The Effect of Combined Aerobic and Muscle Strengthening Exercises on Structural and Functional Cardiovascular Adaptations in Endometrial Cancer Survivors
Phase: NA
Conditions: Endometrial Cancer, Cardiovascular Diseases
Sponsor: Jess S. Gorzelitz

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Title: The effect of combined aerobic and muscle strengthening exercises on structural and functional 
cardiovascular adaptations in endometrial cancer survivors. 
 
Principal Investigator: 
Jessica Gorzelitz, PhD, MS 
110 IBIF 
115 S Grand Ave 
(319) 467-0849 
jessica-gorzelitz@uiowa.edu 
Co-Investigator 
Gary Pierce, PhD, FAHA, FAPS 
520 Fieldhouse 
225 S Grand Ave 
(319) 335-9488 
gary-pierce@uiowa.edu  
Biostatistician: 
Sarah Bell, MS 
N324 CPHB 
(319) 217-0376 
sarah-mott@uiowa.edu  
Research Staff: 
Alyssa Noble, BA 
Research assistant / study coordinator 
127-D IBIF 
(563) 260-4417 
alyssa-e-noble@uiowa.edu 
 
 
 
Physician Collaborator: 
Michael Goodheart, MD 
Gynecologic Oncologist 
31508 PFP 
200 Hawkins Dr 
(319) 356-2015 
michael-goodheart@uiowa.edu 
 
IRB Number: 
2023-11-588 
Version Date: 
4/15/2025 
Version: 
1.7 
 
 
 
 
 

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STUDY SCHEMA 
 
 

3 
 
 
Revision History 
 
Version 1, Version Date 1/13/2025 
 
Protocol 
Version 
Date 
Change 
Initiated 
(Initials) 
Brief description of protocol modification/actions requested, if any 
Version 1.0 
06/05/2024 
JG 
Primary version 
Version 1.1 
07/03/2024 
JG 
Revising protocol for additional health history information, participant 
materials description 
Version 1.2 
09/27/2024 
AB 
Revising protocol to expand inclusion criteria, study population 
description 
Version 1.3 
10/11/2024 
AB 
Adding short performance physical battery measures 
Version 1.4 
11/15/2024 
AB 
Revising protocol to include recruiting participants from the Iowa Cancer 
Registry 
Version 1.5 
1/13/2025 
JG 
Removing Andrea Babcock from the protocol, has left team 
Version 1.6 
2/10/2025 
JG 
Clarifying inclusion criteria regarding treatment resistant hypertension 
and adding triglycerides as one of our blood biomarkers 
Version 1.7 
4/15/2025 
JG 
Updating sample size to n=33 to account for 10% dropout for analytic 
sample size of 30 

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Contents 
STUDY SCHEMA ........................................................................................................................................ 2 
Revision History ........................................................................................................................................... 3 
1. 
Abstract ............................................................................................................................................. 6 
2. 
Background / Rationale ..................................................................................................................... 7 
3. 
Study Objectives and Endpoints ....................................................................................................... 8 
4. 
Study Population ............................................................................................................................... 9 
5. 
Study Design and Methods ............................................................................................................. 10 
5.1 
General Design ............................................................................................................................... 10 
6. 
Study Procedures ............................................................................................................................ 10 
6.1 Study measures ................................................................................................................................... 12 
6.2 Exercise Familiarization .................................................................................................................... 16 
6.3 Exercise intervention ......................................................................................................................... 16 
7. Statistical Considerations ....................................................................................................................... 17 
1. 
Data Collection and Record Keeping .............................................................................................. 19 
8.1 Data Confidentiality ........................................................................................................................... 19 
8.2 Data Capture ..................................................................................................................................... 19 
8.2.1 Fitbit and Fitabase ......................................................................................................................... 20 
9 Study Finances ........................................................................................................................................ 21 
9.1 Subject Stipends or Payments .......................................................................................................... 21 
10. Risks and Benefits ............................................................................................................................... 21 
10.1 Direct benefits. ................................................................................................................................ 21 
10.2 Potential Benefits of the Proposed Research to Human Subjects and Others. .............................. 21 
10.3 Importance of Knowledge to be gained. ......................................................................................... 21 
10.4 Most common or frequent physical risks expected. ........................................................................ 21 
10.5 Potential long-term risks. ................................................................................................................ 21 
10.6 Minimizing risk. ............................................................................................................................... 21 
10.6.1 Risk of blood draw. ................................................................................................................ 21 
10.6.1 Risk of endothelial function test. .......................................................................................... 22 
10.6.2 Risk of psychological distress. ............................................................................................. 22 
10.6.3 Risk of musculoskeletal soreness/injury. ............................................................................ 22 
10.6.5 Risk related to study measures. ........................................................................................... 22 
11. Adverse events and stopping criteria ................................................................................................... 22 
12. Appendix .............................................................................................................................................. 23 
Appendix 1: Muscle strength Exercise tracking log (example) for week 1 of 12 weeks ......................... 23 
Appendix 2: Aerobic Exercise tracking log (example) for week 1 of 12 weeks .......................................... 24 

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Appendix 3: Physical Activity Readiness Questionnaire (PAR-Q) and You ............................................. 25 
Appendix 4: Demographic and health history questionnaire .................................................................. 26 
Appendix 5.1 Self-Efficacy for Exercise (SEE) Aerobic Scale .................................................................. 30 
Appendix 5.2 Self-Efficacy for Exercise (SEE) Muscle strengthening Scale .......................................... 31 
Appendix 6: Basic Psychological Needs in Exercise Scale (BPNES) .................................................... 32 
Appendix 7: Perceived Social Support (PSS) survey ............................................................................. 33 
Appendix 8: Exercise Regulations Questionnaire (BREQ-3) .................................................................. 34 
Appendix 9: OPEN questionnaire ........................................................................................................... 36 
Routine Adverse Event Reporting .......................................................................................................... 51 
Serious Adverse Event Reporting .......................................................................................................... 51 
 
List of Abbreviations 
 
AE 
Adverse Event 
ANOVA 
Analysis of Variance 
ASCVD 
Atherosclerotic cardiovascular disease  
CFR 
Code of Federal Regulations 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
FDA 
U.S. Food & Drug Administration 
FFT 
Functional Fitness Test 
FMD 
Flow mediated dilation  
HCCC 
Holden Comprehensive Cancer Center 
ICH 
International Conference on Harmonization 
IIT 
Investigator Initiated Trial 
IME 
Important Medical Event 
IRB 
Institutional Review Board 
OMB 
Office of Management and Budget  
OPEN 
Observing Protein and Energy Nutrition 
PI 
Principal Investigator 
PRMC 
Protocol Review and Monitoring Committee 
PWV 
Pulse wave velocity 
RPE 
Rate of Perceived Exertion 
SAE 
Serious Adverse Event 
SPPB 
Short performance physical battery 
ICR 
Iowa Cancer Registry 
 
 

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1. Abstract 
Background: Endometrial cancer survivors (ECS) are more likely to die from cardiovascular disease 
(CVD) than any other cause, and exercise is an established intervention to lower the burden of CVD. The 
development of endometrial cancer is associated with obesity, physical inactivity and cardiometabolic 
dysfunction which will often persist without significant intervention. We have an established exercise 
protocol for improving strength and aerobic fitness in ECS but the mechanism by which exercise can 
mitigate secondary and latent effects of cancer treatment, which if controlled could lower longer-term risk 
of CVD or CVD-associated mortality, is unknown. Understanding the mechanistic adaption for exercise as 
a cancer control strategy is essential as ECS have a disproportionately high burden of CVD risk factors, 
metabolic dysfunction, obesity, and effects of treatment.  
In our first year of ACS IRG funding, we successfully completed our two aims which included a qualitative 
analysis of inactive endometrial cancer patients (on treatment) to understand their perceptions, 
knowledge, and preferences for exercise. We found that this group overwhelmingly wanted tailored, 
home-based exercise programs. In our second aim, we successfully completed our aerobic, muscle 
strengthening exercise protocol in ten ECS who had large improvements in strength and aerobic fitness, 
with high exercise adherence and satisfaction with the intervention. 
Objective/Hypothesis: Our primary objective is to measure changes in biomarkers of vascular structure 
and function following our combined aerobic and muscle strengthening exercise in endometrial cancer 
survivors. We hypothesize that there will be clinically meaningful improvements in structural and 
functional vascular biomarkers, and improved composite risk scores. 
Specific Aims: Our two aims are to (1) Quantify the changes in vascular structure (pulse wave velocity) 
and function (flow mediated dilation) following a distance-based exercise program; and (2) Determine the 
magnitude of changes in ASCVD risk profiles following a distance-based exercise program. 
Study Design: A single arm, pre-post experimental study. 
Cancer Relevance: Endometrial cancer is an increasingly common diagnosis, with latent cardiometabolic 
threats to health that persist for years following treatment. Exercise in cancer survivors has the potential 
to reduce cancer burden via cardiovascular fitness, quality of life, strength, longevity, and independence. 
This study focuses on how exercise can improve vessel structure and function in endometrial cancer 
survivors, a population that has a high burden of CVD risk factors prior to treatment, and cancer treatment 
can make these risk factors worse. By understanding how exercise as a supportive therapy to improve 
the health of endometrial cancer survivors, we can reduce the longer-lasting effects of cancer in this 
population. 
 
 

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2. Background / Rationale 
Exercise guidelines for cancer survivors include both aerobic and muscle strengthening exercise 
components to maximize health, reduce the risks of chronic illness including cardiovascular disease 
(CVD), and to combat common patient reported symptoms post-treatment including anxiety, depression, 
and cancer-related fatigue1. Despite these numerous benefits, less than 10% of endometrial cancer 
survivors meet these guidelines2. Endometrial cancer survivors have a high burden of cardiometabolic 
symptoms including metabolic syndrome, diabetes, obesity, and cardiovascular dysfunction which 
threaten both quality and quantity of life2,7. Cancer treatments also directly impact physiologic function. In 
a population-based study of 2648 endometrial cancer survivors, those who received surgery and 
radiation, surgery and chemotherapy, or a combination of all three treatments had 24% (HR 1.24 CI 1.00-
1.53), 242% (HR 3.42 CI 2.24-5.21), and 92% (HR 1.92 CI 1.31-2.83) excess risk (respectively) for 
developing arterial disease within 1-5 years of cancer diagnosis7. For all risk factors, receipt of 
chemotherapy is the most significant risk factor for disease of the arteries, diseases of veins/lymphatics, 
and heart disease within five years of diagnosis7. The highest risks in endometrial cancer survivors were 
observed within the first 1-5 following treatment, but elevated risks persisted for 5-10 years following 
treatment7. In fact, the leading cause of death in endometrial cancer survivors is CVD over all causes. 
This burden of CVD dysfunction and risk factors is a growing threat to cancer control as exercise is one of 
the few well-established interventions for lowering risk of arterial dysfunction, CVD, and premature death. 
 
First year success: Our theory-based exercise approach produced behavior change and fitness 
improvements. In our first year of ACS IRG funding, we demonstrated that our remote, home-based 
exercise format, informed by the Social Cognitive Theory (SCT), was successful on targeting on key 
theoretical constructs of environment, behavioral, and cognitive factors that facilitate exercise8. Our first 
year of ACS IRG funding yielded clinically significant improvements in lower body (effect size ES=0.71) 
and upper body (ES=1.21) strength as well as aerobic endurance (ES=0.56) in endometrial cancer 
survivors. Our ten participants were highly adherent to the aerobic (89% compliant) and the muscle 
strengthening (75% compliant) exercise protocols. In this proof-of-concept design, we efficiently recruited 
ten endometrial cancer survivors who all (n=10) were retained and completed follow up testing, they also 
reported high (100%) satisfaction with intervention components. We will build on our approach to include 
cardiovascular measures as our primary outcome while also measuring exercise behavior, and changes 
in cardiovascular risk profiles.  
 
Cardiovascular and arterial dysfunction are impaired by cancer treatment, and both predict CVD 
and early mortality. In endometrial cancer survivors, cardiometabolic changes and vascular dysfunction 
often predate their cancer diagnosis7, but these conditions are exacerbated by treatment and worsen in 
the early survivorship period within five years of diagnosis7. While vascular adaptions to exercise have 
been established in other populations, to date no study has examined the vascular and cardiometabolic 
response to exercise in endometrial cancer survivors, which has been shown to be impaired following 
cancer treatment7. To examine vascular function, pulse wave velocity (PWV) will be used as a measure of 
vessel structure and stiffness; additionally, we will measure brachial artery flow mediated dilation (FMD) 
as a measure of endothelial function. We will generate atherosclerotic CVD (ASCVD) risk scores, a 
composite measure of traditional risk factors estimating 10-year risk of CVD-death3. The ASCVD risk 
score is sufficiently sensitivity to change (Duttagupta et al. 2022). 
 
OBJECTIVE. We aim to quantify changes in vascular biomarkers of CVD risk including FMD, PWV and 
ACSVD risk scores in endometrial cancer survivors following a home-based exercise program. To our 
knowledge, this would be the first investigation of these clinical biomarkers in endometrial cancer 
survivors, a population with high cardiometabolic risk factors and high burden of CVD. Our first year of 
ACS-IRG funding revealed meaningful functional strength/aerobic improvements following our 
intervention, and thus we are building on our success to target a novel subclinical endpoint to reduce 

8 
 
cancer-related morbidity and mortality. This data will directly inform a competitive R01 application using 
this clinical target to reduce cancer burden in endometrial cancer survivors.  
 
3. Study Objectives and Endpoints 
 
OBJECTIVES 
ENDPOINTS 
Primary  
 
-To evaluate changes in PWV following a 12-week 
home-based aerobic and muscle strengthening 
exercise program  
-Within participant change from pre- to post-
intervention as measured by carotid-femoral pulse 
wave velocity (PWV) 
Secondary  
 
To evaluate changes in FMD following a 12-week 
home-based aerobic and muscle strengthening 
exercise program 
-Within participant change from pre- to post-
intervention as measured by brachial artery flow 
mediated dilation (FMD) 
-To evaluate changes in the modifiable 
components of the ASCVD risk score (total 
cholesterol, HDL cholesterol, triglycerides, and 
systolic blood pressure) following the 12-week 
home-based comprehensive exercise program  
-Within participant change of total cholesterol, 
HDL cholesterol, triglycerides, and systolic blood 
pressure from pre- to post-intervention  
Exploratory 
 
-To evaluate changes in functional fitness  
-Within participant change of functional fitness 
from pre- to post-intervention as measured by the 
Functional Fitness Test 
-To estimate muscle strengthening exercise 
session adherence  
-Proportion of planned exercise sessions in which 
a participant completes at least 50% of prescribed 
exercises  
-To estimate adherence to the aerobic physical 
activity guidelines (150 minutes/week) 
-Proportion of planned weeks a participant 
accumulates 150 minutes of moderate intensity 
activity per week  
-To estimate tele-coaching adherence  
-Proportion of planned coaching sessions in which 
a participant completes 
-To estimate acceptability  
-Likert scale ratings of quality of exercise 
equipment, educational materials, health 
coaching, study feedback and distance delivery 
format 
-To estimate changes in anthropometrics  
-Within participant changes of waist and hip 
circumference, and weight from pre- to post-
intervention  
-To estimate changes in ambulatory activity levels  -Within participant change in average daily steps 
taken within a week from pre- to post-intervention 
as measured via ActiGraph accelerometer  
-To estimate changes in psychosocial behavior 
change measures  
-Within participant change of questionnaire scores 
(SEE, BPNES, PSS, BREQ-3) from pre- to post-
intervention  
-To estimate changes in diet 
-Within participant change of questionnaire score 
(Multifactor Screener in Observing Protein and 
Energy Nutrition (OPEN)) from pre- to post- 
intervention 
-To evaluate changes in the short performance 
physical battery (SPPB)   
-Within participant change from pre- to post-
intervention as measured by the SPPB 

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4. Study Population 
This is a single arm project with no control group. We will recruit from the gynecologic oncology clinic at 
the University of Iowa Holden Comprehensive Cancer Center. In collaboration with the gynecologic 
oncologists including Dr. Michael Goodheart, we will recruit patients who meet our inclusion criteria 
(outlined below) and who do not meet our exclusion criteria (listed below). Alyssa Noble will be the 
primary research coordinator recruiting participants in clinic for this study. As we intend to study adults, 
participants include subjects of at least 18 years of age or older, who are medically able to safely 
participate in adopting a new exercise regimen. 
 
In addition, we will recruit individuals from the Iowa Cancer Registry based on date of diagnosis, 
histology, cancer stage, and sex. Researchers from the ICR will send out recruitment letters for 
individuals to release their contact information. The mailing will provide a brief explanation of the study as 
well as the how and why their contact information would be shared if they consent to release their 
information. Information from individuals who provide their consent to release will be shared with our 
study team via secured platforms to contact for eligibility and screening. These individuals will be 
contacted via telephone to be given a more detailed explanation of the study following a standardized 
script to be further screened for meeting our inclusion criteria. Alyssa Noble will be the primary research 
coordinator screening and recruiting patients via telephone for this study.  
 
4.1 Inclusion criteria 
Inclusion Criteria 
1 
Willing and able (cognitively and intellectually) to provide written informed consent 
2 
Willing to comply with all study procedures and be available for the duration of the study 
3 
Fluent in spoken and written English 
4 
Women ≥18 years of age 
5 
Documented diagnosis of Type I, stage I-IIIc endometrial cancer within the past 5 years 
6 
Completion of current cytotoxic treatment for endometrial cancer 
7 
Technology access (phone call access, broadband internet, Wi-Fi) for tele coaching 
8 
Comfort and willingness to use technology (videoconferencing) throughout the study for 
coaching 
9 
Pass the Physical Activity Readiness Questionnaire (PAR-Q) 
10 
Medical clearances given by their primary provider / oncologist (if indicated by the PAR-
Q) 
 
4.2 Exclusion criteria  
Exclusion Criteria 
1 
Absolute contraindications to exercise (i.e., acute myocardial infarction, severe 
orthopedic or musculoskeletal limitations) 
2 
History of previous myocardial infarction, ischemia, or hemorrhagic stroke 
3 
Medically documented history of heart disease including heart valve disease, coronary 
artery disease, heart failure, peripheral artery disease, aortic disease, pericardial disease, 
cerebrovascular disease, or deep vein thrombosis 
4 
Medical documentation of treatment-resistant hypertension OR taking 3 or more anti-
hypertensives with persistent hypertension 
5 
Medically documented history of cardiovascular disease including (but not limited to): 
bypass surgery, stent procedures, bypass grafts, or coronary angioplasty 

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6 
Medically documented or self-reported type 1 diabetes (insulin-dependents) 
7 
Prescriptions for or use of semaglutide (GLP-1 agonists) including name brands: 
Ozempic, Wegovy or Mounjaro 
8         Current or recent (within last 3 months) use of hormone replacement therapy (HRT) 
9 
Evidence of recurrent or metastatic disease 
10 
Currently performing resistance training ≥2 days per week 
11 
Currently exceeding 150 minutes of at least moderate intensity exercise per week 
12 
Report of chest pain, shortness of breath, fainting, or angina pectoris 
13       Self-reported history of falling, fall risk 
14 
Have physical disability that would limit range of motion through exercises such as 
sitting, standing and inability to walk one block 
15 
Plans to move from the area 
16 
Enrolled in another clinical trial or has used of any investigational drugs, biologics, or 
devices within 30 days prior to study enrollment 
17       Self-reported tobacco use in last 7 days, current smoking, current tobacco use 
including e-cigarettes and vaping devices 
18 
Not suitable for study participation due to other reasons at the discretion of the 
investigator 
 
 
5. Study Design and Methods 
5.1 General Design 
• A single arm exercise study  
• The intervention itself is 12 weeks of exercise, with one week of accelerometer wear prior to 
exercise with an additional week to schedule post-study visit procedures, yielding a total 
intervention length of 14 weeks. 
• The exercise intervention will consist of (a) in-person pre-intervention study measures; (b) 
instructional materials (e.g. detailed exercise manual) and exercise training equipment (e.g. 
resistance bands, adjustable pair of dumbbells, Fitbit Charge 5); (c) a virtually delivered 
instructional session; (d) access to informational web materials; (e) support and feedback provided 
via virtual health coaching sessions; and (f) in-person post-intervention study measures. 
Participants will also receive access to a study specific website (strivecardio-study.lab.uiowa.edu) 
that will include online versions of resources including video demonstrations, device support, 
exercise recommendations and study components.  
• Health coaching sessions will be delivered virtually and consist of (a) an initial health coaching 
session during week one discussing the participant’s visions for health and wellness and overall 
goals of completing the intervention exercises; (b) sessions delivered once per week through week 
four discussing progress, barriers, facilitators, self-efficacy, and motivations for exercise goals to 
facilitate exercise adoption; (c) a midpoint check-in including a non-bias report from their health 
coach describing their progress thus far in the intervention. Participants then have the personal 
option to continue meeting with their health coach on a weekly basis or taper their health coaching 
sessions to include only weeks eight and eleven; (d) a final in person health coaching session to 
conclude. 
 
6. Study Procedures 
All participants will be asked to meet with the research team in-person at the University of Iowa Physical 
Activity and Cancer Survivorship (PACS) Lab in room 127 Iowa Bioscience Innovation Facility (IBIF) in a 
fasted state. Participants will be asked to bring a snack/food that can be refrigerated/stored in the lab after 
physiologic procedures. During the in-person visit in the PACS lab, participants will complete informed 

11 
 
consent from the study coordinator. After which, they will be escorted to the University of Iowa Clinical 
Research Unit (CRU) located in General Hospital 2 Boyd Tower at the University of Iowa Health Care 
main campus. While at the CRU participants will undergo described cardiovascular measurements by a 
trained technician before being escorted to the PACS Lab to break their fast to consume their snack/food, 
and then complete remaining described study protocols, and baseline assessments. They will also 
receive an ActiGraph accelerometer to wear for a seven-day wear protocol and then charge the device at 
home. They will also receive a Fitbit device and will receive instruction on how to use. Each participant 
will be asked to repeat the wear protocol week 12 of the study. These specific measures are described 
below. After completion of study baseline measures, participants will undergo an instructional session to 
the exercise program described below in section 6.2. 
 
 

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Calendar/Schedule of events 
Measure 
Baseline 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Week 6 
Week 7 
Week 8 
Week 9 
Week 10 
Week 11 
Week 12 
Final 
Visit 
Informed 
Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Carotid-femoral pulse 
wave velocity 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Brachial artery flow 
mediated dilation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Blood draw 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Demographics / health 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Self-efficacy for 
exercise surveys (2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Psychosocial behavior 
change questionnaires  
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
OPEN questionnaire 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Anthropometrics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Functional fitness  
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
SPPB 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Device orientation 
(Fitbit/telecoaching) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ActiGraph 
accelerometer  
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Exercise instructional 
session 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Telehealth meetings: 
Weekly option  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Telehealth meetings: 
Tapered option 
X 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
Adverse event 
assessment  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adherence  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Acceptance/satisfaction 
survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
6.1 Study measures  
Below are the study measures that will be collected over the study period:  
 
Anthropometrics and resting cardiovascular measures: Height, weight, waist and hip circumferences 
will be measured using standard protocols by a research team member in the CRU. Resting heart rate 

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and blood pressure will be measured by a trained technician in the CRU using standard protocols. When 
collected: Baseline, final visit (~12 weeks) 
 
Blood based biomarkers: Participants will have blood drawn by trained clinicians within the Clinical 
Research Unit (CRU) including total cholesterol, high-density lipoprotein, low-density lipoprotein, glucose, 
triglycerides, and insulin. Vitals: Participants will have their heart rate and blood pressure measured.  
When collected: Baseline, follow-up (~ 12 weeks).  
 
FMD. Endothelial function will be tested via a non-invasive procedure in the Vascular Physiology 
Assessment core lab at the CRU. This is a commonly used non-invasive assessment of vascular 
endothelial function and biomarker of cardiovascular disease risk. The test is performed by a trained 
researcher using a high-resolution ultrasound machine (Logiq e9, GE Healthcare) to obtain 
measures of the brachial artery diameter and blood flow at rest. The forearm is then occluded with a 
supra-systolic blood pressure cuff placed on the forearm for five minutes followed by immediate 
release. The artery diameter and blood flow are imaged again immediately after the sudden release 
of the cuff for 2 minutes to capture the vasodilation that occurs. The percentage dilation of the 
brachial artery (8-10% in normal, healthy adults) is measured off-line with image detection software 
(Vascular Analysis Tools, Medical Imaging Applications, LLC) and the magnitude of increase in 
blood flow (called reactive hyperemia) are recorded and increase the blood flow velocity or shear 
rate (=blood flow velocity/diameter) are used to quantify the “shear” stimulus for dilation.  
 
Aortic stiffness. After a minimum of 5 minutes rest, three BPs are taken using the NIHem Workstation 
(Cardiovascular Engineering, Inc) two minutes apart. The research participant will be instrumented with a 
small finger cuff that will continuously record blood pressure in the finger. Carotid-femoral artery PWV, the 
‘gold standard’ in vivo assessment of aortic stiffness in humans, will be assessed by applanation 
tonometry using the Sphygmocor pulse wave analysis system (AtCor Medical, Inc.) as previously 
described24. After 10 minutes of supine rest, carotid, brachial, and femoral artery pulse waveforms will be 
recorded non-invasively by sequentially recording of carotid, brachial, and femoral artery pulse waveforms 
with a hand-held transducer for 20 seconds. Pressure waveforms are gated to the 13 lead ECG R wave in 
order to calculate the transit time (t) between the foot of the carotid and the femoral waveforms. The 
carotid-femoral and carotid-brachial transit distance (CFTD) is estimated between the 2 anatomical sites 
as the difference between the suprasternal notch (SSN) to carotid (SSN-C) and femoral (SSN-F) sites. 
Thus, the CFTD=(SSN-F)-(SSN-C) and PWV calculated as CFTD/t. This approach accounts for parallel 
transmission of the pulse wave up the brachiocephalic and carotid arteries, and simultaneously along the 
aortic arch using the SSN as a fiducial point where parallel transmission begins (e.g., bifurcation site of 
aortic arch/brachiocephalic artery). 
 
Carotid artery compliance/stiffness will be determined noninvasively by high-resolution 
ultrasonography (Logiq 7, GE Healthcare) of the right common carotid artery and contralateral 
assessment of carotid artery blood pressure via non-invasive carotid artery applanation tonometry, 
respectively. Carotid artery diameters are measured ~2 cm proximal to the carotid bulb with the 
transducer placed at a 90° angle to the vessel by off-line analysis of DICOM images with image analysis 
software (Medical Imaging Applications, LLC). Maximal diameters (i.e., systolic expansion) and minimal 
diameters (e.g., diastolic relaxation) are measured in sync with carotid artery blood pressure waveforms. 
Carotid blood pressure waveforms are calibrated using diastolic and mean brachial artery blood pressure 
obtained from standard brachial artery cuff blood pressure.25 
Accelerometer. Although participants will have a Fitbit for self-monitoring, we will use a research 
grade device to determine ambulatory activity levels at the beginning and end of the study. At the 
baseline visit, participants will be asked to wear the ActiGraph wGT3X-BT accelerometer 
(ActiGraph, Pensacola, FL) for 7 days during all waking hours. They will then be asked to keep the 

14 
 
device at home, charge it, and then will repeat this wear protocol on week 12 of the study. 
Participants will be instructed to notify (via call or email) the research staff once the baseline 
ActiGraph wear has been completed. ActiGraph is a gold standard method of objective activity 
assessment.
26, 27 In advance of the final week of the protocol participants will be asked to re-wear 
the ActiGraph device and bring the device and associated wear logs back to the final study visit. 
When collected: Baseline pre-intervention, last week of the intervention (~12 weeks) 
Demographics and health history. At baseline, participants will be asked about sociodemographic 
factors, self-reported health history, cancer history will be abstracted from their medical records. In 
order to corroborate medical information for those coming from the Iowa Cancer Registry, we will be 
requesting relevant medical records from the participant’s local oncologist or medical provider. The 
request will be sent in HIPPA compliant manner using a fax machine only accessible by the 
Principal Investigator. These questions will be collected from/stored on our secure REDCap 
database. When collected: Baseline 
Self-efficacy for exercise surveys. At baseline and at follow-up, participants will be asked to 
complete two versions of the self-efficacy for exercise (SEE) scale. This 9-item survey will ask about 
self-efficacy (or confidence) related to aerobic exercise and then about muscle strengthening 
exercise. We will administer these two surveys at baseline and then at the end of the study as 
modality-specific measures of self-efficacy. When collected: Baseline, final visit (~14 weeks) 
Autonomy, competence, and relatedness towards exercise survey. At baseline and follow-up, 
participants will be asked to complete the Basic Psychological Needs in Exercise Scale (BPNES). 
This 11-item survey will ask about feelings of autonomy, competence, and relatedness towards 
exercise in general as opposed to a specific situation. We will administer this survey at baseline and 
again at the end of the study as a measure of psychosocial needs with exercise. When collected: 
Baseline, final visit (~14 weeks) 
Perceived social support survey. At baseline and follow-up, participants will be asked to complete 
the Multidimensional Scale of Perceived Social Support (PSS) survey. This is a 12-item survey 
identifies the source of social support identified by participants. Particularly from friends, family, or a 
significant other. We will administer this survey at baseline and again at the end of the study as a 
measure of social support. When collected: Baseline, final visit (~14 weeks).  
Exercise regulations questionnaire. At baseline and follow-up, participants will be asked to complete 
the Exercise Regulations Questionnaire (BREQ-3). This 24-item survey will address the participant’s 
underlying reasons for engaging or not engaging in exercise. We will administer this survey at 
baseline and again at the end of the study as a measure of motivation for exercise. When 
collected: Baseline, final visit (~14 weeks).  
Multifactor Screener questionnaire. At baseline and follow-up, participants will be asked to complete 
the Multifactor Screener in Observing Protein and Energy Nutrition questionnaire. This 16-item 
survey will approximate intakes of fruits and vegetables, percentage energy from fat, and fiber. The 
screener asks participants to report how frequently they consume foods in 16 categories. We will 
administer this survey at baseline and again at the end of the study as a measure of fruit and 
vegetable intake, percent of calories from fat, and fiber. When collected: Baseline, final visit (~14 
weeks). 
Functional fitness. The functional fitness test (FFT) is a battery of seven tests measuring strength, 
flexibility, fitness, body composition, and agility. It has high test-retest reliability and is suitable for 
tracking within-person changes.31 The functional fitness test battery includes the following 6 
assessments: 1.) The 30 second chair stand, which assesses the strength of the lower body. Each 
person will have 30 seconds to stand up and sit down from a chair as many times as possible within 
the time frame. 2.) The 30 second arm curl assesses the strength of the upper body, where 

15 
 
women will hold a 5-pound dumbbell in a seated position, and they will have 30 seconds to curl their 
arm and extend it as many times as possible within the time frame. 3.) The 6-minute walk test 
measures the total distance that a person can quickly walk on a flat hard surface within a period of 6 
minutes, using a 100ft length of distance. 4.) The chair sit and reach assesses lower body 
flexibility where the participant will sit in a chair, extend one leg in front of them and flex at the waist, 
reaching toward their toes, and we will measure the distance between their toes and fingers. 5.) The 
8-foot-up and go is an assessment of speed agility and balance. With this assessment, the 
participant begins in a seated position, and will be timed for the duration it takes to rise from the 
chair, walk as quickly as possible around a cone 8 feet away from the chair, and return to a seated 
position. 6.) The back scratch test is an assessment of the flexibility of the upper body, where the 
person will be seated and one arm will be flexed behind the head, and the other arm will be 
extended behind the shoulder. The assessment measures the distance between the fingertips of 
both hands. 7.) The handgrip dynamometer test is an assessment of grip strength. In a seated 
position, participants will be handed the dynamometer and instructed to squeeze the handle as hard 
as possible to generate maximum force at the grip, while maintaining the elbow at a flexed 90 
degree angle. The participant will receive three alternating tries with each hand. When collected: 
Baseline, final visit (~14 weeks) 
SPPB. The short performance physical battery (SPPB) is a series of functional mobility 
assessments which measure balance, lower extremity strength, and fitness. Developed by the 
National Institute of Aging, the SPPB has clinically useful implications of predicting physical decline 
in older adults35. The full battery utilizes standardized scoring, for a minimum of 0 points, to a 
maximum of 12 points, and includes the following three subscales: 1.) Balance. Each participant will 
stand for 10 seconds with their feet together, 10 seconds with their feet placed semi-tandem, and a 
final 10 seconds with their feet fully tandem. Participants receive a score from 0-4, based on their 
ability to attempt each position. 2.) Repeated chair stand, measuring lower extremity strength. 
Participants will stand up and sit down five times as quickly as they can. Participants receive a score 
of 0-4, based on total duration it takes to complete five total repetitions. 3.) Gait speed. Each 
participant will walk to a line placed on the floor three meters away at their typical walking pace. 
Participants receive a score from 0-4, based on total duration of walking this distance. When 
collected: Baseline, final visit (~14 weeks).  
Exercise adherence. Adherence to intervention exercises will be measured via detailed exercise 
logs. A participant needs to complete at least 50% of the prescribed exercises in a session to be 
considered adherent to the session. When collected: ongoing, logs will be completed throughout 
the intervention and submitted at the final visit. Additionally, we will be monitoring participant’s Fitbit 
data via Fitabase over the course of the study to monitor total physical activity and minutes of 
strength training logged. 
Health coaching adherence. Adherence to health coaching will be monitored by the health coach on 
a weekly basis. A health coaching will be considered complete if the participant attends and 
participates in the health coaching session. Health coaches will also record the modality in which 
the session was completed, as well as the duration of completed sessions in minutes. When 
collected: ongoing, health coaches will record in REDCap whether a health coaching session was 
completed or not following each scheduled session.  
Acceptability. Participants will receive a satisfaction survey at the end of the study that will ask them 
to report on the relative satisfaction and importance of key intervention components. This 
questionnaire will include Likert scales rating core components of the intervention including the 
quality of the exercise equipment, educational materials, health coaching, study feedback, and 
distance-delivery format. When collected: Final visit (~12 weeks) 

16 
 
Adverse Event Assessment. The NCI Common Terminology Criteria for Adverse Events (CTCAE) 
v5.0 will be used to grade adverse events. Subjects enrolled in this study will be evaluated for 
adverse events, serious adverse events, and adverse events requiring interruptions, modifications 
of discontinuation of the intervention. When collected:  Baseline, and weekly (Weeks 1-12) 
 
6.2 Exercise Familiarization 
During the baseline visit, the study team will help the participant set up and activate their Fitbit device and 
account. They will also be oriented towards the basic functions of the Fitbit, demonstrating how to track 
one’s steps and sync with their phone app. During the first week of participant accelerometer wear, 
following completion of informed consent and described baseline measures, participants will be given an 
exercise orientation and instructional visit virtually instructed by their designated health coach. The 
purpose of this session is for the participants to learn the exercise components of the intervention and 
understand how to safely use the equipment provided to them during their baseline visit. The instructional 
visit includes going through each exercise of the intervention (see Table below) to learn the movement, 
learn the muscle groups involved, and to learn how to monitor themselves by tracking their progress via 
logs. Each participant will receive a recommended starting point for each exercise with respect to intensity 
and progressions/regressions. For example, a participant may be starting on a blue resistance band for 
biceps curls, but the squats may simply be body weight at this time. Table 2 outlines the exercises for the 
intervention.  
 
6.3 Exercise intervention 
During the study period, participants will be instructed to complete the muscle strengthening exercise 
routine twice a week for 12 weeks during the intervention, and to monitor one’s total steps and active 
minutes. Personalized aerobic activity goals will be set and monitored via health coaches on the research 
study team. Participants will be assigned a study coordinator/health coach who will work with each 
participant over the course of the intervention. Study coordinators/health coaches will schedule weekly 
telehealth meetings with the participants for the first five weeks of the intervention, following the fifth week 
participants will be given the choice to continue meeting with their study coordinator/health coach weekly 
or transition to a tapered telehealth session schedule where they will meet with their study 
coordinator/health coach again during week 8 and week 11. At these health coaching sessions, a semi-
standardized template will be used. Study coordinators will check in to determine study progress, help set 
and monitor exercise goals, systematically evaluate for adverse events, and will work to build rapport and 
support the participants on their exercise adoption and maintenance journey. Study coordinators/health 
coaches will also be instructed to assess for volume/intensity/difficulty of each of the exercises. These 

17 
 
sessions are done over video so that the coordinator can build rapport with participants, and that 
participants can show or demonstrate issues with exercises or their form. Participants will have access to 
a study-specific website with resources related to exercise prescription and exercise components 
(strivecardio-study.lab.uiowa.edu).  
 
 
7. Statistical Considerations 
 
7.1 Statistical Methods  
 
The primary objective of this pilot study is to obtain preliminary evidence of changes in PWV with the 
comprehensive exercise program. A 1 m/sec decrease in PWV from pre- to post-intervention reflects 
a clinically relevant change as this has previously been shown to be associated with a 15% risk 
reduction in CVD events. In statistical terms, we are testing the null hypothesis H0: ∆Post-Pre = 0 versus 
the alternative hypothesis H1: ∆Post-Pre ≠ 0. Using a repeated measures design with 1 within subject 
factor (time: pre- and post-intervention), the design achieves 93% power to test for a time effect 
among 30 participants. We will recruit 33 participants to account for a potential 10% dropout rate to 
accommodate a final analytic sample size of 30. Power calculations are based on the following 
assumptions: standard deviation of 1.4, using an F test, 5% significance level, an autocorrelation of 
0.5, and 15% drop out.  
 
7.2 Statistical Analysis 
 
7.2.1 General Approach 
 
Continuous variables will be summarized using descriptive statistics such as mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be summarized by count and 
proportion. 
 
7.2.2 Analysis of Primary Endpoint(s) 
PWV 
The within patient change in PWV will be assessed from pre- to post-intervention. Mixed effects 
regression models will be used to estimate changes in PWV. Random effects will be included to 
account for the longitudinally correlated nature of repeat measurements within a patient. Estimated 
mean changes and associated 95% confidence intervals will be reported. 
 
7.2.3 Analysis of Secondary and Exploratory Endpoint(s) 
FMD 
The within patient change in FMD will be assessed from pre- to post-intervention. Mixed effects 
regression models will be used to estimate changes in FMD. Random effects will be included to 
account for the longitudinally correlated nature of repeat measurements within a patient. Estimated 
mean changes and associated 95% confidence intervals will be reported. 
 
ASCVD Risk 
The within patient change in the modifiable components of the ASCVD Risk score (total cholesterol, 
HDL cholesterol, and systolic blood pressure) will be assessed from pre- to post-intervention. Mixed 
effects regression models will be used to estimate changes in total cholesterol, HDL cholesterol, and 

18 
 
systolic blood pressure. Random effects will be included to account for the longitudinally correlated 
nature of repeat measurements within a patient. Estimated mean changes and associated 95% 
confidence intervals will be reported. 
 
Functional Fitness 
Mixed effects regression models will be used to estimate changes in each of the 6 tests included in 
the Functional Fitness Test from pre- to post-intervention. Random effects will be included to 
account for the longitudinally correlated nature of repeat measurements within a patient. Estimated 
mean changes and associated 95% confidence intervals will be reported.  
 
Muscle Strengthening Exercise Session Adherence 
Exercise session adherence will be defined as the proportion of planned exercise sessions in which 
a participant completes at least 50% of the prescribed exercises. The mean and associated 95% 
confidence interval will be reported.  
 
Aerobic Physical Activity Adherence 
Aerobic physical activity adherence will be defined as the proportion of planned weeks a participant 
accumulates 150 minutes of moderate intensity activity. The mean and associated 95% confidence 
interval will be reported.  
 
Tele-Coaching Adherence 
Tele-coaching adherence will be defined as the proportion of planned exercise sessions in which a 
participant completes. The mean and associated 95% confidence interval will be reported.  
 
Acceptability 
Acceptability will be assessed using Likert scale ratings of quality of exercise equipment, 
educational materials, health coaching, study feedback and distance-delivery format. Means and 
associated 95% confidence intervals will be reported for each item.  
 
Anthropometrics 
The within patient change of weight, waist and hip circumferences will be assessed from pre- to 
post-intervention. Mixed effects regression models will be used to estimate changes in 
anthropometrics. Random effects will be included to account for the longitudinally correlated nature 
of repeat measurements within a patient. Estimated mean changes and associated 95% confidence 
intervals will be reported. 
 
Ambulatory Activity Levels 
The within patient change in average daily steps taken within a week will be assessed from pre- to 
post-intervention. Mixed effects regression models will be used to estimate changes in ambulatory 
activity levels. Random effects will be included to account for the longitudinally correlated nature of 
repeat measurements within a patient. Estimated mean and associated 95% confidence interval will 
be reported. 
 
Psychosocial Behavior Change 

19 
 
The within patient change in psychosocial behavior will be assessed from pre- to post-intervention. 
The SEE, BPNES, PSS, and BREQ-3 self-report questionnaires will be used to assess psychosocial 
behaviors. Mixed effects regression models will be used to estimate changes in questionnaire 
scores. Random effects will be included to account for the longitudinally correlated nature of repeat 
measurements within a patient. Estimated mean and associated 95% confidence interval will be 
reported.  
 
SPPB 
Mixed effects regression models will be used to estimate changes in each of the three tests included 
in the SBBP from pre- to post-intervention. We will follow standardized SPPB scoring for each of the 
three tests, with each individual test score ranging from 0-4. A total sum score for the entire battery 
of 0-12 will also be measured. Random effects will be included to account for the longitudinally 
correlated nature of repeat measurements within a patient. Estimated mean changes and 
associated 95% confidence intervals will be reported.  
 
OPEN questionnaire diet change 
The within patient change in dietary composition will be assessed from pre- to post-intervention. The 
OPEN questionnaire will be used to assess changes in fruits, vegetables, percent energy from fat, 
and fiber. Random effects will be included to account for the longitudinally correlated nature of 
repeat measurements within a patient. Estimated mean and associated 95% confidence interval will 
be reported. 
 
7.2.4 Safety Analyses 
 
The incidence of treatment-emergent adverse events will be summarized by system organ class 
and/or preferred term, type of adverse event, severity (based on NCI CTCAE v5.0 grades), and 
relation to study treatment. The most severe grade per patient will be reported. 
 
7.2.5 Planned Interim Analyses 
 
There are no planned interim analyses.  
 
 
1. Data Collection and Record Keeping  
8.1 Data Confidentiality 
We will take extensive measures to ensure data safety and security. A dedicated study database 
will be constructed on a secure server using the Oncore study management system.  
 
8.2 Data Capture 
To ensure the integrity of the data collected from study participants, several procedures will be 
implemented. All personnel involved in data collection will be thoroughly trained in all assessment 
methods, thus ensuring consistent applications of procedures and measurement consistency across 
participants. All data will be saved to a computer hard drive-in real time and then stored on a secure 
server (i.e., password protected) which is backed up daily. All raw data will be kept electronically within 
REDCap on a server maintained by the Holden Comprehensive Cancer Center. Informed consent 
forms will be kept in hard copy format in a locked file cabinet with restricted access. Issues related to 

20 
 
data integrity will be discussed on a weekly basis as a recurring agenda item in the weekly project 
meeting. Finally, continuing review of all procedures will be obtained by all appropriate institutional 
review boards. 
 
Study data will be labeled with a study ID number. Data linking the study ID numbers with subject identities 
will be stored in hard copy format only. This and other paper files will be kept in a locked file cabinet in 
the Physical Activity and Cancer Survivorship (PACS) Lab (Room 127 Iowa Bioscience Innovation 
Facility (IBIF), 115 S Grand Ave, Iowa City, IA 52245). Only study personnel will have access to 
participant data if necessary for research duties. Electronic data, including accelerometer data files, will 
be kept on a server maintained by the Holden Cancer Center, in a drive accessible only by the PI and 
study staff. Data will be retained for an indefinite amount of time, and all study data will be banked in a 
coded format. Data may be used in the future for a secondary data analysis looking at relationships 
between collected study data and other variables. Study data may only be used by the study team, and 
all future investigations using any data from this study must undergo a separate IRB application. Use of 
study data is limited to the research team for this protocol unless a separate IRB application is 
submitted for use of this banked data for future investigations.  
 
8.2.1 Fitbit and Fitabase  
Fitbit Charge 5 will be provided to all participants in the study. The Charge 5 is not intended to be used as 
a medical device. All participants will have the ability to monitor physical activity, sleep, and heart rate 
with the Fitbit Charge 5. All data from the Fitbit Charge 5 will be continuously streamed to the Fitbit 
servers, and then pulled into the Fitabase data aggregator.  
 
We have applied several data use limitations to respect the privacy and autonomy of research subject’s 
data, including minimizing collection and use of personal data, meaning data that directly identifies an 
individual, or that could reasonably be linked to an individual by an anticipated data recipient. Participants 
will create their Fitbit accounts using coded, de-identified information with all fields that could directly 
identify them removed. After study completion, we will permanently delete these accounts but allow 
individuals to create their own personal Fitbit accounts that are not linked to us or the study in any way.  
 
We do not use or share with third parties any personal data for new research studies, or for any purpose 
different from the original study purposes. 
We will implement mandatory training for researchers on applicable privacy standards, and data 
protection impact assessments as appropriate or required by law. 
We will never use personal data in a way that is likely to cause damage or distress to research subjects. 
We will never sell the personal data of research subjects. We will never use it for advertising, marketing, 
re-identification, adverse decisions about employment or insurance, or any data mining or analysis for 
purposes other than necessary for research purposes. 
We also plan to use best practices for de-identification include: 
• Providing summary-level aggregate data rather than individual-level de-identified data. 
• We also will give research participants control over their personal data. Research participants 
must have the ability to withdraw at any time from the research study, which should include an 
option to delete their personal data or, at a minimum, remove it from future research studies. 
• We will maintain data security by using technical, administrative, and physical controls that are 
appropriate to the sensitivity of the data, meet or exceed industry standards, and are 
reasonably designed to protect against unauthorized access, use, or disclosure of the data. 
The following strategies will be deployed: data encryption, access controls, logging, auditing, 
confidentiality requirements, data use policies (including incident response and breach 
notification plans, as applicable), and training. 
 

21 
 
 
9 Study Finances 
This work was supported by Grant IRG-21-141-46-IRG from the American Cancer Society, administered 
through the Holden Comprehensive Cancer Center at The University of Iowa (PI: Gorzelitz).  
 
9.1 Subject Stipends or Payments 
Participants will be paid $50 in cash at the baseline visit as well as another $50 cash at the final (post- 
intervention) visit. Those who complete the intervention will receive a total of $100 cash, in addition to 
keeping their exercise equipment of the resistance bands and dumbbells. All participants will also be 
allowed to keep the Fitbit used during the study. 
 
10. Risks and Benefits 
10.1 Direct benefits.  
There are no direct benefits to individuals expected because of participating in this trial. 
 
10.2 Potential Benefits of the Proposed Research to Human Subjects and Others.  
Findings from the proposed study will contribute to the scientific knowledge of the feasibility of home-
based exercise interventions in endometrial cancer survivors. Additionally, the knowledge gained will 
contribute to the scientific knowledge aimed at understanding the potential therapeutic benefits of 
resistance training exercise for endometrial cancer survivors. The risks of our study procedures are low 
and therefore are seen as justifiable regarding the knowledge to be gained. 
 
10.3 Importance of Knowledge to be gained. 
 Increasing physical activity after a cancer diagnosis is an important area of researching and finding 
feasible interventions for endometrial cancer survivors are key to sustainable lifestyle changes. This 
research will evaluate the changes in cardiometabolic risk in this population following our exercise 
intervention, and take the first step that will provide valuable information and serve as a scaffolding for the 
continued design and development of future interventions. 
 
10.4 Most common or frequent physical risks expected.  
Potential risks of participating in this study include pain or bruising from blood draw, pain from endothelial 
function test, acute injury, musculoskeletal soreness. Risks/discomfort of the physical testing at 
baseline/follow up include acute injury, musculoskeletal soreness from some of the assessments. We 
have minimized these risks as much as possible, described below.  
 
10.5 Potential long-term risks.  
There are currently no known rare, serious risks related to exercise that are not listed above. Participants 
could suffer an acute musculoskeletal injury because of exercise, but individuals can recover from those 
events, although they are not good events. 
 
10.6 Minimizing risk.  
The aforementioned risks will be minimized in the following ways: 
 
10.6.1 Risk of blood draw.   
Potential risks associated with obtaining blood samples are minimal but include slight bruising, pain, a 
temporary feeling of faintness, and/or a small risk of infection. All blood draws will be performed by a 
research nurse at the CRU,  trained in drawing blood. Only appropriate trained laboratory personnel 
perform the blood draw procedure. A sterile gauze pad and pressure wrap (latex free coban) are applied 
to the site after the blood draw to stop any bleeding and minimize bruising.  
 

22 
 
10.6.1 Risk of endothelial function test. 
Common side effects include following the blood pressure cuff filling may cause a moderate intensity pain 
“pins and needles” or numbing sensation that goes away as soon as the cuff is deflated. We have 
minimized this risk as the procedure itself is noninvasive and should result in only little discomfort.  
 
10.6.2 Risk of psychological distress. 
This study poses low risk of psychological stress. Emotional or psychological distress will be minimized by 
having adequate recruitment criteria, in addition to having adequate informed consent to detail what 
participation includes. All the study questionnaires we are using are validated and appropriate measures, 
which do not ask about sensitive or stigmatizing topics. Finally, we will use adequate privacy and 
confidentiality measures. 
 
10.6.3 Risk of musculoskeletal soreness/injury. 
To avoid unsafe exercise in those who are not able to exercise, we will exclude individuals who report 
difficulty transitioning from sitting to standing, walking 1 block (as a proxy measure of basic physical 
functioning). Additionally, all participants must pass the validated Physical Activity Readiness 
Questionnaire (PAR-Q) prior to enrollment. Participants will be in regular contact with the study 
coordinator throughout the study. If any muscular or skeletal discomfort or soreness should develop, the 
study coordinator will reduce the intervention targets accordingly to resolve the discomfort. The 
prescription of resistance exercise is consistent with guidelines for cancer survivors on what is 
appropriate prescribed exercise including non-maximal intensity (both from the American Cancer Society 
and the American Council of Sports Medicine). Participants in the study will be given training on how to 
conduct the exercises, additionally they will have study staff to call in case of questions, additionally 
having access to resource videos and video-calls with staff. The use of safe and proper form will be 
stressed at all interactions to increase efficacy of exercises and reduce the risk of injury. Participants will 
also be instructed to exercise on non-consecutive days to allow the body to recover. While risk of injury or 
soreness can never be fully prevented, these steps will maximize the risk reduction. 
 
10.6.4 Risk of loss of confidentiality.  
We will take extensive measures to ensure the safety and security of participant data. OnCore data 
recording will be completed as required. All study staff will complete IRB/HIPAA training prior to having 
contact with participants or with study data. Paper files (i.e. informed consent documents) will be kept in a 
locked file cabinet in the PI’s lab in the Fieldhouse (115 S Grand Ave, Iowa City IA 52240). The office 
door is kept always locked.  
 
10.6.5 Risk related to study measures. 
The Functional Fitness Test (FFT) and Short Performance Physical Battery (SPPB) are standardized 
protocols for older adults, and certain criterion are in place to minimize risks including only conducting the 
tests on those with non-hypertensive resting blood pressures, only conducting on those who are low fall 
risk, and using safeguards such as cuing breathing during the 30 second chair stand test and 30 second 
arm curl. For the six-minute walk test and three meter gait speed assessment, participants will walk along 
a hallway with a handrail to reduce risk of falling. 
 
11. Adverse events and stopping criteria 
 
Discontinuation of the exercise protocol is based on the discretion of the PI. 
 
Any individual may self-discontinue the exercise program at any time. There are currently no prespecified 
stopping rules for the exercise program. 
 
 

23 
 
12. Appendix  
Appendix 1: Muscle strength Exercise tracking log (example) for week 1 of 12 weeks 
 
 
 
 

24 
 
 
Appendix 2: Aerobic Exercise tracking log (example) for week 1 of 12 weeks 
 
 
 
 
 

25 
 
Check YES or 
Appendix 3: Physical Activity Readiness Questionnaire (PAR-Q) and You 
Regular physical activity is fun and healthy, and increasingly more people are starting to 
become more active every day. Being more active is very safe for most people. However, some 
people should check with their doctor before they start becoming much more physically active. 
If you are planning to become much more physically active than you are now, start by answering 
the seven questions in the box below.  
Common sense is your best guide when you answer these questions. Please read the questions 
carefully and answer each one honestly: 
 
YES 
□ 
NO 
□ 
 
1. 
Has your doctor ever said that you have a heart condition and that you should only do 
□ 
□ 
physical activity recommended by a doctor? 
2. 
Do you feel pain in your chest when you do physical activity? 
□ 
□ 
3. 
In the past month, have you had chest pain when you were not doing physical activity? 
□ 
□ 
4. 
Do you lose your balance because of dizziness or do you ever lose consciousness? 
□ 
□ 
5. 
Do you have a bone or joint problem that could be made worse by a change in your 
□ 
□ 
physical activity? 
6. 
Is your doctor currently prescribing drugs (for example, water pills) for your blood 
□ 
□ 
pressure or heart condition? 
7. 
Do you know of any other reason why you should not do physical activity? 
 
 
 
 
If 
you 
answered: 
YES to one or more 
Talk to your doctor by phone or in person BEFORE you start becoming much more 
physically active or BEFORE you have a fitness appraisal. Tell your doctor about the 
PAR-Q and which questions you answered YES. 
• 
You may be able to do any activity you want – as long as you start slowly and 
build up gradually. Or, you may need to restrict your activities to those which are 
safe for you. Talk with your doctor about the kinds of activities you wish to 
participate in and follow his/her advice. 
• 
Find out which community programs are safe and helpful for you. 
 
NO to all questions 
 Delay becoming much more active: 
• 
If you are not feeling well because of a 
temporary illness such as a cold or a fever – 
wait until you feel better; or 
• 
If you are or may be pregnant – talk to your 
doctor before you start becoming more 
active. 
If you answered NO honestly to all PAR-Q 
questions, you can be reasonably sure that you 
can: 
• 
Start becoming much more physically 
active – begin slowly and build up 
gradually. This is the safest and 
easiest way to go. 
• 
Take part in a fitness appraisal – this 
is an excellent way to determine your 
basic fitness so that you can plan the 
best way for you to live actively. 
 
Please note: If your health changes so that you then answer 
YES to any of the above questions, tell your fitness or health 
professional. 
Ask whether you should change your physical activity plan. 
Informed use of the PAR-Q: Reprinted from ACSM’s Health/Fitness Facility Standards and Guidelines, 1997 by American College of Sports Medicine 
 
 

 
 
 
 
26 
 
 
Appendix 4: Demographic and health history questionnaire 
 

 
 
 
 
27 
 
 
 

 
 
 
 
28 
 
 
 

 
 
 
 
29 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
30 
 
 
 
Appendix 5.1 Self-Efficacy for Exercise (SEE) Aerobic Scale 
 
How confident are you right now that you could perform aerobic exercise three times 
per week for 20 minutes if: 
 
 
Not Confident 
Very Confident 
1. The weather was 
bothering you 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
2. You were bored by 
the program or activity 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
3. You felt pain when 
exercising 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
4. You had to exercise 
alone 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
5. You did not enjoy it 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
6. You were too busy 
with other activities 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
7. You felt tired 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
8. You felt stressed 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
9. You felt depressed 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
 
 
 

 
 
 
 
31 
 
 
Appendix 5.2 Self-Efficacy for Exercise (SEE) Muscle strengthening 
Scale 
 
How confident are you right now that you could perform muscle strengthening exercise 
three times per week for 20 minutes if: 
 
 
Not Confident 
Very Confident 
1. The weather was 
bothering you 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
2. You were bored by 
the program or activity 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
3. You felt pain when 
exercising 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
4. You had to exercise 
alone 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
5. You did not enjoy it 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
6. You were too busy 
with other activities 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
7. You felt tired 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
8. You felt stressed 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
9. You felt depressed 
0 
1 2 
3 
4 
5 6 
7 8 
9 
10 
 
 
 

 
 
 
 
32 
 
 
Appendix 6: Basic Psychological Needs in Exercise Scale (BPNES)  
 
 
 
 

 
 
 
 
33 
 
 
Appendix 7: Perceived Social Support (PSS) survey  
 
 

 
 
 
 
34 
 
 
Appendix 8: Exercise Regulations Questionnaire (BREQ-3) 
 
 

 
 
 
 
35 
 
 
 
 
 
 

 
 
 
 
36 
 
 
Appendix 9: OPEN questionnaire 

 
 
 
 
37 
 
 
 

 
 
 
 
38 
 
 
 

 
 
 
 
39 
 
 
 

 
 
 
 
40 
 
 
 

 
 
 
 
41 
 
 
Appendix 10: Recruitment letter to be sent from the ICR  
 

 
 
 
 
42 
 
 
 

 
 
 
 
43 
 
 
Appendix 11: Brochure included with ICR mailing 
v 
 
 

 
 
 
 
44 
 
 
 
 
 

 
 
 
 
45 
 
 
Appendix 12: Consent to release information included with ICR 
mailing  
 
 

 
 
 
 
46 
 
 
Appendix 13: Screening script for screening ICR individuals via 
telephone
 

 
 
 
 
47 
 
 
 
 
 

 
 
 
 
48 
 
 
Appendix 14: Questionnaire for telephone eligibility screening 
 
 
 

 
 
 
 
49 
 
 
 

 
 
 
 
50 
 
 
Type of Clinical Trial: 
 
      X Investigator-initiated (UI/HCCC) 
q Investigator-initiated, participating site 
      X Pilot study 
q Phase I 
q Phase I/II 
q Phase II 
q Phase III 
q Compassionate use  
q Interventional Treatment 
X   Interventional Non-Treatment 
q Non-Interventional 
 
 
Study risk-level:  
q Level 1—low risk of morbidity or death, * <1% of death or any adverse 
event  
X   Level 2—risk of death* <1% or any adverse event 1% – 5%  
q Level 3—risk of death* 1% – 5% or grade 4 – 5 SAE 1% – 5%  
q Level 4—risk of death* >5% or grade 4 – 5 SAE >5%  
q Drugs being used on a “compassionate” basis  
* Risk of death” refers specifically to 100-day treatment-related mortality 
 
Reporting and Monitoring Requirements:  
 
All institutional investigator-initiated trials (IITs), regardless of assigned risk level are 
subject to routine DSMC monitoring activities which may include but are not limited to 
review of signed consent documents, eligibility and adverse event reporting.  
 
All institutional IITs have the following reporting requirements as part of their DSMP: 
• Register all subjects in HCCC’s Clinical Trial Management System, OnCore 
• Document Adverse Events  
• Document protocol deviations  
• Provide an annual progress report to the DSMC via OnCore data export 
 
 
 
 
 

 
 
 
 
51 
 
 
Selected monitoring strategy based on risk-level: 
 
Risk Level 2 
Interventional trials with a risk of death* (<1% or any adverse event 1% – 5%), e.g. 
behavioral interventions, nutritional therapies, low risk procedures (e.g., endoscopy, 
glucose-tolerance tests, induced sputum, skin or muscle biopsy, nasal wash, lumbar 
puncture, bone marrow biopsy, imaging requiring sedation), as well as therapeutic trials 
involving agents with known safety profiles already licensed for the indication and age 
group.  Most disease-prevention trials will be considered at least a Risk Level 2.  
 
Study Safety Review 
The PI or designated study personnel will review all study data for completeness 
 
Routine Adverse Event Reporting 
 
For non-serious Adverse Events, documentation must begin from the first day of study 
intervention and typically continue through the 30-day follow-up period after the 
intervention is discontinued.  
 
Collected information should be recorded in the electronic/Case Report Forms 
(eCRF/CRF) for that subject. A description of the event, its severity or toxicity grade 
(according to NCI’s Common Toxicity Criteria (CTCAE)), onset and resolved dates (if 
applicable), and the relationship to the study drug should be included. Documentation 
should occur in real time. The principal investigator has final responsibility for 
determining the attribution of the event as it is related to the study drug. 
 
 
 
Serious Adverse Event Reporting 
 

 
 
 
 
52 
 
 
For any experience or condition that meets the definition of a serious adverse event 
(SAE), recording of the event must begin after signing of the informed consent and 
continue through the 30-day follow-up period after treatment is discontinued.  
Investigators must report to the DSMC any serious adverse events (SAE), whether they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64). 
SAEs must be reported via an OnCore SAE Report within 24 hours of learning of the 
event.  
 
An adverse event is considered serious if it results in ANY of the following outcomes:   
1. Death 
2. A life-threatening adverse event  
3. An adverse event that results in inpatient hospitalization OR prolongation of 
existing hospitalization for ≥ 24 hours  
4. A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions  
5. A congenital anomaly/birth defect.  
6. Important Medical Events (IME) that may not result in death, be life threatening, 
or require hospitalization may be considered serious when, based upon medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. (FDA, 
21 CFR 312.32; ICH E2A and ICH E6). 
 
 
 
 
 
 
Data Monitoring and Management  
Subject Registration 

 
 
 
 
53 
 
 
 
All studies that undergo PRMC review and/or utilize HCCC Clinical Research Services 
(CRS) resources are required to register subjects in OnCore. Each subject registration 
includes the following: 
• The subject’s IRB approved (version date) consent form and the date of their 
consent.  
• Date of eligibility and eligibility status (eligible, not eligible) 
• On study date and subject’s disease site (and histology if applicable) 
• On treatment date (if applicable)  
 
All subject registration information is expected to be entered into OnCore within 2 (two) 
business days after the subject’s study visit. 
 
Subject Data 
 
For HCCC investigator-initiated trials, research staff are responsible for entering subject 
study data (data collection) into OnCore electronic case report forms (eCRFs). These 
eCRFs must be approved by the PI and statistician prior to study activation to ensure 
sufficient and necessary data acquisition. All information entered into eCRFs will be 
traceable to the source documents which are generally maintained in the subject’s file.  
 
eCRF data entry needs to be timely and should be entered into OnCore as soon as 
possible but no later than 14 (fourteen) business days after the subject’s visit, 
including adverse events, tumor measurements, administration of study medication, 
concomitant medications, labs, and vitals. Physical exam assessments must be entered 
no later than 14 (fourteen) business days following completion of the physician’s clinic 
note in the medical record.  
 
Timely data entry facilitates remote monitoring of data, allows the data to progress 
appropriately through the data cleaning process, and helps prevent a backlog of data 
queries. 
 
Forms Monitoring 
 
OnCore eCRF data are monitored on a routine basis (dependent on accrual) to ensure 
all data are entered completely, accurately, and within time requirements outlined 
above. The assigned DSMC monitor will coordinate and complete the data monitoring 
review. When the time comes to monitor a study (based on patient accrual and 
assigned risk level of trial) the monitor arranges for a selection of cases to be reviewed 
from among the subjects registered in OnCore.  As part of the forms monitoring 
process, the assigned monitor will issue queries via OnCore (linked to the eCRF) to 
resolve missing, incomplete, and/or incorrect information. A member of the research 

 
 
 
 
54 
 
 
team is expected to respond to these monitoring queries within 14 (fourteen) business 
days.  
 
The monitoring process can often identify misunderstandings or deficiencies in the 
written, research protocol requirements earlier in the study process and thereby improve 
data quality and reduce rework.  
 
 
Final Reports 
 
A summary of each subject’s data record is continually available to the PI, research 
staff, and DSMC from OnCore’s Biostat Console. The availability of this information is a 
valuable tool for the preparation of final reports and manuscripts as well as ongoing 
deficiency reports. 

 
 
 
 
55 
 
 
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