Assessment of a Tailored Home-Based Exercise Program on Symptoms, Well-Being, and Resilience Among Cancer Survivors With Multiple Chronic Conditions
Phase: NA
Conditions: Cancer, Hypertension, Diabetes
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Title: 
 
Assessment of a Tailored Home-Based Exercise Program on Symptoms, Well-
Being, and Resilience among Cancer Survivors with multiple chronic conditions 
 
 
 
 
 
 
 
NCT number: NCT03874754 
 
 
 
 
 
 
 
 
Study Protocol and Analysis Plan 
 Date: November 14, 2018 
 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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JHM IRB - eForm A – Protocol 
 
 
 
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1. 
Abstract 
The benefits of physical activity on managing chronic illnesses and multiple symptoms are well 
established. However, increasing the physical activity of persons living with Multiple Chronic 
Conditions (MCC), especially low –income cancer survivors with MCC, is challenging. Home-
based exercise improves physical activity and symptoms among persons with the single chronic 
disease. One major challenge of the home-based exercise is the motivation and adherence. The 
mobile technologies (e.g., wearable device and smartphone application) have been used to improve 
motivation and monitor a person physical activity. Guided by the society to cells framework and 
previous preliminary findings, we developed a technology-enhanced home-based exercise program 
using a combination of the integrated mobile technologies (wearable device and phone application) 
and tailored home-based exercise. Participants will choose one of the four home-based exercise 
options (National Institute of Aging [NIA] Go4Life, Iyengar-style yoga, walking, and modified 
Otago exercise) based on their preference and goals. The integrated mobile technologies system will 
allow us to extract heart rate data directly from the wearable device to the research server. This data 
will be used to provide appropriate and personalized feedback on physical performance and trigger 
algorithms to send the survey and notification to the participants in real time. This pilot project will 
examine the feasibility of this technology-enhanced home exercise tailored to participants’ goals 
and preferences.  The intervention will leverage the cancer survivorship phase (post-treatment) to 
motivate self-care by combining tailored existing evidence-based physical activity programs and 
mobile technology for participants to engage in the resilience-enhancing physical activity. 
Identification of BDNF’s role as one of the exercise outcomes provide a novel target for an 
intervention and increase our understanding of the underlying mechanism of symptoms and 
resilience. 
 
2. 
Objectives (include all primary and secondary objectives) 
This study consists of 2 phases. 
Phase 1:  
Aim 1:  Examine the feasibility and acceptability of the iBHE program among low-income 
cancer survivors living with co-morbid conditions.  Eight participants who have completed 
treatment for a solid tumor cancer with at least one comorbidity (e.g., diabetes and/or 
hypertension) will be assigned to an open-label trial of the idea.  We will gather feedback on goal 
setting, problem-solving strategies, exercise choices, and tracking mechanisms, program 
feasibility, and acceptability and modify the intervention as needed prior to Phase 2.   
Phase 2: 
Aim 2: pilot testing the effect of the tailored iHBE on fatigue, pain, affective well-being, 
resilience and BDNF level among low-income cancer survivors living with co-morbid 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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Version 3 Dated:   06/2007 
 
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conditions at completion (12 weeks) and 6 months in comparison to usual care waiting list 
group. After adjustment in the protocol based on Aim 1, 50 participants who meet the inclusion 
criteria will be randomly assigned to a 12-week experimental (preferred physical activities) group 
or a usual care usual care (waiting list) group. Variables will be measured at baseline, completion 
(12 weeks) and 6 months. Hypothesis 2: After controlling for the age, gender, race, and BMI, 
participants in the experimental group will have a great decline in fatigue, pain, and a greater 
increase in AWB, resilience and BDNF level from baseline to program completion and 3 months 
compared to the usual care group. 
Aim 3: Examine the association between the changes in the biomarker (BDNF) in serum and 
sweat after the 12-weeks from baseline and at 3 months post program completion from 
baseline iBHE program.  Hypothesis 3: the change in the serum BDNF level is positively 
associated with a change in the sweat BDNF level at the after the 12-weeks from baseline and at 6 
months from baseline iBHE program. 
The purpose of this phase 1 pilot study is to examine the feasibility, acceptability and preliminary efficacy 
of a promising home-based, tailored, technology-enhanced exercise program (iHBE).  The intervention is 
guided by the Society to Cells framework and tailors activity based on the individual’s preferences, 
resources, and readiness and it harnesses technology to provide a reminder and immediate feedback on 
physical performance.(Blaney, Lowe-Strong, Rankin-Watt, Campbell, & Gracey, 2013; Studenski et al., 
2010)  After pilot testing the feasibility and acceptability of the intervention, we will conduct an RCT to 
examine the preliminary efficacy of the item on health outcomes (fatigue, pain, AWB, resilience, and 
BDNF) among low-income cancer survivors living with MCC.  We will obtain measures at baseline and 4-
week follow-up using a combination of self-report and objective measures. Brain-derived neurotrophic 
factor (BDNF) is a protein in oxidative stress pathway(Markham et al., 2012) that is related to 
fatigue(Saligan, Lukkahatai, Holder, Walitt, & Machado-Vieira, 2015) and resilience.(Holmes, 2014) A 
consistent, light-intensity aerobic exercise can significantly increase 25% of serum BDNF level from 
baseline.(Zimmer et al., 2017)  We propose to examine this biomarker as one of the outcomes to identify 
the potential biological mechanism of pain, fatigue, and resilience. BDNF testing does not account for 
circadian rhythm nor temporality to exercise and requires venipuncture. Therefore, a secondary goal of this 
study is to examine the level of sweat BDNF, non-invasively collected over 72 hours in comparison to 
serum BDNF.   The specific aims of this phase 1 pilot project are to examine the feasibility and 
acceptability of the iBHE program among low-income cancer survivors living with co-morbid 
conditions.  Eight participants who have completed treatment for a solid tumor cancer with at least one 
comorbidity (e.g., diabetes and/or hypertension) will be assigned to an open-label trial of the iBHE.  The 
feasibility of this first study phase is defined as the acceptability, compliance, and delivery of the 
intervention. The feasibility of the intervention program will be determined from the achievement of 
individual physical activity goal. At the end of 4 week program, research team will review the participants 
ability to achieve at least 75% of the individual’s exercise goal (for example, if the goal is to exercise at the 
fat burn level (50-60% maximum heart rate measured by FitBit) for 30 min/day 3 days week, participants 
can exercise for 30 min for at least 2 days or FitBit data showed more than 60 active min). For this first 
phase, at least 50% of participants will need to meet 75% of personal goal in at least 2 weeks for the trial to 
continue onto phase II. For participants who do not achieve 75% of their individual exercise goal, the 
barriers will be identified that the weekly goals will be revised until the 75% of weekly personal exercise 
goals is met. If the feasibility threshold (less than 50% of participants achieve 75% of their weekly goals 
for 2 weeks) does not reach, we will adjust the goal setting process and recruit more participants. We will 
conduct a qualitative semi-structured interviews interview to gather feedback on goal setting, problem-
solving strategies, exercise choices, and tracking mechanisms, program feasibility, and acceptability and 
modify the intervention as needed. The descriptive information in this phase I to help inform alternative 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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approaches to the anticipated analysis, sample size estimates for phase II, and additional key variables to be 
measured in phase II (intervention dose, fidelity, and .additional process variables). 
3. 
Background (briefly describe pre-clinical and clinical data, current experience with procedures, 
drug or device, and any other relevant information to justify the research) 
Nearly 16 million Americans were cancer survivors in 2016, with an additional 1.7 million new cases 
expected in 2017.(American Cancer Society, 2017) With the advancement of cancer diagnosis and 
treatment, 60% of cancer patients will survive at least 5-years.(National Cancer Institute, 2014)  More than 
80% of these cancer survivors have one or more comorbid chronic conditions (e.g., type 2 diabetes, 
cardiovascular diseases, osteoarthritis)(Rothrock et al., 2010) with hypertension as a most frequent 
comorbid condition (prevalence rate of 20-65%).(Braithwaite et al., 2009; Izano et al., 2014; Shin et al., 
2008) This prevalence of these MCCs is double (60-75%) among older adults and even higher among low 
income older adults.(Kramarow, 2017) This growing MCCs prevalence affects health status, disability and 
AWB.(Koolhaas et al., 2013) Studies show that the number of MCCs is associated with the prevalence and 
severity of symptoms such as pain and fatigue.(Annunziata, Muzzatti, Mella, & Bidoli, 2013; Arrieta et al., 
2013; Manning & Bettencourt, 2011; Servaes, Gielissen, Verhagen, & Bleijenberg, 2007) These multiple 
symptoms impact persons’ AWB and adherence to the treatment.(Beck, Towsley, Caserta, Lindau, & 
Dudley, 2009; Shelby et al., 2011) Persons living with MCCs with multiple symptoms have a greater risk 
of premature death than those without symptoms.(Cheville et al., 2011; Yang et al., 2012) Cancer survivors 
with multiple chronic conditions experience significantly higher symptoms such as pain, and fatigue 
prevalence and severity than those without comorbidity.(Annunziata et al., 2013; Arrieta et al., 2013; 
Huang, Hudson, Robison, & Krull, 2017; Manning & Bettencourt, 2011; Servaes et al., 2007) Managing 
these multiple chronic conditions and multiple symptoms requires active participation from the persons and 
family members. Socioeconomic status (SES) complicates the management of these multiple conditions, 
as people with low income can have limited access to health care and resources, limited leisure-time, and 
other non-medical challenges.(Beenackers et al., 2012)  
The US Centers for Disease Control and Prevention recommends increasing physical activity (PA) as one 
of the most effective interventions for managing chronic conditions and symptoms.(National 
Comprehensive Cancer Network (NCCN), 2017) Exercise is a type of PA that required structure, repetition 
of an intentional movement. Studies show a continuous aerobic moderate-intensity exercise program not 
only improves fatigue, pain,(Dodd et al., 2010; Meneses-Echavez, Gonzalez-Jimenez, & Ramirez-Velez, 
2015a, 2015b; Tian, Lu, Lin, & Hu, 2015; van Waart et al., 2015) and AWB,(Cheville et al., 2010) but 
also delays the onset and progression of other chronic conditions. In spite of the benefit of PA, evidence 
shows that less than 10% of cancer survivors are active during treatment and only 20% of cancer survivors 
are active after treatment.(Pinto & Ciccolo, 2011) The number is even lower in low-income cancer 
survivors with comorbidities. To overcome barriers to exercise, home-based exercise programs have been 
developed and report promising effectiveness on pain, fatigue, and AWB among persons with several 
chronic conditions.(Dodd et al., 2010; Hoffman et al., 2013; Spector, Deal, Amos, Yang, & Battaglini, 
2014) However, these studies examined the effectiveness of these program on an individual chronic 
condition. They reported that most home-based exercise programs are challenged by a lack of motivation 
and low engagement rate with the exercise regimen.(Junghaenel, Cohen, Schneider, Neerukonda, & 
Broderick, 2015; Kober et al., 2015; Wright et al., 2015a, 2015b) Recent evidence shows that the use of 
technology to provide immediate feedback on physical performance and reminder messaging can increase 
motivation and adherence to PA.(Blaney et al., 2013; Studenski et al., 2010) This is part of the scientific 
premise for this study. 
Resilience is defined as a positive adaptation and maintenance function during stressful events.(Eicher, 
Matzka, Dubey, & White, 2015) It influences the perception of symptoms including pain and 
fatigue.(Kennedy et al., 2017; Lim, Shon, Paek, & Daly, 2014; Sharpley et al., 2017; Sharpley, Bitsika, 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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Wootten, & Christie, 2014; Strauss et al., 2007; Szanton & Gill, 2010) People with high resilience report 
lower pain, fatigue and better physical functioning and AWB than those with low resilience.(Deshields, 
Heiland, Kracen, & Dua, 2016; Eicher et al., 2015; Hou & Lam, 2014; Matzka et al., 2016) The PA 
intervention can improve resilience by triggering an adaptive mechanism for 
neurodegeneration.(Pedrinolla, Schena, & Venturelli, 2017) Stress suppresses neurogenesis in the 
hippocampal area of the brain through BDNF.(Malberg, 2004; Malberg & Schechter, 2005) BDNF is a 
member of the neurotrophic family of proteins that plays a significant role in neuronal survival.(Markham 
et al., 2012) BDNF can be modulated by oxidative stress during physical and psychological stressful events 
(e.g., inflammation, extreme exhaustion). During stressful events, BDNF is activated to enhance 
neuroprotective mechanisms.(Scuri, Samsell, & Piedimonte, 2010) BDNF has been proposed to influence 
resilience.(Holmes, 2014; Rothman & Mattson, 2013; Tyagi, Zhuang, Agrawal, Ying, & Gomez-Pinilla, 
2015) Exercise can affect the BDNF level. A study in cancer survivors reported that 8 months of a 
personalized light-intensity aerobic exercise (15-25 MET h/week) can significantly increase 25% of serum 
BDNF level from baseline. (Zimmer et al., 2017) Based on the meta-analysis the 12 week is the duration 
for exercise program most studies used to see the change in BDNF level.(Dinoff et al., 2016)  
Framework: The iBHE program is based on the Society to Cells Resilience framework and promising 
findings from two previous studies. The intervention targets two domains; individual and physiological 
factors (neurochemical activities). The intervention aims to promote individual’s ability in reflection, 
affirmation, goal setting, dealing with ambivalence and change in stress-induced neurochemical activity 
through tailoring and physical performance feedback through mobile technologies,  which will improve 
resilience, pain, fatigue, AWB and BDNF level. 
Preliminary works: The scientific premise of the proposed study is based on the findings from two 
preliminary studies. 
Study 1: We tested the feasibility of a home-based exercise 
program that integrated a PA tracking device and an ecological 
momentary assessment mobile phone application (mEMA) to 
enhance and track home-based exercise in one week among 30 
healthy volunteers. We asked the participants to walk or run at 
least 30 min to increase HR to at least 60% of maximum 
possible HR for 5 days while wearing the wearable device and 
response to the survey on the smartphone application. Our 
preliminary results showed that the integrated system is 
feasible and easy to use. We were able to monitor exercise 
adherence through the heart rate monitoring. Participants preferred the information about steps, heart 
rate, and calorie during the PA provided by the wearable device. However, our preliminary study did not 
have a focus on low-income people with MCC who have additional challenges in engaging in the 
recommended amount of exercise.  In addition, our previous work did not tailor the exercise to the context 
or preference of participants which can be improved by assessing persons’ readiness and intention, and 
tailoring the program to individual needs.(Husebo, Dyrstad, Soreide, & Bru, 2013; Puts et al., 2014)  
Study 2: Our recent publication reported the association between BDNF and fatigue. We found that 
cancer survivors with worsening fatigue during radiotherapy had significant lower BDNF level than 
the non-fatigue survivors.(Saligan et al., 2015)  
This study, we will examine an integration of tailored home exercise and mobile technologies to improve 
resilience, pain, fatigue, and AWB among low-income cancer survivors with MCC. To address the 
limitations of engagement to exercise intervention, we will combine our previous smartphone application 
and wearable technology with goal setting and problem-solving intervention to tailor PA to individual daily 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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Version 3 Dated:   06/2007 
 
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life and physical fitness goals, and preference. Participants’ steps count and heart rate will be continuously 
monitored by the wearable device to measure adherence and intensity of the PA at home. 
4. 
Study Procedures 
This study will be conducted in two phases.  
Phase one (Aim 1) is the intervention trial phase (open-label phase):  
Design: Mixed methods design. 
The aim of this phase (specific aim 1) is to obtain participants’ perception and acceptability of the program. 
The number of eligible participants and recruited participants, the number of participants completing the 
intervention program, and the number of drop out participants will be recorded. The program will be 
adjusted based on the participant feedback and will be pilot tested in phase 2. We are submitting this 
application for phase one at this time and will submit phase 2 in the further study action. 
Sample and Setting: 
The study participants will be recruited from the home health care agencies in Baltimore, Maryland, Johns 
Hopkins Comprehensive Cancer Center and Johns Hopkins Hospital.  
Inclusion criteria are (1) participants diagnosed with solid tumor cancer who have completed cancer treatment 
at least 6 months; (2) diagnosed with diabetes and/or hypertension for at least a year; (3) aged 21 years or 
older, (4) have an annual household incomes of below $30,000 for families of three, (5) the average fatigue 
level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse fatigue) Likert scale 
and (6) give informed consent.  
Exclusion criteria are those (1) currently undergoing treatment for cancer; (2) have an active infection (e.g., 
fever, localized redness, swelling, sinus congestion); and/or (3) diagnosed with a psychological disorder (e.g., 
suicidal or homicidal tendencies, extreme anxiety or depression). 
 
Data Collection Schedule and Procedures. Upon receiving approval from the Johns Hopkins University 
Institutional Review Board, the study flyer will be posted and distributed at the home health care agencies 
in Baltimore, Maryland, Johns Hopkins Comprehensive Cancer Center and Johns Hopkins Hospital.  
 
Recruitment, Informed Consent, and Confidentiality. Recruitment methods for this study include (1) 
distributing and posting flyers, with a tear-off phone number to speak with the principal investigator (PI) as 
necessary, posted at the hospital (2) face-to-face recruitment for potential participants during cancer 
support group meetings; and (3) word-of-mouth. Potential participants will receive a verbal explanation by 
phone or face to face meeting in terms suited to their comprehension of the purpose, procedures, and 
potential risks of the study. During the screening for eligibility process, an oncologist will be available for 
consultation. The oncologist will be notified and consulted for the appropriateness of the exercise for 
participants who self-report having co-morbidities. The participants and family or legal guardian will have 
an opportunity to carefully review the consent form and ask questions regarding this study prior to signing. 
Participants will be encouraged to consult with their primary doctor if any concern or an additional 
question. Participants will be informed that they may withdraw from the study at any time without 
prejudice to themselves.  
 
Participants will be approached and screened for the annual income below $30,000 for families of three, 
average fatigue level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse 
fatigue) Likert scale, the self-report perceived ability to walk for six-minute and the exertion level after the 
walk on a 0-10 numeric perceived exertion scale (0 = no exertion at all to 10 = maximal exertion). Eligible 
participants will be asked if they would like to participate and to sign the informed consent. Participants 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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will be asked to have the research team visit their home for the initial assessment and to provide instruction 
on the exercise, the physical activity tracker and how to complete the questionnaire via the phone 
application. Participants will be asked to wear the FitBit Charge 2 on the non-dominant arm and respond to 
the phone application daily for 4 weeks. Participants’ peripheral blood will be drawn at week 1 and week 4 
by a registered nurse or certified phlebotomist. We will ask the participant to have a sweat pad placed on 
their upper abdomen or flank for 72 hours to collect the sweat at baseline (before the program) and week 4 
(at the program completion). 
 
At the end of the program, a research team member will visit participants’ home and evaluate the 
participants’ perception and satisfaction for the program using a quantitative semi-structure interview. The 
interview will be recorded and transcribed for the qualitative analysis. Participants will be asked to 
complete the questionnaires. Participants’ blood and sweat will be collected. The feasibility of the 
intervention program will be determined from the achievement of individual physical activity goal. At the 
end of 4 week program, research team will review the participants ability to achieve at least 75% of the 
individual’s exercise goal (for example, if the goal is to exercise at the fat burn level (50-60% maximum 
heart rate measured by FitBit) for 30 min/day 3 days week, participants can exercise for 30 min for at least 
2 days or FitBit data showed more than 60 active min). For this first phase, at least 50% of participants will 
need to meet 75% of personal goal in at least 2 weeks for the trial to continue onto phase II. For 
participants who do not achieve 75% of their individual exercise goal, the barriers will be identified that the 
weekly goals will be revised until the 75% of weekly personal exercise goals is met. If the feasibility 
threshold (less than 50% of participants achieve 75% of their weekly goals for 2 weeks) does not reach, we 
will adjust the goal setting process and recruit more participants. Moreover, we will descriptive information 
from the phase I to help inform alternative approaches to the anticipated analysis, sample size estimates for 
phase II, and additional key variables to be measured in phase II (intervention dose, fidelity, and .additional 
process variables). 
Intervention 
Tailored Technology-Enhance Home-based Exercise Program:  
The tailored technology enhanced home-based exercise (iHBE) program is a 4-week program with 1 
assessment home visit session, 4 home visits during exercise. The detail activities are presented in table 1. 
The technologies, a wearable device, and a smartphone application, will be used as a tool to monitor 
physical performance (heart rate, step count), provide immediate feedback, send daily reminding message 
through mEMA. The coded raw data without personal identification information from the wearable device 
will be sent to the servers where we can store it in the database alongside the mEMA data and create 
custom reports showing HR 30 minute before each EMA survey, showing HR and previous self-report 
responses before/ after each automatically triggered EMA.     
        
Weeks 
Program Activities 
Assessment 
session 
(home 
visit; Week 
0) 
A research team member (research nurses and/or physical therapist) will meet and assess 
the participants’ perception of PA and goals. Participants will complete the questionnaires 
for baseline symptoms, Affective Well Being (AWB) and resilience. Participants’ blood 
and sweat will be collected. The research team will help the participants to identify the 
barriers, prioritize goals for weekly activity and make a plan to achieve these goals. 
Participants will be asked the perception of their ability to complete the six-minute walk 
and their exertion level, then choose the PA modality, frequency, duration and time of the 
day of their exercise based on their preference, and goals. 
Exercise intervention options 
         Option 1: The NIA Go4Life exercise 
         Option 2: Iyengar-style yoga 10-20 minutes on at least 2 days per week 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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Weeks 
Program Activities 
         Option 3: Walking to achieved the weekly goal (e.g., walk 5 min for 3 days/week and 
increase 1-2 min/week) 
        Option 4: Modified Otago exercise intervention 
 
Participants will be trained to use the FitBit Charge 2 and mEMA application. During this 
home visit, participants will practice their selected exercise with a physical therapist or an 
RN, set the wearable device and record their HR, fatigue and pain level at the end of each 
exercise session on the mEMA. Participants will receive a booklet contains the information 
of their selected exercise intervention and a weekly planner. 
4 home 
visits 
(Week 1-4) 
A research team member will visit participants’ home and evaluate exercise problems. The 
research team will review the physical performance with the participants and help them 
identify problems and solutions. During these visit, the research team will tailor the 
exercise to be suitable for the participants’ conditions and situation. Participants will 
practice their exercise with the research team for 15-20 min. The information on home 
safety will be provided to the participants and their caregivers. 
 
Completion 
session        
(end of 
week 4) 
A research team member will visit participants’ home and evaluate the participants’ 
perception and satisfaction for the program using a quantitative semi-structure interview. 
Participants will be asked to complete the questionnaires. Participants’ blood and sweat 
will be collected. 
 
Table 1: iHBE program activities 
Program fidelity: To maintain fidelity of the program, two research assistants/research nurse will receive 
1-month project specific training on intervention design, all four exercise options and project 
implementation. Nurse researchers will receive additional training on how to demonstrate the use of 
technologies (a wearable device: FitBit Charge 2) and a smartphone application (mEMA) and how to 
conduct a physical function assessment set PA goals and identify problems and solutions. The nurse 
researchers will conduct a home visit and follow up phone call under the supervision of a registered nurse. 
The principal investigator will randomly check home visit and follow up phone call sessions and provide 
timely feedback. The investigator team will work with the nurse researchers and clinical settings for 
quality assurance and address any issues that may occur during the study. 
Variables and measurements. 
Physical function: To ensure participants’ safety during home exercise and provide the best 
recommendation for the type of exercise, the physical function will be measured by asking the participants 
perception on their ability to complete a walk for 6 minutes with the perceived exertion level of 3 or below. 
The study variables will be measured as follows: 
Measure 
Description 
Psychometrics 
NINR Common 
Data Elements 
(CDEs) 
23-item; measure demographic and disease 
information data 
 
PROMIS Short 
Form V1.0-Fatigue 
6a 
6-items; self-reported fatigue (frequency, 
duration, intensity) and the impact on 
physical, mental, and social activities, has 
five response options (1 or never to 5 or 
always). 
Initial psychometric properties 
have shown an internal 
consistency reliability coefficient 
of greater than 0.80.52 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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Measure 
Description 
Psychometrics 
PROMIS Pain 
Intensity – Short 
Form 3a V1.0. 
Universal and not a disease-specific 
instrument for pain, 3-items (worst, average, 
and current pain) measure from 1 (no pain) 
to 5 (very severe). 
Conceptually validated with 
established reliability Test-retest 
values = .83 to .93.(PROMIS, 
2015) 
Wrist-worn wearable 
device: Microsoft 
band 2 
PA (steps count and Heart rate) tracking 
device (wrist-worn) 
Intraclass Correlation Coefficients 
with ActivPAL are 0.81 and 0.96 
respectively, p < .01.(Kooiman et 
al., 2015)  
Connor-Davidson 
Resilience Scale  
10 item self-report rating scale 0 (not true at 
all) to 4 (true nearly all the time) 
Good internal consistency 
(Cronbach’s alpha 0.85) and 
constructs validity.(Campbell-Sills 
& Stein, 2007) 
Short form survey 
(SF-36) 
36 item self-report instrument measure 2 
domains: physical well-being and affective 
well-being. 
Good internal consistency for 
every scales (Cronbach’s alpha ≥ 
0.70).(Busija et al., 2011) 
Serum and Sweat BDNF protein levels will be measured by the enzyme-linked immunosorbent assay 
(ELISA). Participants’ peripheral blood will be drawn during home visits, the sweat patch will be placed on 
the participants’ upper abdomen or flank for 72 hours to collect the sweat at baseline and the program 
completion (week 4). The ELISA will be performed according to the manufacturer’s guide by one 
laboratory technician. 
Data Collection Schedule and Procedures:  
Phase one: intervention trial phase (open-label phase). Upon receiving approval from the Johns Hopkins 
Institutional Review Board and the participant’s informed consent is signed. Eight participants who have 
completed treatment for a solid tumor cancer with at least one comorbidity (e.g., diabetes and/or 
hypertension) will be assigned to an open-label trial of the iBHE (see table 1 for detail activities).   
We will explore measurement of variables, exercise choices and tracking mechanisms with participants 
regarding feasibility and acceptability. The principal investigator will conduct a qualitative semi-structured 
interview, record and take notes of the interview and discussed participants’ feedback with the research 
teams. The exercise plan, wearable device, and phone application feature will be discussed until consensus 
program for each option is made. 
Table : Data collection process 
 
Task 
home visit 
Baseline: 
Assessment 
Week 0 
iBHE program 
Post 
intervention 
Home visits 
week 
Home visit 
1 
2 
3 
4 
 
Assessment: perception, goal, FTSST, and 6MWT 
X 
 
 
 
 
 
Demographic and disease information questionnaire 
X 
 
 
 
 
 
PROMIS fatigue and PROMIS pain 
X 
 
 
 
 
X 
Short form survey (SF-36) 
X 
 
 
 
 
X 
Connor-Davidson Resilience Scale 
X 
 
 
 
 
X 
Physical activity (steps) and HR (from wearable device)* 
X 
X 
X 
X 
X 
X 
Blood sample for BDNF level 
X 
 
 
 
 
X 
Sweat sample for BDNF level 
X 
 
 
 
 
X 
*objective physical activity will be measured daily  
 
 

Date: November 14, 2018    
Principal Investigator: Dr. Nada Lukkahatai 
Application Number: IRB00175781___________ 
 
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5. 
Inclusion/Exclusion Criteria 
 
Inclusion criteria are (1) participants diagnosed with solid tumor cancer who have completed cancer 
treatment at least 6 months; (2) diagnosed with diabetes and/or hypertension for at least a year; (3) aged 21 
years or older, (4) have an annual household incomes of below $30,000 for families of three, (5) the average 
fatigue level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse fatigue) Likert 
scale and (6) give informed consent.  
Exclusion criteria are those (1) currently undergoing treatment for cancer; (2) have an active infection (e.g., 
fever, localized redness, swelling, sinus congestion); and/or (3) diagnosed with a psychological disorder (e.g., 
suicidal or homicidal tendencies, extreme anxiety or depression).  
 
6. Drugs/ Substances/ Devices 
None 
 
7. Study Statistics 
 
Data analysis: 
Phase 1:  
Aim 1:  Examine the feasibility and acceptability of the iBHE program among low-income 
cancer survivors living with co-morbid conditions.   
Primary objectives of this phase are to evaluate the feasibility and acceptability of the iBHE program. Eight 
participants who have completed treatment for a solid tumor cancer with at least one comorbidity (e.g., 
diabetes and/or hypertension) will be assigned to an open-label trial of the iBHE.  At the completion of the 
program (4 weeks), the primary investigator will conduct a semi-structured interview to gather feedback on 
the program feasibility, goal setting, problem-solving strategies, exercise choices and tracking mechanisms, 
program feasibility, and acceptability. The interview will be recorded and transcribed verbatim.  
 
The feasibility of the program 
The feasibility of the intervention program will be determined from the achievement of individual physical 
activity goal. At the end of 4 week program, research team will review the participants ability to achieve at 
least 75% of the individual’s exercise goal (for example, if the goal is to exercise at the fat burn level (50-
60% maximum heart rate measured by FitBit) for 30 min/day 3 days week, participants can exercise for 30 
min for at least 2 days or FitBit data showed more than 60 active min). For this first phase, at least 50% of 
participants will need to meet 75% of personal goal in at least 2 weeks for the trial to continue onto phase 
II. For participants who do not achieve 75% of their individual exercise goal, the barriers will be identified 
that the weekly goals will be revised until the 75% of weekly personal exercise goals is met. If the 
feasibility threshold (less than 50% of participants achieve 75% of their weekly goals for 2 weeks) does not 
reach, we will adjust the goal setting process and recruit more participants. 
The feasibility of the recruitment will be determined by the number of screened participants, eligible 
participants and participants who refuse to be in the study and rational will be examined and recorded as 
indicator of feasibility. The feasibility of delivering the program will be evaluated by examining the 
number and timing for actual versus planned home visit and the duration of each visit. The intervention 
checklist will be filled by the research assistants for each home visit to assess the intervention content 
delivery.  
The acceptability of the program  
The acceptability of the program will be assessed using the semi-structure interview. The common 
feedback and suggestion for intervention during the semi-structure interview will be noted. 

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The compliance of the program 
The compliance of this program will be monitored using active min and daily heart rate zone data from the 
wearable device (FitBit Charge 2). The weekly goals on number of day for physical activity and duration of 
the physical activity will be set. The number active min and duration of the heart rate in at least “Fat Burn” 
zone per day will be recorded for the duration of physical activity/day. The number of days the participant 
achieve the goals (duration and days) for physical activity will be used to measure the compliance of the 
program. 
The descriptive information from the phase I to help inform alternative approaches to the anticipated 
analysis, sample size estimates for phase II, and additional key variables to be measured in phase II 
(intervention dose, fidelity, and .additional process variables). 
The program modification 
Prior to phase 2, the primary investigator will discuss participants’ feedback with the research teams.  
The modification of exercise plan, wearable device, and phone application feature will be discussed until 
consensus program for each option is made.  
 
8. Risks 
Potential Risks:  
The risks of participating in this study are minimal. Potential risks include 
1. complications during the blood drawing for examples pain and bleeding at the drawing site. 
2. complications during the sweat collection for examples rash, itching, redness and swollen. 
3. minimum discomfort might occur during the wearable device (worn like a bracelet). 
4. complications (e.g., fainting, injury) during the exercise program. 
During the proposed study, if there is a serious adverse event, anticipated to be an uncommon 
occurrence, the PI will unmask treatment group assignment when necessary for the safety of the 
participant. The administration of the intervention may be discontinued at the participant’s request 
or by the investigator, based on clinical judgment. Participants will be instructed to report any 
adverse event experienced after treatment without delay. 
 
Adequacy of Protection against Risks: The safety of the study participants is essential. The primary 
investigator and research team will take all precautions to protect the participants against risks. 
 
Protection against Risks: The principal investigator (PI) and research team plan to prevent the 
following risks: 
1. 
Complications of the blood drawn. Participants may experience pain and discomfort during 
the blood drawn. They may also be at risk of bleeding. All of the blood drawn will be 
performed by register nurses. After blood drawn, participants’ conditions will be monitored 
by a registered nurse.  
2. 
Complications of the sweat collection. Participants may experience allergic reactions and 
discomfort during the sweat collection. The sweat pad will be placed by the train research 
team members. Participants will be informed of the sign and symptoms of a potential 
allergic reaction. The pad can be easily removed if participants experience discomfort. 
3. 
Minimum discomfort might occur while wearing the wearable device (worn like a bracelet). 
Participants will be asked to wear a physical tracking wearable device to measure their 
activity and sleep duration. This equipment may cause the discomfort. As with any type of 
jewelry, some people may experience allergies. Some people may experience a rash wearing 
the device. The device can be easily removed if discomfort is experienced.  
4. 
Complications (e.g., fainting, injury, fall) during the exercise program.  All four exercise 
option is low intensity, low impact exercise program, which will be conducted by the trained 
research nurse or physical therapist. During the first four weekly home visit, research nurse 

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and/or physical therapist will monitor the participants exercise to ensure appropriate body 
alignment and posture and participants safely. All participants will be asked to wear 
appropriate shoes and comfortable cloth during the exercise. 
 
 
9. Benefits 
There is no direct benefit to the participant from being in this study. However, the home-based, tailored, 
technology-enhanced exercise program (iHBE) proposed in this study could be used as alternative choices 
for cancer survivors to manage their fatigue and improve patients’ quality of life. The mEMA application 
and wearable device can serve as useful tools for health care providers to monitor intervention outcomes 
and compliance while the patients are at home. 
 
 
10. Payment and Remuneration 
 
Phase 1 (Aim 1) - Participants will receive $40 for their time in completing the baseline data and the 
interview 
 
11. Costs 
There will be no cost for participants to participate in this study. 
 
12. Data Safety Monitoring Plan 
 
The PI will review reports reflecting data quality, safety, and monitor for potential adverse events and 
protocol adherence. The project coordinator, study staffs will meet with the PI weekly to review the 
progress of the study. The members of the investigative team and scientific advisors will meet monthly to 
support the study. A Safety Monitoring Committee (SMC) will be formed, consisting of Johns Hopkins 
University clinician faculty members who are independent of this proposed feasibility study. The SMC will 
be responsible for overall monitoring of the safety of participants in this proposed study and overseeing the 
PI, Co-Is, and research assistant.  
 
The PI will be responsible for managing all data, securing privacy and confidentiality, minimizing and 
identifying risks, monitoring and reporting adverse events or any safety issues, and complying with timely 
reporting requirements to all applicable regulatory bodies for any adverse events or unexpected problems. 
Monthly reports will be completed by the PI detailing participant demographics, recruitment status, 
treatment retention rates, protocol compliance, data gathered and accuracy, and quality assurance or 
regulatory issues that transpired, and summary of any adverse events. The research team (PI, Co-Is, and 
research assistant) will meet weekly via face to face or conference calling to discuss data and safety 
monitoring. 
 
The SMC will meet annually (or more frequently if needed) and review the annual reports completed by the 
PI; review study safety, integrity, and progress including any adverse events; provide advice in relation to 
continuing, changing, or terminating the study when necessary; require more frequent reporting as needed; 
audit the study for compliance and verify authenticity of data; and assess that the research team is 
complying with informed consenting and other required regulations. These annual meetings will be 
conducted face-to-face or through conference calls. 
 

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The PI, in consultation with the SMC, will provide reports at intervals as required by National Institute of 
Health and/or other regulatory bodies as well as provide immediate reports as required regarding any 
adverse or unanticipated problems that may occur.   
Phase 2: Pilot testing the adjusted iHBE program 
 
4. Study Procedures 
 
Design: Randomized waiting list controlled trial design 
Phase 2 Specific Aims 
Aim 2: Pilot testing the effect of the tailored iHBE on fatigue, pain, affective well-being, 
resilience and BDNF level among low-income cancer survivors living with co-morbid conditions at 
completion (12 weeks) and 6 months in comparison to usual care waiting list group.  
After adjustment in the protocol based on Aim 1, 50 participants who meet the inclusion criteria will be 
randomly assigned to a 12-week experimental (preferred physical activities) group or a usual care usual 
care (waiting list) group. Variables will be measured at baseline, completion (12 weeks) and 6 months. 
Hypothesis 2: After controlling for the age, gender, race, and BMI, participants in the experimental group 
will have a greater decline in fatigue, pain, and a greater increase in AWB, resilience and BDNF level 
from baseline to program completion and 3 months compared to the usual care group. 
 
Aim 3: Examine the association between the changes in the biomarker (BDNF) in serum and 
sweat after the 12-weeks from baseline and at 3 months post program completion from baseline 
iBHE program.  Hypothesis 3: the change in the serum BDNF level is positively associated with a change 
in the sweat BDNF level at the after the 12-weeks from baseline and at 6 months from baseline iBHE 
program. 
 
Sample and Setting: 
The study participants will be recruited from the home health care agencies in Baltimore, Maryland, Johns 
Hopkins Comprehensive Cancer Center and Johns Hopkins Hospital.  
Inclusion criteria are (1) participants diagnosed with solid tumor cancer who have completed cancer 
treatment at least 6 months; (2) diagnosed with diabetes and/or hypertension for at least a year; (3) aged 21 
years or older, (4) have an annual household incomes of below $30,000 for families of three, (5) the average 
fatigue level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse fatigue) Likert 
scale and (6) give informed consent.  
Exclusion criteria are those (1) currently undergoing treatment for cancer; (2) have an active infection (e.g., 
fever, localized redness, swelling, sinus congestion); and/or (3) diagnosed with a psychological disorder (e.g., 
suicidal or homicidal tendencies, extreme anxiety or depression). 
 
Sample size justification  
Phase 2: With an alpha level of .05, the statistical power of 0.80, and 25 participants per group, we will be 
able to detect significant differences of moderate to large effect sizes of 0.65 when comparing change 
across baseline, 3-months, and 6-months between the two groups.  With an attrition rate of 12% (22 
participants per group), the detectable effect size increases to 0.69.  Since this is a pilot study and not 
powered to detect small to moderate effect sizes, we will pay close attention to the effect size, rather than 
statistical significance.  These effect size estimates will be used to inform future research trials. 
 

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Randomization: Eligible participants will be randomized in a 1:1 allocation ratio to one of the two 
treatment arms. The electronic Research Electronic Data Capture (REDCap), a randomization application 
will be used to randomly assigned the participants to the groups  
 
Data Collection Schedule and Procedures. Upon receiving approval from the Johns Hopkins University 
Institutional Review Board, the study flyer will be posted and distributed at the home health care agencies 
in Baltimore, Maryland, Johns Hopkins Comprehensive Cancer Center and Johns Hopkins Hospital.  
 
Recruitment, Informed Consent, and Confidentiality. Recruitment methods for this study include (1) 
distributing and posting flyers, with a tear-off phone number to speak with the principal investigator (PI) as 
necessary, posted at the hospital (2) face-to-face recruitment for potential participants during cancer 
support group meetings; and (3) word-of-mouth. Potential participants will receive a verbal explanation by 
phone or face to face meeting in terms suited to their comprehension of the purpose, procedures, and 
potential risks of the study. During the screening for eligibility process, an oncologist will be available for 
consultation. The oncologist will be notified and consulted for the appropriateness of the exercise for 
participants who self-report having co-morbidities. The participants and family or legal guardian will have 
an opportunity to carefully review the consent form and ask questions regarding this study prior to signing. 
Participants will be encouraged to consult with their primary doctor if any concern or an additional 
question. Participants will be informed that they may withdraw from the study at any time without 
prejudice to themselves.  
 
Participants will be approached and screened for the annual income below $30,000 for families of three, 
average fatigue level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse 
fatigue) Likert scale, the self-report perceived ability to walk for six-minute and the exertion level after the 
walk on a 0-10 numeric perceived exertion scale (0 = no exertion at all to 10 = maximal exertion). Eligible 
participants will be asked if they would like to participate and to sign the informed consent. Participants 
will be asked to have the research team visit their home for the initial assessment and to provide instruction 
on the exercise, the physical activity tracker and how to complete the questionnaire via the phone 
application for 4 weeks, followed by phone follow up for 7 weeks. Participants will be asked to wear the 
FitBit Charge 2on the non-dominant arm and respond to the phone application daily for 12 weeks. 
Participants’ peripheral blood will be drawn at week 1 and week 12 by a registered nurse or certified 
phlebotomist. We will ask the participant to have a sweat pad placed on their upper abdomen or flank for 
72 hours to collect the sweat at baseline (before the program) and week 12 (at the program completion). 
 
At the end of the program, a research team member will visit participants’ home and evaluate the 
participants’ perception and satisfaction for the program using a open ended questionnaires. Participants 
will be asked to complete the questionnaires. Participants’ blood and sweat will be collected. 
Intervention/Independent Variables 
Tailored Technology-Enhance Home-based Exercise Program:  
The tailored technology enhanced home-based exercise (iHBE) program: Participants in this group will 
receive an adjusted (based on the feedback from phase 1)12-week program with 1 assessment home visit 
session, 5 home visits during exercise and 7 follow up phone calls. The technologies, a wearable device and 
a smartphone application, will be used as a tool to monitor physical performance (heart rate, step count), 
provide immediate feedback, send daily reminding message through mEMA. The coded raw data without 
personal identification information from the wearable device will be sent to the servers where we can store 
it in the database alongside the mEMA data and create custom reports showing HR 30 minute before each 
EMA survey, showing HR and previous self-report responses before/ after each automatically triggered 

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EMA.            
Usual Care (Waiting List) Group: The usual care waiting list group will receive educational booklets 
about a healthy lifestyle and cancer survivorship. Participants will be asked to wear the wearable device 
during the waiting period to monitor the PA (steps and heart rate).They will receive a notification to rate 
their daily fatigue level for 3 months. Usual Care participants will receive the iHBE after the conclusion of 
the study (as described above). 
Variables and measurements. 
The study variables will be measured as follows: 
Measure 
Description 
Psychometrics 
NINR Common 
Data Elements 
(CDEs) 
23-item; measure demographic and disease 
information data 
 
PROMIS Short 
Form V1.0-Fatigue 
6a 
6-items; self-reported fatigue (frequency, 
duration, intensity) and the impact to 
physical, mental, and social activities, has 
five response options (1 or never to 5 or 
always). 
Initial psychometric properties 
have shown an internal 
consistency reliability coefficient 
of greater than 0.80.52 
PROMIS Pain 
Intensity – Short 
Form 3a V1.0. 
Universal and not disease-specific 
instrument for pain, 3-items (worst, average, 
and current pain) measure from 1 (no pain) 
to 5 (very severe). 
Conceptually validated with 
established reliability Test-retest 
values = .83 to .93.(PROMIS, 
2015) 
Wrist worn wearable 
device: FitBit 
Charge 2 
PA (steps count and Heart rate) tracking 
device (wrist worn) 
Intraclass Correlation Coefficients 
with ActivPAL are 0.81 and 0.96 
respectively, p < .01.(Kooiman et 
al., 2015)  
Connor-Davidson 
Resilience Scale  
10 item self-report rating scale 0 (not true at 
all) to 4 (true nearly all the time) 
Good internal consistency 
(Cronbach’s alpha 0.85) and 
constructs validity.(Campbell-Sills 
& Stein, 2007) 
Short form survey 
(SF-36) 
36 item self-report instrument measure 2 
domains: physical well-being and affective 
well-being. 
Good internal consistency for 
every scales (Cronbach’s alpha ≥ 
0.70).(Busija et al., 2011) 
Serum and Sweat BDNF protein levels will be measured by the enzyme-linked immunosorbent assay 
(ELISA). Participants’ peripheral blood will be drawn during home visits, the sweat patch will be placed on 
the participants’ upper abdomen or flank for 72 hours to collect the sweat at baseline, 12 weeks and 3 
months after the program completion. The ELISA will be performed according to manufacturer’s guide by 
one laboratory technician. 
Data Collection Schedule and Procedures:  
Phase two is a pilot testing of the adjusted iHBE program effectiveness on the symptoms (fatigue and 
pain) affective well-being, resilience and BDNF level. A randomized usual care (waiting list) trial phase 
will be used. The study flyers will be posted at the home health care agencies, Johns Hopkins 
Comprehensive Cancer Center and Johns Hopkins Hospital. Eligible participants will be contacted by the 
principal investigator or research assistant who will explain the purpose of the study and requirements, and 
provided the study information and consent form. After providing the signed consent form, participants 
will complete the baseline assessment including the questionnaire, physical function (FTSST and 6MWT) 

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and blood samples. A pre-installed application smartphone and a wrist-worn wearable device (FitBit 
Charge 2) will be loaned to the participants. The online account specific to the participant will be assigned 
using code. No personal information will be stored separately. Participants will be asked to wear the FitBit 
Charge 2 on the non-dominant arm and respond to the mEMA application to monitor their free-living PA 
level for 7 days then randomly assigned to the experiment and usual care waiting list group. Participants in 
the iHBE group will receive one assessment home visit, 5 home visits and 7 follow up phone calls during 
the iHBE program. Then a home follows up visit at 6 month. The usual care (waiting list) group will 
receive educational booklets about a healthy lifestyle. They will be asked to continue to wear the wearable 
device to monitor PA for 3 months. Participants will then receive the iHBE program after the conclusion 
of the 12-week program. 
5. Inclusion/Exclusion Criteria 
Inclusion criteria are (1) participants diagnosed with solid tumor cancer who have completed cancer 
treatment at least 6 months; (2) diagnosed with diabetes and/or hypertension for at least a year; (3) aged 21 
years or older, (4) have an annual household incomes of below $30,000 for families of three, (5) the average 
fatigue level within the past 7 days at the level of 3 or more on the 0 (no fatigue) to 10 (worse fatigue) Likert 
scale and (6) give informed consent.  
Exclusion criteria are those (1) currently undergoing treatment for cancer; (2) have an active infection (e.g., 
fever, localized redness, swelling, sinus congestion); and/or (3) diagnosed with a psychological disorder (e.g., 
suicidal or homicidal tendencies, extreme anxiety or depression).  
 
6. Drugs/Substances/Devices 
 
None 
7.  Study Statistics 
Phase 2 Data analysis 
To test Hypothesis 2 (Aim 2) examining the effectiveness of iHBE program on fatigue, pain, well-being, 
resilience and BDNF levels, generalized estimating equations (GEE) will be used.  The models will include 
time as a within-subject fixed effect (baseline, 3 months, 6 months), group (intervention vs usual care) as a 
fixed-effect between-subject factor and the group by time interaction.  Baseline age, race gender, and BMI 
will be included as covariates. A significant group by time interaction would signify that the change over 
time in the outcomes differed for the intervention and usual care groups.  GEE was selected because it uses 
all available data and does not require complete data across time for a participant to be included in the 
analyses. Correlation will be used to test the relationship between the changes in serum and sweat BDNF 
levels (Aim 3). Change from baseline to 3 months and change from baseline to 6 months will be computed 
for serum BDNF and separately for sweat BDNF. The correlation between the change scores measured by 
the different modes will be estimated at each time point 
 
8. Risks: Same as phase 1 
 
9. Benefits:  Same as phase 1 
  
10. Payment and Remuneration 
 

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Phase 2 (Aim 2 and 3) - The participants in both the intervention group and the control group will each 
receive a total of $80 ($20 at the start of the intervention, $30 the end of the intervention and $30 at 6 
months) 
 
11. Costs 
There will be no cost for participants to participate in this study. 
 
12. Data Safety Monitoring Plan 
 
The PI will review reports reflecting data quality, safety, and monitor for potential adverse events and 
protocol adherence. The project coordinator, study staffs will meet with the PI weekly to review the 
progress of the study. The members of the investigative team and scientific advisors will meet monthly to 
support the study. A Safety Monitoring Committee (SMC) will be formed, consisting of Johns Hopkins 
University clinician faculty members who are independent of this proposed feasibility study. The SMC will 
be responsible for overall monitoring of the safety of participants in this proposed study and overseeing the 
PI, Co-Is, and research assistant.  
 
The PI will be responsible for managing all data, securing privacy and confidentiality, minimizing and 
identifying risks, monitoring and reporting adverse events or any safety issues, and complying with timely 
reporting requirements to all applicable regulatory bodies for any adverse events or unexpected problems. 
Monthly reports will be completed by the PI detailing participant demographics, recruitment status, 
treatment retention rates, protocol compliance, data gathered and accuracy, and quality assurance or 
regulatory issues that transpired, and summary of any adverse events. The research team (PI, Co-Is, and 
research assistant) will meet weekly via face to face or conference calling to discuss data and safety 
monitoring. 
 
The SMC will meet annually (or more frequently if needed) and review the annual reports completed by the 
PI; review study safety, integrity, and progress including any adverse events; provide advice in relation to 
continuing, changing, or terminating the study when necessary; require more frequent reporting as needed; 
audit the study for compliance and verify authenticity of data; and assess that the research team is 
complying with informed consenting and other required regulations. These annual meetings will be 
conducted face-to-face or through conference calls. 
 
The PI, in consultation with the SMC, will provide reports at intervals as required by National Institute of 
Health and/or other regulatory bodies as well as provide immediate reports as required regarding any 
adverse or unanticipated problems that may occur.   
 
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