Promoting Recovery Optimization With WALKing Exercise After Stroke
Phase: NA
Conditions: Stroke
Sponsor: University of Delaware

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Promoting Recovery Optimization with WALKing Exercise After Stroke (PROWALKS) 
NCT02835313 
4/12/2023 
 
This supplement contains the following items: 
1. Original protocol, final protocol, summary of changes 
2. Original statistical analysis plan (excerpted from grant application, original IRB 
protocol, published study protocol), updates to statistical analysis plan (excerpted 
from final IRB protocol and from ClinicalTrials.gov registry) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Original approved IRB protocol 
3/23/2016 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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HUMAN SUBJECTS PROTOCOL  
University of Delaware 
 
Protocol Title: Promoting Recovery Optimization with WALKing Exercise after Stroke 
(PROWALKS)  
 
 
  
 
Principal Investigator   
 
 
Name: Darcy Reisman, PT, PhD 
 
Department/Center: Physical Therapy- STAR Campus 
 
Contact Phone Number: 302-831-0508 
 
Email Address: dreisman@udel.edu 
 
 
Other Investigators: 
 
 
Ryan Pohlig, PhD 
David Edwards, PhD 
Scott Kasner, MD (University of Pennsylvania) 
Jonathan Raser-Schramm, MD, PhD (Christiana Care Health System) 
 
 
Investigator Assurance: 
 
By submitting this protocol, I acknowledge that this project will be conducted in strict accordance 
with the procedures described. I will not make any modifications to this protocol without prior 
approval by the IRB. Should any unanticipated problems involving risk to subjects occur during this 
project, including breaches of guaranteed confidentiality or departures from any procedures 
specified in approved study documents, I will report such events to the Chair, Institutional Review 
Board immediately.   
 
1.  Is this project externally funded? YES  X NO 
 
Grant revision is in review, with competitive score first cycle.  
 
2. Research Site(s) 
 
x University of Delaware 
X Other (please list external study sites) 
University of Pennsylvania 
Christiana Care Health System 
 
 
Is UD the study lead?  X YES □ NO (If no, list the institution that is serving as the study 
lead) 
 
 

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3.  Project Staff 
Please list all personnel, including students, who will be working with human subjects on this 
protocol (insert additional rows as needed): 
 
NAME 
ROLE 
HS TRAINING COMPLETE? 
Darcy  Reisman  
PI 
YES 
Ryan Pohlig 
Co-Investigator 
YES 
David Edwards 
Co-Investigator 
YES 
Scott Kasner 
Co-Investigator 
YES 
Jonathan Raser-Schramm 
Co-Investigator 
YES 
Jennifer Marmon 
Staff 
YES 
Kelly Danks 
Research Physical Therapist 
YES 
Tamara Wright 
Research Physical Therapist 
YES 
 
4.  Special Populations 
Does this project involve any of the following: 
 
Research on Children?   NO 
 
Research with Prisoners? NO 
 
If yes, complete the Prisoners in Research Form and upload to IRBNet as supporting documentation 
 
Research with Pregnant Women? NO 
 
Research with any other vulnerable population (e.g. cognitively impaired, economically 
disadvantaged, etc.)? please describe  NO 
 
5.  RESEARCH ABSTRACT  Please provide a brief description in LAY language (understandable to 
an 8th grade student) of the aims of this project. 
 
The overarching goal of this research is to develop interventions that improve the overall 
health and quality of life of individuals post-stroke. As a group, stroke survivors are more 
physically inactive than even the most sedentary older adults.  Lack of physical activity has 
serious consequences in persons with stroke, including an increased risk of recurrent stroke, 
developing other diseases and mortality.  Current rehabilitation interventions do little to improve 
real-world walking activity after stroke, suggesting that simply improving walking capacity is not 
sufficient for improving daily physical activity after stroke. Rather, we hypothesize that the 
combination of a fast walking intervention that improves walking capacity, with a step activity 
monitoring program that facilitates translation of gains from the clinic to the “real-world”, would 
generate greater improvements in real world walking activity than with either intervention alone. 
Data from our lab provides support for this hypothesis; however, it suggests that the greater 
efficacy of combining the 2 interventions depends on a participant’s initial walking activity. Thus, 
we do not expect that one intervention will be superior to the others for all participants, but 
rather that the combined intervention will be superior for those with low levels of baseline 
walking activity, speed and endurance. The specific objective of this research is to test 
whether and for whom combining fast walking training with a step activity monitoring program 
(FAST+SAM) is superior in improving real-world walking activity compared to fast walking 
training alone (FAST) or a step activity monitoring and feedback program alone (SAM) in those 
with chronic stroke. Using a randomized controlled experimental design, 225 chronic (> 6 
months) stroke survivors, will complete 12 weeks of fast walking training (FAST), a step activity 

5 
 
monitoring program (SAM) or a fast walking training + step activity monitoring program 
(FAST+SAM).The primary (steps per day), secondary (self-selected and fastest walking speed, 
walking endurance, oxygen consumption) and exploratory (vascular events, blood lipids, 
glucose, blood pressure) outcomes will be assessed by blinded evaluators prior to initiating 
treatment, after the last treatment and at a 6 and 12 month follow-up.  Moderation of specific 
intervention outcomes by baseline characteristics will be evaluated to determine for whom the 
interventions are effective. Following completion of this study, we will not only understand the 
efficacy of the interventions and the individuals for which they are effective, we will have the 
necessary information to design a study investigating the secondary prevention benefits of 
improved physical activity post-stroke. This study is, therefore, an important step in the 
development of secondary prevention guidelines for persons with stroke. 
 
6.  PROCEDURES   
258 adults with a past history of stroke will be recruited to participate in the study. The study will 
take place at 3 sites, the University of Delaware (UD), the University of Pennsylvania (UPenn) 
and Christiana Care Health System (CCHS). With a planned attrition rate of 13%, we anticipate 
225 subjects will complete the study. Thus, approximately 86 subjects will be recruited at each 
of our 3 sites. See information regarding recruitment methods in #7 below. All testing and 
training (intervention) sessions will occur at UPenn and UD, while only training sessions will 
occur at CCHS with testing of CCHS subjects occurring at UD. 
 
Regardless of recruitment method, during the initial phone call or email a member of the 
research team will describe the purpose and general procedures of the study. We will explain 
what to expect and the potential risks and benefits of participation. We will also inform the 
potential participant that joining the study is completely voluntary and that he/she is free to 
reconsider or stop participation at any time. If the potential participant expresses interest in 
agreeing to join, we will then proceed with a series of screening questions to determine if the 
person might be eligible (see Appendices).  
 
Once potential eligibility for a participant is determined, 
medical approval for further screening and participation will be 
sought from the participant’s physician, if it has not already 
been obtained (see IRBNet Protocol ID# 619037-1 in 
Appendices for details). Once medical approval is received the 
subject will be scheduled for the first evaluation session. 
 
At the time of the first evaluation session, a member of the 
research team will first review the informed consent 
documents in detail with the potential participant. This will 
include a description of the study purpose and procedures, 
inclusion and exclusion criteria, the potential risks and 
benefits of participating, alternatives to participating, subjects’ 
rights (such as withdrawal from the study, etc.) and 
compensation. The participant will be encouraged to ask 
questions and express concerns at any time during the consenting procedure or thereafter. If 
the participant agrees to be in the study, he/she will be asked to sign the informed consent 
document.  
 

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The figure illustrates the basic study design. Each evaluation session will last 2-3 hours and 
each training (intervention) session will last approximately 1 hour. There are a total of 8 
evaluation sessions and 36 intervention sessions. 
 
Testing Procedures 
 
Baseline evaluation session.  Subjects will undergo a brief battery of clinical assessments 
conducted by a trained member of the research team. Clinical assessments will include 
collection of medication and co-morbidity information, blood pressure, heart rate and body mass 
index, the 10 meter walk test, the 6 minute walk test, the Activities Specific Balance Confidence 
scale (ABC), the Patient Health Questionnaire nine-item depression scale (PHQ-9), and the 
Montreal Cognitive Assessment (MoCA) (see Appendices). In addition, subjects will be provided 
with a Fitbit activity monitor and instructed in its wear and use. Subjects will wear the monitor for 
1 week. Following this baseline evaluation session and the 1 week step monitoring, the 
inclusion criteria of walking speed less than 1.0 m/s and steps/day less than 8000, can be 
evaluated and continued eligibility confirmed. If subjects do not meet these criteria after 
evaluation, they will be withdrawn from the study. 
If any subject scores ≥5 on the PHQ-9, they will be informed of their score and advised 
to discuss this with their primary physician. In addition, for any participant endorsing suicidal 
ideation on one or more test items on PHQ-9, (1) we will notify the physician and (2) we will give 
the participant the telephone number for Crisis Intervention Services of Northern Delaware (302-
577-2484 or 800-652-2929) which is staffed 24 hours/day, 7 days a week, to whom they can 
reach out if they feel desperate, hopeless and/or at risk for suicide. This is standard procedure 
for clients in the Physical Therapy Clinic. 
Symptom limited graded exercise test.  Prior to beginning the intervention, all subjects will 
undergo a symptom limited graded exercise test (GXT) on a motorized treadmill in the Nurse 
Managed Health Center (NMHC) under the supervision of a nurse practitioner and an exercise 
physiologist. During the GXT a12 lead electrocardiogram and breath by breath analysis of 
oxygen consumption with a metabolic cart will be recorded. The results of the test will be 
reviewed by a cardiologist for abnormal responses that would prevent the subject from safe 
participation. 
Subjects will also have their blood drawn by a trained practitioner in the NHMC for 
measurement of blood lipids and glucose. 
 
Post-intervention and follow-up evaluations. Post, 6 and 12 month evaluation sessions will be 
identical to the baseline evaluation including the graded exercise test for the purposes of 
measuring changes in oxygen consumption that may have occurred with the intervention and 
measurement of blood lipids and glucose. 
 
In order to examine the potential secondary prevention benefits of the intervention, at the 6 and 
12 month follow-up appointment subjects will be asked about major adverse cardiovascular and 
cerebrovascular events (MACCE); specifically if they have had: recurrent stroke, myocardial 
infarction, unstable angina requiring hospitalization or peripheral artery event and the date of 
that event. This data will be confirmed for accuracy through contact with the subject’s physician. 
Phone follow-up at 2 years will be completed for subjects enrolled in the first 2 years of the 
study to collect longer term follow-up data on these events. Information received from subjects 
will be confirmed by their physician (see Appendices). If subjects have any of these events 
during the course of the study, they will be withdrawn from all testing and training, except we will 
continue to track them for MACCE. 
 

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Intervention Procedures 
Subjects will be randomly assigned to one of 3 groups: fast walking training (FAST), a 
step activity monitoring program (SAM) or a fast walking training + step activity monitoring 
program (FAST+SAM).  
 
Walking training. All subjects in the FAST and FAST+SAM groups will complete walking training 
for 30 minutes, 3x/week for 12 weeks. These participants will complete a fast walking treadmill 
training program followed by approximately 10 minutes of over-ground walking activities. All 
treadmill walking will be completed while subjects wear an overhead chest-harness system for 
safety; no body weight support will be provided. Subjects will walk for 30 minutes with the goal 
of walking at the fast training speed, one at which Target Heart Rate (calculated using the 
Karvonen formula)1 is achieved: (THR) = ((220-age) - Resting heart rate) x 80%)+ Resting heart 
rate1. The fast training speed interval is reduced if the subject requests to walk slower, the fast 
speed is no longer safe (e.g. increased toe scuffing or tripping), the subject reports a rate of 
perceived exertion of  ≥17 on the 6-20 Borg Rate of Perceived Exertion Scale2 and/if THR is 
exceeded. The treadmill speed is lowered to allow the heart rate to return to, ((220-age) – 
Resting heart rate) x 50-60%)+ Resting heart rate (Karvonen formula)1, or to a rate of perceived 
exertion ≤13. If the HR is not steadily decreasing and the recovery criteria are not achieved 
within approximately 1 minute by walking slower, the treadmill is stopped and the subject takes 
a standing or seated rest break to achieve recovery. Once recovery is reached, the subject is 
transitioned to the fast training speed again.  
 
Following treadmill walking, 10 minutes of over-ground walking activities are performed with the 
same THR and perceived exertion criteria as on the treadmill. Subjects are guarded and 
activities are progressed by a physical therapist. The purpose of this portion of the session is for 
the participant to practice walking activities experienced during everyday activities (e.g. turning, 
backward stepping, walking while carrying objects) to gain both skill and confidence with these 
routine walking activities that are important in real-world walking.  
 
During training, the RPE2 will be assessed every 2 minutes and heart rate will be continuously 
monitored.  Blood pressure is tested prior to the initiation of any activity. It is also checked any 
time walking is stopped, including rest breaks, at the end of treadmill walking (prior to the start 
of over ground walking) and following over ground walking. For all sessions, the guidelines set 
forth by the American College of Sports Medicine for individuals in phase III or IV of cardiac 
rehabilitation will be followed1. Based on these guidelines, we have developed session 
termination criteria. A session will be terminated if any of the following occur: 
 
Drop in Systolic blood pressure of > 10mmHg from baseline (resting for that day) despite 
increase in workload 
 
Hypertensive response with a systolic blood pressure >240 mmHg and diastolic blood 
pressure >110 
 
Presence of nervous system symptoms: ataxia, dizziness, or near syncope 
 
Any chest pain or angina symptoms 
 
Signs of poor perfusion cyanosis or pallor 
 
Excessive fatigue, excessive shortness of breath, leg cramps, claudication 
If any of the above occurs, the subject’s physician will be contacted and informed of the 
subject’s response to the activity.  Subjects can also terminate any session or training bout by 
stating their desire to stop. 
   

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Step activity monitoring program. Subjects in the SAM and FAST+SAM groups will participate in 
the step activity monitoring program and will be provided with a Fitbit. If the device is lost or 
damaged, it will be replaced to allow continued participation in the step activity monitoring 
program. Baseline step activity data for subjects in the FAST+SAM and SAM groups will be 
used to categorize and assign step activity goals. It is important to note that goals are set not 
based on an absolute number for all subjects, but rather individually, based on their own 
baseline walking. Goals are advanced based on subject achievement of previous goals. For 
subjects in the FAST+SAM group, step activity data is reviewed at each treadmill training 
session and used to determine and promote goal achievement. Subjects in the SAM group will 
visit the clinic 3x/week for this review. Step activity data in the interim days between sessions 
will reviewed and used to assist subjects in understanding how much walking activity they 
performed during certain daily activities, like walking to the mailbox or walking laps around their 
home, and how that added to their total steps per day. Subjects are also advised of how their 
steps per day related to goal achievement; a discussion of individualized ideas to increase 
activity and of any barriers and how to overcome those barriers occurred. These discussions 
have been shown to be critical for the success of a step activity monitoring program.  
Subjects in the FAST group will be instructed not to begin the use of a step monitor during the 
study.  
 
7.  STUDY POPULATION AND RECRUITMENT 
Recruitment and Enrollment Procedures: 
 
Subjects will be recruited from a variety of sources. For recruitment at the University of 
Delaware we will utilize the University of Delaware Stroke Studies Registry, a database of 
stroke survivors who are interested in participating in research. The use and maintenance of the 
Registry is described in detail in IRBNet Protocol ID# 619037-1, entitled “Shared Pre-enrollment 
Process for Stroke Research Team Studies”, PI Reisman, Co-PI Morton (see Appendices). 
People are recruited and phone-screened through this protocol. Additionally, medical clearance 
from the acting physician is also obtained through this protocol. Individuals from the registry who 
appear likely to meet eligibility requirements will be contacted by telephone. See details of 
registry protocol procedures in attached Appendices. In addition, other persons with stroke will 
be recruited via local physical therapy practices, physicians’ offices and support groups. Other 
recruiting could occur through the PI(s) public speaking engagements or by word of mouth from 
visitors to the lab or past participants in stroke studies.  
 
Describe what exclusionary criteria, if any will be applied. 
 
The specific subject inclusion and exclusion criteria are: 
Inclusion Criteria: 1) Age 21-85, 2) Chronic stroke (>6 months post stroke), 3) Able to walk at 
self-selected speed without assistance from another person (assistive devices are allowed), 4) 
Self-selected walking speed <1.0 m/s, 5) Average steps/day <8,000, 6) Resting heart rate 
between 40-100 beats per minute, 5) Resting blood pressure between 90/60 to 170/90. 
Exclusion Criteria: 1) Evidence of cerebellar stroke, 2) Other potentially disabling neurologic 
conditions in addition to stroke, 3) Lower limb Botulinum toxin injection <4 months earlier, 4) 
Current participation in physical therapy, 5) Inability to walk outside the home prior to the stroke, 
5) Coronary artery bypass graft, stent placement or myocardial infarction within past 3 months, 6) 
Musculoskeletal pain that limits activity, 7) Inability to communicate with investigators, 8) score 
>1 on question 1b and >0 on question 1c on the NIH Stroke Scale. 
 
 
The inclusion and exclusion criteria are discussed at the initial screening and again on the first 
testing day when the informed consent document is reviewed. Determining whether all criteria 
on the Inclusion and Exclusion Criteria Checklist (see Appendices) are met is based on a 

9 
 
combination of subjects’ individual responses and information from other documentation. Two 
inclusion criteria (walking speed <1.0 m/s and steps per day <8,000) cannot be evaluated until 
the baseline evaluation is completed. Therefore, subjects will be withdrawn from the study if 
these criteria are not met following this evaluation.  
 
Describe what (if any) conditions will result in PI termination of subject participation. 
 
Participation in the study is voluntary. Any subject may withdraw from the study at any time 
without any negative consequences. In addition, the PI may terminate a subject’s participation if 
the subject is viewed by the PI to be placing him/herself at risk. This is not expected, but could 
potentially occur. Similarly, the subject may be withdrawn from the study based on abnormal 
results identified on the symptom-limited graded exercise test. 
 
8.  RISKS AND BENEFITS 
List all potential physical, psychological, social, financial or legal risks to subjects (risks 
listed here should be included on the consent form). 
 
Participation in any physical activity or exercise has risk.  These risks include but are not limited 
to, pain, fainting, dizziness, fatigue, nausea, shortness of breath, chest pain or angina, 
myocardial infarction, swelling, bruising, muscle/bone/joint soreness, joint damage, bone 
fracture, ligament/tendon/connective tissue damage, hospitalization, and death.  
 
Psychological risks include possible discomfort, frustration, and/or anxiety related to difficulty with 
the physical testing or completion of questionnaires. 
 
Graded exercise testing carries a low risk of myocardial infarction/cardiac arrest (1/2500; 
ACC/AHA) and patients will be made aware of this risk prior to testing. However, graded exercise 
testing is a standard procedure for diagnostic purposes, evaluation of functional capacity, and the 
effectiveness of both exercise and pharmacological interventions. 
The risks of taking blood include pain and/or bruising where the blood is taken, redness and 
swelling of the vein and infection, and a rare risk of fainting. 
 
In your opinion, are risks listed above minimal* or more than minimal? If more than minimal, 
please justify why risks are reasonable in relation to anticipated direct or future benefits. 
 
The risks of the study are not more than minimal. 
 
What steps will be taken to minimize risks? 
 
During treadmill walking subjects are allowed rest breaks whenever requested or deemed 
appropriate by the experimenter. Because participants who have sustained a stroke may be at 
increased cardiovascular risk, when a potential post-stroke participant contacts the team, they 
will be asked to provide consent to allow the investigators to contact the referring or primary 
physician to obtain medical clearance for participation. Potential participants will only be brought 
to the laboratory for testing once this clearance has been obtained. Prior to the initiation of 
training, all subjects will undergo a 12 lead symptom limited graded exercise test reviewed by a 
cardiologist. All subjects will wear a heart rate monitor during testing and training. During all 
treadmill walking, subjects will wear a harness connected to an overhead support. During 
walking training,  the Borg Scale of perceived exertion (RPE) 1 will be measured every 2 
minutes and heart rate will be continuously monitored.  For all training sessions, the guidelines 

10 
 
set forth by the American College of Sports Medicine (ACSM) for individuals in phase III or IV of 
cardiac rehabilitation will be followed. Based on these guidelines, a session will be terminated if 
any of the following conditions occur: 
 
 Drop in Systolic blood pressure of > 10mmHg from baseline (resting for that day) despite 
increase in workload 
 
Hypertensive response with a systolic blood pressure >240 mmHg and diastolic blood 
pressure >110 
 
Presence of nervous system symptoms: ataxia, dizziness, or near syncope 
 
Any chest pain or angina symptoms 
 
Signs of poor perfusion cyanosis or pallor 
 
Excessive fatigue, excessive shortness of breath, leg cramps, claudication  
 If any of the above occurs, the subject’s physician will be contacted and informed of the 
subject’s response to the activity.  Subjects can also terminate any session or training bout by 
stating their desire to stop. 
Any incidents involving injury to study subjects will be presented to the Data and Safety 
Monitoring Board and the IRB immediately.   Please see information related to the Data and 
Safety Monitoring Board below. 
 
Describe any potential direct benefits to participants. 
The direct benefit to the subjects participating in training could be substantial. Previous research 
has shown that 12 weeks of treadmill training can lead to improvements in walking speed and 
activity. So regardless of the effects of our specific intervention, subjects are likely to obtain 
some benefit of participation. This will be explained to all subjects. The methods of study will 
provide sensitive, objective measures of walking function and activity, which would be useful in 
monitoring progress, or the lack of it, across time and therapy. This will be explained to all 
subjects. 
 
Describe any potential future benefits to this class of participants, others, or society. 
 
The potential benefits of this study are that we may understand mechanisms and interventions 
to improve physical activity in chronic stroke survivors. The knowledge gained will provide an 
understanding of the optimal characteristics of rehabilitation interventions to promote functional 
walking recovery post stroke. Because of the potential for these results to lead to development 
of new approaches to rehabilitation interventions for stroke survivors that could significantly 
impact secondary prevention of future stroke and other conditions, the potential benefits far 
outweigh the minimal risks. 
 
If there is a Data Monitoring Committee (DMC) in place for this project, please describe 
when and how often it meets.  
There is a Data and Safety Monitoring Board (DSMB) for this study. Please see the description 
of the example DSMB Charter in the Appendices. 
 
 
9.  COMPENSATION 

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Will participants be compensated for participation?  Yes. 
 
If so, please include details. 
 
Subjects will be paid $100.00 for participation, $25.00 after each of the evaluation time points is 
completed. 
 
Participants are responsible for transportation to the study site for each visit. In some situations, 
if a participant cannot arrange transportation alone, transportation will be arranged for them.  
 
10.  DATA 
Will subjects be anonymous to the researcher? 
 
 
Subjects will not be anonymous to the researchers.  As part of the consent process and 
verification of eligibility, subjects must provide their name, date of birth and other identifying 
information to members of the research team. However, identities will be kept confidential to the 
extent possible (see Confidentiality section below). De-identified data may be presented in 
abstract, poster, presentation, or published manuscript format. 
 
If subjects are identifiable, will their identities be kept confidential? (If yes, please specify 
how) 
 
Subject identities will be kept confidential by assigning each subject a number.   
 
How will data be stored and kept secure (specify data storage plans for both paper and 
electronic files. For guidance see http://www.udel.edu/research/preparing/datastorage.html )    
 
All data sheets will be stored in the subject’s folder in a locked file cabinet.  Encrypted electronic 
data will be stored in a database on a password protected UD managed server. Identifiable data 
will be shared between sites through this database.  Paper copies of consent forms for each site 
will be stored on-site. Electronic copies of consents will be encrypted and placed on a UD 
managed password protected server. 
 
 
How long will data be stored? 
 
All de-identified data will be stored indefinitely and may be used in future research studies. 
 
Will data be destroyed?  X YES  □  NO (if yes, please specify how the data will be destroyed)  
Data with identifying information will be saved until the project is complete or the data are 
published, whichever comes first and then the identifiable data will be destroyed. This will 
involve all electronic data being wiped from hard-drives and servers and all paper data being 
shredded. Raw de-identified data will be stored indefinitely and may be used in future related 
studies. 
 
Will the data be shared with anyone outside of the research team?  x YES   NO  
These data will be used by the current investigative team, and then, in compliance with NIH 
policy, shared with others through the NICHD DASH repository so that additional analyses can 
be performed. Once the primary hypotheses of the current proposal are tested, all data will be 

12 
 
cleaned, de-identified, and be deposited in the DASH repository. To ensure that the identities of 
research subjects cannot be readily ascertained with the data, NICHD DASH will store only data 
that are without identifiers and coded. According to NICHS DASH requirements, before 
submitting the data to NICHD DASH, investigators must:  
a. Strip the data of individually identifying information according to:  
o 
the standards set forth in the HHS Regulations for the Protection of Human 
Subjects and related guidance (which covers individually identifiable private 
information), and 
o 
the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule 
(which covers protected health information); and 
b. Assign to the de-identified data random, unique codes. 
How will data be analyzed and reported?  
 
Appropriate statistical analysis of the primary (General Linear Mixed Modeling) and exploratory 
(Cox Proportional Hazards Model and a Generalized Estimating Equation) outcomes will be 
completed under the direction of the biostatistician on the project.   The results will be reported 
to professionals interested in research via journals and presentations. 
 
11. CONFIDENTIALITY 
Will participants be audiotaped, photographed or videotaped during this study? 
 
Individual subjects may be approached and asked to be photographed or videotaped for recruitment, 
educational or research purposes. A photo release form will be signed by participants prior to any 
photographs or videotape taken. Subjects will be told that this is an optional activity and not a 
requirement of participation. Photographs or video will have the face covered. 
 
How will subject identity be protected? 
 
All participants’ identifying information will be stored in a locked file cabinet (paper forms) or on 
password-protected computers or servers (electronic forms) and will be utilized only by 
investigators on the protocol who have a specific need for the identifying information. All data 
collection sheets and all data will be de-identified and, instead, coded using a numerical system, 
the key to which will be maintained on a password-protected computer. These de-identified data 
and data collection sheets will also be stored in a locked file cabinet (paper forms) or on 
password-protected computers or servers (electronic forms) that are kept separate from the 
identifying information. 
 
Is there a Certificate of Confidentiality in place for this project?  (If so, please provide a copy). 
 
There is no Certificate of Confidentiality in place for this project.   
 
 
12. CONFLICT OF INTEREST 
(For information on disclosure reporting see: http://www.udel.edu/research/preparing/conflict.html ) 
 
Do you have a current conflict of interest disclosure form on file through UD Web forms? Yes 
Does this project involve a potential conflict of interest*?  NO 
 
* As defined in the University of Delaware's Policies and Procedures ,a potential conflict of interest (COI) occurs 

13 
 
when there is a divergence between an individual's private interests and his or her professional obligations, such that 
an independent observer might reasonably question whether the individual's professional judgment, commitment, 
actions, or decisions could be influenced by considerations of personal gain, financial or otherwise. 
 
 
 
If yes, please describe the nature of the interest: 
 
 
 
13.  CONSENT and ASSENT 
 
___X_ Consent forms will be used and are attached for review (see Consent Template under Forms 
and Templates in IRBNet) 
 
____ Additionally, child assent forms will be used and are attached. 
 
____ Waiver of Documentation of Consent (attach a consent script/information sheet with the 
signature block removed). 
 
____ Waiver of Consent (Justify request for waiver) 
 
14.  Other IRB Approval 
Has this protocol been submitted to any other IRBs? Not yet, but it will be submitted to the 
University of Pennsylvania and Christiana Care Health System IRBs. 
 
 
15.  Supporting Documentation 
Please list all additional documents uploaded to IRBNet in support of this application. 
 
Appendices which include IRBNet Protocol ID# 619037-1, entitled “Shared Pre-enrollment Process 
for Stroke Research Team Studies”, that is referenced in this protocol, along with copies of 
specific clinical tests, screening questions and the inclusion/exclusion checklist for this protocol. 
 
A separate Appendix is attached with the example DSMB charter. 
 
REFERENCES 
1. 7th ed. Philadelphia: Lippincott, Williams and Wilkines; 2006. American College Of Sports 
Medicine (ACSM) – Guidelines for exercise testing and prescription. 
2. Borg G. Perceived exertion as an indicator of somatic stress. Scand J Rehabil Med 1970;2(2):92-
8. 
 
 
 
 
 
 
 
 
 
 
 
 
Rev. 10/2012 

14 
 
Final approved IRB protocol 
3/13/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

15 
 
 
HUMAN SUBJECTS PROTOCOL  
University of Delaware 
 
Protocol Title: Promoting Recovery Optimization with WALKing Exercise after Stroke 
(PROWALKS)  
 
 
  
 
Principal Investigator   
 
 
Name: Darcy Reisman, PT, PhD 
 
Department/Center: Physical Therapy- STAR Campus 
 
Contact Phone Number: 302-831-0508 
 
Email Address: dreisman@udel.edu 
 
 
Other Investigators: 
 
 
Ryan Pohlig, PhD 
David Edwards, PhD 
 
 
Investigator Assurance: 
 
By submitting this protocol, I acknowledge that this project will be conducted in strict accordance 
with the procedures described. I will not make any modifications to this protocol without prior 
approval by the IRB. Should any unanticipated problems involving risk to subjects occur during this 
project, including breaches of guaranteed confidentiality or departures from any procedures 
specified in approved study documents, I will report such events to the Chair, Institutional Review 
Board immediately.   
 
1.  Is this project externally funded? XYES  NO 
PHYT322245 
 
2. Research Site(s) 
 
x University of Delaware 
X Other (please list external study sites) 
Christiana Care Health System 
Indiana University 
 
 
Is UD the study lead?  X YES □ NO (If no, list the institution that is serving as the study 
lead) 
 
 

16 
 
3.  Project Staff 
Please list all personnel, including students, who will be working with human subjects on this 
protocol (insert additional rows as needed): 
 
NAME 
ROLE 
HS TRAINING COMPLETE? 
Darcy  Reisman  
PI 
YES 
Ryan Pohlig 
Co-Investigator 
YES 
David Edwards 
Co-Investigator 
YES 
Jennifer Marmon 
Staff 
YES 
Alicia Adkins 
Staff 
YES 
Tamara Wright 
Research Physical Therapist 
YES 
Henry Wright 
Research Physical Therapist 
Yes 
Martha Callahan 
Staff 
YES 
Jane Diehl 
Staff 
YES 
Elizabeth Thompson 
Research Scientist 
Yes 
Kiersten McCartney 
Student Researcher 
YES 
Kenna Gilley 
Staff 
Yes 
 
4.  Special Populations 
Does this project involve any of the following: 
 
Research on Children?   NO 
 
Research with Prisoners? NO 
 
If yes, complete the Prisoners in Research Form and upload to IRBNet as supporting documentation 
 
Research with Pregnant Women? NO 
 
Research with any other vulnerable population (e.g. cognitively impaired, economically 
disadvantaged, etc.)? please describe  NO 
 
5.  RESEARCH ABSTRACT  Please provide a brief description in LAY language (understandable to 
an 8th grade student) of the aims of this project. 
 
The overarching goal of this research is to develop interventions that improve the overall 
health and quality of life of individuals post-stroke. As a group, stroke survivors are more 
physically inactive than even the most sedentary older adults.  Lack of physical activity has 
serious consequences in persons with stroke, including an increased risk of recurrent stroke, 
developing other diseases and mortality.  Current rehabilitation interventions do little to improve 
real-world walking activity after stroke, suggesting that simply improving walking capacity is not 
sufficient for improving daily physical activity after stroke. Rather, we hypothesize that the 
combination of a fast walking intervention that improves walking capacity, with a step activity 
monitoring program that facilitates translation of gains from the clinic to the “real-world”, would 
generate greater improvements in real world walking activity than with either intervention alone. 
Data from our lab provides support for this hypothesis; however, it suggests that the greater 
efficacy of combining the 2 interventions depends on a participant’s initial walking activity. Thus, 
we do not expect that one intervention will be superior to the others for all participants, but 
rather that the combined intervention will be superior for those with low levels of baseline 
walking activity, speed and endurance. The specific objective of this research is to test 
whether and for whom combining fast walking training with a step activity monitoring program 

17 
 
(FAST+SAM) is superior in improving real-world walking activity compared to fast walking 
training alone (FAST) or a step activity monitoring and feedback program alone (SAM) in those 
with chronic stroke. Using a randomized controlled experimental design, 225 chronic (> 6 
months) stroke survivors, will complete approximately 12 weeks (goal of 36 sessions) of fast 
walking training (FAST), a step activity monitoring program (SAM) or a fast walking training + 
step activity monitoring program (FAST+SAM).The primary (steps per day), secondary (self-
selected and fastest walking speed, walking endurance, oxygen consumption) and exploratory 
(vascular events, blood lipids, glucose, blood pressure) outcomes will be assessed by blinded 
evaluators prior to initiating treatment, after the last treatment and at a 6 and 12 month follow-
up.  Moderation of specific intervention outcomes by baseline characteristics will be evaluated to 
determine for whom the interventions are effective. Following completion of this study, we will 
not only understand the efficacy of the interventions and the individuals for which they are 
effective, we will have the necessary information to design a study investigating the secondary 
prevention benefits of improved physical activity post-stroke. This study is, therefore, an 
important step in the development of secondary prevention guidelines for persons with stroke. 
 
6.  PROCEDURES   
750 adults with a past history of stroke will be recruited to participate in the study. The study will 
take place at 4 sites, the University of Delaware (UD), the University of Pennsylvania (UPenn), 
Christiana Care Health System (CCHS) and Indiana University (IU). We anticipate 225 subjects 
will complete the study. The number recruited at each study site will be flexible as recruitment 
varies across sites. Subject numbers are monitored on an ongoing basis through the REDCap 
database. See information regarding recruitment methods in #7 below. All testing and training 
(intervention) sessions will occur at  IU, UPenn and UD, while only training sessions will occur at 
CCHS with testing of CCHS subjects occurring at UD. Data collection sessions at the University 
of Pennsylvania were ended as of July 2020, but analysis of data collected at that site will 
continue through the end of the project. 
 
We may recruit participants from the University of Delaware Stroke Research Registry (IRB# 
1642798). Please see attached Study Approval Letter. Participants recruited through other 
means will be offered the opportunity to enroll in the Stroke Research Registry when they 
consent to this study. Lab members will be instructed to emphasize that enrolling in the Registry 
is completely voluntary and the participant’s choice to enroll or not has no effect on their 
participation in this study or any other studies conducted at the University of Delaware. 
 
Regardless of recruitment method, during the initial phone call or email a member of the 
research team will describe the purpose and general procedures of the study. We will explain 
what to expect and the potential risks and benefits of participation. We will also inform the 
potential participant that joining the study is completely voluntary and that he/she is free to 
reconsider or stop participation at any time. If the potential participant expresses interest in 
agreeing to join, we will then proceed with a series of screening questions to determine if the 
person might be eligible (see Appendices). For subjects that do not appear to be eligible, 
screening forms will be destroyed. No additional documentation (e.g.- consent forms, HIPPA 
forms) will be handled by UD in regards to UPenn or IU subjects.   
 

18 
 
Once potential eligibility for a participant is determined, 
subjects will be scheduled for PRE Clinical Baseline Testing.  
During the PRE Clinical Baseline Testing, subjects will fill out 
the PROWALKS Consent form, the Stroke Registry Consent 
form and the PROWALKS Medical Clearance formThe 
medical clearance must be completed prior to participating in 
the submaximal stress test.  Medical clearance can be given 
verbally to a Stroke Team member following discussion with 
the provider. The medical clearance form will be noted to 
indicate the information that was provided verbally, along with 
the date of the receipt of that information, the provider’s name, 
and the signature of the person obtaining the information. If we 
become aware of a new medical issue with a participant that 
would likely impact their participation in future studies we will 
relay this information for inclusion in the Stroke Research 
Registry (IRBNet Protocol ID# 1642798, Stroke Research Registry) so that other investigators 
potentially interested in recruiting this person into a different study are aware. 
 
At the time of the first evaluation session, a member of the research team will first review the 
informed consent documents in detail with the potential participant. This will include a 
description of the study purpose and procedures, inclusion and exclusion criteria, the potential 
risks and benefits of participating, alternatives to participating, subjects’ rights (such as 
withdrawal from the study, etc.) and compensation. The participant will be encouraged to ask 
questions and express concerns at any time during the consenting procedure or thereafter. If 
the participant agrees to be in the study, he/she will be asked to sign the informed consent 
document.  
 
The figure illustrates the basic study design. Each evaluation session will last 1-3 hours and 
each training (intervention) session will last approximately 1 hour. There are a total of 8-12 
evaluation sessions and 36 intervention sessions. 
 
Testing Procedures 
 
Baseline evaluation session.  Subjects will undergo a brief battery of clinical assessments 
conducted by a trained member of the research team. Clinical assessments will include 
collection of medication and co-morbidity information, blood pressure, heart rate and body mass 
index, the 10 meter walk test, the 6 minute walk test, the Activities Specific Balance Confidence 
scale (ABC), the Patient Health Questionnaire nine-item depression scale (PHQ-9), and the 
Montreal Cognitive Assessment (MoCA) (see Appendices). In addition, subjects will be provided 
with a Stepwatch Activity Monitor and/or Fitbit activity monitor and instructed in its wear and 
use. Subjects will wear the monitor for 1 week. Following this baseline evaluation session and 
the 1 week step monitoring, the inclusion criteria of walking speed between 0.3 and 1.0 m/s and 
steps/day less than 8000, can be evaluated and continued eligibility confirmed. If subjects do 
not meet these criteria after evaluation, they will be withdrawn from the study. 
If any subject scores ≥5 on the PHQ-9, they will be informed of their score and advised 
to discuss this with their primary physician. In addition, for any participant endorsing suicidal 
ideation on one or more test items on PHQ-9, (1) we will notify the physician and (2) we will give 
the participant the telephone number for Crisis Intervention Services of Northern Delaware (302-
577-2484 or 800-652-2929) which is staffed 24 hours/day, 7 days a week, to whom they can 
reach out if they feel desperate, hopeless and/or at risk for suicide. This is standard procedure 
for clients in the Physical Therapy Clinic. 

19 
 
Symptom limited graded exercise test.  Prior to beginning the intervention, all subjects will 
undergo a symptom limited graded exercise test (GXT) on a motorized treadmill in the Nurse 
Managed Health Center (NMHC) under the supervision of a nurse practitioner and an exercise 
physiologist. During the GXT a12 lead electrocardiogram and breath by breath analysis of 
oxygen consumption with a metabolic cart will be recorded. The results of the test will be 
reviewed by a cardiologist for abnormal responses that would prevent the subject from safe 
participation. 
Subjects will have up to 5 ml of blood drawn by a trained practitioner in the NHMC for 
measurement of blood lipids and glucose at each of the testing time points (baseline, post-
intervention and 6 and 12 month follow-up evaluation sessions). 
 
Post-intervention and follow-up evaluations. Post, 6 and 12 month evaluation sessions will be 
identical to the baseline evaluation including the graded exercise test for the purposes of 
measuring changes in oxygen consumption that may have occurred with the intervention and 
measurement of blood lipids and glucose. 
 
In order to examine the potential secondary prevention benefits of the intervention, at the 6 and 
12 month follow-up appointment subjects will be asked about major adverse cardiovascular and 
cerebrovascular events (MACCE); specifically if they have had: recurrent stroke, myocardial 
infarction, unstable angina requiring hospitalization or peripheral artery event and the date of 
that event. This data will be confirmed for accuracy through contact with the subject’s physician. 
Phone follow-up at 2 years will be completed for subjects enrolled in the first 2 years of the 
study to collect longer term follow-up data on these events. Information received from subjects 
will be confirmed by their physician (see Appendices). If subjects have any of these events 
during the course of the study, they will be withdrawn from all testing and training, except we will 
continue to track them for MACCE. 
 
Decisions will be made regarding withdrawing subjects at 6 and 12 months by gathering medical 
record information as needed for subjects who report changes in their health history.    Self-
reported and non-physical measures may still be collected at 6 and 12 month time points even if 
they are not able to perform physical testing.  
 
In addition to the 6 and 12 month follow-up, subjects will be contacted by the Stroke Studies 
Coordinator at UD at 4.5, and 9 months post baseline testing to check in as a means to 
improve subject retention. Subjects will be told that we are calling to check in. We will ask them 
if anything has changed since their last visit/phone call, including address, contact information, 
physician. Any changes in this information will be updated in the database.  
 
 
Intervention Procedures 
Subjects will be randomly assigned to one of 3 groups: fast walking training (FAST), a 
step activity monitoring program (SAM) or a fast walking training + step activity monitoring 
program (FAST+SAM).  
 
Walking training. All subjects in the FAST and FAST+SAM groups will complete walking training 
for 30 minutes, with a goal of 3x/week for 12 weeks. These participants will complete a fast 
walking treadmill training program followed by approximately 10 minutes of over-ground walking 
activities. All treadmill walking will be completed while subjects wear an overhead chest-harness 
system for safety; no body weight support will be provided. Subjects will walk for 30 minutes 
with the goal of walking at the fast training speed, one at which Target Heart Rate (calculated 
using the Karvonen formula)1 is achieved: (THR) = ((max HR found on GXT) - Resting heart 

20 
 
rate) x 80%)+ Resting heart rate1. The fast training speed interval is reduced if the subject 
requests to walk slower, the fast speed is no longer safe (e.g. increased toe scuffing or tripping), 
the subject reports a rate of perceived exertion of  ≥17 on the 6-20 Borg Rate of Perceived 
Exertion Scale2 and/if THR is exceeded. The treadmill speed is lowered to allow the heart rate 
to return to, ((max HR found on GXT) – Resting heart rate) x 50-60%)+ Resting heart rate 
(Karvonen formula)1, or to a rate of perceived exertion ≤13. If the HR is not steadily decreasing 
and the recovery criteria are not achieved within approximately 1 minute by walking slower, the 
treadmill is stopped and the subject takes a standing or seated rest break to achieve recovery. 
Once recovery is reached, the subject is transitioned to the fast training speed again.  
 
Following treadmill walking, 10 minutes of over-ground walking activities are performed with the 
same THR and perceived exertion criteria as on the treadmill. Subjects are guarded and 
activities are progressed by a physical therapist. The purpose of this portion of the session is for 
the participant to practice walking activities experienced during everyday activities (e.g. turning, 
backward stepping, walking while carrying objects) to gain both skill and confidence with these 
routine walking activities that are important in real-world walking.  
 
During training, the RPE2 will be assessed every 2 minutes and heart rate will be continuously 
monitored.  Blood pressure is tested prior to the initiation of any activity. It is also checked at the 
Research PT's discretion any time walking is stopped, including rest breaks, at the end of 
treadmill walking (prior to the start of over ground walking) and following over ground walking. 
For all sessions, the guidelines set forth by the American College of Sports Medicine for 
individuals in phase III or IV of cardiac rehabilitation will be followed1. Based on these 
guidelines, we have developed session termination criteria. A session will be terminated if any 
of the following occur: 
 
Drop in Systolic blood pressure of > 10mmHg from baseline (resting for that day) despite 
increase in workload 
 
Hypertensive response with a systolic blood pressure >240 mmHg and diastolic blood 
pressure >110 
 
Presence of nervous system symptoms: ataxia, dizziness, or near syncope 
 
Any chest pain or angina symptoms 
 
Signs of poor perfusion cyanosis or pallor 
 
Excessive fatigue, excessive shortness of breath, leg cramps, claudication 
If any of the above occurs, the subject’s physician will be contacted and informed of the 
subject’s response to the activity.  Subjects can also terminate any session or training bout by 
stating their desire to stop. 
   
Step activity monitoring program. Subjects in the SAM and FAST+SAM groups will participate in 
the step activity monitoring program and will be provided with a Stepwatch Activity Monitor 
and/or Fitbit. If the device is lost or damaged, it will be replaced to allow continued participation 
in the step activity monitoring program. Baseline step activity data for subjects in the 
FAST+SAM and SAM groups will be used to categorize and assign step activity goals. It is 
important to note that goals are set not based on an absolute number for all subjects, but rather 
individually, based on their own baseline walking. Goals are advanced based on subject 
achievement of previous goals. For subjects in the FAST+SAM group, step activity data is 
reviewed at each treadmill training session and used to determine and promote goal 
achievement. Subjects in the SAM group will visit the clinic 3x/week for this review. Step activity 
data in the interim days between sessions will reviewed and used to assist subjects in 

21 
 
understanding how much walking activity they performed during certain daily activities, like 
walking to the mailbox or walking laps around their home, and how that added to their total 
steps per day. Subjects are also advised of how their steps per day related to goal achievement; 
a discussion of individualized ideas to increase activity and of any barriers and how to overcome 
those barriers. These discussions have been shown to be critical for the success of a step 
activity monitoring program.  
Subjects in the FAST group will be instructed not to begin the use of a step monitor during the 
study.  
 
7.  STUDY POPULATION AND RECRUITMENT 
Recruitment and Enrollment Procedures: 
 
Subjects will be recruited from a variety of sources. For recruitment at the University of 
Delaware we will utilize the University of Delaware Stroke Studies Registry, a database of 
stroke survivors who are interested in participating in research. The use and maintenance of the 
Registry is described in detail in IRBNet Protocol ID# 619037-1, entitled “Shared Pre-enrollment 
Process for Stroke Research Team Studies”, PI Reisman, Co-PI Morton (see Appendices). 
People are recruited and phone-screened through this protocol. Additionally, medical opinion of 
fitness to participate in research form is obtained from the acting physician through this protocol. 
Individuals from the registry who appear likely to meet eligibility requirements will be contacted 
by telephone. See details of registry protocol procedures in attached Appendices. In addition, 
other persons with stroke will be recruited via local physical therapy practices, physicians’ 
offices and support groups. Other recruiting could occur through the PI(s) public speaking 
engagements or by word of mouth from visitors to the lab or past participants in stroke studies.  
 
Recruitment will also take place through the Christiana Care Portal and Focus.  The portal is the  
internal Christiana Care Home Page with internal breaking news and announcements of interest 
across the organization.  All CCHS employees would see this. The FOCUS, is a biweekly 
publication distributed to CCHS employees, volunteers, and retirees of Christiana Care Health 
System. Recruitment will also include contact of CCHS patients who have been admitted in the 
CCHS system with a diagnosis of stroke (See Appendix I for CCHS documentation that allows 
for contact of patients for research).  
 
If the potential participant is found to be interested and potentially eligible, we will schedule an 
appointment for the laboratory testing. In addition, the participant’s primary care physician will 
be contacted to obtain the Medical opinion of fitness to participate in research form for full 
participation in the study if it has not already been obtained (see IRBNet Protocol ID# 619037-1 
in Appendices for details). This form is reviewed upon receipt. If it is noted that the medical 
provider does not check off either "Any serious cardiovascular or cardiopulmonary condition 
preventing participation" or "Any serious musculoskeletal or other medical condition preventing 
participation" on the Medical opinion of fitness to participate in research form, the potential 
participant will be scheduled for participation in the study. If the medical provider does check off 
either "Any serious cardiovascular or cardiopulmonary condition preventing participation" or 
"Any serious musculoskeletal or other medical condition preventing participation" on the form, a 
member of the research team will contact the medical provider to get more information on the 
specific medical condition, if it is not provided on the form. If appropriate, the investigator will 
provide specific information regarding the study protocol to the medical provider. If, after this 
conversation, the medical provider no longer feels there are any serious conditions preventing 
participation, this will be indicated on the form and the potential participant will be scheduled for 
the study.  
 

22 
 
Medical records may also be obtained for CCHS and UD subjects via the DHIN (Delaware 
Health Information Network) if subjects agree to this when signing the HIPAA form. These 
records for PROWALKS subjects will not be stored with information from IRB  Protocol ID# 
619037-1, through which HIPAA form is completed. 
Appendix H highlights the policies related to accessing the DHIN and its security.   
Personnel accessing the DHIN will be lmited to PI- Darcy Reisman and Research PT’s- Tamara 
Wright and Henry Wright.  Only subjects enrolled following approval of this amended protocol 
will be eligible to have medical records retrieved through the DHIN. The DHIN will provide 
access to the following: 
 
Community Health Record: Provides on-demand, patient level access to clinical and 
demographic information that has been collected on DHIN since 2007 
 
Event Notification System (ENS): Provides near real-time alerts when a participants 
admitted to a DHIN participating hospital, including all hospitals I Delaware, Maryland 
and Washington DC. 
 
Clinical Gateway: A real time feed of labs, radiology studies, transcription summaries 
and ambulator practice care summaries from all of DHINS’s clinical data senders, A 
historical load of clinical data may also be provided 
Event Notification and Clinical Gateway are panel based services so only information for 
patients matching the roster as provided by PROWALKS will be delivered by DHIN.  DHIN 
restricts access to the Community Health Record (CHR) and strictly monitors the access 
behaviors of its users.  For PROWALKS, DHIN will receive and retain the disclosures of 
participating patients and will review their access to the CHR on a weekly basis and will conduct 
a reconciliation of the records accessed by PROWALKS staff versus their patient panel to 
ensure that patient records are not inappropriately being accessed.  Per DHIN PHI access 
policies, any variation will be escalated to PROWALKS executive leadership for their review and 
for an explanation as to the access, as there may be a valid clinical reason for the 
access.  DHIN procedures for escalating issues will be applied in circumstances where a valid 
access reason does not apply to a system access. 
 
Describe what exclusionary criteria, if any will be applied. 
 
The specific subject inclusion and exclusion criteria are: 
Inclusion Criteria: 1) Age 21-85*, 2) Chronic stroke (>6 months post stroke)*, 3) Able to walk at 
self-selected speed without assistance from another person (assistive devices are allowed), 4) 
Self-selected walking speed <1.0 m/s*, 5) Average steps/day <8,000, 6) Resting heart rate 
between 40-100 beats per minute*, 5) Resting blood pressure between 90/60 to 170/90*. 
Exclusion Criteria: 1) Evidence of cerebellar stroke*, 2) Other potentially disabling neurologic 
conditions in addition to stroke*, 3) Lower limb Botulinum toxin injection <4 months earlier, 4) 
Current participation in physical therapy, 5) Inability to walk outside the home prior to the stroke, 
5) Coronary artery bypass graft, stent placement or myocardial infarction within past 3 months*, 
6) Musculoskeletal pain that limits activity, 7) Inability to communicate with investigators, 8) score 
>1 on question 1b and >0 on question 1c on the NIH Stroke Scale, 9) Self-selected walking speed 
<0.3 m/s*. 
 
*For recruiting participants from the Stroke Research Registry, criteria with asterisks represent 
data found in the Registry and may be used in search queries to more efficiently find individuals 
to contact who would be qualified to participate in this study. 
 
 
The inclusion and exclusion criteria are discussed at the initial screening and again on the first 

23 
 
testing day when the informed consent document is reviewed. Determining whether all criteria 
on the Inclusion and Exclusion Criteria Checklist (see Appendices) are met is based on a 
combination of subjects’ individual responses and information from other documentation. Two 
inclusion criteria (walking speed between 0.3 and 1.0 m/s and steps per day <8,000) cannot be 
evaluated until the baseline evaluation is completed. Therefore, subjects will be withdrawn from 
the study if these criteria are not met following this evaluation.  
 
Describe what (if any) conditions will result in PI termination of subject participation. 
 
Participation in the study is voluntary. Any subject may withdraw from the study at any time 
without any negative consequences. In addition, the PI may terminate a subject’s participation if 
the subject is viewed by the PI to be placing him/herself at risk. This is not expected, but could 
potentially occur. Similarly, the subject may be withdrawn from the study based on abnormal 
results identified on the symptom-limited graded exercise test. 
 
8.  RISKS AND BENEFITS 
List all potential physical, psychological, social, financial or legal risks to subjects (risks 
listed here should be included on the consent form). 
 
Participation in any physical activity or exercise has risk.  These risks include but are not limited 
to, pain, fainting, dizziness, fatigue, nausea, shortness of breath, chest pain or angina, 
myocardial infarction, swelling, bruising, muscle/bone/joint soreness, joint damage, bone 
fracture, ligament/tendon/connective tissue damage, hospitalization, and death.  
 
Psychological risks include possible discomfort, frustration, and/or anxiety related to difficulty with 
the physical testing or completion of questionnaires. 
 
Graded exercise testing carries a low risk of myocardial infarction/cardiac arrest (1/2500; 
ACC/AHA) and patients will be made aware of this risk prior to testing. However, graded exercise 
testing is a standard procedure for diagnostic purposes, evaluation of functional capacity, and the 
effectiveness of both exercise and pharmacological interventions. 
The risks of taking blood include pain and/or bruising where the blood is taken, redness and 
swelling of the vein and infection, and a rare risk of fainting. 
 
In your opinion, are risks listed above minimal* or more than minimal? If more than minimal, 
please justify why risks are reasonable in relation to anticipated direct or future benefits. 
 
The risks of the study are not more than minimal. 
 
What steps will be taken to minimize risks? 
 
During treadmill walking subjects are allowed rest breaks whenever requested or deemed 
appropriate by the experimenter. Because participants who have sustained a stroke may be at 
increased cardiovascular risk, when a potential post-stroke participant contacts the team, they 
will be asked to provide consent to allow the investigators to contact the referring or primary 
physician to obtain medical opinion of fitness to participate in research. Potential participants will 
only be brought to the laboratory for testing once the medical opinion of fitness has been 
obtained. Prior to the initiation of training, all subjects will undergo a 12 lead symptom limited 
graded exercise test reviewed by a cardiologist. All subjects will wear a heart rate monitor 
during testing and training. During all treadmill walking, subjects will wear a harness connected 

24 
 
to an overhead support. During walking training,  the Borg Scale of perceived exertion (RPE) 1 
will be measured every 2 minutes and heart rate will be continuously monitored.  For all training 
sessions, the guidelines set forth by the American College of Sports Medicine (ACSM) for 
individuals in phase III or IV of cardiac rehabilitation will be followed. Based on these guidelines, 
a session will be terminated if any of the following conditions occur: 
 
 Drop in Systolic blood pressure of > 10mmHg from baseline (resting for that day) despite 
increase in workload 
 
Hypertensive response with a systolic blood pressure >240 mmHg and diastolic blood 
pressure >110 
 
Presence of nervous system symptoms: ataxia, dizziness, or near syncope 
 
Any chest pain or angina symptoms 
 
Signs of poor perfusion cyanosis or pallor 
 
Excessive fatigue, excessive shortness of breath, leg cramps, claudication  
 If any of the above occurs, the subject’s physician will be contacted and informed of the 
subject’s response to the activity.  Subjects can also terminate any session or training bout by 
stating their desire to stop. 
 Prior to the Graded Exercise Test (GXT), a Cardiac Guidelines Letter (Appendix E) will be sent 
to the subjects' MD when deemed necessary based on medical history. This will allow the MD to 
place any additional guidelines they would like us to follow during the GXT,  training 
intervention/future evaluations in regards to heart rate and/or blood pressure.  
Any incidents involving injury to study subjects will be presented to the Data and Safety 
Monitoring Board and the IRB immediately.   Please see information related to the Data and 
Safety Monitoring Board below. 
 
Describe any potential direct benefits to participants. 
The direct benefit to the subjects participating in training could be substantial. Previous research 
has shown that 12 weeks of treadmill training can lead to improvements in walking speed and 
activity. So regardless of the effects of our specific intervention, subjects are likely to obtain 
some benefit of participation. This will be explained to all subjects. The methods of study will 
provide sensitive, objective measures of walking function and activity, which would be useful in 
monitoring progress, or the lack of it, across time and therapy. This will be explained to all 
subjects. 
 
Describe any potential future benefits to this class of participants, others, or society. 
 
The potential benefits of this study are that we may understand mechanisms and interventions 
to improve physical activity in chronic stroke survivors. The knowledge gained will provide an 
understanding of the optimal characteristics of rehabilitation interventions to promote functional 
walking recovery post stroke. Because of the potential for these results to lead to development 
of new approaches to rehabilitation interventions for stroke survivors that could significantly 
impact secondary prevention of future stroke and other conditions, the potential benefits far 
outweigh the minimal risks. 
 

25 
 
If there is a Data Monitoring Committee (DMC) in place for this project, please describe 
when and how often it meets.  
There is a Data and Safety Monitoring Board (DSMB) for this study. Please see the description 
of the example DSMB Charter in the Appendices. 
 
 
9.  COMPENSATION 
Will participants be compensated for participation?  Yes. 
 
If so, please include details. 
 
Subjects will be paid $100.00 for participation, $25.00 after each of the evaluation time points is 
completed. 
 
Participants are responsible for transportation to the study site for each visit. In some situations, 
if a participant cannot arrange transportation alone, transportation will be arranged for them.  
 
10.  DATA 
Will subjects be anonymous to the researcher? 
 
 
Subjects will not be anonymous to the researchers.  As part of the consent process and 
verification of eligibility, subjects must provide their name, date of birth and other identifying 
information to members of the research team. However, identities will be kept confidential to the 
extent possible (see Confidentiality section below). De-identified data may be presented in 
abstract, poster, presentation, or published manuscript format. 
 
If subjects are identifiable, will their identities be kept confidential? (If yes, please specify 
how) 
 
Subject identities will be kept confidential by assigning each subject a number.   
 
How will data be stored and kept secure (specify data storage plans for both paper and 
electronic files. For guidance see http://www.udel.edu/research/preparing/datastorage.html )    
 
Encrypted electronic files that connect subject identities to their subject code will be stored in a 
database on a password protected UD managed server for the UD and CCHS subjects. Similar 
processes are in place at UPenn and IU for their subjects. These files are not shared between 
sites.  Paper copies of consent forms for each site will be stored on-site. Paper copies of the 
screening form for subjects that sign the Informed Consent are also stored at each site.  
All coded subject data will be collected and managed using REDCap electronic data capture 
tools hosted by the University of Delaware's Delaware Rehabilitation Institute.  REDCap 
(Research Electronic Data Capture) is a secure, web-based application designed to support 
data capture for research studies.  All sites will have access to the coded data in the REDCap 
database. 
 
 
How long will data be stored? 
 
All de-identified data will be stored indefinitely and may be used in future research studies. 
 

26 
 
Will data be destroyed?  X YES  □  NO (if yes, please specify how the data will be destroyed)  
Data with identifying information will be saved until the project is complete or the data are 
published, whichever comes first and then the identifiable data will be destroyed. This will 
involve all electronic data being wiped from hard-drives and servers and all paper data being 
shredded. Raw de-identified data will be stored indefinitely and may be used in future related 
studies. 
 
Will the data be shared with anyone outside of the research team?  x YES   NO  
These data will be used by the current investigative team, and then, in compliance with NIH 
policy, shared with others through the NICHD DASH repository so that additional analyses can 
be performed. Once the primary hypotheses of the current proposal are tested, all data will be 
cleaned, de-identified, and be deposited in the DASH repository. To ensure that the identities of 
research subjects cannot be readily ascertained with the data, NICHD DASH will store only data 
that are without identifiers and coded. According to NICHS DASH requirements, before 
submitting the data to NICHD DASH, investigators must:  
c. Strip the data of individually identifying information according to:  
o 
the standards set forth in the HHS Regulations for the Protection of Human 
Subjects and related guidance (which covers individually identifiable private 
information), and 
o 
the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule 
(which covers protected health information); and 
d. Assign to the de-identified data random, unique codes. 
How will data be analyzed and reported?  
 
Appropriate statistical analysis of the primary (General Linear Mixed Modeling) and exploratory 
(Cox Proportional Hazards Model and a Generalized Estimating Equation) outcomes will be 
completed under the direction of the biostatistician on the project.   The results will be reported 
to professionals interested in research via journals and presentations. 
 
11. CONFIDENTIALITY 
Will participants be audiotaped, photographed or videotaped during this study? 
 
Individual subjects may be approached and asked to be photographed or videotaped for 
recruitment, educational or research purposes. A photo release form will be signed by 
participants prior to any photographs or videotape taken. Subjects will be told that this is an 
optional activity and not a requirement of participation. Photographs or video will have the face 
covered. 
 
How will subject identity be protected? 
 
All participants’ identifying information will be stored in a locked file cabinet (paper forms) or on 
password-protected computers or servers (electronic forms) and will be utilized only by 
investigators on the protocol who have a specific need for the identifying information. All data 
will be coded using a numerical system, the key to which will be maintained on a password-
protected computer at UD for the UD and CCHS subjects and at UPenn and IU for their 
subjects. This data is maintained in the REDCap database as described above. 

27 
 
For medical information obtained through the DHIN:  
DHIN restricts access to the Community Health Record (CHR) and strictly monitors the access 
behaviors of its users.  For PROWALKS, DHIN will receive and retain the disclosures of 
participating patients and will review their access to the CHR on a weekly basis and will conduct 
a reconciliation of the records accessed by PROWALKS staff versus their patient panel to 
ensure that patient records are not inappropriately being accessed.  Per DHIN PHI access 
policies, any variation will be escalated to PROWALKS executive leadership for their review and 
for an explanation as to the access, as there may be a valid clinical reason for the 
access.  DHIN procedures for escalating issues will be applied in circumstances where a valid 
access reason does not apply to a system access. 
Medical records obtained through the DHIN for PROWALKS subjects will not be stored with 
information from IRB  Protocol ID# 619037-1, through which HIPAA form is completed. 
 
 
Is there a Certificate of Confidentiality in place for this project?  (If so, please provide a copy). 
 
There is no Certificate of Confidentiality in place for this project.   
 
 
12. CONFLICT OF INTEREST 
(For information on disclosure reporting see: http://www.udel.edu/research/preparing/conflict.html ) 
 
Do you have a current conflict of interest disclosure form on file through UD Web forms? Yes 
Does this project involve a potential conflict of interest*?  NO 
 
* As defined in the University of Delaware's Policies and Procedures ,a potential conflict of interest (COI) occurs 
when there is a divergence between an individual's private interests and his or her professional obligations, such that 
an independent observer might reasonably question whether the individual's professional judgment, commitment, 
actions, or decisions could be influenced by considerations of personal gain, financial or otherwise. 
 
 
 
If yes, please describe the nature of the interest: 
 
 
 
13.  CONSENT and ASSENT 
 
__X__ Consent forms will be used and are attached for review (see Consent Template under Forms 
and Templates in IRBNet) 
 
 
____ Additionally, child assent forms will be used and are attached. 
 
 
____ Waiver of Documentation of Consent (attach a consent script/information sheet with the 
signature block removed). 
 
 
____ Waiver of Consent (Justify request for waiver) 
 

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14.  Other IRB Approval 
Has this protocol been submitted to any other IRBs? This study has been approved by the 
University of Pennsylvania’s and  Indiana University’s IRB and that approval has been 
submitted as an amendment to this protocol. An Institutional Review Board Authorization 
Agreement has been signed between CCHS and UD. 
 
15.  Supporting Documentation 
Please list all additional documents uploaded to IRBNet in support of this application. 
 
Appendices which include IRBNet Protocol ID# 619037-1, entitled “Shared Pre-enrollment Process 
for Stroke Research Team Studies”, that is referenced in this protocol, along with copies of 
specific clinical tests, screening questions and the inclusion/exclusion checklist for this protocol. 
 
A separate Appendix is attached with the example DSMB charter. 
 
REFERENCES 
3. 7th ed. Philadelphia: Lippincott, Williams and Wilkines; 2006. American College Of Sports 
Medicine (ACSM) – Guidelines for exercise testing and prescription. 
4. Borg G. Perceived exertion as an indicator of somatic stress. Scand J Rehabil Med 1970;2(2):92-
8. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

29 
 
Summary of protocol changes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

30 
 
Summary of protocol changes  
 
Approval date 
Description of protocol changes 
3/23/2016 Initial approval 
5/1/2017 
To exclude individuals who walk at <0.3m/s (due to limitations of Fitbit sensitivity); to ensure 
consistency in language describing training phase in protocol and consent form 
10/16/2018 To add IU as an evaluation and training site 
9/28/2020 
To add language to consent form to reflect that while risk of COVID-19 exposure will be 
minimized, the risk of exposure cannot be completely eliminated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

31 
 
Original statistical analysis plan 
(excerpted from original IRB protocol 
(2016), NIH grant application (2014), and 
published protocol (2018)1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

32 
 
General data management & analysis  
Encrypted electronic files that connect subject identities to their subject code will be 
stored in a database on a password protected server.  Paper copies of consent forms 
for each site will be stored on-site. Paper copies of the screening form for subjects that 
sign the Informed Consent are also stored at each site. 
The Biostatistician running analyses is blinded to group assignment. An “intent to treat” 
analysis will be performed. To ensure that the randomization worked, potential 
covariates (e.g. age, time since stroke, cognition) will be compared between groups 
using t-tests and χ2 tests. If a covariate is significantly different between groups, this will 
be an indication that the groups are not balanced and the covariate will be included in 
the models. The alpha is set at 0.05 for primary analyses and .01 for secondary 
analyses. 
Aims 1 & 2 will be tested using General Linear Mixed Models (GLMM). To compare the 
efficacy of the FAST+SAM, FAST and SAM interventions for improving real-world 
walking activity in chronic stroke survivors and to determine for whom the interventions 
are most effective General Linear Mixed Models (GLMM) will be developed. All model 
assumptions will be tested (including linearity, normality, homoscedasticity, and 
multicollinearity). Outliers and influential cases will be screened for and removed. 
Violations of the assumptions will be remedied using transformations or a Generalized 
Linear Model. Post-hoc tests in the GLMMS will use Bonferroni adjustment and for the 
regression models post-hoc probing of interactions will be done using simple slopes 
method.2 
For the GLMMs, the covariance structure will be chosen using nested model 
comparisons. The regression models also have the assumptions of homoscedasticity 
and multicollinearity, which will be tested using the Breusch-Pagan test, and by 
examining the condition index and variance inflation factor, respectively. To eliminate 
ignorable collinearity caused by the inclusion of interaction terms, continuous variables 
will be centered before being entered into the models. Site differences will also be 
tested, and if differences exist, will be included in the model to control for them. 
Power analysis & sample size 
The precise increase in steps/day necessary to reduce the risk of secondary health 
complications and disability post-stroke is not known, however, studies in other at risk 
populations have shown a reduction in cardiovascular events with an increase of 2,000 
steps/day.5  Previous studies in chronic stroke, along with our data, suggest an 
improvement in ~1000 steps/day with fast walking training alone3 and our recent study 
suggests an improvement of ~1100 steps/day with a step activity monitoring program 
alone.4  Our data from the FAST+SAM intervention suggests an improvement of ~1700 
steps/day in those with low steps/day at baseline and an improvement of ~250 
steps/day for those in FAST with low baseline steps/day. Given this, we would consider 
an average improvement of ≥1700 steps/day in the FAST+SAM group worthy of further 
study in future clinical trials. Power calculations indicate that a total of 225 participants 

33 
 
are needed (75 in each of the 3 groups) in order to detect this differential increase 
based on baseline steps/day and intervention received with power greater than 0.90. 
These calculations assume equal group sizes, a moderate correlation among repeated 
measures of r=0.50, and a standard deviation for steps/day of 2,500.3,4      
Expected outcomes and aim specific analysis 
Aim 1. To compare the efficacy of the FAST+SAM, FAST and SAM interventions for 
improving real-world walking activity in chronic stroke survivors and to determine for 
whom the interventions are most effective. The primary measure for this Aim is number 
of steps per day (SPD). Data will be calculated at each time point (Baseline, post-
treatment, 6 and 12 month follow-up) by finding the average number of SPD over one 
week. 
H1.1. All 3 interventions will improve real world walking activity immediately post-
intervention. 
A GLMM will be used to evaluate changes in SPD from pre- to post-training. For this 
hypothesis the main effect of time will be compared, averaged across groups. If the 
main effect of time is significant, this research question can be answered using the 
marginal pairwise comparisons of SPD at baseline with post-training. If an interaction is 
significant, the simple main effect of time will be compared between interventions.  
Aim 2. To compare the efficacy of the FAST+SAM, FAST and SAM interventions for 
improving walking speed, endurance and cardiorespiratory function in chronic stroke 
survivors and to determine for whom the interventions are most effective. The primary 
measure for this Aim is distance covered during the 6 minute walk test (6MWT). The 
secondary measures for this Aim are self-selected walking speed as measured during 
the 10 meter walk test (SSWS) and cardiorespiratory function as measured by peak 
oxygen consumption during graded exercise testing (VO2 peak).  Data will be calculated 
at each time point (Baseline, post-treatment, 6 and 12 month follow-up). 
The same exact analyses used in Aim 1 for all the hypotheses will be used in Aim 2 but 
with the outcomes of 6MWT, SSWS and VO2 peak. Separate models will be completed 
for the 6 and 12 month time point. 
 
 
 
 
 
 

34 
 
 
 
 
Updates to statistical analysis plan 
(excerpted from final IRB protocol 
(2023), ClinicalTrials.gov registry (2022)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

35 
 
General data management & analysis - all changes from initial plan were to 
incorporate use of REDCap electronic databases to increase data accuracy, 
accessibility, and security: 
Encrypted electronic files that connect subject identities to their subject code will be 
stored in a database on a password protected UD managed server for the UD and 
CCHS subjects. Similar processes are in place at UPenn and IU for their subjects. 
These files are not shared between sites.  Paper copies of consent forms for each site 
will be stored on-site. Paper copies of the screening form for subjects that sign the 
Informed Consent are also stored at each site. 
All coded subject data will be collected and managed using REDCap electronic data 
capture tools hosted by the University of Delaware's Delaware Rehabilitation 
Institute.  REDCap (Research Electronic Data Capture) is a secure, web-based 
application designed to support data capture for research studies.  All sites will have 
access to the coded data in the REDCap database. 
Data from each evaluation session will be entered directly into the PROWALKS 
REDCap Clinical database. This database is designed with built in quality control 
checks (e.g., range checks, checking for missing data for required data points). In 
addition, each month the UD Research PT will examine frequency distributions of 
outcome variables to identify questionable data points. 
Data from each training session will be entered directly into the PROWALKS REDCap 
Training database. This database is designed with built in quality control checks (e.g., 
range checks, checking for missing data for required data points). In addition, each 
quarter the UD Stroke Studies Coordinator will review a random sampling of data from 6 
sessions at each site according to the Treatment Fidelity checklist webform. 
Expected outcomes and aim specific analysis 
There were no changes to expected outcomes and planned aim specific analysis 
between the start and end of the study. 
 
 
 
 
 
 
 
 
 
 

36 
 
References 
1. Wright H, Wright T, Pohlig RT, Kasner SE, Raser-Schramm J, Reisman D. Protocol for 
promoting recovery optimization of walking activity in stroke (PROWALKS): a randomized 
controlled trial. BMC Neurol. 2018;18(1):39. doi:10.1186/s12883-018-1044-1 
2. Aiken LS, West SG, Reno RR. Multiple Regression: Testing and Interpreting Interactions. 
SAGE; 1991. 
3. Moore JL, Roth EJ, Killian C, Hornby TG. Locomotor Training Improves Daily Stepping Activity 
and Gait Efficiency in Individuals Poststroke Who Have Reached a “Plateau” in Recovery. 
Stroke. 2010;41(1):129-135. doi:10.1161/STROKEAHA.109.563247 
4. Danks KA, Roos MA, McCoy D, Reisman DS. A step activity monitoring program improves real 
world walking activity post stroke. Disability and Rehabilitation. 2014;36(26):2233-2236. 
doi:10.3109/09638288.2014.903303