Effectiveness of the Combined Technology-enhanced Home Exercise Program and Other Non-pharmacological Interventions on Fatigue, Physical Function and Well-being Among Cancer Survivors
Phase: NA
Conditions: Cancer-related Problem/Condition, Exercise, Acupressure
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Study Protocol and Statistical Analysis Plan 
NCT03576274 
Combined Technology Enhanced Home Exercise Program and Other Non-pharmacological 
Intervention for Cancer Survivors 
09/26/2024 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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JHM IRB - eForm A – Protocol 
 
 
 
• Use the section headings to write the JHM IRB eForm A, inserting the appropriate 
material in each. If a section is not applicable, leave heading in and insert N/A. 
• When submitting JHM IRB eForm A (new or revised), enter the date submitted to 
the field at the top of JHM IRB eForm A. 
 
********************************************************************************************* 
Title: Effectiveness of the combined technology-enhanced home exercise program and other 
non-pharmacological interventions on fatigue, physical function and well-being among cancer 
survivors  
 
1. 
Abstract 
Home-based exercise interventions have a significant effect on fatigue; however, 
motivation and intervention compliance are the main challenges. The use of personalized 
exercise and immediate feedback has been found to increase motivation. We developed a 12 
weeks technology-enhanced home exercise (TEHE) program using mobile technologies that 
provide immediate feedback and sends reminder messages to improve exercise motivation. 
Moreover, to enhance the effectiveness of exercise, we combine this TEHE program with 
techniques--acupressure and mindfulness based intervention--, which have been found to affect 
fatigue and physical activities. The acupressure and Mindfulness-Based Intervention (MBI) may 
enhance the effect of exercise on fatigue; however, the feasibility and effectiveness of this 
combination have not been tested. This study will examine the feasibility of the TEHE program 
and ascertain the effect of TEHE program alone (TEHE only), the combined acupressure and 
TEHE program (TEHEplus), acupressure alone (Acupressure only), the combined MBI and 
TEHE program and usual care on fatigue, physical function and well-being among cancer 
survivors.  In addition, we will explore peripheral and central markers (e.g., Phosphorous levels) 
of cancer-related fatigue using magnetic resonance spectroscopy (MRS). This study will also 
investigate whether specific types of fatigue (e.g., physical fatigue, cognitive fatigue) will have 
different levels of these peripheral and central energy markers). 
 
Conceptual Framework: The biopsychosocial model will be used.  
Main Research Variable(s): The independent variables are (1) the 12-week program of TEHE 
alone, (2) the 12-week program of acupressure only, (3) the 12-week program of combined 
acupressure and TEHE (TEHE Plus), (4) the 12-week program of combined MBI and TEHE 
and (5) control (usual care). Outcome variables are fatigue, physical activity, contributing 
factors of fatigue (depressive symptom, anxiety, sleep, relationship with others), and 
biomarkers.  
Design: Repeated measures randomized controlled trial design. 
Setting: Participants will be recruited through the Comprehensive Cancer Center, Johns Hopkins 
University. 
Sample: A total of 105 participants will be recruited from 2 populations 
Population 1: Individuals diagnosed with solid tumor cancer; who had completed all 
primary cancer treatment (surgery, chemotherapy, and radiation therapy) within at least 3 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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months OR prostate cancer completed all primary cancer treatment and have hormone therapy 
for at least 6 month, aged 21 years or older, experiencing fatigue in the past 7 days on average 
of ≥ 3/10, self-report ability to complete the 6 min walk test with a perceived exertion of 6 or 
below on a scale 1 (hardly any exertion) to 10 (feels almost impossible to keep going), can 
communicate in English and own a smart phone. 
 
Population 2: individuals diagnosed with solid tumor cancer; who are receiving 
immunotherapy for at least 3 months before enrollment, aged 21 years or older, experiencing 
fatigue in the past 7 days on average of ≥ 3/10, self-report ability to complete the 6 min walk 
test with a perceived exertion of 6 or below on a scale 1 (hardly any exertion) to 10 (feels 
almost impossible to keep going), can communicate in English and own a smart phone. 
 
Methods: Participants who meet the inclusion criteria will be randomly assigned to the TEHE 
only or Acupressure only or combined acupressure and TEHE (TEHE plus) or combined MBI 
and TEHE or control (usual care) group. All exercise groups will be offered a 12-week exercise 
program. They will be instructed to exercise at home to achieve weekly activity/step goals. 
Activity/steps and symptoms will be monitored daily using the FitBit and a smart phone 
application. Weekly summary report of physical activity and symptoms will be sent to 
participants through a web-based mobile phone application. In addition to the TEHE, the 
TEHEplus group will receive instructions on how to locate and apply the pressure on the 
acupressure points and weekly recommendation for acupressure points. The acupressure only 
group will receive only instruction on how to apply the pressure on the acupressure points 
through the online training or in person training with weekly recommendation for acupressure 
points. The MBI+TEHE group will receive a weekly recommendation to add mindfulness based 
intervention including body scan mindful breathing, and mindful movement. The control (usual 
care) group will report their symptoms level and monitor physical activity through Fitbit and 
smartphone application daily. At the end of week 12, in addition to the questionnaires, 
participants will answer open-ended questions about their opinions on the program. Symptoms 
will be assessed and blood will be drawn before and after the program. Participants who 
enrolled in the sub-study will be scheduled for one visit for an MRS. 
 
2. 
Objectives (include all primary and secondary objectives) 
Purpose/Specific Aims:  
The study primary aims are to (1) test the feasibility of a 12-week technology-enhanced home 
exercise (TEHE) program and combined technology-enhanced home exercise and Acupressure 
(TEHEplus) program among cancer survivors; (2) to determine the effect of the TEHE plus 
program on fatigue, physical activity and serum biomarkers (Heat Shock Protein 90 and Brain-
Derived Neurotrophic Factor) compared to the control (usual care) group. 
 
The secondary aims are to (3) compare the effect of the TEHE only, TEHEplus, Acupressure 
only, combined MBI and TEHE on fatigue and physical activity; and (4) determine the change in 
serum biomarkers at week 12 compared to baseline in the TEHE only, TEHE plus, Acupressure 
only, MBI+TEHE, and control (usual care) groups (5) explore the associations of muscle and 
brain energetic markers using magnetic resonance spectroscopy (MRS) with fatigue symptoms 
of cancer survivors. 
 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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3. 
Background  
With the advancement of cancer diagnosis and treatment, localized cancer patients have 
nearly a 100% 5-year survival rate.1 Approximately 40% of these cancer survivors experienced 
severe fatigue up to 2 years post-treatment, which impact the quality of life of these 
individuals.2 Furthermore, 20% of patients receiving ICIs (PD-1/PD-L1 checkpoint inhibitors) 
report severe fatigue at the any-grade adverse event,3 which impact the patients’ quality of life and 
hamper the clinical benefit with ICI.3, 4 To date, there are no US FDA approved medications to 
treat cancer-related fatigue (CRF). Several clinical trials have investigated medications for CRF 
such as psychostimulants (e.g., Methylphenidate, Modafinil) and antidepressants (e.g., 
nortriptyline, amitriptyline, and bupropion), however, they have shown inconsistent results on 
effectiveness.5-8 9The National Comprehensive Cancer Network (NCCN; 2015) recommends 
five non-pharmacological interventions to manage CRF, physical activity is one of the most 
effective interventions for CRF.10 The American cancer society recommended 150 
minutes/week of moderate-intensity aerobic physical activity (exercise performed at 60-80% of 
maximum heart rate) for cancer survivors with no physical limitation.11 The aerobic moderate-
intensity exercise program significantly improved fatigue among cancer patients.12-16 
Cancer survivors are less likely to exercise due to the limitation of access to an exercise facility 
and scheduling conflict.17 To overcome these barriers, a home-based exercise intervention was 
used. Studies suggested a significant effect of home-based exercised on fatigue severity.14 Most 
home-based exercise programs were challenged by the lack of motivation and low adherence 
rate to the exercise regimen.18-21 The use of technology e.g., exergaming (Wii-Fit) can increase 
motivation and exercise adherence.22-24 However, the use of Wii-Fit can be limited because it 
required exercise equipment, television, or monitor and exercise space at home. This proposed 
study will use the goal-setting by using step count from the physical tracker, which will be 
easier to implement than exergaming and require no additional equipment and space for 
exercise. To enhance the effectiveness of home-based exercise on fatigue, we hypothesized 
combining exercise with other nonpharmacological interventions such as acupressure or 
mindfulness-based intervention may provide a greater effect on fatigue reduction.  
Acupressure is a noninvasive complementary method, which is easy to learn. People can 
learn and self-administer this technique at home as needed. Studies found that relaxation 
acupressure on the body significantly reduce cancer-related fatigue among breast cancer 
patients.25-27 The Auricular Point Acupressure (APA is the application of the pressure on the ear 
points. The method is to apply the pressure on the selected point through a small adhesive tape 
with small plant seeds, Vaccaria segetalis, which is easy to self-administer the technique to 
manage symptoms. Studies among breast cancer patients found that APA improves fatigue, 
pain, and sleep.28, 29 Based on the previous study result, this technique for both body points and 
ear points may enhance the effectiveness of exercise on fatigue; however, it has never been 
tested. Moreover, studies found a significant effect on fatigue among women. The 
understanding of this effect of APA among men with cancer is limited.   
The mindfulness-based intervention (MBI) is a method that uses the open, nonjudgmental 
attention to one’s present moment experience. The MBI alone effectively improve symptoms 
such as psychological and fatigue among cancer survivors.30, 31 The body scan, mindful 
movement and mindful breathing are mindfulness based techniques that trains a person to move 
one’s attention calmly to the different parts of their body and be mindful with the movement 
and breathing. During the mindful practice, a person will be trained to notice and accept the 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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sensations they experience in an open and nonjudgmental way. This may improve the awareness 
of physical sensation during exercise, which may affect the fatigue. The effectiveness of the 
combined home-based exercise and mindfulness on fatigue is unknown. 
Based on the preliminary studies, patients with chronic fatigue had a high level of 
Heat Shock Protein 90 (HSP90) and low brain-derived neurotrophic factor (BDNF). HSPs 
are known as stress proteins that maintain proper protein folding for cell growth and survival 
against stress.32 BDNF is a member of the neurotrophic family of proteins that plays a 
significant role in neuronal survival.33 Both BDNF and HSPs can be modulated by oxidative 
stress during physical and psychological stressful events (e.g., inflammation, extreme 
exhaustion). During stressful events, HSP90’s function related to protein folding is altered 
leading to cell death,34, and BDNF are activated to enhance neuroprotective mechanisms.35 
BDNF has been proposed to influence change in behaviors like depression.36, 37 In cancer, high 
HSP90 is believed to support a malignant transformation and is currently a new anti-cancer 
treatment target. High HSP90 levels are associated with an advanced stage of cancer and poor 
treatment prognosis.38 Studies in prostate cancer have shown that the HSP-based chaperone 
mechanism is involved in prostate cancer progression.39 Both HSP90 and BDNF levels can be 
changed by interventions such as exercise.40, 41 A study in patients with chronic fatigue 
syndrome (CFS) reported significantly higher blood HSP90 levels among patients with CFS 
than healthy control and significantly decrease 30% from baseline after the exercise.42 No 
studies have investigated the effect of exercise on HSP90 and BDNF in patients with CRF. 
Information about the relationship between HSP90, BDNF, and CRF is highly important, for it 
may also trigger a discussion on the potential of CRF as a predictor of cancer prognosis and 
treatment outcomes.  
The organizing framework for this study will be guided by the biopsychosocial model, 
which incorporates biological influences, social influences, and psycho-behavioral influences 
on CRF. We hypothesize that CRF is influenced by social (e.g., interpersonal relationships with 
caregivers), psycho-behavioral (e.g., depressive symptoms, anxiety, physical activity and sleep 
disturbance), and biological factors (HSP90 and BDNF levels) (figure 1). 
 
 
 
 
 
A technology-enhanced home-based exercise program can reduce CRF by having an 
impact on the biological and psychological aspects of fatigue. The group training exercise 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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program during study visits impact on social, psycho-behavioral components of CRF 
experience.   
Phosphorous bioenergetics in muscles and brain areas using magnetic resonance 
spectroscopy (MRS) has been used to estimate mitochondrial oxidative phosphorylation (i.e. 
oxidative stress) in vivo. For example, one study observed that peripheral fatigue in healthy men 
was associated with a perturbation in skeletal muscle pH and deprotonated phosphate ion. 
Another study found that patients with chronic fatigue syndrome have abnormal recovery of 
intramuscular pH following standardized exercise compared to normal controls. It has been 
proposed that oxidative stress explains the biologic underpinnings of cancer-related fatigue, but 
no study has yet to explore whether these markers are associated with fatigue symptoms in 
cancer survivors. The sub-study seeks to explore peripheral and central energy markers of 
cancer-related fatigue using magnetic resonance spectroscopy (MRS). This study will also 
investigate whether specific types of fatigue (e.g., physical fatigue, cognitive fatigue) will have 
different levels of these peripheral and central energy markers. Information derived from this 
study will be clinically relevant to identify potential therapeutic targets to optimize the 
management of this debilitating symptom. 
 
4. 
Study Procedures 
Design. The repeated measure randomized control trial will be used to test the study hypotheses. 
 
Sample and Setting. Participants will be recruited from the Sidney Kimmel Comprehensive 
Cancer Center, Johns Hopkins University. 
 
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 
Sidney Kimmer Comprehensive Cancer Center, Maryland. The study information and link to 
eligibility screening survey will be posted on social media platforms (Facebook, Instagram, 
Twitter). The Johns Hopkins Institute for Clinical and Translational Research (JHU-ICTR) 
MYChart Recruitment Service will be used to send a message to potential participants through 
database queries that are embedded in Epic. 
 
Recruitment, Informed Consent, and Confidentiality.  
 
Recruitment methods for this study include  
(1) distributing and posting flyers and bookmarks, with study e-mail and Recap screening 
survey link and/or QR code for potential participants to contact the principal investigator (PI) 
and research staff to inquire more information about the study or to leave contact information for 
the study team to reach out and send the study information. Flyers and bookmarks will be 
distributed to patients who come in for follow-up visits at Sibley Memorial Hospital, Johns 
Hopkins Bayview Medical Center, Johns Hopkins Hospital;  
(2) posting study information on social media platforms;  
(3) referral by co-investigators; and  
(4) sending messages to potential participants through JHU-ICTR MyChart Recruitment 
Service. 
 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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The participants who completed the Redcap screening survey will be contacted by the 
principal investigator (Nada Lukkahatai) or a research team member. Potential participants will 
receive a verbal explanation by phone or face-to-face meetings in terms suited to their 
comprehension of the purpose, procedures, and potential risks of the study. During the screening 
for the 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 guardians will have an opportunity to 
carefully review the consent form and ask questions regarding this study before signing. 
Participants will be encouraged to consult with their primary doctor if any concerns or additional 
questions. Participants will be informed that they may withdraw from the study at any time 
without prejudice to themselves. The information of potential participants collected through the 
redcap survey will be kept confidential. The personally identifiable information will be kept in 
the password log computer. The identifiable information of participants who refuse to participate 
or are ineligible will be removed from the stored file. 
 
 
Exercise study: In the eligibility screening process, potential participants will be approached and 
screened by phone for 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, 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 electronic informed consent.  
 
Sub-study (MRS imaging): Participants who are eligible for the exercise study will be asked to 
answer additional screening questions by phone to assess the eligibility for the study including 
1. In the last five years, have you been diagnosed as having a substance abuse disorder? 
2. Do you currently drink alcohol? If yes, how many drinks per day on average? (ineligible 
if answer 5 or more drinks per day for male and 4 or more drinks per day for female). 
3. Do you have 
a. Implanted cardiac pacemakers, metal aneurysm clips; 
b. Broken bones repaired with metal pins, screws, rods, plates; 
c. Prosthetic eye implants, 
d. Transdermal medications or infusion pumps; 
e. Bullet fragments or other metal pieces in the body from old wounds; 
f. Significant work exposure to metal particles; 
g. Clinically relevant claustrophobia; 
h. Unable to lie comfortably on the back for up to 4 hours; 
i. Being pregnant or lactating 
 
Only the participants who eligible for the MRS (answer “No” to the above questions), will be 
invited to participate in the sub-study. 
 
Recruitment for the MRS imaging 
 
 Those participants who consent to participate in the exercise study and eligible for the 
sub-study will have the option to enroll in the sub-study (MRS). Declining to participate in the 
sub-study will not affect their participation in the main study. This will be a convenience 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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sampling. Once the participant reviews and sign the sub-study section in the consent form. A 
study visit for the MRS will be scheduled before the first exercise intervention. 
 
Data collection schedule and procedures: 
Exercise study: 
Once the informed consent is signed, instruction video on how to install a smartphone 
application and activity tracker (Fitbit), study materials will be sent to the participant. The 
participants will be meet with a research team member online using the participant’s preferred 
method (e.g., FaceTime, Zoom, etc.) to review the equipment instruction, and measure cognitive 
function and perceived short physical performance online. If travel is feasible, participants will 
be meet with the research team member in person at the East Baltimore (Wald) Community 
Nursing Center and Outreach or Sidney Kimmel Comprehensive Cancer Center to set up the 
study device and measure muscle strength, physical performance and heart rate variability (table 
1). Participants will be asked complete the questionnaire package through Redcap survey. The 
physical activity tracker (Fitbit) and the mEMA application will be installed on the participants’ 
smartphone with written instructions on how to use both devices. Participants will be asked to 
wear the Fitbit on the non-dominant arm and respond to the mEMA daily for 12 weeks. 
Peripheral blood will be drawn at week 1 and week 12 for participants who can complete the 
study visit in person by a registered nurse or trained research staff at the East Baltimore (Wald) 
Community Nursing Center and Outreach or at the phlebotomy (research clinical blood draw) at 
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University.  The collection of 
blood samples by venipuncture in this study will include the amount of 15 mL, one time per 
study visit, 2 visits in 12 weeks.  (Confirmation that the blood collection by venipuncture from 
study subjects, the amounts were drawn will be less than 550 ml in 8 weeks and collection occur 
less than 2 times per week). Blood will be transferred and processed at the Johns Hopkins School 
of Nursing biophysiological laboratory.  
 
Sub-study (MRS imaging): 
Participants enrolled in the sub-study will be scheduled for the MRS at the National Institute on 
Aging (NIA) located at Medstar Harbor Hospital. The MRS will be done by the NIA staff. The 
research assistant will accompany the participants and a registered nurse will be available for 
consultation throughout the MRS process. Only de-identified data will be shared with the 
Medstar for data analysis. 
 
 
Table 1: Data collection process  
Tasks 
Study 
visit 1 
Weeks 
Study 
visit 2 
Baseline 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Demographic and disease information questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
FACT-F and PROMIS fatigue 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
PROMIS Adult profile 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Cognitive function (MOCA and MASQ) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical activity (steps) and HR (from the wearable 
device)* 
X 
X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
Muscle strength test 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Short-form survey (SF-36) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Connor-Davidson Resilience Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Coping self-efficacy scale 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Pittsburg Fatigability Scale (PFS) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical performance 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Heart rate variability 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Blood sample for HSP90 and BDNF level 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Open-ended questions about the feasibility of the 
program 
 
 
 
 
 
 
 
 
 
 
 
 
X 
MRS for the central and peripheral markers (sub-
study) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Randomization: 
After the baseline data collection and blood draw, the participants will be stratified by type of 
cancer (breast cancer vs. prostate cancer), age, and treatment (completed treatment vs. receiving 
immunotherapy). Participants will be randomly assigned to the control and intervention (TEHE 
only, TEHE plus, Acupressure only, TEHE +MBI groups) groups. The participants’ random 
group assignment will be determined using the Excel program. 
 
Participants in the experimental groups will receive either a) 45-60 min online exercise 
training/consultation session only, b) an online exercise training session and online and written 
APA instruction (TEHE +Acupressure group), c) online and written APA instruction only or d) 
exercise training instructions and mindfulness relaxation instructions (TEHE + MBI groups). 
After the exercise training session, participants will select their preferred exercise type and their 
preferred follow-up methods, duration of exercise, exercise schedule, and exercise frequency for 
the next 12 weeks.  Participants will receive weekly recommendation for physical activity goals, 
recommended acupressure points (for TEHEplus and Acupressure only groups) and 
recommended mindfulness techques (for TEHE + MBI group). Participants in the control group 
will continue with their daily usual physical activity. 
 
The feasibility of the TEHE plus program includes the evaluation of the recruitment and 
retention, acceptability, compliance, and delivery of the intervention. This study aims to measure 
the feasibility of the TEHE groups (including all five intervention arms). In the data collection 
process, the eligible participants recruited patients, a number of participants completing the 
intervention program will be recorded. Adherence to the intervention will be assessed using data 
collected from the activity tracker on minutes of moderate-intensity or greater activity. During 
the weekly exercise training, participants will discuss their home-based exercise barriers and 
potential solutions. At the end of the 12 weeks, participants will answer open-ended questions 
about their satisfaction and opinion about the programs (intervention groups) and the use of 
physical activity trackers and mobile phone application (control group). 
  
By participating in the study, participants will spend 12 weeks, with 2 study visits. 
Participants will continue to receive their routine care and current therapy. They will continue 
with their therapy when the study ends or if the participation end prematurely. During the study, 
unexpected circumstances (e.g., worsening of cancer, extreme anemia, or another late side effect 
of cancer treatment). Participants will be removed from the study if his/her disease and/or 
condition is worsening. 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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Participants’ personal information will be kept as private as possible and participants’ 
names will not appear on any of the data forms. Blood sample tubes will be coded but de-
identified and will be stored in locked freezers at Johns Hopkins School of Nursing 
biophysiological laboratory freezer until analyzed. Participants’ health information will only be 
disclosed for this research study. Data will be stored for five years using assigned codes and will 
be kept on a password-protected computer held at the Johns Hopkins School of Nursing. Only 
study investigators will have access to the study data. After five years, the data will be shredded 
and discarded.  
 
5. 
Inclusion/Exclusion Criteria 
Exercise study: 
Inclusion criteria are (1) diagnosed with a) breast cancer; who had completed primary 
cancer treatment  (surgery, chemotherapy, and radiation therapy) or b) prostate cancer, 
completed primary cancer treatment and have hormone therapy for at least 6 months prior 
to enrollment or c) diagnosed with a solid tumor cancer; who are receiving 
immunotherapy for at least 3 months prior to enrollment; (2) aged 21 years or older; (3) 
experiencing fatigue in the past 7 days on average of ≥ 3/10; (4) self-report ability to 
complete the 6 min walk test with a perceived exertion of 6 or below on a scale 1 (hardly 
any exertion) to 10 (feels almost impossible to keep going); (5) able to communicate in 
English; (6) own a smartphone.  
 
Exclusion criteria are those (1) have an active infection (e.g., fever, localized redness, 
swelling, sinus congestion); and (2) diagnosed with a psychological disorder (e.g., suicidal 
or homicidal tendencies, extreme anxiety or depression).  
 
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. Participants who meet the inclusion criteria will be 
randomly assigned to the intervention groups (TEHE only, Acupressure only, TEHEplus, TEHE + 
MBI) or the control group. 
 
Sub-study (MRS imaging): participants eligible for the exercise study will be screened for the sub-
study. 
 
Additional exclusion criteria for sub-study are those 1) self-identified as a high-risk drinker 
(≥5 drinks/day for men, ≥4 drinks per day for women). (“Dietary Guidelines for Americans 2015-
2020,” U.S. Department of Health and Human Services and U.S. Department of Agriculture); or 2) 
have any of a) implanted cardiac pacemakers, metal aneurysm clips; b) broken bones repaired with 
metal pins, screws, rods, plates; c) prosthetic eye implants; d) transdermal medications or infusion 
pumps; e) bullet fragments or other metal pieces in the body from old wounds; f) significant work 
exposure to metal particles; g) clinically relevant claustrophobia; h) unable to lie comfortably on 
the back for up to 4 hours; and/or i) individuals who are pregnant or lactating. 
 
6. 
Drugs/ Substances/ Devices 
There will be no drugs or substances used in this study. The wearable device (Fitbit) is a wrist-
worn commercially available device in the market, which was found to be safe for most users. 

Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
JHMIRB eFormA  01 
Version 3 Dated:   06/2007 
 
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7. 
Study Statistics 
The feasibility of the TEHE plus program includes the evaluation of the recruitment and 
retention, acceptability, compliance, and delivery of the intervention. This study aims to 
measure the feasibility of the TEHE groups (including all three intervention arms). In the data 
collection process, the eligible participants recruited patients, a number of participants 
completing the intervention program will be recorded. Compliance with the intervention will be 
assessed using data collected from the activity tracker on minutes of moderate-intensity or 
greater activity. At the end of the program (12 weeks), participants will be asked to complete 
open questions on their satisfaction and opinion on the intervention and delivery method. 
 
Primary and secondary objectives 
 
The study primary aims are to (1) test the feasibility of a 12-week technology-enhanced home 
exercise (TEHE) program and combined technology-enhanced home exercise and Acupressure 
(TEHE plus) program among cancer survivors; (2) the effect of the TEHE program and TEHE 
plus on fatigue, physical activity and serum biomarkers (Heat Shock Protein 90 and Brain-
Derived Neurotrophic Factor) compare to the control (usual care) group. 
 
The secondary aims are (3) compare the effect of the TEHE only, Acupressure only, TEHEplus, 
and combined TEHE and MBI on fatigue and physical activity; and (4) determine the change in 
serum biomarkers at week 12 compared to baseline in the TEHE only, Acupressure only, 
TEHEplus, MBI+TEHE, and control (usual care) groups 
 
Analysis plan 
Exercise study: 
The mean and standard deviation of each outcome measure, recruitment rate, drop out, 
acceptability, tolerability will be calculated per group per study visit. The study primary aim the 
feasibility of a 12-week technology-enhanced home exercise (TEHE) program and TEHE plus 
program (Aim 1) will be analyzed using descriptive statistics of eligible participants and 
recruited participants, a number of participants completing the intervention program, 
compliance (number of participants complete the daily step goal), and participants’ satisfaction 
and opinion of the intervention. To examine the effect of the TEHE program on fatigue, 
physical activity and serum biomarkers (Heat Shock Protein 90 and Brain-Derived 
Neurotrophic Factor) (Aim 2), the paired t-test will be used to analyze the effect of the program 
on fatigue, PA and biomarkers at the end of the program compared to baseline. The student t-
test will be used to compare the variables among participants in the TEHE program, 
Acupressure only, TEHEplus, and TEHE +MBI compare to the usual care (control) group. 
 
The secondary aims: The change of fatigue and physical activity level in week 12 compared to 
baseline will be calculated. Analysis of Variance (ANOVA) will be used to compare the effect of 
the TEHEplus, combined TEHE, and MBI with the TEHE only and Acupressure only on fatigue 
and physical activity (Aim 3). Change from baseline to 12 weeks will be computed for serum 
HSP90AA1 and BDNF levels. ANOVA will be used to examine the differences of change in 
serum biomarkers at week 12 compared to baseline in the TEHE only, Acupressure only, 
TEHEplus, TEHE +MBI and control (usual care) groups (Aim 4). 

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Sample size justification  
Sufficient information from prior studies is not available for us to conduct a sample size 
calculation for the proposed multilevel analyses. The purpose of this pilot project is to explore 
the feasibility of the program and the relationships between the trajectories of the outcome 
measures, and not to achieve high power. The proposed N of 110 (22 participants/group) will 
likely result in low (below 0.60) statistical power. Results obtained will inform future power 
analyses for full-scale studies.  
 
Early stopping criterion for safety/futility/efficacy as needed. 
The purpose of this pilot study is to examine the feasibility of the interventions. Therefore, 
participants may be asked to stop their participation early if there are serious complications 
include metastasis of the disease is found, serious injuries (broken bone, severe muscle injury) 
that prohibit the participants to exercise, severe infection during the 12 weeks intervention (e.g., 
fever, redness, swelling, etc.). 
 
Inclusion and exclusion criterion: please see section 5. 
 
Intervention/Independent Variables.  
Technology-Enhanced Home Exercise (TEHE) Program: An online individual exercise 
session will be offered at the first study visit. Participants will be complete an exercise training 
program (45-60 min) to reach a moderate intensity using the heart rate monitor and exertion 
level.  
The online exercise training/consultation program will include 
- 
Goal setting/discussion of the progress (25 min): Participants will spend 25 min to 
discuss the physical activity barriers and set up a goal for the program. 
- 
Exercise safety and body alignment (10 min): Participants will learning about 
posturing and body alignment to maintain their safety during exercise and monitoring 
the heart rate using the wearable device. 
- 
Review physical activity and symptoms (15 min) 
- 
At the end of the program, participants will select follow up methods (phone or video 
call), reminder message scheduled time and frequency. 
At home: Participants will receive a weekly recommendation through a smartphone application 
and be instructed to follow their physical activity/step goals. Participants will receive a summary 
report of their weekly physical activity and symptoms (Fitbit and mobile phone application data).  
 
The PI (Dr. Lukkahatai) will monitor the intervention session to ensure intervention fidelity. 
Adherence to the intervention will be assessed by data collected from the activity tracker on 
minutes of moderate-intensity or greater activity. At the end of the 12 weeks, participants will 
answer open-ended questions about their satisfaction with the program. 
 
The Acupressure program: Participants in this group will receive 
online or in person auricular point acupressure (APA) and body 
pressure points training at the first study visit. An online educational 
video and written material developed by interventionists and PI, will 

Date:  September 26, 2024   
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be provided. The participants will review the instruction video. During the online study visit, 
participants will be asked to locate the ear point, place the seed on the ear points, and pressing 
the ear points. 
The training information will include  
1) The selection of the ear point: The points that will receive acupressure include 
sympathetic, nervous subcortex, Sanjian, kidney, liver, spleen, mouth, and anxious point 
(see Figure 3). 43, 44  The selection of sympathetic and nervous subcortex are for 
regulating the function of the central nervous system; sanjian is related to increase the 
metabolism of food; liver, spleen and kidney points are to help strengthen the energy; the 
mouth is also called speed recovered fatigue, and the anxious point is used to promote 
relaxation.43, 44   
2) Placing the seeds: After the points are located, the outer ear and the earlobe will be 
cleaned with 75% alcohol, then place pieces of pre-prepared tape with seeds on the 
participant’s ear. Points on both ears will be identified and used for treatment in the 
proposed study.  
3) Applying pressure on the ear points: evenly press the tape and seeds covering each ear 
point without rubbing (to avoid skin damage and infection at the acupuncture point) for 
10 seconds per time for 3 times/point four times daily, even if they do not experience 
fatigue. The optimal pressure is considered to have been achieved when the participants 
feel localized tingling or mild discomfort.  
4) Pressure points on the body: Participants will be asked to apply pressure using thump on  
the following points for fatigue and energy include outer gate point (locates between 2 
tendons on the backside of the arm, free finger above the wrist) Spirit Gate or Heart 7 or 
Shen Men body point (locates on the wrist crease in between little finger and ring finger), 
large intestine 4, stomach 36, liver 3 and kidney 3. Participants will be instructed to apply 
pressure 10 seconds per time for 3 times/point four times daily, even if they do not 
experience fatigue.  
 
At home: Participants will be received a weekly recommendation for points that tailored for their 
weekly symptoms experience and instructed to press the tape and seeds covering each ear point 
for 10 seconds per time for 3 times/point four times daily (morning, afternoon, evening and 
before bed), even when they do not experience fatigue. The optimal pressure is considered to 
have been achieved when the participants feel localized tingling or mild discomfort. The tape 
and seeds will remain on ear points for 5 days. Participants will be instructed to remove both at 
the end of the 5th day and apply the new seeds. 
 
To ensure the accuracy of the ear points, participants will be asked to send the photo of their ear 
after the seeds are placed for comments and suggestions. 
 
The combined Acupressure and TEHE program (TEHE plus): In addition to the TEHE 
program, participants will receive Acupressure training at the first study visit and weekly 
recommendations that include both exercise goal and suggested pressure points. 
 
The combined MBI and TEHE program: In addition to the TEHE program, the TEHE+MBI 
group will receive a 10-15 min audio-recording of a mindfulness-based body scan or mindful 
movement or mindful breathing. This technique is often used as an entry point to mindfulness 

Date:  September 26, 2024   
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meditation.45, 46 This recording guided the participants to focus on specific bodily and breathing 
sensations.  
At home: Participants will be instructed to include mindfulness-based body scan or mindful 
breathing, mindful movement. The participant will be instructed to acknowledge all sensation 
with the non-judgemental acceptance and not attempting to change the experience. Participants 
will receive a weekly recommendation for the activity goals and suggested mindfulness 
techniques. 
 
Control Group: The control group will receive instructions on how to use the physical activity 
tracker and the smartphone application. Participants will be asked to meet with a research team 
member on the first week to review the equipment set up instruction. Participants will be asked 
to monitor their physical activity daily using Fitbit and receive a daily notification to complete 
the short on fatigue and other symptoms from the smartphone application.  
 
Dependent variables and instruments. The study variables will be measured as follows: 
Questionnaires 
• Fatigue will be measured by the Functional Assessment of Cancer Therapy-Fatigue subscale 
(FACT-F). A 13-item questionnaire with good test-retest reliability (r = 0.90), internal 
consistency (α = 0.93 and 0.95) on initial and test-retest administration suggesting that it can 
be administered as an independent, unidimensional measure of fatigue.25 and the Patient-
Reported Outcome Measurement Information System short form-Fatigue (PROMIS-F) 6-
items; self-reported fatigue (frequency, duration, intensity) and the impact of physical, 
mental, & social activities influencing one's daily lives, including work & social roles; has 
five response options (1 or never to 5 or always). Initial psychometric properties showed an 
internal consistency reliability coefficient of greater than 0.80. 
• Self-perceived cognitive dysfunctions were measured by the 38-item Multiple Ability Self-
Report Questionnaire (MASQ) in 5 domains: language, visual-perceptual ability, verbal 
memory, visual-spatial memory, and attention/ concentration, using a 1-5 Likert scale 
rating.47 The language subscale includes items relating to speech, the ability to follow 
conversations, and the ability to convey thoughts. Visual perceptual ability items measure the 
patient’s ability to follow visual directions and solve puzzles.  Items in the verbal memory 
subscale evaluate forgetfulness with events, important information, and names, and visual-
spatial memory items relate to faces, pictures, and places. The attention/concentration 
subscale items assess perceived difficulties with performing tasks, simple calculations, 
alertness, and maintaining a train of thought. The total score for each domain ranged from 8-
40, except for visual-perceptual ability, which ranged from 6-30.48 Higher MASQ scores 
indicate a greater perception of cognitive dysfunctions. Each MASQ subscale had high 
internal consistency reliability (Cronbach’s coefficient alpha ranging from 0.72-0.74).47 
• Psychosocial factors contributing to fatigue (e.g., physical function, anxiety, depressive 
symptom, sleep disturbance, pain intensity, pain interference, and ability to participate in the 
social activities) will be measured by the Patient-Reported Outcome Measurement 
Information System (PROMIS)-Adult Profile short form. The items were rated on the past 
seven days using a 5-point response scale from “never” to “almost always.” Initial 
psychometric properties showed an internal consistency reliability coefficient of greater than 
0.80. Disease stage, PSA, and testosterone levels will be obtained by chart review. 

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• Resilience will be measured using the Connor-Davidson Resilience Scale. This is a 10 items 
self-report scale ask the participant to rate their opinion on the Likert scale range from 0 (not 
true at all) to 4 (true nearly all the time). This instrument has good internal consistency 
(Cronbach’s alpha of 0.85) and constructs validity. 
• Well-being will be measured using the Short-form survey (SF-36). This is a 36-items self-
report instrument measure 2 domains: physical and affective well-being. SF-36 has good 
internal consistency (Cronbach’s alpha 0.70). 
• Self-efficacy will be measured by the coping self-efficacy (CSE) scale. The 13-items measure 
perceived self-efficacy for coping with challenges or threats. The CSE has a good internal 
consistency (Cronbach’s alpha ranged from 0.8-0.91 
• Sleep difficulty will be measured by the Insomnia severity index. This 7 items questionnaire 
has acceptable reliability (Cronbach’s alpha =0.73) 
• Fatigability or fatigue associated with specific physical activity will be measured by the 
Pittsburg Fatigability Scale (PFS). The 10 items scale has strong internal consistency 
(Cronbach’s alpha =0.88) and excellent rest-re-test reliability (interclass correlation 0.86).  
• MD Anderson Symptoms inventory will be used to measure cancer related symptoms severity 
and interference. This 13-items questionnaire has acceptable reliability and validity. 
 
Physiological and Biological Measurements 
• Physical activity (number of steps) and sleep duration will be objectively measured by Fitbit 
Charge. This device can track 7 days of detailed motion, sleep, and physical activity data 
(e.g., steps, distance, active minutes, sleep duration, heart rate, and caloric usage) and store 
activity data in the Microsoft platform. Comparing the wearable devices (FitBit and 
Microsoft band 2) with the physical measurement gold standard (ActivPAL) in healthy 
participants during treadmill walking and during the free-living environment, the wearable 
device had an excellent agreement with the ActivPAL (Intraclass Correlation Coefficients = 
0.81 and 0.96 respectively, p  < .01).49 When compared to the commercially available 
wearable devices (FitBit, Apple Watch, Garmin Vivofit and Microsoft Band 2), Fitbit has  
acceptable performance on the accuracy of the heart rate and precise calculation of carries 
burnt and distances.50 
• Skeletal muscle strength will be measured with a hand-held dynamometer. Grip strength will 
be measured on both hands in a neutral position of the arm, forearm, and wrist. Two 
consecutive attempts at 1-minute intervals will be measured. Each attempt will require a 
participant to exert a maximum possible grip force for about 5 seconds. After a minute of 
rest, the third attempt will measure fatigue resistance by asking the participant to hold the 
maximum hand grip as long as able until the 50% maximum grip force (based on the highest 
maximum handgrip force obtained from the first 2 attempts) is reached, which is often 
reached in less than a minute. The test will be repeated on the other hand. The same 
dynamometer will be used for all participants. 
• Plasma HSP90 and BDNF protein levels will be measured by ELISA. ELISA will be 
performed according to the manufacturer’s guide by one laboratory technician. 
The physical performance will be measured using the short physical performance battery 
assessment (SPPB) and virtual SPPB (vSPPB) at baseline, 12 weeks at the program completion.  

Date:  September 26, 2024   
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Cognitive function will be measured by the Montreal Cognitive Assessment (MOCA) and the 
Multiple Ability Self-Report (MASQ) questionnaire. It is a 38-item measure that assesses 5 
domains of perceived cognitive difficulties: language, visual perception, verbal memory, visual-
spatial function, and attention/concentration.64 
HRV Data Collection:  
An electrocardiogram approximately 5 minutes in length will be captured using the 
commercially available KardiaMobile ECG device (AliveCor, San Francisco, CA, USA).  
Participants will place their forefingers on the touchpad while seated and resting for the reading.  
Data will be captured using Kubios HRV software, a software tool for heart rate variability 
analysis (Kubios, Inc. Kuopio, Eastern Finland).  Data will be analyzed by Dr. Stavros Stavrakis 
(mentor for this project) who has extensive experience with both these technologies and has 
published on them.9  Differences between adjacent NN intervals will be assessed. Frequency 
domain analysis will be used to assess low-frequency power (LF power), high-frequency power 
(HF power), and the LF/HF ratio. 
 
Magnetic Resonance Spectroscopy (MRS): 
Before the first exercise intervention session, the diffusion-weighted (DW) imaging and 31P 
spectroscopy data will be collected using a 3T Philips Achieva MR scanner (Philips, Best, 
Netherlands) in the same imaging session. The data collection protocol and analysis will be done 
at NIA by Dr. Richard G. Spencer (The NIA Magnetic Resonance Spectroscopy expert) and his 
team. 
 
Table 1: Data collection process  
 
Tasks 
Study 
visit 1 
Weeks 
Study 
visit 2 
Baseline 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Screening: perceived exertion of 6MWT 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic and disease information questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
FACT-F and PROMIS fatigue 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
PROMIS Adult profile 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Cognitive function (MOCA and MASQ) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical activity (steps from the wearable device)* 
X 
X 
X 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
Muscle strength test 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Short-form survey (SF-36) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Connor-Davidson Resilience Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Coping self-efficacy scale 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Pittsburg Fatigability Scale (PFS) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical performance (SPPB and vSPPB) 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Heart rate variability 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Blood sample for HSP90 and BDNF level 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
MRS for the central and peripheral markers (sub-
study) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Open-ended questions about the feasibility of the 
program 
 
 
 
 
 
 
 
 
 
 
 
 
X 
  
 
8. 
Risks 

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Potential Risks and Protection Against Risks. Potential risks include (1) complications during 
the blood draw including pain and bleeding at the drawing site, (2) complications of the APA 
procedure, (3) minimum discomfort might occur while wearing the Fitbit charge (worn like a 
bracelet), (4) complications such as fainting or injury during the exercise program may occur. 
The MBI and responding to the questionnaires has no medical risk. The PI and research team 
plan to prevent the following risks: 
1. Complications during the blood draw. Participants may experience pain and discomfort 
during the blood draw. They may also be at risk of bleeding. All blood draws will be 
performed by a certified phlebotomist. After the blood draw, participants’ conditions will 
be monitored by a registered nurse (RN).  
2. Complications of APA procedure: The auricular acupuncture procedure is considered 
safe with minimal risk. The most frequently reported adverse events were local skin 
irritation and discomfort, mild tenderness or pain, and dizziness. These events were 
transient, mild, and tolerable. Participants will be instructed to remove the tap with the 
seed when adverse events occur. 
3. Minimum discomfort might occur while wearing the Fitbit charge (worn like a bracelet). 
Participants will be asked to wear a Fitbit to measure physical activity and sleep duration 
during their participation in the study. Participants will be instructed to take the band off 
when taking a shower. This equipment may cause discomfort. The material does not 
contain latex; however, the clasp is made of surgical grade stainless steel and contains 
traces of nickel, which may cause a rash. The device can be easily removed if discomfort 
is experienced. Participants will be asked to record the time and reason when and why 
they removed the band. 
4. Complications (e.g., fainting, injury) during the exercise program. Participants will be 
instructed to walk and exercise at their own pace in the safety of their environment. All 
participants will be instructed to wear tennis shoes, comfortable clothing, and to eat a 
light snack before exercise.  
5. The MBI and responding to the questionnaire has no medical risk. Participants will be 
asked to spend 20-30 min completing the questionnaire and listening to the instructions 
on how to use the smartphone application and Fitbit. All subjects will be informed that 
they can stop answering questions if they feel tired; they can resume the questionnaire at 
a later time. Participants will spend less than 5 min responding to a short survey on 
fatigue level, daily, through the application. Participation in this study involves the 
completion of questions (4 questions) about depressive symptoms. Scores from these 
questions (range from 4-20) would not be a sufficient basis for clinical decisions or 
diagnosis, contain substantial margins of error, and are not used for diagnostic purposes 
in this study. This score might hint at health conditions. Therefore, participants will 
receive the score for this depressive symptom subscale. If the depression score is higher 
than 16 (T score of > 70: severe depressive symptom), a registered nurse will suggest the 
participant discuss this issue with his/her primary health care provider. 
6. Magnetic Resonance Spectroscopy (MRS) 
There is a risk for injury from the magnetic resonance imaging (MRI) magnet if the 
participant has some type of metal in their body. It may be unsafe to have an MRI scan if 
the participant has a pacemaker or other implanted electrical device, brain stimulator, 
some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), 

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metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), 
permanent eyeliner, implanted delivery pump, or shrapnel fragments.  
Welders and metal workers may have small metal fragments in the eye. Each participant 
will be screened for such metal before having any scan. If the participant has any metal, 
they will not receive an MRI scan. If the participant has a question about metal in their 
body, they should inform the research team.  
Each participant will be asked to complete an MRI screening form before each MRI scan. 
All magnetic objects must be removed before entering the MRI scan room. This includes 
items like watches, coins, jewelry, and credit cards. 
It is not known if MRI is completely safe for a developing fetus. Therefore, female 
participants in childbearing age will have a pregnancy test done no more than 24 hours 
before each MRI scan. The scan will not be done if the pregnancy test is positive. 
People with a fear of confined spaces may become anxious during an MRI. Those with 
back problems may have back pain or discomfort from lying in the scanner. The noise 
from the scanner is loud enough to damage hearing, especially in people who already 
have hearing loss. Everyone having a research MRI scan will be fitted with hearing 
protection. If the hearing protection comes loose during the scan, the participant should 
inform the research staff right away. 
 
9. 
Benefits 
There is no direct benefit to the participant from being in this study. However, the technology-
enhanced home-based exercise (TEHE) program and the combination of the Acupressure and 
MBI with the TEHE programs proposed in this study could be used as choices for cancer 
survivors to manage their fatigue and improve patients’ quality of life. The mEMA application 
and Fitbit will serve as useful tools for health care providers to monitor intervention outcomes 
and compliance. 
 
10. 
Payment and Remuneration 
Participants will receive a total of $40 incentive and a Fitbit for completing 12 weeks program 
with 2 study visits and phone/video calls follow up. Participants who participate in the sub-
study (MRS) will receive an additional of $70 for participation.   
If participants withdraw from the study before the 12week, participants will be asked to return 
the device through the mail and there will be no penalties for withdrawal. 
 
 
11. 
Costs 
There will be no cost for participants to participate in this study. 
 
 
12. 
Data Safety Monitoring Plan 
 
This proposed study intends to evaluate the feasibility and preliminary efficacy of a 12-week 
technology-enhanced home exercise (TEHE) program and TEHE plus program with physical 

Date:  September 26, 2024   
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activity and fatigue; (2) explore the effect of the combined TEHE program with Acupressure and 
MBI on fatigue and physical activity; and (3) determine the effectiveness of the TEHE alone, 
TEHEplus, and MBI+TEHE programs on serum biomarkers (Heat Shock Protein 90 and Brain-
Derived Neurotrophic Factor) compare to control (usual care) group. 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 about continuing, changing, or terminating the study when necessary; require 
more frequent reporting as needed; audit the study for compliance and verify the 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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Date:  September 26, 2024   
Principal Investigator: Nada Lukkahatai 
Application Number: IRB00154198 
 
 
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Version 3 Dated:   06/2007 
 
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