Caregiver Support in the Context of Multiple Chronic Conditions: Randomized Waitlist Control Trial
Phase: NA
Conditions: Caregiver Burnout
Sponsor: Johns Hopkins University

 
 
 
 
 
 
 
 
 
 
 
Caregiver Support in the Context of Multiple Chronic Conditions 
(NCT04090749) 
Updated 3/29/23 
 
 
 
 
 
 
 
 
 

 
 
Protocol 
 
 
 
 
1. 
Abstract 
 
Family caregivers who care for older adults living with multiple chronic conditions, including heart failure 
(HF), provide substantial cost savings to the US healthcare system.1  While caregiving can be meaningful 
and rewarding, extensive research also demonstrates high rates of chronic disease, fatigue and physiologic 
measures such as stress hormones among caregivers.2 Family caregivers are often left juggling their loved 
one’s healthcare as well as their own. Unmet needs have been identified including increased stress, 
financial strain and social isolation, but interventions to address these needs in HF caregivers have had 
mixed results.3 Due to the limited impact of many caregiver interventions, experts have called for a greater 
understanding of the dynamic and contextual factors of family caregiving including resources, needs and 
social support with an increased focus on individualization of interventions for high-risk caregivers to 
improve outcomes.3–6 Following a mixed methods study to better understand these contextual factors and to 
address this gap between the evidence and uptake of proven strategies by caregivers, we have developed a 
resilience-promoting intervention to improve quality of life for family caregivers of individuals with 
multiple chronic conditions, including HF, Caregiver-Support.7–9 This home-based intervention is guided 
by effective strategies implemented by our co-investigator, Dr. Sarah Szanton, to support older adults in 
goal setting to promote healthy aging.  Using these strategies, Caregiver-Support will help caregivers 
articulate statements of purpose in life, set goals to address fatigue and caregiver burden, provide 
instrumental support through a benefits check-up and promote identification and increased connection with 
the caregiver’s social network.  
 
The first phase of the study will be an open label pilot (N=5) followed by a single-masked, two-group, 
randomized trial (N=40) to test the feasibility and gauge an initial effect size of the intervention. 
Participants will be visited by study staff in their homes for data collection and intervention visits. 
Participants will be randomized to receive either the immediate intervention group or the waitlist control 
group. In the waitlist control group, participants will receive usual care for the first 16 weeks (which is 
limited to printed materials provided in the clinic) and then begin the intervention. The intervention will 
consist of 5 in-home sessions with a nurse interventionist. Each participant will receive each intervention 
component but interventionists will systematically tailor content to the participants' goals based on 
protocols. All participants will be reassessed at 16 weeks and 32 weeks by a research assistant (RA) 
masked to treatment condition. The primary outcome will be improvement in quality of life between 
baseline and 16 weeks. Other endpoints include group differences in fatigue, caregiver burden, self-
reported and physiological measures of resilience up through 32 weeks after the intervention. We will also 
examine the acceptability of the intervention using intervention compliance and participant satisfaction 
data.  
 
 
 
2. 
Objectives  
Aim 1:  Test the feasibility and gauge an initial effect size of the intervention to improve QOL (primary 
outcome), fatigue and caregiver burden (secondary outcomes) among family caregivers from baseline to 16 
weeks.   
 
Aim 2:  Test whether fatigue and caregiver burden are associated with a physiological measure of 
resilience, inflammatory cytokines (Il-6 and IL-10) detected in sweat patches and a self-reported measure 
of resilience, controlling for covariates. 
 

 
 
Aim 3: Evaluate changes in heart rate variability (HRV), an indicator of physiologic stress, pre- and post-
intervention.  
 
Aim 4: Describe care recipient 6-month palliative care utilization, all-cause hospitalization, and mortality, 
comparing intervention and control.  
 
3. 
Background  
 
Heart failure (HF) is a syndrome of multiple chronic symptoms and commonly co-occurs with 10 
other chronic conditions.10 Nearly 30% of patients who have been hospitalized for HF will be readmitted 
within 30-60 days and 53% of patients hospitalized for HF will die within 5 years.11,12 As older adults 
manage worsening HF, caregiving responsibilities often increase, a phenomenon that has a greater impact 
among vulnerable populations.4,13–15 Throughout the provision of care, family caregivers must address a 
wide range of patient needs: assistance with everyday activities, help with a range of healthcare activities, 
transitions between settings of care, medication management and wound care. However, because family 
caregivers are not routinely assessed in health care delivery, little is known about the context of 
their contributions to health care activities or the caregiving-related effects they experience.16 
 
Previous studies of family caregivers of patients with HF have identified worsening quality of life 
(QOL) over the course of the patient’s illness.13,17,18 For patients, being able to stay in the home as HF 
worsens, provides a sense of security, freedom and improved symptom awareness. However, many 
caregivers report increased distress while supporting the patient in the home, feeling alone and fully 
responsible for care.19 Fatigue and burden have been found to be significantly associated with decreased 
QOL, demonstrating the need to improve caregiver outcomes.13 Additionally, caregivers of patients with 
high symptoms perceive they spend more time on difficult tasks, have worse affective symptoms, and 
have poorer physical health-related QOL than those caring for patients with low symptoms.18 Thus, there 
is great need to provide interventions that improve QOL and decrease fatigue and caregiver burden of 
family caregivers of patients with HF, particularly in the home when patient symptoms are high. 
 
Stress response and autonomic nervous system dysregulation have been noted among caregivers.20,21 
Several cellular and systemic changes accompany the stress response network including: cytokines, namely 
Interleukin 6 and 10 (IL-6 and IL-10) and tumor necrosis factor alpha receptor 1 (TNFαR1), brain derived 
neurotropic factor (BDNF) and heart rate variability (HRV). Heart-rate variability detects variation in the 
length of time between heart beats and is considered an indirect view of autonomic nervous system 
function.  Autonomic nervous system dysregulation is important in chronic diseases such as depression, 
diabetes, cardiovascular disease, stroke and certain neurological disorders.22  Symptoms like sleep, fatigue, 
and pain are also correlated with autonomic nervous system activity.23,24 
 
The proposed study will implement a program using evidence-based strategies.  This study builds 
on our success in previous randomized control studies that support community dwelling, low-income, 
older adults with functional limitations age in place by addressing individually tailored goals to improve 
resilience.8,25 We will also contribute to caregiving science by evaluating implementation and maintenance 
of goals by participants. We will measure response to the intervention by examining both self-reported 
measures and physiological measures such as IL-6, IL-10 and HRV.  The proposed study will address the 
National Academies of Sciences, Engineering, and Medicine recent call to promote the well-being of 
family caregivers for older adults with a focus on ensuring respect for families’ diverse contexts, beliefs, 
and preferences. 
 
Investigators 
Our research team has worked together on studies in various combinations for years and represents 
nationally and internationally known investigators with expertise in the proposed methods.  The PI is a 

 
 
junior investigator (Dr. Abshire) with extensive clinical and research experience with heart failure patients 
and caregivers.  As a junior investigator, she will be mentored by Drs. Szanton and Davidson. Dr. Sarah 
Szanton has fielded multiple community trials that involve nurse-led home visits and goal setting.7,  8 Dean 
Patricia Davidson is a global leader in HF and has an established program of research improving 
cardiovascular care and caregiving.   
 
Innovation 
The proposed study is innovative in several critical ways:  1) Supporting caregivers of patients with HF to 
discuss their purpose in life, set their own individualized goals, while providing instrumental and social 
support is both a person- and family-centered approach to improve QOL; 2) it addresses both intrinsic, 
individual factors and extrinsic factors through the instrumental support and social network strategies 
which has not been reported previously; 3) it allows participants the opportunity to tailor their goals to 
their own needs, rather than the heart failure management needs of the patient.   
 
Conceptual Framework  
This study will be guided by the Society to Cells Resilience Framework (Figure 1), first-authored 
by Dr. Sarah Szanton (co-Investigator for this pilot). The Society to Cells Resilience Framework posits 
that intervening on more than one socio-ecologic domain (in this case, physiologic, individual, and family) 
leads to more lasting effects on individual resilience compared to intervening on one domain.  Second, that 
resilience can be fostered at critical times in the life course, such as when there are increased caregiving 
responsibilities that can both create meaning and strain. Based on these tenets, the resilience framework 
ties together the many proposed levels of measurement such as fatigue, caregiver burden and quality of 
life by intervening simultaneously on them to improve overall resilience.  
 
 
 
 
 
 
4. 
Study Procedures 
 
 
Factors
Physiology: 
- Cytokines IL-6 and 
IL-10 (sweat patch)
- Heart Rate 
Variability (HRV)
Individual: 
- Fatigue
-Caregiver Burden
- Coping and Self-
Efficacy
Family: 
-Social Support
-Family 
Functioning
Resilience 
Intervention
Statements of 
Purpose in Life 
and Goal-Setting
Instrumental 
Support
Social Support
Outcome
Quality of Life
Figure 1:  
Conceptual 
Framework 
including 
Resilience-
building 
intervention and 
Key Variables 
Figure 2:  Flowchart of Study Design 

 
 
Overview of Study Design (Figure 2): We 
propose an open label pilot (n=5) with a 
subsequent single-blind, two group randomized 
pilot trial to test the feasibility and gauge an initial 
effect size of the Caregiver-Support intervention to 
improve QOL. The immediate intervention group 
(n=20) will receive the intervention during weeks 
0-16.  The waitlist control group (n=20) will be 
provided written materials with community 
resources for caregivers during the first 16 weeks, 
then they will begin the intervention. Waitlist 
control groups are used to first provide an untreated comparison and second to allow wait-listed 
participants an opportunity to receive the intervention at a later date.26,27 This is especially appropriate 
given that very few services are currently offered to HF caregivers. To account for estimated 20% attrition 
we will recruit 53 participants.  
 
 
Johns Hopkins Clinic Recruitment:   
Method 1: We will enroll caregivers of patients with HF treated in the Johns Hopkins Health System. Once 
we find potentially interested participants through clinic referral, we will screen the caregiver for eligibility 
then contact them by phone, zoom, or in person in clinic to explain study procedures. If eligible by 
screening and interested in participating, we will schedule the caregiver’s baseline interview within 10 days 
of initial contact. During the baseline interview the research assistant will re-explain the study, obtain 
written consent (if interview is in-person), or e-consent (if the interview is by phone or DoxyMe or Zoom 
video call).  
 
Method 2: We will distribute a recruitment flyer in adult medical/surgical clinics in the Johns Hopkins 
Health System. Caregivers that respond to the recruitment flyer will be screened for eligibility. If they are 
eligible, we will contact them by phone to explain study procedures. If interested in participating, we will 
schedule the caregiver’s baseline interview within 10 days of initial contact. During the baseline interview 
the research assistant will re-explain the study, obtain written consent (if interview is in-person), or e-
consent (if the interview is by phone or DoxyMe or Zoom video call). 
 
 
Method 3: Caregivers of patients with heart failure will be identified through recruitment screening of Dr. 
Martha Abshire Saylor’s study “Palliative Care Needs of Community-Dwelling Patients with Heart Failure 
and Physical Frailty” (IRB00262188). Patients will be sent a recruitment flyer for their caregiver. 
Caregivers that respond to the recruitment flyer will be screened for eligibility. If they are eligible, we will 
contact them by phone to explain study procedures. If interested in participating, we will schedule the 
caregiver’s baseline interview within 10 days of initial contact. During the baseline interview the research 
assistant will re-explain the study, obtain written consent (if interview is in-person), or e-consent (if the 
interview is by phone or DoxyMe or Zoom video call). 
 
Johns Hopkins Bayview Clinic Recruitment: 
We will distribute a recruitment flyer in the heart failure clinic at the Johns Hopkins Bayview Medical 
Center. Caregivers that respond to the recruitment flyer will be screened for eligibility. If they are eligible, 
we will contact them by phone to explain study procedures. If interested in participating, we will schedule 
the caregiver’s baseline interview within 10 days of initial contact. During the baseline interview the 
research assistant will re-explain the study, obtain written consent (if interview is in-person), or e-consent 
(if the interview is by phone or DoxyMe or Zoom video call). 
 

 
 
 
Heart Failure Center at Ascension St. Agnes Hospital Recruitment: 
We will distribute a recruitment flyer in the heart failure clinic at St. Agnes. Once we find potentially 
interested participants through self-referral though the recruitment flyer, we will screen the caregiver for 
eligibility then contact them by phone, zoom, or in person in clinic to explain study procedures. If eligible 
by screening and interested in participating, we will schedule the caregiver’s baseline interview within 10 
days of initial contact. During the baseline interview the research assistant will re-explain the study, obtain 
written consent (if interview is in-person), or e-consent (if the interview is by phone or DoxyMe or Zoom 
video call). 
 
Open Label Phase:   
The first five participants will be enrolled into an open label pilot study, in which they will automatically 
receive the Caregiver-Support intervention. The participants will be interviewed after program completion 
to get feedback on the data collection instruments, intervention content including the number of visits and 
user-friendliness of intervention components (e.g. purpose in life activity), and satisfaction with the overall 
program process. This feedback will be used to modify the Caregiver-Support intervention for the waitlist 
control trial that will begin enrollment following the open label phase.  
Randomization:  Within 48 hours of the baseline interview, we will randomize using redcap 
randomization and communicate the assignment to participants by letter. At that same time, we will inform 
the nurse interventionist of the new participant. The intervention nurse will contact the participant within 
one week to schedule the first appointment.  The waitlisted group will receive usual care for caregivers for 
the first 16 weeks, which is normally limited to inclusion in some clinical assessment and teaching during 
patient visits.  Waitlisted participants will receive monthly study postcards to encourage retention.  After 16 
weeks, they will begin the intervention. The 32- week assessment will measure whether immediate 
intervention participants continue the strategies on their own and whether they continue to improve on the 
self-report scales and will measure improvement following the intervention for waitlisted participants. 
 
Intervention Delivery Characteristics:  
The intervention delivery characteristics will consist of an assessment-driven, tailored package of 
interventions delivered by a nurse interventionist. The intervention will be guided by the theory and 
evidence-based practices that have been successful in our previous work drawing upon clinical approaches 
such as patient-centered care and motivational interviewing.23,38 Every participant receives each component 
of the intervention (assessment, goal setting, interactive problem-solving, training) but interventionists 
clinically tailor content to each participant’s goals. Nurse interventionists will be trained and equipped with 
education materials vetted by national organizations leading caregiving research such as the National 
Alliance for Caregiving, National Council on the Aging (NCOA) and the, American Association for 
Retired Persons (AARP). We propose an intervention incorporating 5 individualized, nurse-led, home-
based or virtual sessions, with telephone check-ins and text reminders, according to participant preference. 
Baseline, 16 and 32-week data will be collected by interviewers masked to treatment assignment and 
without interventionist contact. Each design component, related evidence supporting component selection 
and intervention delivery is described below.   
 
Table 1 Intervention Components and Evidence Basis for Component Selection 
Intervention 
Component 
Evidence Basis for Component 
Intervention Delivery 
1) Whole-person 
physical and 
psychosocial 
assessment including 
personal goals 
- Caregiver physical and 
psychosocial assessment is suggested 
by HF guidelines, but not commonly 
used in practice28–31 
- Involving the caregiver in 
assessment and encouraging them to 
A trained nurse will assess the caregiver 
using a holistic physical and psychosocial 
assessment used in previous studies.  The 
nurse will focus on caregiving tasks and 
factors contributing to a sense of burden. 

 
 
set their own goals is person-
centered, builds rapport and 
increases participation.25,32,33 
The nurse will share observations with the 
caregiver to inform goal-setting. 
2) Discussing 
caregiving in the 
context of the 
caregiver’s identified 
‘purpose.’ A nurse will 
lead the caregiver 
through activities 
designed to help 
identify or refine a 
statement of purpose in 
life. 
- Purpose in life was associated with 
lower mortality and CVD34, stroke35, 
MI36, better preventive health 
behaviors37, lower allostatic load38 
- Purpose in life can be improved 
through intervention39–41 and is 
linked to down-regulation of pro-
inflammatory genes42 
A trained nurse will lead the caregiver 
through activities designed to help the 
caregiver identify and write a statement of 
purpose in life.  For this purpose, a deck 
of question cards have been developed.  
The caregiver will choose one or more 
cards from each of 4 themes:  purpose, 
experience caregiving, caring for yourself 
and emotions.  Comments made will be 
used to create a summary purpose 
statement. 
 
3) Co-development of 
incremental action 
plans that address 
personal goals to 
improve quality of life 
and reduce fatigue and 
caregiver burden.  A 
list of goals will be 
constructed and 
prioritized.  Caregivers 
will design and work 
on incremental action 
steps related to goals, 
through tailored 
strategies developed 
through collaboration 
with the nurse. 
- Incremental action plans based on 
individually tailored goals, allowing 
the participant to prioritize their own 
goals and strategies, increases self-
efficacy and encourages participants 
to use their new skills with other 
problems.25,32 
- Studies incorporating this technique 
have resulted in improved QOL, self-
efficacy related to falls, depression 
and decreased disability.8,25,33 
- Goal attainment achieved in 73% of 
functionally impaired older adults- 
independent of age, race, gender – 
higher pain group less likely to 
achieve goals.33 
A list of goals related to addressing 
fatigue, caregiver burden and perceived 
threats to QOL will be constructed and 
prioritized.  During the nurse-led sessions, 
caregivers will work on action steps 
related to goals in order of priority 
through tailored strategies developed 
through collaboration with the nurse.  
Instrumental Support 
refers to the tangible 
help that others may 
provide (e.g., help with 
financial needs, 
provision of 
transportation or 
support with 
medication 
management). 
- Instrumental support may enhance 
emotionally supportive 
interventions43–45 
- Addressing needs to support 
instrumental activities of daily living 
may improve retention from 
participants 
- Interventions that provide 
instrumental support while equipping 
community members are more 
sustainable and impactful than 
providing the support without 
considering social support/network. 
BenefitsCheckUp is a free, confidential 
service provided by the National Council 
on the Aging (NCOA) for people 55 and 
over and their caregivers. The nurse 
interventionist will help the caregiver 
explore the modules which include topics 
such as medications, healthcare, income 
assistance etc.  Common unaccessed 
benefits caregivers may be eligible for 
include:  Medicaid, Food bank access, 
home energy assistance and tax credits. In 
addition, the nurse will provide support 
for caregiving challenges such as 
medication management or 
communication with providers of multiple 
chronic conditions. 
 

 
 
Social Support 
- Perceived social support can be 
enhanced through interventions43 
- Helping the caregiver identify ways 
they are already supported may 
support a sense of perceived support 
- Setting goals to engage the existing 
social network may increase self-
efficacy for future needs and 
engagement46 
A trained nurse will lead the caregiver 
through activities to help caregivers 
connect to their existing family and 
community to engage these relationships 
for support in caregiving.  The nurse and 
caregiver will work through these 
activities during an in-home visit. 
 
 
 
Intervention Protocol: 
The RN will meet with the caregiver in-home or virtually to perform the whole person assessment 
in which the nurse will focus on caregiving tasks and factors contributing to a sense of burden.  In this 
assessment, the RN and the caregiver identify and prioritize goals, and make plans to achieve those goals. 
The study will provide the Caregiver-Support Handbook, including evidence-based educational materials, 
contact information, and a calendar of sessions that the participant keeps for reference. In each session, the 
RN assesses goal attainment, reinforces strategy use, reviews problem-solving, refines strategies (examples 
in Table 3 such as Go4Life and AARP materials), and provides education and resources to address future 
needs. If sessions are held virtually via phone or DoxyMe video call or Zoom video call, no physical 
activity goals will be pursued as part of this intervention due to the inability to safely assess the participants 
physical activity readiness.  
Following the session, the RN will find additional resources, tailored to each caregiver. In the final 
session, the RN reviews the participants’ strategies and helps to generalize them to other possible 
challenges or goals. Sessions will be spaced to encourage practicing new strategies independently after 
developing them together with the nurse.  Although this intervention structure has been successful in work 
by the mentorship team, we will adjust the timing and frequency of study interactions based on feedback in 
the open label phase. Bi-monthly meetings of the RNs with the Research Coordinator and the PI will ensure 
smooth communication, address challenges, supervision, and adherence to intervention fidelity.  
 
Table 2:  Exemplar caregiver goals and intervention approaches 
Example Goals 
Intervention Approaches 
Physical activity:  
Increase physical 
activity by 10% or 1 
day per week 
1) RN will assess current physical activities, weekly duration and intensity.  2) 
RN will assess safety of physical activity with Physical Activity Readiness 
assessment with final evaluation by nurse practitioner 3) RN implements NIA 
Go4Life physical activities, with emphasis on variety, strength training and cardio 
in a safe environment.  3) RN will assess interest in group activities or engaging 
social support to increase accountability and help participant get connected. 
Stress management:  
Decrease exposure 
to stressors, increase 
use of coping 
strategies 
1) RN will assess stressors with focus on caregiving-related stress 2) RN will 
work with caregiver to draft a list of caregiving concerns to be addressed at the 
next visit with the patient’s cardiologist 3) Participant will identify coping 
strategies such as positive self-talk, ways to defuse stressful situations and 
prevent stress through restorative activities focused on purpose in life. 
Rest: 
Improve nighttime 
sleep quality  
1) RN to assess for duration, quality and sleep hygiene 2) RN will help caregiver 
identify modifications to sleep environment and bedtime routine 3) RN will 
assess for daytime fatigue and sleepiness. 
 
 
 
 
 

 
 
 
Table 3:  Study Visit Timeline for Immediate Intervention Group* 
Format and 
timing of visits 
Key activities  
Baseline Data Collection 
Sweatpatch application 
Heartrate Variability Measurement 
Survey  
Sweatpatch Pickup 
72 hours post-application, remove sweatpatch and deliver for storage 
and analysis 
Randomization 
Mail randomization results 
Home Visit 
Week 1 
Assessment 
Set goals and discuss priorities 
Remove sweatpatch and deliver for storage and analysis (if not already 
performed) 
Home Visit 
Week 3 
Purpose in Life activity 
Instrumental Support activity: Benefits Check Up 
Assess goal attainment and revisit strategies 
Phone Check-in 
Week 4 
Review/edit purpose statement 
Assess goal attainment and strategies to achieve goal 
Home Visit 
Week 6 
Social Support Activity 
Assess goal attainment and strategies to achieve goal 
Follow-up re: instrumental support 
Phone Check-in 
Week 8 
Review/edit purpose statement 
Assess goal attainment and strategies to achieve goal 
Home Visit 
Week 10 
Assess goal attainment and strategies to achieve goal 
Follow-up re: instrumental and social support 
Phone Check-in 
Week 12 
Review/edit purpose statement 
Assess goal attainment and strategies to achieve goal 
Home Visit 
Week 14 
Review of progress, goals and purpose 
Discuss how caregiver will involve social support in next goals 
Data Collection Visit  
Week 16 
Sweatpatch application 
Heartrate Variability Measurement 
Survey  
Sweatpatch Pickup 
72 hours post application 
Data Collection Visit 
Week 32 
Sweatpatch application 
Heartrate Variability Measurement 
Survey  
Sweatpatch Pickup 
72 hours post application 
* Waitlist control group will begin intervention at week 16. 
 
 
Research Variables and Measurement 
We chose measures (Table 1) based on previous RCT experience as well as those that met the following 
criteria: 1) possess known reliability and validity with ethnically diverse samples; 2) are sensitive to change 
from an intervention; 3) have clinical relevance to QOL; 4) Common Data Elements to connect this work 
with the broader literature, other pilots and other P30 Center work and 5) represent objective as well as 
subjective indicators of the domains we seek to impact. Finally, we sought to achieve a balance between 
psychometric quality and practical considerations such as respondent burden.  All instruments with the 
exception of demographics will be measured at baseline and 16 weeks post-intervention. 
 

 
 
Data collection and management:  
Questionnaire Data: 
Trained research assistants will verbally elicit questionnaire data from participants in person or in virtual 
meetings. Virtual meetings include either telephone conversations or video calls via DoxyMe or Zoom. 
DoxyMe is a HIPAA compliant virtual meeting software used for telehealth purposes. We have created a 
HIPAA compliant Zoom account for video calls as well. Research assistants will directly enter data into 
the RedCap data entry and management system.  
 
Due to COVID-19 research restrictions we will not collect sweat patch or HRV data until approved by the 
School of Nursing research restart committee.  
 
Sweat patch:  
Table 4:  Constructs, Instruments and Reliability 
Theoretical 
Construct 
Instruments and variables 
Number 
of Items 
Cronbach’s 
alpha 
Caregiver 
demographics and 
characteristics 
Demographics 
Characteristics:  Caregiving physical and supportive 
tasks description, employment 
Physical Activity Readiness Assessment 
23 
- 
Fatigue 
PROMIS-Fatigue Short form 
7 
0.947 
Caregiver Burden 
  
Oberst Caregiver Burden Scale  
2 domains:  time caregiving and task difficulty 
15 
0.9048 
Modified Caregiver Strain Index 
13 
0.8649 
Social Support 
ENRICHD Social Support 
7 
0.8950 
Family Functioning – Family Assessment Device 
Questionnaire:  Global Family Functioning Scale 
(only) 
12 
0.951 
 
Resilience 
Sweatpatch (IL6, IL10)  
- 
- 
Coping Self-Efficacy Scale  
13 
0.9152 
Heart Rate Variability  
- 
- 
Brief Resilience Scale 
8 
0.9153 
Quality of Life 
 
36-Item Short Form Health Survey (SF-36) 
2 scales:  Affective well-being and Physical health 
36 
0.8554 
Depression  
PHQ-8  
8 
0.8255 
Care Recipient 
Palliative Care 
Utilization 
Palliative care referral or encounter in electronic 
medical record within 6 months after caregiver 
completion of intervention 
- 
- 
Care Recipient 
Hospitalization 
Hospitalization (admission) encounter in electronic 
medical record within 6 months after caregiver 
completion of the intervention 
- 
- 
Care Recipient 
Mortality 
Documented as deceased in electronic medical record 
within 6 months after caregiver completion of the 
intervention 
- 
- 
Care Recipient 
Hospice 
Enrollment 
Enrollment in hospice in the electronic medical record 
within 6 months after caregiver completion of the 
intervention 
- 
- 

 
 
Interleukin 6 & 10 will be collected via a non-occlusive adhesive patch which remains in place on the 
caregivers’ skin for 72 hours. The sweat patch will be placed on the participant’s skin at their baseline data 
collection visit. The participant will be instructed to leave the sweat patch in place for 72 hours. A study 
team member will then return to the participant’s home to remove the sweat patch. The sweat patches will 
be prepared and delivered to the Johns Hopkins School of Nursing for temporary storage. Then the patches 
will be analyzed at the Johns Hopkins School of Nursing according to the Gill Lab Sweat Patch Extraction 
protocol and analyzed using a 3-step digital immunoassay, running all samples in duplicate. Due to 
COVID-19 research restrictions, sweat patches will not be utilized until the Johns Hopkins University IRB 
phase 2A to allow study team members to go to participants homes.  
 
 
 
HRV: 
An electrocardiogram approximately 5 minutes in length will be captured using the commercially available 
KardiaMobile ECG device (AliveCor, San Francisco, CA, USA).  Participants will place their forefingers 
on the touch pad while seated and resting for the reading.  Data will be captured using Kubios HRV 
software, a software tool for heart rate variability analysis (Kubios, Inc. Kuopio, Eastern Finland). The 
device will automatically save the rhythm strip on the iPod app and study personnel will download the 
rhythm strip after the home visit when it is performed. The file will be sent to the University of Oklahoma 
Heart Rate Variability Laboratory where it will be analyzed for measures of heart rate variability and 
counts of abnormal beats (if any). These files will have no identifying data other than time and date of 
measurement. If any suspected abnormality is seen on the analysis, the PI will be notified of any 
abnormalities that could impact health, and the subject would be notified and informed to contact their 
physician. Due to COVID-19 research restrictions, sweat patches will not be utilized until the Johns 
Hopkins University IRB phase 2A to allow study team members to go to participants homes.  
  
Physical Readiness Assessment 
During the course of this intervention, the participant will be developing personal goals with the guidance 
of the nurse interventionist. If a physical activity goal is identified, the nurse interventionist will administer 
the Physical Readiness Assessment tool. The results of the physical activity readiness assessment will be 
evaluated by the study nurse practitioner - Melissa Hladek, PhD, CRNP, FNP-BC - to determine the safety 
of the participant’s physical activity goal. Due to COVID-19 research restrictions, the physical readiness 
assessment will not be performed, and physical activity goals will not be pursued for participants who have 
virtual data collection and intervention interactions.  
 
Care Recipient Data: 
Six months after the caregiver completes the intervention, trained research assistants will search the 
electronic medical record of the caregiver’s care recipient related to palliative care utilization (referral), 
hospice enrollment, hospitalization (admission), and death. Research assistants will directly enter data into 
the RedCap data entry and management system. 
Data Management: 
Data from screening, intervention sessions, and final data collection will be entered onto forms that the data 
manager will check for completeness and appropriateness.  The data manager will send reports of missing 
or inappropriate entries to the PI every week for clarification and resolution.  As a phase 1 pilot study, a 
Data Safety and Monitoring Board is not required, however, as part of the P30 PROMOTE Center, a Data 
Safety and Monitoring Board has been established.  Details are provided in the human subjects section. 
 
Fidelity: The fidelity plan is based on the NIH Behavior Change consortium developed by national leaders.  
We will enhance fidelity through design elements (intervention is distinct and based on theory), training 
(using an intervention manual), delivery (reminder calls the night before intervention sessions, and measure 
fidelity through records of home sessions (by date and duration), checklists completed by study team 

 
 
members and direct observations and discussions concerning intervention engagement to evaluate receipt, 
and enactment. Ten percent of sessions will be audio taped which will be reviewed by the research 
coordinator using a priori monitoring checklists developed for this pilot trial. All data collection and 
intervention interactions will be recorded.  Evaluation will include periodic assessments of data quality, 
participant recruitment, accrual, and retention. Feedback will be provided to each interventionist who will 
provide case presentations in supervisory sessions.  Bi-weekly meetings of the nurse interventionist with 
the Research Coordinator, the PI, and Dr. Szanton will assure on-going fidelity to the intervention. 
 
 
 
Study duration and number of study visits required of research participants:  Participation in the 
study will consist of initial study consent, baseline, 16 and 32-week data collection and 5 study interactions 
for the intervention.  Based on participant preference, the nurse interventionist may also arrange phone calls 
between visits to assess progress towards goals.   
 
Blinding, including justification for blinding: 
Research staff performing outcome assessments will be masked to assignment. Prior to follow-up 
assessment, staff will use standardized language to instruct participants not to discuss their treatment 
allocation with staff.  
 
Justification of why participants will not receive routine care or will have current therapy stopped:  n/a 
 
Justification for inclusion of a placebo or non-treatment group:  Both groups will receive the 
intervention.  We are using a waitlist design to have a comparison to usual care. 
 
Definition of treatment failure or participant removal criteria:  n/a 
 
Description of what happens to participants receiving therapy when study ends or if a participant’s 
participation in the study ends prematurely:  n/a 
 
 
5. 
Inclusion/Exclusion Criteria 
Screening: 
1) Six-Item Screener; Callahan CM et al., 2003 
 
To be eligible for inclusion caregivers must:  
1) 18 years or older and  
2) English speaking 
3) Live with the heart failure patient or visit the patient at least 3 days per week to provide 
care or support. 
4) Provide support to the patient for at least 1 Instrumental Activity of Daily Living 
5) Care for a heart failure patient hospitalized in the last 6 months 
6) Live within a 1 hour driving radius of the Johns Hopkins Hospital 
 
Exclusion Criteria:   
1) Caregivers with cognitive impairment using the six-item screener will be excluded.  Severe 
Cognitive Impairment would make active participation in interviews and survey completion 
very difficult.  
2) Non-english speakers will be excluded. Non-english speakers may have unknown needs that 
cannot be addressed with this intervention. 

 
 
3) Caregivers with terminal diagnosis will be excluded as goal-setting at end of life may be 
different than without a terminal diagnosis. 
 
 
6. 
Drugs/ Substances/ Devices 
N/A 
 
7. 
Study Statistics 
 
Exploratory and descriptive analysis will be completed for all study variables. Variables will be examined 
for normality and examined with means and standard deviations or medians and interquartile ranges 
accordingly. Baseline characteristics comparing the two groups (waitlist vs. immediate intervention) will be 
assessed. Any differences between the groups will be adjusted for further analysis. The significance level 
will be set at 0.05. Sensitivity analyses will be conducted adjusting for variables on which the group differ 
and compared to the pattern of results in the main analyses.  
 
a. Primary outcome variable. 
Generalized estimating equations (GEE) will be used to examine the difference between intervention and 
waitlist groups in change from baseline to 16 and to 32 weeks for QOL (primary outcome), considering 
affective well-being and physical health separately and together as an aggregate measure of QOL.  Time, 
group and the group by time interaction will be included in the model. We will also calculate Hedges’ g for 
differences in change over time between the groups in change in primary outcomes. Hedges’ g is 
recommended over Cohen’s d’ to correct of an upward bias in small sample sizes.55 The effect size 
associated with the variables will be compared to established clinically significant improvement reported in 
the literature, rather than placing emphasis on statistical significance.  
 
b. Secondary outcome variables. 
Generalized estimating equations (GEE) will be used to examine the difference between intervention and 
waitlist groups in change from baseline to 16 and to 32 weeks for fatigue and caregiver burden (secondary 
outcomes) using a similar approach (as described for primary outcome).   We will use a similar approach to 
analyze cytokines and HRV.  Given previous research in adults with chronic disease, we assume that the 
cytokine data will require log transformation to approach normality. 
 
We compare differences in care recipient palliative care utilization, hospice enrollment, hospital admission, 
and mortality 6 months after caregiver completion of the intervention between intervention and control 
groups. We will use chi-square test to determine differences in rates of these outcomes and t-tests to 
compare average time to event between groups. 
 
c. Statistical plan including sample size justification and interim data analysis. 
As a pilot study, the analyses will likely not have adequate power to detect significant 
differences.  Therefore, effect sizes, rather than statistical significance will be examined for evidence of the 
effectiveness of the intervention.  With a total sample size of 53 we will be able to estimate the effect size 
associated with the intervention.  This effect size will be compared to the literature for similar interventions 
and used to estimate the needed sample size to a fully powered effectiveness trial. There will be no interim 
data analysis.   
 
Understanding the factors that predict which intervention components are successfully implemented and for 
which participant subgroups will be critical for fine-tuning this multicomponent intervention for future 
proposals that will extend efficacy examinations and effect modification analyses.  Acceptability of the 
intervention will be examined in multiple ways.  We will examine percentages of people who stayed in 
each arm of the study and conduct numerous descriptive correlational analyses of the association between 

 
 
the intervention compliance and other variables.  These analyses will quantify intervention implementation 
by demographic and participant health variables.  Analyses that utilize the post-randomization data (e.g. 
treatment compliance) 40-43 will be evaluated in supplementary analyses. We will distinguish non-
compliance with intervention from attrition or loss to follow-up, i.e. missing data.  We will also use the 
participant satisfaction data to examine acceptability of the intervention. 
 
d. Early stopping rules. 
As this is a low-risk behavioral intervention pilot, we have not defined any early stopping rules.  
 
8. 
Risks 
Minimal risks to study participants are expected. Some participants may experience some discomfort or 
fatigue in study interactions or in answering questions about their caregiving. Interviewers and 
interventionists will be trained to handle these minimal discomforts if they should occur, offering 
opportunities to rest throughout the interviews and intervention sessions. 
 
Education in protection of human research participants: All investigators have completed the Johns 
Hopkins University School of Medicine Research Compliance course and have been certified to conduct 
human research. The course consists of the University of Minnesota Web modules on Informed Consent, 
the consent Process, and After Informed Consent, Johns Hopkins University School of Medicine module on 
local IRB requirements, and achievement of a passing score on the Johns Hopkins Knowledge Assessment 
module. According to the policies of the Johns Hopkins University, approval for this research will be 
obtained from the IRB office for research using human subjects prior to collecting data. Minorities and 
women are included in this study, and all data will be presented in group format. Participants will be 
assigned a code number on initial entry and all subsequent questionnaires will be identified only by code 
number. Information needed for follow-up contact (names and addresses) will be kept separately from all 
other data. 
 
Procedures for protecting against and minimizing potential risks: The interviewer will notify the 
Principal Investigator (a nurse) of any concerns for distress related to the study and participants will receive 
a follow-up telephone call to assure that the mild distress has resolved. In situations where there is initial 
severe distress or when the distress has not been resolved, we will consult with our Co-Investigator, 
Melissa Hladek, PhD, FNP-BC. Furthermore, if any physical problems emerge during any of the study for 
either patients or caregivers, immediate medical attention will be sought for the participant. The research 
assistants will all be nurses and will be trained to call 911 if they have serious concerns of an emergent 
issue.   
 
The risk of invasion of privacy will be addressed with participants during the informed consent process. All 
personnel involved in the study will be fully trained and certified in the protection of human subjects and 
HIPAA regulations. This certification will be kept current throughout the study. As part of the informed 
consent process, participants will be notified of their rights pertaining to protected health information. 
Participants will be informed that they can stop the questionnaire and rest at any time. All study 
participants will be provided referral information to existing health services as in typical or usual care. 
Thus, participants have the information to access any services that they may perceive as necessary 
independent of their study participation. 
 
The risk of breaching study participant confidentiality will be minimized by identifying all participants by 
code numbers and securing all data collected in locked files in the PI’s office and screening information to 
locked file cabinets with limited staff access. Pre-coded data collection instruments are prepared for use 
with study participants at each testing occasion. Identification numbers to assure subject confidentiality will 
be used. Only one master log of subject name, address and telephone number and study identification 
assignment will be maintained on site in the locked PI’s office. This log, in both hard copy and electronic 

 
 
file saved to an encrypted USB drive, will be stored in a locked filing cabinet separate from other 
identifying information. All completed data collection instruments are stored in locked filing cabinets. 
Audio recording of screens, interviews, and intervention will be identified by numbers only and stored on 
the Johns Hopkins Secure Analytic Framework Environment (SAFE) virtual desktop of Dr. Abshire who 
will provide fidelity oversight of the interventionists. Access to these computer files will be password 
protected, audio recordings will not contain respondent name or other personal identifying information.  
Recorded interviews and key stakeholder meetings will be transcribed by a transcription service.All 
recordings and transcripts will be password protected and stored on the Johns Hopkins SAFE virtual 
desktop. Each transcript will be redacted for identifiers prior to analysis. Audio recordings from 
intervention sessions will be used only for quality control and training purposes and then destroyed (deleted 
from computers) within one year of trial completion. We will use either DoxyMe or Zoom. DoxyMe is 
encrypted, collects no protected health information (PHI) and any data transmitted during the call is 
destroyed when the call ends.  It is both HIPAA and HITECH compliant (https://doxy.me/en/about/).  We 
have created a HIPAA compliant Zoom account through the Johns Hopkins School of Nursing IT 
department dedicated to this research study and it will only be used for study participant virtual visits and 
will only be available to the study team. 
 
Data Safety and Monitoring: The PROMOTE Center will have a standing DSMB to review this pilot 
study. The Center will provide for collection and storage of data across pilot studies. These data will be de-
identified and stored in databases on the Johns Hopkins Secure Analytic Framework Environment (SAFE) 
virtual desktop. Data will be restricted to those with permission to access it. Investigators will use the 
REDCAP data entry system. However, any paper copies of consents or other study data will be stored in 
locked file cabinets. 
 
The DSMB will be responsible for reviewing the safety of study participants during the conduct of this 
study and provide recommendations to the research team on specific aspects of the research protocol as it 
pertains to safety, potential study alerts and adverse events. Specific responsibilities of the DSMB will be 
to: a) provide an independent periodic review of recruitment and enrollment progress; b) review adverse 
events (AEs) including serious events and offer recommendations regarding the trial based on such 
observed events; c) serve in a consultative capacity to the research team regarding study procedures to 
address ethical dilemmas (e.g., reporting of abuse), safety of subjects in the trial, and appropriateness of all 
study procedures.  We will not conduct interim analyses for this pilot study. 
 
Recruitment, Adverse Events (AE) and Alert Reports: Reports presented to the DSMB will include data 
on enrollment (study accrual by month; comparison of expected to actual enrollment; number of 
individuals screened, number eligible and number ineligible, number randomized by gender), AEs, and 
alerts. Also, the DSMB will receive reports of the number of study participants who discontinue from the 
treatment group and/or the study and reasons for discontinuation. We propose that reports be provided to 
the DSMB twice yearly. However, the DSMB will decide upon the schedule of reports at their first 
organizational meeting. Also, the DSMB may request reports as needed as well as the unmasking of the 
data should they deem this necessary. If unmasked efficacy data is required, the biostatistician for this 
study (Dr. Nancy Perrin) will serve as a liaison between the PI, database and the DSMB in order to assure 
that the PI and investigative team remains masked. For the first meeting of the DSMB, members will 
receive and review the following materials: a) Grant proposal, relevant appendices, reviewers’ comments; 
b) Standard Quality control procedures (see Facilities/Resources); c) IRB approved consent forms; d) 
Baseline and follow-up batteries; e) Shell of data base for management of interview schedules and 
enrollment information; f) Subject tracking forms; g) Alerts and Adverse event procedures and forms; h) 
Intervention treatment documentation forms; i) Shell for reporting recruitment and enrollment; j) Data 
shells for reporting tracking information and baseline characteristics; k) 
Decision rules for intervention termination (e.g., death, extended hospitalization, relocation); 
 

 
 
Adverse Event (AE) Reporting: The DSMB is notified by the principal investigator of any serious AE 
within 48 hours of initial notification to the project team. All members of the DSMB will receive copies of 
all safety reports at the time of submission to the IRB of JHU. In addition, a listing of all AEs and their 
attribution (e.g., study related, intervention related, or unrelated to study or treatment) will be provided to 
the DSMB on a monthly basis. We do not anticipate any adverse reactions to the intervention. Based on our 
previous work and studies in this area by others, there is only a small risk that participants will become 
increasingly anxious as a consequence of the intervention and being involved in an active problem-solving, 
behavioral activation approach. However, interventionists will be well trained to manage this reaction or 
make an effective referral if necessary. Given that both data collection and interventions may occur in 
people’s homes, there is the potential for a member of our research team to encounter a potential 
emergency situation that is not related to study participation (e.g., dehydration, environmental risk, medical 
emergency). We refer to such events as alerts and have well developed procedures for their management. 
All alerts are reported to the DSMB on a biannual basis. However, the reporting of alerts to the IRB of JHU 
is not required (see Chart below of potential alert events and plan for their management and reporting). 
 
Plan for reporting unanticipated problems or study deviations: There are only minimal risks associated 
with the trial. It is anticipated that participants will experience more benefits than risks from their 
participation in the trial. 
 
Table 5:  Specific Alerts and Actions Taken  
Alert  
Action to be taken 
Medical emergency:  
• Chest pains  
• Excessive bleeding  
• Fall and cannot get up  
• Difficulty breathing 
If a JHU research staff person encounters this situation over the phone, the 
participant is put on hold and the research staff calls 911 immediately. If 
situation occurs within home, then staff person calls 911 immediately, and 
stays with participant until help arrives. Research coordinator (RC) and PI 
are informed within 24 hours of the event. RC then contacts individual as a 
follow up within two days. Research staff member completes alert form and 
gives to RC (or designate) 
Evidence of abuse 
Evidence of physical abuse is as follows:  
• Participant states to research staff that abuse occurs;  
• Research staff observes physical evidence (e.g. black eye, black and 
blue marks on arms/legs)  
 
Research staff member informs participant that a senior member of the 
research team will contact him/her later that day. Staff member informs RC 
immediately upon completion of interview or intervention session. RC (or 
designate) contacts participant to obtain further information. Participant is 
strongly encouraged to call his/her physician and/or Adult Protective 
Services (phone number will be provided). Based on the situation, the RC 
may notify Adult Protective Services. RC (or designate) completes Alert 
form. Note –The possibility of informing an agency about an abusive 
situation is stated in the informed consent. 
Extreme Home Hazards 
• Exposed electrical  
• External door missing 
or cannot be locked  
• Ceiling, floors caved 
in  
• No temperature 
control (no air or heat; 
must be extreme)  
Research staff member notifies RC within 24 hours. RC (or designate) 
completes Alert form. 
 

 
 
• Major infestation 
PI – Principal investigator; RC = Research Coordinator 
 
Legal risks such as the risks that would be associated with breach of confidentiality:  The risk of 
breaching study participant confidentiality will be minimized by identifying all participants by code 
numbers and securing all data collected in locked files in the PI’s office and screening information to 
locked file cabinets with limited staff access. Pre-coded data collection instruments are prepared for use 
with study participants at each testing occasion. Identification numbers to assure subject confidentiality will 
be used. Only one master log of subject name, address and telephone number and study identification 
assignment will be maintained on site in the locked PI’s office. This log, in both hard copy and electronic 
file saved to an encrypted USB drive, will be stored in a locked filing cabinet separate from other 
identifying information. All completed data collection instruments are stored in locked filing cabinets. 
Audio recording of interviews and intervention sessions will be identified by numbers only and stored on 
the Johns Hopkins Secure Analytic Framework Environment (SAFE) virtual desktop. Access to these 
computer files will be password protected, audio recordings will not contain respondent name or other 
personal identifying information.  Recorded interviews will be transcribed by a transcription service. All 
recordings and transcripts will be password protected and stored on the Johns Hopkins SAFE virtual 
desktop.   Each transcript will be redacted for identifiers prior to analysis. Audio recordings from 
intervention sessions will be used only for quality control and training purposes and then destroyed (deleted 
from computers) within one year of trial completion. We will use either  DoxyMe or Zoom for video calls. 
DoxyMe is encrypted, collects no protected health information (PHI) and any data transmitted during the 
call is destroyed when the call ends.  It is both HIPAA and HITECH compliant (https://doxy.me/en/about/). 
We have created a HIPAA compliant Zoom account through the Johns Hopkins School of Nursing IT 
department dedicated to this research study and it will only be used for study participant virtual visits and 
will only be available to the study team. 
 
 
Financial risks to the participants:  There are no anticipated financial risks to the participants. 
 
9. 
Benefits 
 
Participants in the waitlist control group will not directly benefit during the waitlisted period of 16 weeks. 
Participants will receive study visits from a nurse when receiving the intervention. 
 
 
10. 
Payment and Remuneration 
The research participants in both the immediate intervention group and the waitlist group will each receive 
$20 at the start of the intervention, 16 weeks and 32 weeks following completion of surveys. Participants 
will also each receive an Amazon Fire 7 tablet in order to facilitate virtual intervention visits.  
 
 
 
11. 
Costs 
a. 
Detail costs of study procedure(s) or drug (s) or substance(s) to participants and identify 
who will pay for them. 
 
There will be no costs to study participants.  
 
 
 

 
 
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