Activate For Life: A Nurse Delivered Hybrid Telehealth/mHealth Aging In Place Intervention To Address Pain And Fatigue In Low-income Older Adults
Phase: NA
Conditions: Pain, Chronic, Fatigue Syndrome, Chronic, Aging
Sponsor: Medical University of South Carolina

Version #7.1 3/4/21 
 
Page 1 of 34 
 
Official title: Activate For Life: mHealth Intervention To Address Pain And Fatigue In Low-income Older 
Adults Aging In Place 
 
 
NCT03853148 
 
 
Document date: 03/12/2021 
 
 
 
 
 
 
 
PROTOCOL TITLE: 
 
ACTIVATE FOR LIFE: A NURSE DELIVERED HYBRID TELEHEALTH/mHealth AGING 
IN PLACE INTERVENTION TO ADDRESS PAIN AND FATIGUE IN LOW-INCOME 
OLDER ADULTS 
 
PRINCIPAL INVESTIGATOR: 
 
 
 
Teresa Kelechi, PhD, RN, FAAN 
 
MUSC College of Nursing 
 
 
 

Version #7.1 3/4/21 
 
Page 2 of 34 
 
  
1.0 
Objectives / Specific Aims 
Overview: Chronic pain and fatigue are among the most pervasive and expensive health complaints 
in the United States, with 53% of adults aged 65 and older (about 18.7 million) reporting pain at any 
one time (Patel et al., 2013), and 31% of those over 51 reporting fatigue.1 Adults, and older adults 
in particular with pain and fatigue, have reduced ability to successfully Age in Place, as these 
symptoms can impact activities of daily living, increase fall risk2-6 and diminish mental health 
and subsequent motivation to remain physically active. Unfortunately, integrated programs to 
address pain and fatigue, and thereby increase likelihood of aging in place, such as those that target 
muscle tone, mobility, strength and mental health are not common, and those that exist may be 
beyond the reach financially and logistically to poor older adults who might most benefit from them.  
This project proposes to evaluate feasibility of Activate for Life, an integrated home-telehealth 
delivered intervention that combines Otago +Yoga + Behavioral Activation to address both physical 
and mental health factors to increase likelihood of successful Aging in Place. The Otago Exercise 
Program (OEP) focuses on strength and balance training7, and is endorsed by the CDC8 as an 
effective fall prevention intervention8,9; Yoga (including asana/poses and pranayama/breathing;) 
emphasizes balance and stretching, and can be practiced even by individuals with significant physical 
disabilities, and Behavioral Activation (BA) addresses withdrawal and social isolation to enhance 
mental health and is an evidence based intervention for depression validated with older adults, 
including validation of its effectiveness by our team, when delivered via home based telehealth10-12. 
PREMISE: This project conceptualizes factors that negatively influence aging in place, namely pain, 
fatigue and mental health problems within the socio-ecological model to explain the multiple dynamic 
and complex influences that impact their presentation. For example, pain and fatigue in older adults 
may reduce their mobility, which reduces muscle tone and increases risk of falls. Reduced mobility 
also contributes to social isolation, thereby increasing depression and further reducing motivation to 
engage in exercise. These factors constitute a negative feedback loop, amplified in many older adults 
by limited income and resources, that perpetuate deterioration in both physical and mental spheres, 
leading to reduced ability to Age in Place. Therefore, the potential benefit of a comprehensive, 
integrated treatment, delivered directly into older adults’ homes via telehealth technology, to address 
both physical and emotional health dimensions, as well as limited access to transportation, is high. 
Preliminary pilot data on telehealth-delivered Otago Exercise Program revealed high rates of 
participation and satisfaction, and most important, significant improvement in physical stability and 
movement. However, high levels of anxiety and depression were observed, indicating a potential 
need to complement Otago with mindfulness and action-based strategies to reduce negative mental 
health symptoms while addressing pain and fatigue symptoms.  We subsequently added Yoga and 
telehealth delivered Behavioral Activation to the program in one series of participants and would like 
to fully explore the effectiveness of this integrated intervention. 
 
Thus, the Overall Aim of the present proposal is to evaluate the feasibility of an integrated mind-body 
intervention, Activate for Life, to improve overall physical activity and mental health and reduce pain 
and fatigue, resulting in increased likelihood of Aging in Place. Both subjective self-report (i.e., NIH 
PROMIS measures of pain, fatigue, depression and anxiety) and objective accelerometer data will be 
collected, along with standardized measures of balance, strength, and stability.  In addition, the 
measures will be complemented with biomarker-based measures of stress, including cortisol based 
and 1,5-AG assays before, during, and after treatment that are correlated with stress, and fatigue 
symptoms.  
 
 

Version #7.1 3/4/21 
 
Page 3 of 34 
 
Thus, the Specific Aims of the project are to: 
AIM 1. Integrate evidence-based components of “Activate for Life” a telehealth delivered, nurse-led 
behavioral health program for low income older adults targeting pain and fatigue through balance 
training (Otago), strengthening and mindfulness (Yoga), and affective state (Behavioral Activation). 
We hypothesize that the evidence-based Otago and Yoga components of this intervention will 
integrate with the ‘infrastructure’ format of the Behavioral Activation mental health treatment insofar 
as a 60-minute session, 6-10 session intervention will be developed. 
 
Aim 2. Test the feasibility of Activate for Life in terms of its individual components by comparing 
Otago vs. Otago+Yoga vs. Otago+Yoga+Behavioral Activation in a pilot RCT design with 10 
participants in each of the 3 conditions in terms of recruitment, intervention ‘dosage’ 
(frequency/density), adherence, treatment satisfaction, attrition, rates of missing data, and other 
feasibility metrics, including qualitative feedback from participants for final intervention refinement.  
We hypothesize that adherence will be adequate (65% scheduled activity compliance), satisfaction 
will be high (above 80%), attrition will be limited (below 25%), and followup data collected (below 20% 
missing data) 
 
AIM 3. Determine an initial efficacy signal for the intervention that will inform future power estimates. 
We hypothesize that the combined intervention will show significant within subject improvement over   
baseline on measures of pain, fatigue, and depression. 
 
Supplemental ARM 4 - AIM 4. Test the feasibility of a 12-week e/mHealth gentle yoga+yogic 
breathing (GYYB) intervention for alleviating symptoms of burden in aging Cargivers (CG) of persons 
(N=20) with dementia (PWD); measure initial changes in stress and QoL indicators in CG and PWD 
(post- vs. pre-intervention). 
 
Impact. This pilot feasibility study will set the stage for a full scale RCT demonstrating the additive   
benefit (if present) of each additional component over the CDC approved balance intervention Otago. 
Self-management of pain and fatigue through strength and balance training in low-income older 
adults can improve quality of life, decrease health care costs, and increase the ability of the person 
with these symptoms to age in place.  
 
2.0 
Background 
Aging in Place is by far, the preferred option for older adults from both the perspectives of 
older adults themselves, and the healthcare community. The population of older adults in the 
United States is growing rapidly and will double in size by 206013.  Older adults numbered 46.2 million 
in 2014, which represents about 14.5% of the total U.S. population13. By 2060 the projected number 
of older adults will be about 98 million13. However, this population is financially ill equipped to address 
care needs that often accompany aging, hence, maintaining health to ‘age in place’ is key. For 
example, in 2013 4.2 million (9.5%) older adults were below the poverty level13.  This was an increase 
from 9.1% in 201213. Another 5.6% or 2.5 million older adults were classified as “near poor” or having 
income between the poverty level and 25% above this level in the United States13. Not only is there a 
lack of resources to pay for qualified caregivers, and a lack of qualified caregivers themselves, there 
is also a lack of facilities to accommodate the elderly who may not be able to care for themselves in 
their home environment even if they could afford it14. This underscores the importance of 
interventions to facilitate aging in place, especially for the low-income elderly.  Moreover, 90% of 
adults 65 and older prefer to age in place15. One of the main reasons for this is cost. The National 
Aging in Place Council reported that care per person annually can cost on average $86,000 in a 

Version #7.1 3/4/21 
 
Page 4 of 34 
 
nursing home, $60,000 for someone in assisted living and $23,000 for someone aging in place at 
home16. In addition, older adults view aging in place as being synonymous with increased quality of 
life. In fact, older adults fear losing independence (26%) and moving to a nursing home (13%) much 
more than they fear death (3%)17. 
 
Pain and fatigue are significant barriers to aging in place. A retrospective study conducted in the 
United States based on the National Health and Aging Trends Study found the incidence of chronic 
pain in adults aged 65 and older to be 52.9% (about 18.7 million)18. Similarly, fatigue affects 31% of 
adults 51 years of age and older1.  Older adults with pain and fatigue are less likely to successfully 
age in place, as these symptoms can impact activities of daily living, reduce exercise, and increase 
fall risk2-6,19. Programs to address pain and fatigue, such as those that target increasing mobility, are 
not always within the reach of these older adults, both literally, due to geographic isolation and 
rurality, and figuratively, due to cost. Indeed, low income older adults who suffer from pain and fatigue 
face a multitude of barriers that prevent them from participating in traditional physical activity or 
behavioral self-management programs.  These include access to transportation, financial resources, 
ability to participate due to preexisting mobility problems, the need for assistive devices, being chair 
bound and or bed bound. Medicare does not cover programs to enhance aging in place through 
physical conditioning and self-management interventions, except in the small minority of instances 
where the Medicare eligible recipient is in need of Physical Therapy (PT) and determined to be: 1) 
homebound, 2) to qualify due to specific criteria, or 3) is under the order of their physician. In addition, 
PT for qualifying Medicare patients is episodic, or time and visit limited, and not ongoing20. As such, 
PT, and PT under Medicare is not a viable option to address pain and fatigue in older adults. 
 
The need for Comprehensive behavioral health pain and fatigue management programs.   
Physical activity can improve strength and endurance, overall health, and quality of life among older 
adults with chronic conditions, which in turn may reduce hospitalizations and nursing home stays21.  
The impact of physical activity on joints may reduce a person’s pain by improving flexibility, density 
and quality of connective tissues, and potentially on bony mass22. There is no evidence of increased 
pain with physical activities such as exercise, although this belief may be a barrier for older adults 
with pain in starting an exercise routine2.  
 A large meta-analysis of self-management programs for pain reported by Taylor et al.23 substantiated 
the need not only for a physical activity component for pain self-management programs, but also the 
addition of a supportive component that is delivered by health care providers. From this meta-
analysis, Taylor et al.23 also concluded that there was evidence that self-efficacy and depression at 
baseline can predict outcome and that pain catastrophizing and physical activity can mediate 
outcome from self-management23, indicating that a mental health component may also be needed.  
 
Three Evidence Based Programs that address aforementioned need and may, once integrated, 
enhance Aging In Place: Otago (Balance), Yoga (Strengthening and Mindfulness), and 
Behavioral Activation (Motivation and Affect).  
 
Otago and Balance:  Otago is a muscle strengthening and balance retraining program that can be 
delivered to the participant in their home. Otago was implemented and test in four randomized control 
trials of 1016 men and women aged 65-97 years of age. Findings from the trial showed that The 
Otago Exercise Program can reduce falls and fall related injuries, the program was most effective for 
adults 80 years and older, men and women benefited equally, and participants’ strength and balance 
improved markedly as assessed by the Chair Stand and the Four-Stage Balance tests. The Otago 
exercise program is endorsed by the Centers for Disease Control as an effective fall intervention 
program for men and women19, decreasing falls in older adults by 35%. 20-23 
 

Version #7.1 3/4/21 
 
Page 5 of 34 
 
Gentle Yoga and Yogic Breathing (GYYB) and Pain: In chronic pain, there is high contribution of 
the static load, due to habitual deep muscle tension that adversely affect microcirculation within 
muscles and the underlying viscera24. Yoga reduces the electromyographic activity in the 
musculoskeletal system and promotes relaxation (Balambekar, 1969)25. Awareness and progressive 
relaxation attained by Yoga practice could eliminate a substantial proportion of pain and the person 
feels more in control, which itself promotes pain reduction24. Yoga influences the endocrine system by 
increasing local blood flow by gravity, muscle contraction and pressure release resulting in reduced 
abdominal pain26 Muscle stretching could potentially lead to the release of endogenous opioids27 thus 
could reduce the need for exogenous opioids. While pain modifies frequency, depth and pattern of 
respiration confining it to strained, shallow, and thoracic breathing, the practice of Pranayama with 
long exhalation cycles relaxes the musculoskeletal system, increases the tonicity of parasympathetic 
response, and reduces overall stress, which together could reduce pain28-29. Diaphragmatic breathing 
is probably the single most valuable thing that a patient in chronic pain can learn on the road to 
recuperation24. Yoga practices, more commonly the ones involved in postures, has been used to test 
its usefulness in improving the quality of life in the aging population. In a pilot RCT in a community 
dwellers (mean age 68), the participants performed twice a week group yoga with an instructor for 12 
weeks. The results showed the feasibility, and an improvement in balance and movement-related 
benefits30. Dr. Balasubramanian (co-I) has developed a combination of gentle yoga and yogic 
breathing (GYYB) program for people with limited mobility (GYYB handout, Balasubramanian). The 
GYYB program has been pilot tested among patients with scleroderma, and in a community dwelling 
elderly population and have shown feasibility, acceptance and a strong interest to continue the 
practice because of the perceived improvement (unpublished data). 
 
Yoga and Biomarkers:  The Balasubramanian lab (Co-I) has shown that acute practice of 20 
minutes yogic breathing exercises stimulate salivary expression of nerve growth factor, immune 
response markers, and a reduction in inflammatory cytokines31-33. In a recent study 90 minutes of 
Yoga practice among the elderly (mean age 60) has been shown to stimulate salivary immune 
function (increased salivary IgA and testosterone), and decreased stress hormones (cortisol)34. 
Several recent studies have suggested saliva as a potential biomarker source in various physiological 
conditions35,36. Due to the non-invasive collection method involved, and the availability of procedures 
to quantify stress, mood and pain related biomolecules saliva could be preferred over blood sampling 
among the elderly. Cortisol is a glucocorticoid hormone expressed in the saliva and is commonly 
used as an indicator of stress due to the activation of hypothalamus - pituitary - adrenal cortex (HPA) 
axis, and aging is associated with an increased levels of salivary cortisol 
(https://www.ncbi.nlm.nih.gov/pubmed/27377692). Yoga practice reduces the salivary cortisol level 
among older adults. 1,5-anhydroglucitol (1,5-AG) is a biomarker for hyperglycemia 
(https://www.ncbi.nlm.nih.gov/pubmed/25249070) and is found to be reduced in aging 
(https://www.ncbi.nlm.nih.gov/pubmed/7835210; https://www.ncbi.nlm.nih.gov/pubmed/27036001) . 
Both clinical and preclinical studies suggest that exercises could increase the levels of 1,5-AG 
(https://www.ncbi.nlm.nih.gov/pubmed/15094482; https://www.ncbi.nlm.nih.gov/pubmed/28210043). 
This will be the first study that fully examines the impact of yoga practice on the levels of 1,5-AG.  
 
Behavioral activation (BA) and Depression. Behavioral Activation is a manualized treatment for 
depression (Lejuez, Hopko, & Hopko, 2001) that has gained support for its efficacy11,  Lejuez, Hopko, 
LePage, Hopko, & McNeil, 2001; Hopko et al., 2002). The primary goal of this intervention is to 
increase patients’ engagement in social and healthy activities (e.g., interacting with supportive family 
and friends, community bingo, yoga, Otago) that are likely to produce reinforcement in the natural 
environment. Learning theory47 forms the theoretical model supporting Behavioral Activation, which is 
hypothesized to reduce depression symptoms via increased frequency and density of reinforcing and 
personal values-consistent activities. This shift in balance of activities and reinforcement density 

Version #7.1 3/4/21 
 
Page 6 of 34 
 
facilitates increased positive mood and cognitions (see47, 48), and is achieved by first identifying, then 
operationally defining, and ultimately formally scheduling the aforementioned reinforcing or 
functionally useful behaviors. One of the strengths of BA, relative to other cognitive behavioral and 
activation-based interventions, is that it is designed to incorporate components of complementary 
treatments. Specifically, BA is heavily reliant on identifying and scheduling healthy behaviors, and on 
identify and resolving barriers to implementation of these scheduled behaviors.  These healthy 
activities are often specifically derived from complementary interventions. As such, it may be 
conceptualized as an ‘framework’ intervention, upon which other intervention components, such as 
Otego and Yoga, can be hung.  
 
Gap in knowledge related to using telehealth delivered programs to improve pain/fatigue and 
facilitate self-management in older adults. There is little literature regarding the use of mHealth 
(e.g., tablet based applications) and eHealth (e.g., televideo via tablet) as a platform for nurse-
managed (and eventual self-managed) pain in older adults.22 A recent integrative review of the 
literature noted that a large proportion of older adults own a computer, tablet, and/or smartphone and 
regularly access the Internet.22 This review points out that while there is little evidence of using digital 
technology for pain management in older adults, using an interprofessional approach along with high 
quality interventions, strong technical support and training, and connectedness with clinicians and 
increased self-awareness through personal diaries  may provide a strong platform for its use in 
clinical practice.22 Incidentally, none of the studies in this review addressed low-income older adults.  
 
PREMISE: This project conceptualizes factors that negatively influence aging in place, namely 
problems associated with pain, fatigue and mental health, within the socio-ecological model to explain 
the multiple dynamic and complex influences that impact their presentation. For example, pain and 
fatigue in older adults may reduce their mobility, which reduces muscle tone and increases risk of 
falls. Reduced mobility also contributes to social isolation, thereby increasing depression and further 
reducing motivation to engage in exercise. These factors constitute a negative feedback loop, 
amplified in many older adults by limited income and resources, that perpetuate deterioration in both 
physical and mental spheres, leading to reduced ability to Age in Place. Therefore, the potential 
benefit of a comprehensive, integrated treatment, delivered directly into older adults’ homes via 
telehealth technology, to address both physical and emotional health dimensions, as well as limited 
access to transportation, is high. 
 
Preliminary studies. Preliminary pilot data on telehealth-delivered Otago Exercise Program revealed 
high rates of participation and satisfaction, and most important, significant improvement in physical 
stability and movement. However, high levels of anxiety and depression were observed, indicating a 
potential need to complement Otago with mindfulness and action-based strategies to reduce negative 
mental health symptoms while addressing pain and fatigue symptoms.  We subsequently added Yoga 
and telehealth delivered Behavioral Activation to the program in one series of participants and intend 
to fully explore the effectiveness of this integrated intervention. 
 
INNOVATION: Otago only does balance and strengthening, y+O does balance and 
strengthening, and pain control, adding ba addresses motivation and depression so Activate 
for Life adds motivation 
An interprofessional (IP) team of nursing, physical therapy and behavioral health clinical researchers 
will be collaborating to develop “Activate for Life” to address pain and fatigue by increasing physical 
activity and self- efficacy in low-income elderly. This project is innovative in the following ways: 
• Integrates mHealth and eHealth 

Version #7.1 3/4/21 
 
Page 7 of 34 
 
• Uses eHealth (televideo) to deliver interventions directly into participant’s homes, dramatically 
enhancing convenience and overcoming barriers related to rurality 
• Uses real time (EMA) activity monitoring and feedback with easily understood data presentation 
graphics to inform both patient and provider on progress through an application (app) on the tablet  
• Uses ECA to assess parameter violations and trigger televideo visit for motivation/problem solving 
session with nurse 
 
3.0 
Intervention to be studied 
ARMS 1, 2, and 3. Design Overview. Design Overview and Project Timeline:  
This 12-week feasibility trial will use a 3x3 repeated measures (treatment x time) between groups 
randomized trial design to compare Otago (OG) vs. Otago + Yoga (GYYB) vs. Otago + GYYB + 
Behavioral Activation (ie., the complete Activate for Life intervention) in low-income older adults with 
chronic pain and/or fatigue at baseline, post-treatment and 3- month follow-up. Participants will be 
randomly assigned to one of the three conditions. Daily self-monitoring of program component 
adherence, PROMIS self-report measures of pain, fatigue, anxiety, depression, and social support. 
Physical activity measures will include actigrography, steps per day, 2-minute timed walk test, sit-to-
stand test, and Mini-Best. Participants will be 30 adults (10 per group) age 60 and above with a 
PROMIS pain interference score of eight or above and/or a PROMIS pain behavior score of 15 or 
above (cut points based on a T-score that rescales the raw score into a standardized score with a 
mean of 50 and a standard deviation (SD) of 10 for each of these instruments). 
 
Alternative design: The progressive nature of this feasibility trial allows the proven evidence-based 
modalities of OEP and GYYB to be combined with behavioral activation to not only address physical 
activity but also the mental health aspects of chronic pain and fatigue. Therefore, this feasibility trial 
scaffolds the components to show that the modalities of OEP and GYYB are effective and their 
success is dependent on motivation. However, we are not testing these three interventions alone, or 
in every possible combination. 
 
Supplemental ARM 4 - Design Overview:  
For the supplement, the CON SSMC will leverage its expertise in technology-enhanced SM 
interventions and community-engaged research to establish the feasibility of an mHealth GYYB 
(physical activity + breathing) intervention on adherence, acceptability, and short-term health 
outcomes related to burden in CG of PWD. We will recruit 20 older CG who are caring for 
PWAD/ADRD receiving services in social and medical RCCs connected with an active R01 
investigation, Mealtime Partnerships for People with Dementia at Respite Centers and at Home (R01 
NR016466; PI: Kelechi). Two data collection points will occur at the beginning (Week 1, pre-
intervention, or baseline, “V1”) and end (Week 12, post-intervention; “V2”) of the 12-week study. 
Preliminary changes in CG health indicators such as physical function, fatigue, depression, and social 
isolation as well as CG/PWD QoL will be examined to support a future RCT and build opportunities 
for faculty training in dyadic analyses. The relationship between salivary stress biomarkers (cortisol 
and 1,5-anhydroglucitol, or 1,5- AG) and self-reported reduction in stress symptoms will also be 
examined. Based on results from past SSMC studies, we posit that adherence will be adequate 
(≥80% scheduled activity compliance), satisfaction will be high (≥80%), attrition will be limited (≤25%), 
and follow-up data collection sufficient (≤20% missing data) to establish the validity of a future, full-
scale RCT. 
 
4.0 
Study Enpoints (all ARMS) 
Study end points include: Successful study completion, participant consent withdrawal, and PI 
termination due to failure to adhere to the protocol, loss of contact with the patient, and/or unexpected 
adverse events.  

Version #7.1 3/4/21 
 
Page 8 of 34 
 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
Inclusion criteria for ARMS 1, 2, and 3 are as follows:  
• Males and females 60 years of age and older living in a Humanities Foundation apartment 
complex, HUD funded housing or living at 150% of poverty level 
• PROMIS pain interference score of eight or above and/or a PROMIS pain behavior score of 15 
or above 
• Able to ambulate 150 feet with or without the use of an assistive device 
• Able to follow simple instructions 
• Able to read, speak, and write English,  
• Able to operate tablet device and wearable activity tracker,  
• Not currently enrolled in an exercise program.  
 
Exclusion criteria for ARMS 1, 2, and 3 are:  
• Inability or unwillingness of participant to give informed consent,  
• Physical, cognitive, sensory or psychiatric disability that would limit participants from engaging 
in self-management program as noted by a Mini-Cog26 score of 0-2. 
• Unwillingness to wear a physical activity tracker during the course of the study. 
 
Inclusion criteria for Supplemental ARM 4 are: 
• CG must be able to speak and read English  
• CG must be 45 years of age or older 
• CG must be able to provide consent for themself 
• CG must live with or on same property as the PWD 
• CG be primarily responsible for care provision of the PWD in the home (i.e., is not paid for 
services; provides 4 hours or more of care/day; assists with ADLs) 
 
Exclusion criteria for Supplemental ARM 4 are: 
• CG for whom yoga techniques would be detrimental due to physical limitations, 
• CG who are enrolled in other Yoga-related clinical trials, or who are currently engaged in 
regular Yoga activity once per week or more. 
 
6.0 
Number of Subjects 
The number of Pparticipants enrolled under ARMS 1, 2, and 3 will be 30 adults age 60 and over. 
Thirty participants should allow for recruitment of 10 participants from at least 3 different Humanities 
sites to avoid cross-contamination of study groups. The number of participants enrolled under 
Supplemental ARM 4 will be 20 adults aged 45 and older. The total number of participants under this 
research project will be 50. 
 
7.0 
Setting 
ARMS 1, 2, and 3. The Humanities Foundation is a non-profit affordable housing provider in South 
Carolina, Georgia, Virginia, and Louisiana. The Foundation, in place for over 20 years, has 1400 units 
of affordable housing for low-income populations including disabled, single mothers, and senior 
citizens. To qualify to live in these low-income facilities the residents must have income that is no 
more than 60% of the Area Median Income.  The study sites will be the six Humanities Foundation 
older adult living complexes in the Charleston, SC area, other HUD funded housing, or low-income 
persons living at 150% of poverty level. The study would be conducted within the facilities community 
meeting room and in individual participants apartments. All research activities and study procedures 

Version #7.1 3/4/21 
 
Page 9 of 34 
 
will be conducted by IRB approved MUSC study personnel. No employees and/or agents of 
Humanities Foundation will engaged in any research activities. 
 
Supplemental ARM 4 Setting: All CG participants will be recruited from within the greater Charleston 
Tri-county area. All research activities and study procedures will be conducted by IRB approved 
MUSC study personnel. Research activities will take place at CON as well as at participant’s homes. 
 
8.0 
Recruitment Methods 
ARMS 1, 2, and 3 
IRB approved flyers will be distributed to the residents at each of the Humanities Foundation 
apartment complexes as well as posted in general public community areas.  Educational sessions, 
headed by the PI, will also be held at the complexes to allow potential participants to learn about the 
program and ask pertinent questions. Individuals who are interested in the program will be directed to 
contact the study PI or their designee via phone or at the information sessions. If interested 
participants meet the eligibility criteria and voluntarily consent to join the study they will be enrolled.  
 
Additionally, we will recruit individuals who have had recent services through MUSC ED that have 
authorized research contact permission in MyChart through the MUSC electronic ‘opt in’ EPIC 
designation and have been identified by the Bioinformatics Center (BMIC) as over 60 years old, have 
had a recent fall and reside at one of the Humanities Foundation complexes. We will then contact 
potentially eligible patients by telephone to determine if they are interested in participating in the study 
and if so, schedule an informed consent meeting.  
 
Supplemental ARM 4: 
All CGs will be recruited through local affiliations with social and medical Respite Care Centers (RCC) 
and home health services for families of PWD established through our Mealtime Partnerships R01 
study. We will devise and use IRB approved study recruitment flyers and letters that will be 
dessimated electronically and handed to RCC caregivers, as well as directly contact CGs by phone 
that have previously expressed and noted their agreement to be contacted regarding other research 
studies as documented on their consent form. In addition, we will conduct outreach activities and 
enage outside network RCC providers in the local community to inform them of the opportunity for 
their clients to participate in this study. 
 
9.0 
Consent Process (ALL ARMS) 
In-person 
Research activities will not be conducted without the patient’s written informed consent. Informed 
consent will be conducted by the PI and/or their designee as noted on the IRB study delegation log, 
and will occur in the comfort and privacy of a private room at the facility or the participant’s place of 
residence prior to any screening procedures being conducted and/or data collection. Potential 
participants will be given the informed consent document to read and review in advance, and/or may 
have it read to them by the researchers, if they prefer. After reviewing the consent document, the 
patient will be given the opportunity to ask any questions about the study that they may have, and will 
be requested to demonstrate what is expected from them should they agree to enroll in the study 
through a questioning of their understanding of study procedures and risks. Prior to consenting, all 
questions will be resolved to the patient’s satisfaction. If a participant does not appear to understand 
the information contained within the Consent document or of what is expected of them as a study 
subject, then the study coordinator will review the consent document again with the participant. If after 
this second review, the subject does not demonstrate an understanding, they will not be enrolled in 
the study. Only participants, with no observed cognitive impairment, will be consented and enrolled 
into the study.  

Version #7.1 3/4/21 
 
Page 10 of 34 
 
 
The consent form will meet the requirements of the Code of Federal Regulations and the MUSC 
Institutional Review Board; and, include the following elements: 
• The purpose, nature, and objectives, potential risks and benefits of the intended study. 
• The length of study and the likely follow-up required. 
• The name and a contact of the investigator(s) responsible for the protocol. 
• The right of the participant to accept or refuse study interactions and to withdraw from 
participation at any time. 
 
All consented subjects will be given a copy of their executed and countersigned Consent form. The 
researchers will maintain a means of contact with all enrolled study participants in the eventuality that 
reconsenting of currently enrolled participants is needed and/or the disclosure of new study 
information is warranted to previously enrolled participants. 
 
E-Consent  
In light of institutional guidelines pertaining to COVID-19 and the conduct of human subject research, 
study participants may also be consented using MUSC IRB approved REDCap e-consent process. 
 
In the case of obtaining e-consent, potential participants will have been introduced to the opportunity 
to participate in the study. All potentially interested participants will be referred to the MUSC research 
team either directly with the participant’s verbal permission or self-referred through contact 
information on the study recruitment flyers.  Upon making contact with the referred individual, the 
researchers will identify themselves, indicate how they received the individual’s personal contact 
information, provide the reason for the call and an overview of the study and study procedures. If the 
individual expresses an interest in learning more about the study and/or becoming a participant, the 
researchers will ask the individual for a working email address where the e-consent will be sent and 
set-up a follow-up telephone call for the e-consent process. These individuals will be 
allowed as much time as needed to read and review the e-consent document in the privacy of their 
own home or at a place of their choosing. During the e-consent call, the researcher will review the e-
consent document in its entirety and be available to further answer any questions that they may have 
prior to the individual adding their respective signature to the form and submitting the e-consent. 
Upon submitting the e-consent, a REDCap trigger will immediately notify the researcher, who will then 
provide their countersignature to the document. All e-consents will be maintained in the 
REDCap study e-consent database for regulatory purposes and compliance monitoring. 
All participants will be electronically sent a copy of the fully executed e-consent form to their email 
address. Hard copies will be mailed to participants upon request. 
 
10.0 Study Design / Methods 
ARMS 1, 2, and 3: Once a participant has consented and been enrolled they will be randomized by 
computer (stratified by gender) to one of three treatment groups and the PI and/or their designee will 
set up a home visit appointment to meet with the participant to obtain baseline data (Table 1). Part of 
the baseline screening includes the PROMIS Emotional Distress-Depression Short Form 8a. If a 
participant scores in the severe depression category (raw score 33 and above) a referral will be 
placed to a mental health professional. Additionally, participants that score in the moderate 
depression category (raw score 23 to 32) further screening for suicidal ideation will take place. If the 
participant would admit to suicidal ideation at any time during the study, an emergent mental health 
consult will be placed through the Charleston/Dorchester Mental Health Center Assessment/Mobile 
Crisis.  
 

Version #7.1 3/4/21 
 
Page 11 of 34 
 
The participant will then be trained on the use of the tablet including the application that will record 
and transmit their self-entered pain and fatigue symptom scores, the vital sign measuring equipment 
as well as the video platform for the nurse and self-management program to which they are randomly 
assigned. The vital sign recording equipment have all been FDA approved and gone through multiple 
rounds of formal verification. These are also Medical University of South Carolina (MUSC) and South 
Carolina (SC) Telehealth recommended devices as MUSC is arm of SC Telehealth Alliance. The 
tablet will be an iPad air 2, which has the communication protocol to connect to all these devices and 
send encrypted data securely back to servers. In addition, the participants will be given and receive 
training on a Garmin Vivofit wearable activity tracker that is able to record, steps taken per day, heart 
rate, distance walked, stairs climbed, and sleep. Garmin Vivofit wearable fitness trackers meet high 
reliability and validity requirements for parameters such as step counts (Simunek et al., 2016). The 
training will  be conducted via a prerecorded video shown to participants on their tablet at the initial 
meeting that also explains the program rationale, use of the tablet, activity tracker, and video and app 
platforms. This video will allow participants access to training at all times in case of issues or 
questions surrounding the equipment. The PI will contact the participant via their tablet on a weekly 
basis via the HIPAA compliant telehealth platform Vidyo. Vidyo, a real-time software video 
communication tool, is HIPAA Compliant with all of the media, signaling, and user login being 
encrypted to ensure patient privacy and compliance (Vidyo, 2014).28 Each tablet will contain the app  
“Activate for Life”. This app will allow the participant to transmit, via Bluetooth technology their blood 
pressure and pulse. The app also allows the participant to rate their pain and fatigue scores on a 1-10 
scale, document their daily activity and their use of pain medication, and has the ability for the 
pariticipants to record a voice diary of their daily progress or thoughts. Each participant will receive a 
blood pressure cuff and will take their blood pressure prior to participating in their PA for the day. The 
blood pressure and pulse information from the blood pressure monitor will be transferred via 
Bluetooth to the Activate For Life app on the participants iPad. Once the app has received the data, it 
will automatically upload the information to the server at MUSC and will be available to be reviewed 
by the research team. The app will also allow for the participants to input their pain and fatigue scores 
which will be utilized to monitor pain scores on a daily basis. The vital signs and pain scores will allow 
for individualizing of the physical activity program to increase or decrease activity based on 
worsening, improving, or stability of participant’s pain as measured by the pain score or through 
prolonged elevations in blood pressure or pulse. Weekly telehealth visits will allow for delivery of each 
conditions intervention components, review of pain and/or fatigue, VS, and sleep data. These data 
will be assessed by the PI and discussed during the weekly telehealth visits with the participants. The 
burden of self-monitoring and data entry will be captured 
during feasibility assessments. Saliva samples will be 
collected from all groups at the beginning and end of the 
sessions on week 1 and 12 to measure salivary 
biomarkers including cortisol, and 1,5-AG. Feasibility  
 
Otago. Once a participant has been enrolled and 
oriented to their tablet, a certified physical therapist (PT) 
will contact the participant to set up an in-person 
appointment for initial assessment. During the initial 
assessment, the nurse PI will conduct the physical 
assessment screening tests as noted in Table 2. The 
nurse will then discuss the Otago exercise program with 
the participant and provide a printed binder of the Otago 
exercise as well as demonstration on how to 
appropriately conduct each exercise. The Otago 
exercise program consists of the following: 1) A series of 

Version #7.1 3/4/21 
 
Page 12 of 34 
 
warm-up exercises, 2) Select exercises from the 17 Otago exercises which challenge the participant’s 
strength and balance for up to 30 minutes, three times a week, 3) A walking program for up to 30 
minutes, three times a week. Each Otago will be tailored for each participant’s ability level. See 
exercise prescription in Table 1.  
 
3C3.B. Otago + GYYB + (GYYB): The GYYB program will be administered to the participants by a 
qualified and certified Yoga instructor in a group setting once a week for 12 weeks. The GYYB is a 
one-hour program containing gentle physical Yoga postures that participants could practice sitting on 
a chair for 30 minutes. These exercises are designed based on improving the overall flexibility, bodily 
control and mindfulness in movements. Following the gentle yoga postures, the participants will 
perform Yogic breathing exercises for 30 minutes. These exercises are known to promote relaxation, 
mood, pain and anxiety scores that are highly relevant to the target population and are reported to 
stimulate measurable biomarker changes in the saliva. During the in-person session the Yoga 
instructor will explain the GYYB program to participants in the Otago+GYYB group each exercise and 
their perceived benefits. The participants will have a chance to practice the exercises in the presence 
of the instructor and clarify any question that they might have about the exercises. The instructor will 
make sure that the participants can perform the exercises independently. The participants will be 
provided with a video and a handout for the study exercises that they will follow for 1 hour every day 
(any time at their preference). Any deviations in the practice will be noted by the participants in a diary 
indicating the length of the practice with date on it. Saliva samples will be collected at the beginning 
and end of the sessions on week 1 and 12 to measure salivary biomarkers including cortisol, and 1,5-
AG. The OEP and self-management as detailed above will also take place in this group.  
 
3C3.C. Otago plus GYYB + Behavior Activation (Activate for Life).  
This condition will incorporate OEP and GYYB as above and will also include behavioral activation to 
address motivation and affect. Behavioral Activation incorporates daily planners and worksheets to 
identify and rate reinforcing behaviors and is often used in conjunction with other interventions 
because components of these interventions are easily incorporated into the daily planner based 
activities. Each participant outlines general values and specific behaviors that ‘demonstrate’ each 
value, compiling a list of the latter. This list is then used to generate 10 to 20 highly defined values-
based, reinforcing activities. Next, this list is combined with the activities outlines in Otago and GYYB 
and this master list is used to schedule these values-based activities for the next two days. One of the 
strengths of the BA protocol, relative to other cognitive behavioral and activation-based interventions, 
is that it is designed for implementation over a brief period. Additionally, sessions of the often require 
as few as 15-30 minutes of contact time due to the straightforward, simple structure of these 
sessions. Patients begin with a weekly self-monitoring exercise, charting behaviors and mood every 
hour, that serves as a baseline assessment of daily activities, and orients the patient to the quality 
and quantity of his or her activities on a daily basis. Also, baseline assessment assists in generating 
ideas about activities to target during treatment.  
 
Session 1: Begins with rationales for Behavioral Activation. The core points made are that what one 
does often plays a role in how one feels. Clients then proceed to identify 5 classes of values (e.g., 
family, work, spirituality) with specific behaviors that ‘show’ the patient’s value, thus the treatment is 
tailored for each individual. For example, the value ‘time with family’ might be shown by ‘throwing the 
baseball with son for 20 minutes’. Lists of specific behaviors are derived for each value and written on 
the daily planner. Participants are then given a daily planning calendar and behaviors that are 
reinforcing and relatively easily accomplished are planned each day, for two days in advance with the 
objective of planning at least 2 hours of reinforcing activities and scheduled homework from Otago 
and GYYB each day. Session 2: Begins with a review of homework and verbal reinforcement of 
completed planners, completed reinforcing behaviors, completed Otago and GYYB homework, 

Version #7.1 3/4/21 
 
Page 13 of 34 
 
restatement of the rationale (ie., that what one does affects how one feels and doing positive things 
will help one to feel positively), and problem solving. Behaviors that were consistently planned but not 
completed are removed and alternative behaviors suggested. The next 2 days’ activities are planned. 
This session usually involves a significant amount of problem solving, and identification of avoidance, 
with planning in place to counter this avoidance. Sessions 3-4: These sessions begin with a review of 
homework, followed by asking the patient to state, in their own words, their interpretation of the 
rationale for Behavioral Activation. Obstacles to completing behaviors are discussed and additional 
exposure-based and reinforcing behaviors are generated. The next 2 day’s activities are planned. 
Session 5: Includes discussion of the rationale and treatment gains obtained thus far. Discussion is 
also centered on the need to continue planning activities and using a daily planner for at least 6 
months. Relapse prevention strategies are reviewed. Additional sessions are conducted every other 
week until week 12 (Otago and GYYB completion). 
 
Table 2: Measurements/Instruments/Interventions and Time Points 
 
Major tasks and domains; monitor/ 
evaluate 
Measures/instruments/questions and Cronbach’s alpha (  ) 
Data sources and time 
points 
Screening 
 
 
 
 
 
 
 
Demographics 
 
 
 
 
Weekly nursing self-management  
 
 
 
Reach: 
Sample 
Recruitment 
   
 
 
Effectiveness: 
Functional impacts 
 Pain 
 
  
Fatigue 
 Lower extremity strength 
 Balance and Function 
 Walking capacity 
  
 
Self-report measures 
  Function 
  Depression 
  Social support 
  Self-efficacy 
 
Adoption 
Adherence    
 
 
 
 
 
 
Acceptability 
Ability to ambulate 150 feet with or without assistive device;  
Short version of Test for Functional Health Literacy in Adults 
(0.97)37 
Tablet Computer Familiarity Questionnaire (0.92)38 
Mini-Cog26 
 
 
 
Personal health, medical, health history—co-morbidities, 
medications, use of pain medications, race/ethnicity 
 
 
 
Review weekly diary entries, pain scores, yoga and /or Otago 
progress, fatigue, and sleep.  
Participant interview and 
observation; Baseline 
 
 
 
 
 
 
Participant interview; 
Baseline  
 
 
Weekly 
 
 
 
 
Tracking forms;  
weekly quality checks by PI; 
weekly team meetings 
 
 
 
 
Baseline; Daily; Study end 
Baseline; Study end 
Baseline; Study end 
Baseline; Daily; Study end 
 
Baseline; Study end 
Baseline; Study end 
Baseline; Study end 
 
 
Baseline; Study end 
Baseline; Study end 
Baseline; Study end 
Baseline; Study end 
 
 
 
Tracking forms; weekly 
review of participant diary; 
weekly assessment of 
feedback; end of study 
participant interviews and 
satisfaction questionnaires 
 
 
 
Progress monitoring of sample representativeness; types of 
recruitment activities and rates; % eligible, consented, oriented  
 
 
 
 
 
Numerical rating scale NRS (0.99)39 
PROMIS Pain Interference Short Form 6b (0.98)40 
PROMIS Pain Behavior Short Form 7a (0.98)40 
PROMIS Fatigue Short Form 6a (0.91)41 
 
30 Second Chair Stand Test (not determined)42 
Mini Balance Evaluation Systems Test (MiniBEST) (0.91)43 
Two Minute Walk Test (0.82)44 
 
 
PROMIS Physical Function (0.95)45 
PROMIS Depression Short Form 8a (0.95)46 
Revised UCLA Loneliness Scale (0.94)47 
Pain Self-Efficacy Scale (0.93)48 
 
 
 
Participation in weekly self-management telehealth visits; 
frequency of participation in Otago and/or Yoga as recorded in 
participant diary and data from activity tracker; frequency of use 
of self-management techniques as recorded in participant diary; 
# of patients who successfully complete self-management 
program; # of and reasons for dropouts  
 

Version #7.1 3/4/21 
 
Page 14 of 34 
 
Endorsement 
 
 
 
 
 
Implementation 
 Technology 
 Site set up 
 Consistency of    
   intervention 
 
 
Maintenance 
 Projection of  
   future adoption  
Usability of tablet technology and activity tracker; # and types of 
problems encountered; participant satisfaction with self-
management program and technology 
 
 
 
 
# of problems encountered with tablet, activity tracker, vital sign 
equipment; # and types of problems encountered with study 
setup; was fidelity to training protocol maintained; was 
orientation completed as planned; was standardized checklist 
used to instruct participants; assessment of participant for 
suggestions; # of changes made to intervention based on 
suggestions  
 
# patients who would continue intervention; potential for future 
applications 
Assess at weekly team 
meetings; acceptability 
checklist and tracking forms; 
end of study participant 
interviews and satisfaction 
questionnaires 
 
Tracking forms; weekly team 
meetings; end of study 
participant interviews and 
satisfaction questionnaires 
 
 
 
 
End of study participant 
interviews and satisfaction 
questionnaires 
 
End of Study Interviews: At the end of Visit 2, participants under ARMS 1, 2, and 3 are scheduled 
an end of study phone exit-interview with Dr. Davis at University NC Charlotte (UNCC). This interview 
will be recorded and temporarily stored on a digital voice recorder while the participant is on speaker 
phone. Prior to the beginning of the recording, Dr. Davis will inform the participant that the recording 
is about to commence and at the end of the interview he will notify them that the recording has 
ceased. In this manner, no PHI will be collected. Prior to performing qualitative analysis, Dr. Davis will 
immediately upload the recording to the patient's electronic case record in the REDCap database on 
MUSC secure servers and the delete the recording from the portable storage device.  
 
Supplemental ARM 4 Study Design:  
Participants enrolled under this study arm will solely receive the gentle yoga and yoga breathing 12-
week (GYYB) component exercise program which will be loaded on to a tablet that will given to the 
participant while enrolled in the study. There are only two study visits (baseline and week 12) with no 
3 month follow-up, at which timepoints saliva samples will be collected. 
 
CG measures to be collected under the Supplemental ARM at the two timepoints include: 
 
• Demographics. Age, race/ethnicity, sex, marital status, socioeconomic status, education, living 
arrangement, medications, # co-morbid conditions (health status) will be recorded. 
• PROMIS v1.0/1.1 Short Forms (intraclass correlation coefficient) 
• Health status: Global Health Scale (0.81) 
• Functional health: Physical Function (0.95) 
• Fatigue: Fatigue 6a (0.91) 
• Sleep disturbance: Sleep Disturbance 6a 
• Depression: Depression 8a (0.95) and CES-D (0.90) 
• Anxiety: Anxiety 6a (0.94) 
• Loneliness: UCLA Loneliness Scale (0.96) 
• Social support: Medical Outcomes Study Social Support Survey Instrument (MOS-SS) (0.97) 
• Burden: Zarit Burden Scale (0.89) 
• Relationship quality (CG): Mutuality Scale (0.94) 
• QoL (CG): Euroqol-5D (0.83) 
• QoL (PWD): Quality of Life-Alzheimer’s Disease (0.82) 
• Function (PWD): Functional Assessment Staging Tool (0.87) 
• Activities of Daily Living Questionnaire (dementia) (0.86) 
• International Physical Activity Questionnaire for the Elderly (IPAQ-Short Form) 

Version #7.1 3/4/21 
 
Page 15 of 34 
 
• End of study satisfaction survey (researcher developed) 
 
The participant sample will be characterized using univariate descriptive statistics and frequency 
distributions for all variables as appropriate. We will also explore differences in demographic and 
other variables such as age (45-74, ≥75 years), sex, health status, functional activity, and QoL across 
the 2 time points. 
 
Participant Compensation: Participants under ARMS 1, 2, and 3 will receive $20 for screening, and 
$20 at the initial enrollment visit for completion of the initial enrollment assessment and baseline 
surveys (total of $40 if eligible and enrolled). Additionally, participants will receive another $40 at 
suiccessful completion of the post-treatment (week 12) and 3 month followup visits. Total 
compensation for successful study completion is $120.00. All payments will be made to the 
participant in the form of a gift card. 
 
Participants under the Supplemental ARM 4 will be provided a total amount of $80 in study 
compensation $40 for enrollment and completion of the baseline visit, and $40 at successful 
completion of study at visit 2. Payment will be made in the form of a check that will be mailed to the 
participant’s home address. Will will collect social security numbers for MUSC IRS tax reporting 
purposes. 
 
11.0 Specimen Collection and Banking  
Saliva Sample Collection (all ARMS): One 3mL saliva samples will be collected from participants at 
each of the three study visits. At the first two visits (baseline and week 12) the samples will be 
collected before and after the 30 minutes GYYB session. Saliva will be naturally allowed to 
accumulate in the oral cavity and the participant will discharge it into the specimen tube (5 mL 
capacity) with lid. Due to COVID-19 precautions, participants will be given the option to either 1) drop 
off their saliva samples at MUSC CON, or 2) to arrange to have their saliva sample picked up from 
their place of residence or at a location that is convenient to both themselves and the 
researchers. Immediately after collection the saliva samples will labelled with the participant’s study 
ID number and the collection dates, and then placed on ice for immediate transporation to MUSC in a 
biohazard cooler. The samples will subsequently be stored at -80 degree C until analysis by Dr. 
Balasubramanian at his lab. For analysis, the samples will be slowly thawed, centrifugation at 14000 
RPM at 4 degree C.  
 
Salivary Biomarker Measurement (all ARMS): Owing to their possible involvement in pain and/or 
fatigue, the following biomarkers will be assessed in saliva: cortisol and 1,5-AG. Dr. Balasubramanian 
(Co-I) will perform the analysis of salivary biomarker expression in the saliva samples similar to their 
laboratory’s recent reports (https://www.ncbi.nlm.nih.gov/pubmed/27538513; 
https://www.ncbi.nlm.nih.gov/pubmed/25873979; https://www.ncbi.nlm.nih.gov/pubmed/25101659). 
Dr. Balasubramanian has over 20 years of experience in ELISA and other biochemical techniques for 
biomarker measurement (Balasubramanian, & Kuppuswamy, 2003; Balasubramanian et al., 2006; 
Balasubramanian, Mani, Kasiganesan, Baicu, & Kuppuswamy, 2010; Balasubramanian et al., 2012; 
Moschella et al., 2013; Prabhasankar, Ragupathi, Sundaravavidel, Annapoorani, & Damodaran, 
1993).  
 
Specimen access and disposal (all ARMS): A chain of custody log will be maintained for the 
collection, handling and disposition of all participant biological specimens. Dr. Balasubramanian will 
only have access to unidentifiable biological data, which will be stored on MUSC secure servers. No 
genetic analysis or specimen banking will be conducted. Data will not be sent outside of the MUSC 
enterprise, and all specimens will be destroyed six months after study completion. As specified in the 

Version #7.1 3/4/21 
 
Page 16 of 34 
 
Informed Consent document, participant’s may withdraw their consent to participant in the study at 
any time. Revocation of consent either verbally or in writing will immediately withdraw the consent of 
the participant’s specimen analysis for any collected and unanalyzed saliva samples to date. The PI 
will work directly with Dr. Balasubramanian to notify him of consent withdrawals and to unblind group 
allocations for analysis purposes. 
 
12.0 Data Management  
Sample Size Determination. This feasibility study will recruit 30 participants under ARMS 1, 2, and 
3. Thirty participants should allow for recruitment of 10 participants from at least 3 different 
Humanities sites to avoid cross-contamination of study groups. 20 participants will be recruited under 
the Supplemental ARM AIM 4 to allow for outcome size effect determinations.  
 
Data analysis plan.  Measures of feasibility including recruitment and reach, fidelity and adherence, 
formal satisfaction, and drop-out proportions will be evaluated. Then 95% confidence intervals for 
proportions will be used to estimate dichotomous outcomes (e.g., the proportion of subjects who: 
agree to participate out of the number that are approached, the proportion who complete the 
intervention, the proportion who report satisfaction with the intervention, and the proportion who exit 
the study prematurely [drop out]). Further, the participants' reasons for drop out, and problems/issues 
encountered with the intervention will be described via frequency distributions. For continuous 
measures (e.g. satisfaction scores), frequency distributions and the median and mean responses 
(with 95% confidence intervals) will be obtained. Formative and summative qualitative interviews will 
be recorded with the residents and students, transcribed, analyzed with discourse analysis36 and 
interpreted to evaluate the program design and effectiveness and to make necessary changes based 
on feedback. Univariate descriptive statistics and frequency distributions will be calculated as 
appropriate for all variables. Demographic variables obtained at baseline will be described via 
measures of central tendency (mean, median), variability and frequency distributions as appropriate. 
Additionally, characteristics for those who were eligible for study versus those who were not eligible 
and for those who adhered to the study protocol (study completers) versus those who did not adhere 
(non-adherers and drop-outs) will be compared to better describe the population for this study. 
 
Data sharing with the NINR/NIH: As a condition of this National Institutes of Nursing Research 
(NINR) award, de-identified patient data will be shared by the researchers with the NINR and stored 
electronically on an NIH password protected secure server (https://cdrns.nih.gov/). The purpose of 
sharing this information is to build a NINR repository of data using Common Data Elements (CDE) for 
future research purposes among the general scientific community and for public health benefit. 
Patients will be allocated a random identifier through the NIH supported GUID Tool. The GUID Tool 
(https://cdrns.nih.gov/node/39) is a customized software application that generates a Global Unique 
Identifier for each study participant. The GUID is a subject ID that allows researchers to share data 
specific to a study participant without exposing personally identifiable information (PII). The GUID is 
made up of random alpha-numeric characters and is NOT generated from PII/PHI. As such, it has 
been approved by the NIH Office of General Counsel.  GUID Generation complies with HIPPA 
regulations for the protection of PII/PHI. Patients are made aware of this data sharing agreement with 
the NINR/NIH in the study’s Informed Consent document. Further protections are afforded to 
participants through an NIH Certificate of Confidentiality conferred upon the study. 
 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
There is a well-developed and NIH/NINR prepared Data and Safety Monitoring Plan (DSMP) that 
involves the use of a Safety Monitoring Committee (SMC) which shall meet semi-annually post initial 
participant study enrollment. The Committee is comprised of key individuals that include: an 

Version #7.1 3/4/21 
 
Page 17 of 34 
 
independent safety monitor (ISM), a biostatistician (BS), and the Program Manager (PM). Post initial 
study enrollment, the SMC will convene semi-annually and all reports will be forwarded to the IRB and 
Sponsor in accordance with institutional policies and sponsor requirements. 
 
DATA AND SAFTEY MONITORING PLAN (ARMS 1,2, and 3) 
SECTION A. Monitoring Entity. 
Considering the study rationale, population, procedures, and the risk:benefit profile as outlined, the 
overall risk level for participation in this study is classified as: Minimum Risk.  As such, this study will 
utiize a Safety Monitoring Committee (SMC) with an Independent Safety Monitor (ISM). Post initial 
study enrollment, the SMC will convene semi-annually. 
 
Principal Investigator, (PI). Although not part of the SMC, as PI, Dr. Kelechi will overall be responsible 
for the immediate protection of all human participant study participants enrolled in the study. 
 
1) 
Safety Monitoring Committee (SMC) 
The study’s SMC will be comprised of the following individuals, who will perform data safety 
management and monitoring of the study: 
• Dr. Charlene Pope, PhD, MPH, BSN, RN, FAAN (ISM) 
• Martina Mueller, PhD (BS) 
• Mohan Madisetti, MSc. (PM) 
 
2) 
Individual Roles and Responsibilities 
Independent Safety Monitor, (ISM). Dr. Pope is a Research Associate Professor in the College of 
Medicine (COM), Medical University of South Carolina with secondary appointments I the MUSC 
Department of Internal Medicine and College of Nursing. She is also Chief Nurse for Research aht 
the Ralph H. Johnson VA Med Center, Charleston, SC. She is trained as a health service researcher 
and a sociolinguist who studies variations in communication, in how patients and health providers 
speak with one another, and in an array of circumstances as a mixed methods and qualitative 
methodologist. Dr. Pope has collaborated with multidisciplinary health and social science teams in 
studies of health service and community-based disparities and participated in rural outreach. Dr. 
Pope will act as the study’s Independent Safety Monitor (ISM). Dr. Pope has no real or apparent 
conflict of interest that would affect her performance in this role on the study. Dr. Pope will correspond 
semi-annually with the SMC to review de-identified cumulative AE study data to assess any impact on 
the safety of participants or on the ethics of the study. As the ISM, she will be responsible for 
reviewing all cumulative reported SAE related to study treatment and data safety monitoring reports 
generated by the BS to provide study recommendations to the PI, MUSC’s IRB and NINR. Dr. Pope 
will be immediately notified of the occurrence of any SAE by the PI or PM and will be provided with 
the necessary study information to provide an informed recommendation in real-time regarding the 
protocol and human participant safety.  
 
 
Martina Mueller PhD, Biostatiscian (BS). Dr. Mueller is a Professor in the College of Nursing with a 
joint appointment in the Department of Biostatistics, Bioinformatics and Epidemiology (DBBE) at 
MUSC. Dr. Mueller has served and is currently serving as a member of several NIH/NINR R01/R21 
DSMB Committees and SMCs. Dr. Mueller will be responsible for conducting semi-annual interim 
analyses, generating semi-annual AE safety reports from the electronic study research database and 
disseminating de-identified information to the ISM and other members of the SMC. The interim data 
analyses will only include safety related results; analyses in regards to study outcome will not be 
performed. The interim AE reports will provide typology, frequency data and outcomes of all reported 
and documented AE in the electronic study database. With no patient contact, Dr. Mueller has no 
apparent conflict of interests to serve in this capacity. 

Version #7.1 3/4/21 
 
Page 18 of 34 
 
 
 
Mohan Madisetti MSc, Program Manager (PM). Mr. Madisetti is the P20 Progam Manager at the 
College of Nursing and a member of MUSC Institute of Human Values with Fellowship certification in 
Research Ethics. Mr. Madisetti has served and is currently serving as a member of several NIH/NINR 
R01/R21 and FDA Industry Sponsored Clinical Trials DSMCs and DSMB. With no patient contact, Mr. 
Madisetti will be responsible for the classification of all reported adverse events (AE) and for ensuring 
that all serious adverse events (SAE) are forwarded to the PI and ISM in real time and in compliance 
with MUSC IRB policies and procedures. In addition, and in conjunction with the PI, Mr. Madisetti will 
be responsible for amending the protocol in accordance with the ISM recommendations, submitting 
reportable SAEs and protocol deviations to MUSC IRB, and, submitting annual Progress Reports to 
the NIH/NINR through MUSC’s OSRP. He will also be responsible for maintaining the regulatory 
binder, ensuring data management validation and verification of the electronic study research 
database, conducting monthly internal quality control audits on all participant records, notifying the PI 
of any deficiencies, and the forwarding of reportable SAE to the NIH/NINR Program Official through 
MUSC’s OSRP within 72hrs of IRB review and acknowledgement 
 
SECTION B. Procedures for Safety, Risk and Confidentiality 
1) 
Monitoring Study Safety 
From the initial screening of participant by inclusion and exclusion criteria to the informed consent 
process to the provision of participant study instruction to staff training in Good Clinical Practices 
(GCP) and regulations pertaining to the Conduct of Human Participant Research to study contact with 
participants to internal monthly quality control audits and protocol fidelity monitoring to the real-time 
review of AE by the ISM to the oversight of MUSC’s IRB, procedures for monitoring study safety are 
consistently afforded throughout study. Specific procedures include: 
• Participants will be screened for inclusion and exclusion per the protocol; the PI shall verify 
100% of participants’ eligibility prior to study enrollment through review of inclusion and 
exclusion criteria with potential participants.  
• Participants will be fully informed as to all know risks and the possibility of risk from study 
participation in the informed consent process. These risks are minimal. 
• Participants will be instructed to notify the researchers of any/all suspected or experienced 
adverse events whether they believe them to be related or not to the intervention. 
• All reported participant AEs will be tracked through to resolution. 
• All investigators and researchers will maintain active CITI Human Subject Research and Good 
Clinical Practice training. 
• The PM will conduct a monthly internal quality control audit of all participant records to ensure 
compliance with MUSC IRB regulations; the PI and Program Coordinator (PC) will work 
together to correct any errors. 
• The PI and/or designee will observe and evaluate ten (10%) percent of eligibility screening 
visits, informed consents and study instructions performed by IRB approved study personnel 
and provide feedback and/or retraining of study personnel if fidelity to both applicable federal 
regulations and the protocol is not observed. 
• The BS willl generate semi-annual AE reports for the PI and SMC to review. 
• The ISM will have access to real-time study data and will be able to provide immediate 
recommendations to the PI. 
• Investigator performance and compliance will be provided for through MUSC IRB and ORI 
study oversight. 
 
 

Version #7.1 3/4/21 
 
Page 19 of 34 
 
 
2) 
Minimizing Research-Associated Risk 
Diligent study safety monitoring will be conducted by all member of the research team and the SMC 
throughout the conduct of this study in compliance with the following required elements of MUSC 
IRB’s continuing review process: 
1. Tracking and follow-up of participant accrual (inc. withdrawn consents) will minimize risk by 
identifying, disclosing, and mitigating any potentially unknown risk(s) of harm to study participants. 
The risks associated with this intervention are not considered greater than those that 
patients would otherwise be exposed to when receiving normal standard of care. 
2. Timely and appropriate reporting of informed consent process deficiencies, protocol deviations, 
privacy breaches, conflicts of interest, and/or changes in personnel. 
3. Ongoing soliciting, monitoring and appropriate reporting of adverse event activities. 
4. Timely and appropriate IRB submission of safety-related documents such as audit reports, sponsor 
progress reports, ISM reports, and other materials or communications that might impact the safe 
conduct of this study. 
5. Active cooperation with the IRB, ACO, sponsor, and other applicable entities in the event of a 
random or for-cause internal or external audit. 
 
Institution-Wide Assurances 
This protocol will be conducted fully in keeping with the signed MUSC IRB Principal Investigator 
Statement of Assurance and Department Chair’s Statement of Assurance, when submitted to the 
IRB as a required component of the MUSC IRB Human Research Review Application.  
 
3) 
Protecting Confidentiality of Participant data 
Certificate of Confidentiality. This study will be conducted in accordance with recently enacted 
policy regarding the automatic granting of Certificates of Confidentiality to NIH/NINR  federally funded 
research. Participants will be made aware of their rights and the limitations of the release of Protected 
Health Information through the Informed Consent document. 
 
Participant Screening and Enrollment. All data from participants screened for the study will be 
entered directly into an electronic study database. Designated research staff will collect, gather, and 
enter required data (written informed consent, HIPAA Authorization, and demographics) onto study 
data forms. Screened patients who do not meet study eligibility will have specific screening data 
entered into the study database. The collected data will be helpful in examining the patient population 
and feasibility of enrollment criteria and will include reason for exclusion. All dates will be shifted and 
other Personal Health Information (PHI) will be removed from the study database upon study 
completion. All data obtained from this study will be used for research purposes only and will comply 
with Federal HIPAA regulations.  Master Screening and Enrollment Logs will used by the PM to 
prepare reports on accrual and attrition for the PI and SMC. 
 
Case Report Forms (CRF). All proposed study specific case report forms (source documents) for 
data collection will be designed by the PI, and, when possible, transferred into electronic Case Report 
Forms (eCRFs) for use in the study’s REDCap database. These study specific eCRFs source 
documents (study logs for correspondence, compensation and other forms such as pre-eligibility 
screens) will be coded by the participant’s unique study ID# for all data collected including study 
instruments will be maintained in the participant research record. Completed instruments that require 
signature on a paper CRF will be scanned and uploaded into the study database to all for remote 
electronic safety monitoring as well as maintained on file in accordance with MUSC policies and 
applicable Federal Regulations for the Conduct of Human Participant Research.  
 

Version #7.1 3/4/21 
 
Page 20 of 34 
 
Binders. The PC will prepare and maintain a participant-specific CRF binder for each participant 
containing all non-eCRFs records. A regulatory file will be maintainedby the PM to include the IRB-
approved Protocol, original Informed Consent documents, HIPAA forms and other required study-
related regulatory documents. All paper research records and CRFs will be maintained in a locked file 
cabinet, stored in a room for research files that is accessible only via a password protected entry 
system that features security cameras, within the College of Nursing. Access to the research records, 
study database and PHI’s will be restricted to study personnel as approved by the PI and MUSC IRB. 
As with all studies conducted at MUSC, this study is also eligible for a random audit by MUSC Office 
of Compliance. 
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data 
capture and management. REDCap is a software toolset and workflow methodology for the 
electronic collection and management of research and clinical trials data. REDCap provides 
secure, web-based, flexible applications, including real-time validation rules with automated data 
type and range checks at the time of data entry. Exports are made available for several statistical 
packages including SPSS, SAS, SATA, R and Microsoft Excel. The study-specific REDCap 
electronic database will be designed and developed by the PI, CI, or PC.  The provision of REDCap is 
made available through the South Carolina Clinical & Translational Research (SCTR) Institute at 
MUSC with NIH Grant awards UL1RR029882 and UL1TR000062.  
 
Data Security. Ensuring data security, compliance with 45 CFR 46 and maintaining the integrity of 
PHI is a top priority. MUSC has Standard Operating Procedures (SOP) to ensure a high level of data 
security while coordinating electronic and paper data management activities for clinical research trials. 
The REDCap study database will be hosted in the Biomedical Informatics secure data center at 
MUSC, a secure environment for data systems and servers on campus, and includes firewall, 
redundancy, failover capability, backups and extensive security checks. The secure data center has 
strict access control; only authorized core personnel may access the facility un-escorted. Only 
authorized users are allowed to connect to the network, and the security of the network is actively 
monitored.  Power and environmental controls have several layers of backups, from interruptible 
power supplies to alternate and redundant feeds to the local utility company. The REDCap system 
administrator contributes to the maintenance of institutional disaster recovery and business continuity 
plans.  Load balancers and a highly fault tolerant SAN infrastructure contribute to high availability.  
 
The REDCap system itself has several additional layers of protection including password protection. 
Access to the data and its security is managed institutionally by sponsored login IDs through a 
Shibboleth login with an MUSC issued NetID and features a user account management filter that 
controls who can access the data and to what degree. All personnel must pass an employment 
background check before being issued an ID. Password complexity, history and expiration standards 
are implemented at the institutional level. Access to individual REDCap projects and their data is 
managed by the owner of the project. All transactions are securely delivered to the application using 
Secure Sockets Layer (SSL – SHA-1 with RSA Encryption; 2048-bits). It is then transmitted internally 
(behind the firewall) to the database server. All transactions are logged at the server layer (httpd 
logging), application layers (REDCap logs activity to a database table), and the database layer, using 
both query and binary logging. This feature provides audit trails for all changes, queries, data exports 
and reports. MUSC Information security policies are available at: https://mainweb-
v.musc.edu/security/policy/  
 
Data Entry. Only MUSC IRB approved study personnel that are authorized to have access to the 
REDCap study database will be granted password access. Study personnel using computers that are 
connected to the Internet will directly enter data into the remotely housed database. As such, no 

Version #7.1 3/4/21 
 
Page 21 of 34 
 
electronic study data will be stored on hard drives and/or any portable electronic devices. Additionally, 
all personnel with access to the database will have current University of Miami CITI training in the 
Conduct of Human Subject Protections, and HIPAA and Information Security trainings that are 
completed annually. Each participant will be assigned a unique study identifier, all PHIs will be 
masked, and data exports will be limited to the PI or the PC for generating reports and the conduct of 
statistical data analysis. 
 
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, storage 
and processing. The PM will conduct routine monthly monitoring of the study database and generate 
a report for review at study team meetings. Standing agenda items for these meetings will include 
participant recruitment and retention, AE’s, protocol deviations, data integrity and overall study 
conduct. The PI and PC will work to resolve and validate discrepant data. Discrepancies that warrant 
clarification will be sent to appropriate parties for review and resolution. All data entry and changes 
made in the study database by authorized study personnel will be automatically logged by REDCap, 
and provide a transparent visible audit trail for reviewers. 
 
SECTION C. 
Procedures for Identifying, Reviewing and Reporting Adverse Events 
1) 
Identifying. Potential minimum risks identified for participants are outlined in the Protection of 
Human Participants and will also be outlined in the IRB-approved informed consent document. 
Additional unknown risks may occur and, if so, will be identified through diligent monitoring by the PI 
or PC throughout the conduct of this study. During the informed consent process, participants will be 
advised of the potential risks of participation as identified in the IRB-approved informed consent 
document and reminded throughout the study that the researchers should be promptly informed 
about any concerns regarding potential side effects, adverse events, or clinical deterioration. 
Participants will also be instructed to notify the PI, PC, and/or designee of any suspected adverse 
events immediately if possible. The PI or PC will maintain an electronic record of all reported adverse 
events and notify the ISM of all reportable events as they occur. The ISM will have real-time access 
to the study database to review and monitor all reported SAE that were reported as related to the 
intervention. Additionally, the BS will generate and provide de-identified cumulative administrative 
human participant semi-annual safety reports for the ISM and SMC to review. 
 
2) 
Reviewing. Adverse events will be initially be assessed and graded by PM and then reviewed 
by the members of the SMC according to the following MUSC’s IRB Adverse Event Reporting Policy  
http://academicdepartments.musc.edu/research/ori/irb/HRPP/HRPP Guide Section 4.7 
• Expected/Anticipated—Identified in nature, severity, or frequency in the current protocol, 
informed consent, investigator brochure, or with other current risk information. 
• Unexpected/Unanticipated—Not identified in nature, severity, or frequency in the current 
protocol, informed consent, investigator brochure, or with other current risk information. 
• More Prevalent—Occurs more frequently than anticipated or at a higher prevalence than 
expected. 
• Serious—Results in death, is life threatening, requires inpatient hospitalization or prolongs 
existing hospitalization, results in persistent or significant disability/incapacity, cancer, 
overdose, or causes a congenital anomaly/birth defect. 
 
The relationship of adverse events to study participation will be determined by the SMC according to 
the MUSC IRB Adverse Event Reporting Policy: 
• Unrelated—There is not a reasonable possibility that the adverse event may have been 
caused by the drug, device or intervention. 

Version #7.1 3/4/21 
 
Page 22 of 34 
 
• Possibly Related—The adverse event may have been caused by the drug, device, or 
intervention, however there is insufficient information to determine the likelihood of this 
possibility. 
• Related—There is a reasonable possibility that the adverse event may have been caused by 
the drug, device or intervention. 
 
3) 
Reporting. All reportable AE, SAE and unanticipated problems experienced by participants will 
be reported to the NIH/NINR and MUSC IRB in compliance with their Adverse Event Reporting Policy 
requirements, using the IRB's password protected on-line secure server adverse event reporting 
system. Within 24 hours after a reportable AE, SAE or unanticipated problem has been reported by 
the participant, it will be graded by the PM, forwarded to the study’s ISM for review, and then will be 
submitted by the PI to MUSC IRB. The Institutional Official(s) will review the event and discuss the 
report with the IRB Chair and the Director of the Office of Research Integrity. After IRB review and 
acknowledgement, the PI will further review, and the PI or PM will forward a copy of the reportable AE, 
SAE or unanticipated problem and IRB acknowledgement letter to the NIH/NINR Program Officer 
through MUSC’s OSRP. The activities will be reported to the NIH/NINR within 72hrs. In addition, all 
cumulative reportable AE, SAE and unanticipated problems included in the ISM reports will be 
submitted to the NIH/NINR in the PI’s Annual Progress Reports. 
 
4) 
Examples of Potential Reportable Adverse Events: In accordance with MUSC IRB Adverse 
Event Reporting Policy, an AE is reportable is it meets all of the following criteria: 1) is unexpected 2) 
is related and/or possibly related, and 3) is serious and/or suggests that the research places subjects 
or others at a greater risk of physical or psychological harm than was previously known or 
recognized. Additionally, per MUSC’s policy all participant deaths, protocol deviations, complaints 
about the research, and breaches of confidentiality are reportable events. An example of an AE would 
be new onset chest pain and discomfort (symptom) that could potentially be associated with increased 
physical activity. The participant’s parent reported he/she recently ran out of his/her medication. The 
steps to be taken include withdrawing the subject from the study and inviting him or her to restart the 
study after symptoms subside. An example of an SAE would be the death of a participant from acute 
chest syndrome or stroke, which although would be viewed as unexpected and unrelated to the 
intervention is nonetheless a reportable serious event. No further steps would be taken except to 
review, grade and report the event. An example of an unanticipated problem would be the participant 
trips and falls while participating in the exercise program. The steps in this case would be to report the 
event as per the IRB and NINR policy, and to discuss appropriate actions regarding whether the 
participant should remain in the study with the ISM and SMC. These events and problems will be 
reported in accordance with the IRB and NIH/NINR policy as noted in Section C.3. 
 
SECTION D. Multi-site Monitoring and Compliance 
This is not a multi-site study. 
 
SECTION E. Assessment of External Factors 
The PI will conduct a semi-annual assessment of external factors through a review of literature 
related to new developments in the areas of self-management and symptom management of chronic 
pain and/or fatigue, symptom reporting and other approaches that may have an impact on the safety 
of participants or on the ethics of the study.  
 
SECTION F. Interim Analysis 
This study aims to test the feasibility of a multi-component, technology-based intervention to promote 
self-management and symptom management of chronic pain and fatigue among low- income older 
adults. To our knowledge, there are no similar interventions specifically designed for this patient 

Version #7.1 3/4/21 
 
Page 23 of 34 
 
population and purpose. As such, the PI and BS will generate semi-annual qualitative interim analysis 
reports on a) adverse events; and b) data obtained during phone call and returned end-of-study 
surveys to understand issues related to the uptake, usability, and adoption of this platform among this 
population. We will evaluate the screening and enrollment procedures, barriers to participation and 
retention, including, safety, adherence, acceptability, technology problems encountered if any, and 
user feedback from the participants and providers. This information gained from this structured 
process will be used to both guide the refinement of the current protocol and to inform the design of a 
larger efficacy trial. Interim analysis of outcome variables (pain, and fatigue) was not considered to 
avoid inexact inferences and increased chance of error due to few data points, as well as potential for 
bias if interim results were known to the investigators. Therefore, there are no planned stopping rules 
for this study. 
 
SUPPLEMENTAL ARM 4: DATA SAFETY AND MONITORING PLAN (DSMP)  
 
SECTION A. Monitoring Entity 
Considering the study rationale, population, procedures, and the risk to benefit profile, the overall 
risk level for participation in this study is classified as: Minimum Risk. Accordingly, the study will 
employ the use of a Safety Monitoring Committee (SMC) that will meet semi-annually post enrollment 
of the first participant into the study. The SMC members are charged with reviewing safety, trial 
progress, ethics, and with providing recommendations to the PI and MUSC IRB with respect to study 
continuation modification, and termination.  
 
1) Data Safety Monitoring Committee (SMC) 
The study’s SMC is comprised of the following individual members: 
• Elaine Krug, PhD, RN, FAAN; Gerontological and Alzheimer’s Disease Expert (G/ADE) and Chair 
(C); 
• Martina Mueller, PhD; Biostatistician (BS); and, 
• Mohan Madisetti, MSc; Project Director (PD)   
 
2) Individual Roles and Responsibilities 
Principal Investigator, (PI). As PI, Dr. Kelechi will overall be responsible for the immediate protection 
of all human participant study participants.  
 
Gerontological Expert, Dr. Krug is a Geriatric Nurse Practitioner and Professor Emeritus at the 
College of Nursing, MUSC. Dr. Amella will serve as the Chair of the DSMC and will correspond semi-
annually with the SMC to review de-identified cumulative AE study data to assess any impact on the 
safety of participants or on the ethics of the study. As Chair, Dr. Amella will be primarily responsible 
for the reviewing of all cumulative reported SAE that are related to study treatment, and the provision 
of SMC recommendations from data safety monitoring reports to the PI, MUSC’s IRB and the NIH. 
Dr. Krug will be immediately notified of the occurrence of any reportable SAE by the PD and will be 
provided with the necessary information to provide an informed recommendation in real-time 
regarding the protocol and human subject safety.  
 
Biostatistician, (BS). Dr. Mueller is a Professor at the College of Nursing at MUSC with a joint 
appointment in the Department of Public Health Sciences. Dr. Mueller will be responsible for 
conducting semi-annual interim data analyses, generating semi-annual AE safety reports from the 
REDCap study database and disseminating de-identified information to all members of the SMC. The 
interim data analyses will only include safety related results; analyses in regards to study outcome will 
not be performed. The interim AE safety reports will provide typology, frequency data and outcomes 

Version #7.1 3/4/21 
 
Page 24 of 34 
 
of all reported and documented AEs in the electronic study database. As a member of the SMC, Dr. 
Mueller will also participate in semi-annual DSMC meetings. 
 
Project Director, (PD). Mr. Madisetti is a Research Associate at the College of Nursing at MUSC. Mr. 
Madisetti will be responsible for the classification of all reported adverse events (AE) and for ensuring 
that all serious adverse events (SAE) are forwarded to the PI, C, and IRB, and in compliance with 
MUSC IRB and NIH’s reporting requirements. In addition, and in conjunction with the PI, the Mr. 
Madisetti will be responsible for amending the protocol in accordance with the SMC’s 
recommendations, submitting reportable SAEs to the IRB, and submitting annual SMC reports to the 
IRB and NIH. As part of the SMC, he will be responsible for: conducting internal quality control audits 
on all participant records and notifying the PI of any deficiencies; assisting in the generation of ad hoc 
participant data safety reports; and, forwarding reportable SAE to the NIH/NINR Program Official 
through MUSC’s OSRP within 72hrs of IRB review and acknowledgement. Mr. Madisetti will also be 
responsible for following up on reported AEs to monitor outcomes and provide for the continuity of 
care for participants. 
 
SECTION B. Procedures for Safety, Risk and Confidentiality 
1) Monitoring Study Safety 
From the initial screening of study participants by inclusion and exclusion criteria to the informed 
consent process to the provision of participant study instruction to staff training in Good Clinical 
Practices (GCP) and regulations pertaining to the Conduct of Human Participant Research to 
regularly scheduled study contact with participants to internal quality control audits and protocol 
fidelity monitoring to the real-time review of AEs, and to the oversight of MUSC’s IRB -  procedures for 
monitoring study safety are consistently afforded throughout study. Specific procedures include: 
• All participants will be screened for inclusion and exclusion per the protocol 
• All participants will be fully informed as to all known risks and the possibility of risk from study 
participation in the informed consent process. These risks are minimal. 
• AEs and changes in medical status will be elicited at every participant visit and contact. 
• All participants will be given a 24 hrs. AE reporting phone number and will instructed to notify 
the researchers of any/all suspected or experienced adverse events whether they believe 
them to be related to the intervention or not. 
• The PD will track all reported participant AEs through to resolution. Please see Section C. 1 – 
4. 
• The BS shall generate semi-annual AE reports for the PI and SMC to review. 
• The PD will conduct quarterly internal quality control audits of the study and all records to 
ensure compliance with MUSC IRB regulations and notify the PI of any deficiencies; the PD 
will work with the PI and Program Coordinator to correct any errors. 
• The PI and/or designee will observe and evaluate ten (10%) percent of eligibility screening 
visits, informed consents and study instructions performed by IRB approved study personnel 
and provide feedback and/or retraining of study personnel if fidelity to both applicable federal 
regulations and the protocol is not observed. 
• All investigators and researchers will maintain active CITI training. 
• Investigator performance and compliance will be provided for through MUSC IRB and ORI 
study oversight. 
• All reportable events, including protocol deviations will be forwarded to the NIH Program Official 
through MUSC’s OSRP within 72hrs of IRB review and acknowledgement. 
 
 
 

Version #7.1 3/4/21 
 
Page 25 of 34 
 
2) Minimizing Research-Associated Risk 
Diligent study safety monitoring will be conducted by the PI and all members of the DSMC throughout 
the conduct of this study in compliance with the following required elements of MUSC IRB’s 
continuing review process: 
1. Tracking and follow-up of participant accrual including withdrawn consents will minimize risk by 
identifying, disclosing, and mitigating any potentially unknown risk(s) of harm to study 
participants. These risks are minimal. 
2. Timely and appropriate reporting of informed consent process deficiencies, protocol 
deviations, privacy breaches, conflicts of interest, and/or changes in personnel. 
3. Ongoing soliciting, monitoring and appropriate reporting of adverse event activities. 
4. Timely and appropriate IRB submission of safety-related documents such as audit reports, 
sponsor progress reports, ISM reports, and other materials or communications that might 
impact the safe conduct of this study. 
5. Active cooperation with the IRB, ACO, sponsor, and other applicable entities in the event of a 
random or for-cause internal or external audit. 
 
Institution-Wide Assurances 
This protocol will be conducted fully in keeping with the signed MUSC IRB Principal Investigator 
Statement of Assurance and Department Chair’s Statement of Assurance, when submitted to the 
IRB as a required component of the MUSC IRB Human Research Review Application. An application 
will be submitted to the MUSC IRB if/when this project is approved and funded by NIH/NINR. 
Assurances include the following safety-related agreements, signed and dated by the PI. 
 
3) Protecting Confidentiality of Participant Data 
Participant Screening and Enrollment. All data from participants screened for the study will be 
entered into electronic study database. Designated research staff will collect, gather, and enter 
required data (written informed consent, HIPAA Authorization, medical history and demographics) 
onto study data forms. Screened patients who do not meet study eligibility will have specific 
screening data entered into the study database. The collected data will be helpful in examining the 
patient population and feasibility of enrollment criteria and will include gender, age, race and reason 
for exclusion. All dates will be shifted and other Personal Health Information (PHI) will be removed 
from the study database upon study completion. All data obtained from this study will be used for 
research purposes only and will comply with Federal HIPAA regulations.  Master Screening and 
Enrollment Logs will be maintained by the PD and will be used to prepare reports on accrual and 
attrition for the PI and SMC. 
 
Case Report Forms. All proposed study specific case report forms (source documents) for data 
collection will be designed by the PD in concert with the PI and BS, and transferred by the PD into 
electronic Case Report Forms (eCRFs) for use in the study’s REDCap database. These study 
specific eCRFs source documents (study logs for correspondence, contact with provider, 
compensation and other forms such as pre-eligibility screens) will be coded by the participant’s 
unique study ID# for all data collected including study instruments will be maintained in the participant 
research record and/or their electronic medical record that will be made accessible to study monitors. 
Completed instruments that require signature on a paper CRF will be scanned and uploaded into the 
study database to all for remote electronic safety monitoring as well as maintained on file in 
accordance with MUSC policies and applicable Federal Regulations for the Conduct of Human 
Participant Research.  
 
Binders. The PD will prepare and maintain a participant-specific binder for each participant 
containing all non-eCRFs records. A regulatory file will also be maintained to include the IRB-

Version #7.1 3/4/21 
 
Page 26 of 34 
 
approved Protocol, original Informed Consent documents, HIPAA forms and other study-related 
regulatory documents. All paper research records and CRFs will be maintained in a locked file 
cabinet, stored in a room for research files that is accessible only via a password protected entry 
system that features security cameras, within the College of Nursing. Access to the research records, 
study database and PHI’s will be restricted to study personnel as approved by the PI and MUSC IRB. 
As with all studies conducted at MUSC, this study is also eligible for a random audit by MUSC Office 
of Compliance. 
 
Data Processing. This study will use Research Electronic Data Capture (REDCap) for data 
capture and management. REDCap is a software toolset and workflow methodology for the 
electronic collection and management of research and clinical trials data. REDCap provides 
secure, web-based, flexible applications, including real-time validation rules with automated data 
type and range checks at the time of data entry. Exports are made available for several statistical 
packages including SPSS, SAS, SATA, R and Microsoft Excel. The study-specific REDCap 
electronic database will be designed and developed by the PD in concert with the BS.  The provision 
of REDCap is made available through the South Carolina Clinical & Translational Research (SCTR) 
Institute at MUSC with NIH Grant awards UL1RR029882 and UL1TR000062.  
 
Data Security. Ensuring data security, compliance with 45 CFR 46 and maintaining the integrity of 
PHI is a top priority. MUSC has Standard Operating Procedures (SOP) to ensure a high level of data 
security while coordinating electronic and paper data management activities for clinical research 
trials. The REDCap study database will be hosted in the Biomedical Informatics secure data center at 
MUSC, a secure environment for data systems and servers on campus, and includes firewall, 
redundancy, failover capability, backups and extensive security checks. The secure data center has 
strict access control; only authorized core personnel may access the facility un-escorted. Only 
authorized users are allowed to connect to the network, and the security of the network is actively 
monitored.  Power and environmental controls have several layers of backups, from interruptible 
power supplies to alternate and redundant feeds to the local utility company. The REDCap system 
administrator contributes to the maintenance of institutional disaster recovery and business continuity 
plans.  Load balancers and a highly fault tolerant SAN infrastructure contribute to high availability.  
 
The REDCap system itself has several additional layers of protection including password protection. 
Access to the data and its security is managed institutionally by sponsored login IDs through a 
Shibboleth login with an MUSC issued NetID and features a user account management filter that 
controls who can access the data and to what degree. All personnel must pass an employment 
background check before being issued an ID. Password complexity, history and expiration standards 
are implemented at the institutional level. Access to individual REDCap projects and their data is 
managed by the owner of the project. All transactions are securely delivered to the application using 
Secure Sockets Layer (SSL – SHA-1 with RSA Encryption; 2048-bits). It is then transmitted internally 
(behind the firewall) to the database server. All transactions are logged at the server layer (httpd 
logging), application layers (REDCap logs activity to a database table), and the database layer, using 
both query and binary logging. This feature provides audit trails for all changes, queries, data exports 
and reports. MUSC Information security policies are available at: https://mainweb-
v.musc.edu/security/policy/  
 
Data Entry. Only MUSC IRB approved study personnel that are authorized to have access to the 
REDCap study database will be granted password access. Study personnel using computers that are 
connected to the Internet will directly enter data into the remotely housed database. As such, no 
electronic study data will be stored on hard drives and/or any portable electronic devices. Additionally, 
all personnel with access to the database will have current University of Miami CITI training in the 

Version #7.1 3/4/21 
 
Page 27 of 34 
 
Conduct of Human Subject Protections, and their respective institution’s HIPAA and Information 
Security trainings that are completed annually. Each participant will be assigned a unique study 
identifier, all PHIs will be masked, and data exports will be limited to the PI, the PD and the BS for 
generating reports and the conduct of statistical data analysis. 
 
Data Monitoring. Ongoing quality control procedures will be implemented for data collection, 
storage and processing. The PD will conduct monthly monitoring of the study database and generate 
a report for the PI to review at team meetings. Standing agenda items for these meetings will include 
participant recruitment and retention, AE’s, protocol deviations, data integrity and overall study 
conduct. The PD will work to resolve and validate discrepant data. Discrepancies that warrant 
clarification will be sent to appropriate parties for review and resolution. All data entry and changes 
made in the study database by authorized study personnel will be automatically logged by REDCap, 
and provide a transparent visible audit trail for reviewers. 
 
SECTION C.  
Procedures for Identifying, Reviewing and Reporting Adverse Events 
1) Identifying. Potential minimum risks identified for participants are outlined in the Protection of 
Human Participants and will also be outlined in the IRB-approved informed consent document. 
Additional unknown risks may occur and, if so, will be identified through diligent monitoring by the PD 
and the frontline research team throughout the conduct of this study. During the informed consent 
process, participants will be advised of the potential minimum risks of participation as identified in the 
IRB-approved informed consent document and reminded throughout the study that the researchers 
should be promptly informed about any concerns regarding potential side effects, adverse events, or 
clinical deterioration. Participants will also be instructed to immediately notify the PI and/or designee 
of any suspected adverse events, if possible. Throughout the course of study, at each study contact, 
the researchers will elicit information about experienced AEs and monitor participant progress. The 
PD will maintain an electronic record of all reported adverse events and notify the PI and GE of all 
reportable events as they occur. The PD will generate and provide de-identified semi-annual 
administrative human participant safety reports for the SMC to review participant progress, accrual 
and attrition rates. Additionally, the BS will generate semi-annual safety reports for the SMC to 
provide for the monitoring of the frequency of all reported side effects and AEs. 
2) Reviewing. Adverse events will be assessed and evaluated by the members of the SMC 
according to the following MUSC’s IRB Adverse Event Reporting Policy 
http://academicdepartments.musc.edu/research/ori/irb/HRPP/HRPP%20Guide%20Section%204.7: 
● 
Expected/Anticipated—Identified in nature, severity, or frequency in the current protocol, 
 
informed consent, investigator brochure, or with other current risk information. 
● 
Unexpected/Unanticipated—Not identified in nature, severity, or frequency in the current 
 
protocol, informed consent, investigator brochure, or with other current risk information. 
● 
More Prevalent—Occurs more frequently than anticipated or at a higher prevalence  
than 
expected. 
● 
Serious—Results in death, is life threatening, requires inpatient hospitalization or  prolongs 
existing hospitalization, results in persistent or significant disability/incapacity,  
cancer, overdose, 
or causes a congenital anomaly/birth defect. 
 
The relationship of adverse events to study participation will be determined by the DSMC according 
to the MUSC IRB Adverse Event Reporting Policy: 
● 
Unrelated—There is not a reasonable possibility that the adverse event may have been 
 
caused by the drug, device or intervention. 

Version #7.1 3/4/21 
 
Page 28 of 34 
 
● 
Possibly Related—The adverse event may have been caused by the drug, device, or 
 
intervention, however there is insufficient information to determine the likelihood of this 
 
possibility. 
● 
Related—There is a reasonable possibility that the adverse event may have been 
 
caused by the drug, device or intervention. 
 
3) Reporting. All reportable AE, SAE and unanticipated problems experienced by participants will be 
reported to the NIH/NINR and MUSC IRB in compliance with their Adverse Event Reporting Policy 
requirements, using the IRB's password protected on-line secure server adverse event reporting 
system. Within 24 hours after a reportable AE, SAE or unanticipated problem has been reported by 
the participant, it will be initially graded by the PD, forwarded to the study’s C for review and approval, 
and then will be submitted by the PI to MUSC IRB. The Institutional Official(s) will review the event 
and discuss the report with the IRB Chair and the Director of the Office of Research Integrity. After 
IRB review and acknowledgement, the PI will further review, and the PD will forward a copy of the 
reportable AE, SAE or unanticipated problem and IRB acknowledgement letter to the NIH/NINR 
Program Officer through MUSC’s OSRP. The activities will be reported to the NIH/NINR within 72hrs. 
In addition, all cumulative reportable AE, SAE and unanticipated problems included in the ISM 
reports will be submitted to the NIH/NINR in the PI’s Annual Progress Reports. 
 
4) Examples of Potential Reportable Adverse Events: In accordance with MUSC IRB Adverse 
Event Reporting Policy, an AE is reportable is it meets all of the following criteria: 1) is unexpected 2) 
is related and/or possibly related, and 3) is serious and/or suggests that the research places 
participants or others at a greater risk of physical or psychological harm than was previously known or 
recognized. Additionally, per MUSC’s policy all participant deaths, protocol deviations, complaints 
about the research, and breaches of confidentiality are reportable events. From our previous work 
among this study population, an example of an AE would be feeling lightheaded or dizziness while or 
after performing the yoga breathing exercises. Depending on the severity, the possible steps to be 
taken include referral to a medical provider, resting in a prone position until the feeling subsides, and/or 
withdrawing the participant from the study. An example of an SAE would be the death of a 
participant from renal failure, which although would be viewed as unexpected and unrelated to the 
intervention is nonetheless a reportable serious event. No further steps would be taken except to 
review, grade and report the event to all applicable agencies. An example of an unanticipated 
problem would be the participant strains his or her neck while performing the yoga breathing. The 
steps in this case would be to withdraw the participant from the study and invite him or her to restart 
the study after the strain has resolved. These events and problems will be reported in accordance 
with the IRB and NIH/NINR policy as noted in Section C.3. 
 
SECTION D. Multi-site Monitoring and Compliance 
This is not a multi-site study. 
 
SECTION E. Assessment of External Factors 
The PI will conduct a semi-annual assessment of external factors through a review of literature 
related to new developments in the areas of yoga breathing among older populations, and other 
approaches that may have an impact on the safety of participants or on the ethics of the study. To 
determine whether any changes are necessitated to the study protocol, the SMC will review any 
identified literature or product safety data that may pose as a potential impact to the risk benefit ratio 
study and/or safety of study participants. 
 
 
 

Version #7.1 3/4/21 
 
Page 29 of 34 
 
SECTION F. Interim Analysis 
Based upon our prior research in this field among this same population and the minimal risk 
associated with the intervention, there are no stopping rules for this study. Accordingly, interim futility 
analysis will not be performed. However, the BS and PD will generate semi-annual qualitative interim 
analysis reports on a) adverse events; and b) data obtained during phone calls and returned end-of-
study surveys to understand issues related to the uptake, usability, and adoption of the yoga 
breathing exercises among this population. We will also evaluate the screening and enrollment 
procedures, barriers to participation and retention, including, safety, adherence, acceptability, and 
feedback from the participants.  
 
15.0 Risks to Subjects 
The risks associated with this intervention are not considered greater than those that patients would 
otherwise be exposed to when engaged in an routine physical activity exercise program. Overall, 
potential risks associated with participation in the study are viewed to be minimal. However, as with 
all studies, there are inherent risks involved with the conduct of human subject research that gathers 
Protected Health Information (PHI). Participants will be made aware of these risks during the 
Informed Consent process. Identified study risks include: Physical discomfort, emotional distress, 
social wellbeing, Loss of privacy, and randomization.  
 
Physical discomfort. Participants with pre-existing medical conditions that would make increase in 
physical activity dangerous to their health will be excluded from the study. There may be minor 
physical discomfort from the increase in physical activity; however, the potential risk to all subjects is 
minimal. The participants’ pain and fatigue scores will be assessed on a weekly basis by the PI, who 
is a Board-Certified Family Nurse Practitioner, which will allow for further determination of any 
untoward effects of participation in the physical activity program. The PI will be communicating with 
the participants via telehealth visits on a weekly basis to allow for further follow-up of any physical 
issues with the program. 
 
Emotional distress. Participants will be asked to provide information about their self-reported pain 
and fatigue, social isolation, depression and demographic data. These questions pose an anticipated 
low psychological risk, e.g. for anxiety, if participants appear upset by questions about their health 
issues, they will be instructed that if they do not wish to answer a question, they can skip it and go to 
the next question. 
 
Social well-being. There is low potential for adverse social effects in this research study. Through bi-
weekly telehealth visits with nurses, participants will have social support during their participation.  
 
Loss of privacy. PHI from participants will be gathered and stored electronically on secure and 
encrypted servers and there are risks associated for the loss of privacy and confidentiality. As well as 
having a comprehensive DSMP that details data safety, handling, monitoring, storage and security 
procedures, we will further minimize the potential for loss of confidentiality through the physical 
separation of participant names from their research record. 
 
All participants will be screened for depression using the PROMIS Emotional Distress-Depression 
Short Form 8a. If a participant scores in the severe depression category (raw score 33 and above) a 
referral will be placed to a mental health professional which could result in loss of confidentiality. 
Additionally, participants that score in the moderate depression category (raw score 23 to 32) further 
screening for suicidal ideation will take place. If the participant would admit to suicidal ideation at any 
time during the study, an emergent mental health consult will be placed which could also lead to loss 
of confidentiality.  

Version #7.1 3/4/21 
 
Page 30 of 34 
 
 
Randomization. Participants are being assigned to one of three study groups and treatment 
programs by chance. Each exercise program may prove to be less or more effective or have more or 
less or unknown side effects than the other or other available treatments. Participation in the study is 
completely voluntary and participants may withdraw their consent at any time. 
 
If participants should experience any symptoms during physical activity and medical attention is 
needed, resource numbers of local healthcare providers and hospital system emergency services are 
provided to all subjects to access in the same manner they would with any emergency that they 
encountered. The PI is a board-certified Family Nurse Practitioner and will be available as a resource 
by telephone during regular business hours. This information (contact resources) is provided in 
writing to all subjects who choose to consent and enroll in the study.  
 
16.0 Potential Benefits to Subjects or Others 
There may be no direct and immediate benefit to the participants from this research study. 
Participants in the study may accrue the benefit of improved mobility, strength and balance and along 
with the benefits of the yoga and behavioral activiation, more motivation to be physically active which 
could improve symptoms of chornic pain and/or fatigue. The benefit to others is that if this program is 
proven effective, other low-income older adults, might benefit as well from its future implementation. 
 
18.0 Drugs or Devices 
This study does not involve the use or storage of any drug product. All investigational supplies and 
materials are readily commercially available and are not industry regulated. All study supplies 
(tablets) will be inventoried and stored in a locked cabinet, behind a locked door by the researchers. 
Study supplies will be dispensed individually to each participants after enrollment and group 
assignment.  
A&D Medical Premium Wireless Blood Pressure Monitor is an FDA approved, Bluetooth blood 
pressure cuff that will be utilized to collect participants blood pressure and pulse and transmit the data 
to the “Activate for Life” application. 
The “Activate for Life” app is an application that will be available on participants tablets. This app has 
the ability to receive Bluetooth data from the A&D wireless blood pressure monitor. The app will also 
allow participants to enter there pain and fatigue levels on a “1-10” scale, ask participants to input 
their PA and their use of pain medication for the day, and record thoughts on a voice recorded daily 
diary. This information will transmit from the application to a firewall protected server at MUSC where 
it will be available to the research team. No medical information will be stored on the app.  
 
 
 
 
 
 

Version #7.1 3/4/21 
 
Page 31 of 34 
 
References: 
1. Meng, H., Hale, L., & Friedberg, F. (2010). Prevalence and predictors of fatigue among middle-aged 
and older adults: Evidence for the Health and Retirement Study. Journal of the American Geriatric 
Society, 58(10), 2033-2034. doi:  10.1111/j.1532-5415.2010.03088.x 
2. Laubenstein, S., & Beissner, K. (2016). Exercise and Movement-based Therapies in Geriatric Pain 
Management. Clinical Geriatric Medicine, 32, 737–762. http://dx.doi.org/10.1016/j.cger.2016.06.002  
3. Liu, C.J. & Latham, N.K. (2009). Progressive resistance strength training for improving physical 
function in older adults. Cochrane Database Systematic Review, 8(3), CD002759. 
doi:10.1002/14651858.CD002759.pub2.  
4. Mazzeo, R.S., Cavanagh, P., Evans, W.J., et al. (1998).  ACSM position stand: Exercise and physical 
activity for older adults. Medical Science Sports and Exercise. 30(6), 992–1008.  
5. McNamara, A.J., Pavol, M.J., & Gunter, K.B. (2013). Meeting physical activity guidelines through 
community-based group exercise: “Better bones and balance.” Journal of Aging and Physical Activity, 
21(2), 155–166.  
6. Miller, J., MacDermid, J.C., Walton, D.M., & Richardson, J. (2015). Chronic pain self-management 
support with pain science education and exercise (COMMENCE): Study protocol for a randomized 
controlled trial. Trials, 16, 462. doi:10.1186/s13063-015-0994-5 
7. Thomas, S., Mackintosh, S., & Halbert, J. (2010). Does the ‘Otago exercise programme’ reduce 
mortality and falls in older adults?: a systematic review and meta-analysis. Age and Ageing, 39,(6), 
681-687,https://doi.org/10.1093/ageing/afq102 
8. Stevens, J.A. & Burns, E.R. (2015). A CDC compendium of effective fall interventions: What works for 
community-dwelling older adults (3rd ed.). Atlanta, GA: Centers for Disease Control and Prevention, 
National Center for Injury Prevention and Control. 
9. Robertson, M.C., Devlin, N., Gardner, M.M., & Campbell, A.J. (2001). Effectiveness and economic 
evaluation of a nurse delivered home exercise programme to prevent falls: Randomised controlled 
trial. BMJ, 322(7288):697-701. 
10. Egede, L.E., Frueh, C.B., Richardson, L.K., Acierno, R., … Lejuez, C. (2009). Rationale and design: 
telepsychology service delivery for depressed elderly veterans. Randomized controlled trial 
Trials, 10, 22. doi: 10.1186/1745-6215-10-22. 
11. Acierno, R., Gros, D.F., Ruggiero, K.J. Hernandez-Tejada, B.M., Knapp, R.G., …Tuerk, P.W. (2016). 
Behavioral activation and therapeutic exposure for posttraumatic stress disorder: a noninferiority trial 
of treatment delivered in person versus home-based telehealth. Depression and Anxiety, 33(5), 415-
423. doi: 10.1002/da.22476 
12. Polenick, C.A. & Flora, S.R. (2013). Behavioral activation for depression in older adults: theoretical 
and practical considerations. Behav Anal., 36(1), 35-55.  
13. U.S. Department of Health and Human Services, Administration on Aging (AoA) Profile of Older 
Americans:  2014.  Retrieved from, www.aoa.acl.gov/Aging_Statistics/index.aspx 
14. Metlife (2013). The MetLife report on aging in place 2.0: Rethinking solutions to the home care 
challenge. New York, NY: MetLife Mature Market Institute. 
15. American Association of Retired Persons, 2011. Aging in place: A state survey of livability policies 
and practices. 
16. McGill, N. (2013). As senior population grows, aging in place gains popularity: Communities 
conducting outreach. The Nation’s Health, 43(8), 1-16. Retrieved from 
http://thenationshealth.aphapublications.org/content/43/8/1.2.full 
17. Clarity (2007). Attitudes of Seniors and Baby Boomers on Aging in Place. Retrieved from 
http://www.retirement-living.com/proaging-network/research-study-“aging-in-place-in-america”/ 
18. Patel, K.V., Guralnik, J.M., Dansie, E.J., & Turk, D.C. (2013). Prevalence and impact of pain among 
older adults in the United States: Findings from the 2011 National Health and Aging Trends Study. 
Pain,  
154(12). doi:  10.1016/j.pain.2013.07.029 

Version #7.1 3/4/21 
 
Page 32 of 34 
 
19. National Center for Health Statistics (2012). Health, United States, 2011: With Special Feature on 
Socioeconomic Status and Health. Hyattsville, MD: National Center for Health Statistics,  
http://www.cdc.gov/nchs/data/hus/hus11.pdf#073.  
20. Tennstedt, S., Howland, J., Lachman, M., Peterson, E., Kasten, L., & Jette, A. (1998).  A randomized, 
controlled trial of a group intervention to reduce fear of falling and associated activity restriction in 
older adults. Journal of Gerontology and Psychology Science and Social Science, 53(6), P384–P392. 
doi: 10.1093/geronb/53B.6.P384 
21. Bhattarai, B.N. Hons, P., & Philips, J.L. (2016). The role of digital health technologies in management 
of  
pain in older people: An integrative review. Archives of Gerontology and Geriatrics, 68,14-20.  
doi: http://dx.doi.org/10.1016/j.archger.2016.08.008 
22. Kim, S., Lockhart, T., & Roberto, K. (2009). The effects of 8-week balance training or weight training: 
For the elderly on fear of falling measures and social activity levels. Quality in Aging: Policy, Practice 
and Research, 10(4), 37–48. 
23. Taylor, S.J.C., Carnes. D., Homer, K., Pincus, T., Kahan, B.C., Hounsome, N., et al. (2016). 
Improving the  
self-management of chronic pain: Coping with persistent Pain, Effectiveness Research in Self-
management (COPERS). Programme Grants Application Research, 4(14). doi: 10.3310/pgfar04140 
24. Vallath, N. (2010). Perspectives on Yoga Inputs in the Management of Chronic Pain. Indian Journal of 
Palliative Care, 16(1): 1–7. doi:10.4103/0973-1075.63127. 
25.  
26. Brands, MM., Purperhart, H., & Deckers-Kocken, JM. (2011). A pilot study of yoga treatment in 
children with functional abdominal pain and irritable bowel syndrome. Complementary Therapies in 
Medicine, 19(3):109-14. doi: 10.1016/j.ctim.2011.05.004. 
27. Raub, JA. (2002). Psychophysiologic effects of Hatha Yoga on musculoskeletal and cardiopulmonary 
function: a literature review. Journal of Alternative and Complementary Medicine, 8(6):797-812. 
28. Werntz, DA., Bickford, RG., Bloom, FE., & Shannahoff-Khalsa, DS. (1983) Alternating cerebral 
hemispheric activity and the lateralization of autonomic nervous function. Human Neurobiology, 
2(1):39-43. 
29. Hughes, CM., Quinn, F., & Baxter, GD. (2011). Complementary and alternative medicine: perception 
and use by physiotherapists in the management of low back pain. Complementary Therapies in 
Medicine, 19(3):149-54. doi: 10.1016/j.ctim.2011.03.003. 
30. Tiedemann, A., O’Rourke, S., Sesto, R. & Sherrington, C. (2013). A 12-week Iyengar yoga program 
improved balance and mobility in older community-dwelling people: a pilot randomized controlled trial. 
J Gerontol A Biol Sci Med Sci., 68(9),1068-1075. doi: 10.1093/gerona/glt087. 
31. Twai, W.O., Wahlquist, A.E., & Balasubramanian, S. (2016). Yogic breathing when compared to 
attention control reduces the levels of pro-inflammatory biomarkers in saliva: a pilot randomized 
controlled trial. BMC Complement Altern Med.,18, 294. doi: 10.1186/s12906-016-1286-7. 
32. Balasubramanian, S., Janech, M.G., & Warren, G.W. (2015). Alterations in Salivary Proteome 
following Single Twenty-Minute Session of Yogic Breathing. Evid Based Complement Alternat Med., 
376029. doi: 10.1155/2015/376029.  
33. Balasubramanian, S. Mintzer, J.E., & Wahlquist, A.E. (2014). Induction of salivary nerve growth factor 
by Yogic breathing: a randomized controlled trial. Int Psychogeriatr., 27(1):168-70. doi: 
10.1017/S1041610214001616. Epub 2014 Aug 7. 
34. Eda, N., Ito, H., Shimizu, K., Suzuki, S., Lee, E., & Akama, T. (2017). J Women Aging., 3, 1-15. doi: 
10.1080/08952841.2017.1295689.  
35. Slavish, D.C., Graham-Engeland, J.E., Smyth, J.M., & Engeland, C.G. (2015). Salivary markers of 
inflammation in response to acute stress. Brain Behav Immun., 44:253-69. doi: 
10.1016/j.bbi.2014.08.008.  

Version #7.1 3/4/21 
 
Page 33 of 34 
 
36. Strahler, J., Skoluda, N., Kappert, M.B., & Nater, U.M (2017). Simultaneous measurement of salivary 
cortisol and alpha-amylase: Application and recommendations. Neurosci Biobehav Rev., 83, 657-677. 
doi: 10.1016/j.neubiorev.2017.08.015.  
37.  
38. Bandura, A. (1989). Social cognitive theory. In R. Vasta (Ed.), Annals of child development. Vol.6. Six 
theories of child development (1-60). Greenwich, CT: JAI Press. 
39. Bandura, A. (1977). Self-efficacy: Toward a unifying theory of behavioral change. Psychological 
Review, 84(2), 191-215. 
40. Borson S, Scanlan J, Brush M, et al. (2000). The mini-cog: a cognitive vital signs measure for 
dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry,15, 10217. 
41. Evenson, K.R., Goto, M.M., & Furberg, R.D. (2015). Systematic review of the validity and reliability of 
consumer-wearable activity trackers. International Journal of Behavioral Nutrition and Physical 
Activity, 12. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683756/ 
42. Vidyo (2014). Video enabled healthcare solutions. Retrieved from https://www.vidyo.com/wp-
content/uploads/Solution-Brief/Healthcare/SB-VidyoEnabledHealthcare.pdf 
43. Boschen, K.A., Robinson, E., Campbell, K.A., Muir, S., Oey, E., Janes, K., Fashler, S.R., & Katz, J. 
(2016).  
Results from 10 years of a CBT pain self-management outpatient program for complex chronic 
conditions.  
Pain Research and Management. http://dx.doi.org/10.1155/2016/4678083 
44. Wilson, M., Roll, J.M., Corbett, C., & Barbosa-Leiker, C. (2015). Empowering patients with persistent 
pain  
using an internet based self-management program. Pain Management Nursing, 16(4), 503-514.  
doi: 10.1016/j.pmn.2014.09.009 
45. Pescatello L.S., Arena, R., Riebe, D., & Thompson, P.D. (2014). ACSM’s Guidelines for Exercise 
Testing & Prescription (9thed). Baltimore MD: Lippincott, Williams & Wilkins. 
46. National Institute on Aging (2016). Exercise and physical activity: Your everyday guide. 
https://www.nia.nih.gov/health/publication/exercise-physical-activity/sample-exercises-balance.  
47. Glasgow, R.E., Vogt, T.M., & Boles, S.M. (1999). Evaluating the public health impact of health 
promotion  
interventions: the RE-AIM framework. American Journal of Public Health, 89, 1322–1327. 
48. Glasgow, R.E., McKay, H.G., Piette, J.D., & Reynolds, K.D. (2001). The RE-AIM framework for 
evaluating interventions: What can it tell us about approaches to chronic illness management? Patient 
Education and Counseling, 44(2), 119-127. doi: http://dx.doi.org/10.1016/S0738-3991(00)00186-5 
49. Chen, I., Mondy, D., Yong, P., Williams, C., & Allaire, C. (2015). An evaluation model for a 
multidisciplinary chronic pelvic pain clinic: Application of the RE-AIM Framework. Journal of 
Obstetrics and Gynaecology Canada, 37(9), 804-809. doi: http://dx.doi.org/10.1016/S1701-
2163(15)30151-1 
50. Johnstone, B. (2007). Discourse analysis (2nd ed.). New York: Wiley. 
51. Baker, D.W., Williams, M.V., Parker, R.M., Gazmararian, J.A., & Nurss, J. (1999). Development of a 
brief test to measure functional health literacy. Patient Educ. Couns, 38(1), 33-42. 
52. Zheng, X., Cheng, W., Xu, B., Guang, C., & Ronghuai, H. (2015). An initial development and 
validation of tablet computer familiarity questionnaire. In Emerging Issues in Smart Learning (G. Chen 
et al. eds). DOI 10.1007/978-3-662-44188-6_9 
53. Hjermstad, M. J., Fayers, P. M., Haugen, D. F., Caraceni, A., Hanks, G. W., Loge, J. H., & European 
Palliative Care Research, C. (2011). Studies comparing Numerical Rating Scales, Verbal Rating 
Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature 
review. Journal of Pain Symptom Management, 41(6), 1073-1093. doi: 
10.1016/j.jpainsymman.2010.08.016 

Version #7.1 3/4/21 
 
Page 34 of 34 
 
54. Revicki, D.A., Chen, W.H., Harnam, N., Cook, K.F., Amtmann, D., Callahan, L.F., Jensen, M.P., & 
Keefe, F.J. (2009). Development and psychometric analysis of the PROMIS pain behavior item bank. 
Pain, 146(1-2), 158-169. doi:  10.1016/j.pain.2009.07.029 
55. Carle, A.C., Riley, W., Hays, R.D., & Cella, D. (2015). Confirmatory factor analysis of the Patient-
Reported Outcomes Measurement Information System (PROMIS) adult domain framework using item 
response theory scores. Medical Care, 53(10), 894-900. doi:  10.1097/MLR.0000000000000413 
56. Jones, C., Rikli, R., et al. (1999). A 30-s chair-stand test as a measure of lower body strength in 
community-residing older adults. Research Quarterly for Exercise and Sport, 70(2), 113. 
57. Godi, M., Franchignoni, F., Caligari, M., Giordano, A., Turcato, A.M., & Nardone, A. (2013). 
Comparison of reliability, validity, and responsiveness of the Mini-BESTest and Berg Balance Scale in 
patients with balance disorders. Journal of the American Physical Therapy Association 93(2). doi: 
10.2522/ptj.20120171 
58. Bohannon, R.W., Wang, Y.C., & Gershon, R.C. (2015). Two-minute walk test performance by adults 
18 to 85 years: Normative values, reliability, and responsiveness. Archives of Physical Medicine and 
Rehabilitation, 96(3), 472-477. doi: 10.1016/j.apmr.2014.10.006 
59. Rose, M., Bjorner, J.B., Gandek, B., Bruce, B., Fries, J.F.& Ware, J.E. (2014). The PROMIS physical 
function item bank was calibrated to a standardized metric and shown to improve measurement 
efficiency. Journal of Clinical Epidemiology, 67(5), 516-526. doi:  10.1016/j.jclinepi.2013.10.024 
60. Pilkonis, P.A., Choi, S.W., Reise, S.P., Stover, A.M., Riley, W.T., & Cella, D. (2011). Item banks for 
measuring emotional distress from the Patient-Reported Outcomes Measurement Information System 
(PROMIS): Depression, anxiety, and anger. Assessment, 18(3), 263-283. 
doi:  10.1177/1073191111411667 
61. Russell, D.W. (1996). UCLA Loneliness Scale (Version 3): Reliability, validity, and factor structure. 
Journal of Personality Assessment, 66(1), 20-40. 
62. Nicholas, M.K. (2007). The pain self-efficacy questionnaire: Taking pain into account. European 
Journal of Pain, 11, 153-163. 
 
 
Egede, L.E., Frueh, C.B., Richardson, L.K., Acierno, R., … Lejuez, C. (2009). Rationale and design: 
telepsychology service delivery for depressed elderly veterans. Randomized controlled trial 
Trials, 10, 22. doi: 10.1186/1745-6215-10-22. 
 
Acierno, R., Gros, D.F., Ruggiero, K.J. Hernandez-Tejada, B.M., Knapp, R.G., …Tuerk, P.W. (2016). 
Behavioral activation and therapeutic exposure for posttraumatic stress disorder: a noninferiority trial 
of treatment delivered in person versus home-based telehealth. Depression and Anxiety, 33(5), 415-
423. doi: 10.1002/da.22476 
 
Polenick, C.A. & Flora, S.R. (2013). Behavioral activation for depression in older adults: theoretical 
and practical considerations. Behav Anal., 36(1), 35-55.