleaning, and analysis efforts to assure that these activities take place as planned. In addition, a clinical research 
coordinator will be hired to facilitate smooth and efficient data collection, help with recruitment and identification of potential 
subjects. 
 
Health coaches. We will hire 2-3 experienced health coaches with excellent interpersonal communication skills, and comfort 
with technology. The coaches will receive two days of initial training in health coaching from Dr. Riegel and her team and 
then completed 7 hours of online training in motivational interviewing provided by the University of Colorado, College of 
Nursing. Dr. Massimo will also provide the coaches with a day of training related to FTD and they will receive the book, “What 
if it’s Not Alzheimer’s,” developed for FTD families, which contains a chapter written by Dr. Massimo on common behavioral 
symptoms in persons with FTD. Thereafter, weekly training and supervision will be conducted by Drs. Riegel, Hirschman and 
Massimo as the coaches begin sessions with the caregivers. As part of this supervision, audio-recordings of coaching 
sessions will be reviewed by independent raters using the Behavior Change Technique taxonomy. Two trained raters have 
judged randomly selected session recordings for each coach, assessing completeness and thoroughness of the therapeutic 
techniques used. We will continue to assess the quality of the coaching as we add this group of caregivers with unique 
issues.               
 
Internet Access. We will leverage the current technology infrastructure from R01NR01819. We will provide tablet devices to 
all participating caregivers. Tablets are versatile, allowing privacy for coaching sessions and website access to those in the 
HI group. The tablet uses an embedded computer camera capable of full 2-way duplex video and audio transmissions for 
real-time communication. Existing broadband Internet connection is not required because we supply devices with mobile 
connectivity. Technology experts (Caryl Technologies, with whom the team currently work) will train research staff to set up 

 
 
 
Internet service and devices with Caregivers during a virtual visit.  Caregivers will be left with a step-by-step manual and the 
research assistant phone number in case technology issues occur. 
 
Data Coordinating Center - Data coordination for the trial will be done by the BECCA (Biostatistics * Evaluation * 
Collaboration * Consultation * Analysis) Lab in the School of Nursing. The BECCA Lab is comprised of a team of highly 
skilled doctoral and masters level statisticians, along with Penn Nursing research assistants and biostatistics graduate interns 
who oversee data management and analytic activities. The lead statistician and Co-Investigator, Dr. Aryal will ensure 
statistical rigor and appropriateness of all analyses. 
 
Research Technology staff will develop and maintain a REDCap data management system. They will collaborate with the 
investigators to identify relevant clinical data from electronic medical record data (EMR) in the Penn Data Store and design, 
test and implement a process to import data at a scheduled frequency to data tables, which will be part of the research 
database. Research Technology staff will also develop programs to identify new hospital encounters for study participants 
using EMR information in order to initiate communication to the research staff that follow up action may be required. 
 
Data Management staff will develop the case report forms and modify standard or template questionnaires as needed. They 
will design and develop the trial database and required modules. All research data for the trial will be stored in an electronic 
database that is managed by BECCA Lab. The database will be hosted on secure School of Nursing computing servers with 
access restricted to only those individuals who are authorized to work on the trial. Individual user accounts with passwords 
will be used to restrict access to the database. Specific privilege assignments within the database will be employed to limit 
the types of functions that authorized users can perform to those functions that are appropriate for their role in the trial. 
Additional measures to prevent unauthorized external access to the database environment will be employed using network 
firewall technologies. 
 
BECCA Lab personnel will work closely with Dr. Massimo, Dr. Riegel, and the Project Manager to design, develop, and test 
an appropriate database structure to support the requirements of the study to promote data security and integrity. Electronic 
audit trails of changes to database contents are incorporated into the design and will capture and record those changes 
automatically. BECCA Lab personnel will configure a module to allow remote data entry from the enrollment sites. The 
module will be available to any computer with a persistent internet connection and will be run using standard web browser 
software. The data entry screens will look like the existing or reconfigured data collection forms and will allow for direct 
source-to database data entry, eliminating the need for paper Case Report Forms (CRFs). Data entry checks will be included 
in the entry screen designs where appropriate to limit the opportunity for erroneous entries due to mistyping. Such data entry 
checks would include value range comparisons, valid data type checks, required value checks, and skip pattern enforcement. 
This data entry module will be configured for single data entry. 
 
BECCA Lab personnel will configure a module to assess data entered into the database in relation to a set of rules that 
describe expectations for those data items. This set of data validation rules will be defined by clinical data management 
personnel, working closely with Dr. Riegel and the Project Manager, to identify data items that may have been collected 
incorrectly or entered into the database inaccurately. The module will inspect all newly entered or modified data. Clinical data 
management staff will review the results of the data validation and contact research staff to request corrective action for 
invalid data. All changes made will be recorded in an electronic audit trail and documented using change control procedures. 
Prior to deployment and use in the trial, the database will be subjected to extensive functional testing. Testing will include an 
evaluation by representative users. 
 
Trial Close-Out: Once all data have been collected, BECCA Lab staff will lock the database. Trial data will be packaged for 
data sharing purposes. A snapshot of the database will be taken and stored in a secure folder.