Ischemic Conditioning Improves Walking Function Post Stroke
Phase: NA
Conditions: Stroke, Stroke, Ischemic, Stroke Hemorrhagic, Stroke, Cardiovascular
Sponsor: Medical College of Wisconsin

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STUDY PROTOCOL 
 
STUDY TITLE:  ISCHEMIC CONDITIONING IMPROVES WALKING FUNCTION POST 
STROKE 
 
DATE OF DOCUMENT: 7/26/2019 
 

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1  
 
Institutional Review Board 
Study Protocol Form 
 
This sheet and the entire protocol form will be maintained throughout the life of the study.  
 New Study Submission 
 
 
 
 
 
Date submitted 
Date approved 
12/7/18 
12/20/18 
 
Amendment submissions (add rows at bottom of table as needed) 
For each amendment submission complete one row of the table below. 
Indicate all changes by modifying the Protocol Form and any other applicable study documents using track 
changes, or highlights, as a means to distinguish between previously approved information and current requested 
changes. Documents submitted without distinguishing between “new” vs “old” content will be returned to the PI.  
DO NOT DELETE PAST ACTIONS FROM THIS TABLE 
Date 
submitted  
List changes requested 
Justification for the change 
Date approved 
3/2019 
MCW Reliance 
Request 
Matthew Durand and Jennifer Nguyen are 
employees of MCW. All study activities 
occur at MU. 
4/2019 
5/6/2019 
Addition of study 
personnel. 
Assist with data collection (Zhilun Zhou, 
Ashley Dejaco) 
5/7/2019 
7/3/2019 
1. Addition of 
cardiovascular 
testing. 
2. Addition of study 
personnel 
3. Change in 
exclusion criteria 
4. Addition of 
recruiting via 
MCW 
1. Measuring estimated VO2 max ( a sub-
maximal, modified version of VO2 max 
testing) will allow us to better understand 
how ischemic conditioning improves 
cardiovascular function during exercise in 
chronic stroke. 
2. Matthew Durand and Jennifer Nguyen 
(Dept. of PMR, MCW), Saad Alqahtani 
(Grad. Student MU), Toni Uhrich (Staff, 
MU,Health Performance Assessment core) 
3. Removing the exclusion criteria of multiple 
strokes. 
07/19/2019 
 
 
 
 
 
 
 
 

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Principal 
Investigator 
(PI): 
Allison Hyngstrom PT, PhD 
PI Status: 
Department:  
Physical Therapy 
[  ] Undergraduate 
[  x] 
Faculty/Administrator 
Email Address: Allison.hyngstrom@marquette.edu 
[  ] Graduate 
[  ] Other (specify):  
Faculty 
Advisor: 
 
Project Title: 
Ischemic Conditioning Improves Walking Function Post Stroke 
Study Start 
Date: 
Expected End Date:  
 
PI Certification 
By entering my name below and submitting this document, I certify the following: 
• 
I accept primary responsibility for the ethical conduct of this project and for safeguarding the rights and 
welfare of all involved human participants and/or their information.  
• 
The information in this submission accurately reflects the proposed research. 
• 
I will communicate any changes to this protocol by submitting an amendment request and receiving 
approval before implementing the change. 
• 
I will submit a Final Report, Study Complete or Study Closed Form when this project is complete.  
• 
I am responsible for making sure the investigators on the study team have received appropriate training in 
human subjects research. 
• 
I accept responsibility for assuring adherence to applicable Federal and State research regulations and 
Marquette University policies applicable to this project. 
I understand that this project cannot begin until I receive documentation of IRB final approval. 
 
 
Principal Investigator Name 
 
 
 
Date 
 
FOR STUDENTS, a Marquette faculty supervisor must review this completed form and enter his/her name and 
date of review below prior to submission. The supervisor must also be copied on the email when this document is 
submitted. 
 
Faculty Supervisor: As faculty supervisor for the student investigator named above, I certify the following: 
Allison Hyngstrom PT PhD 
11/28/18 

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• 
I have reviewed the research plan and this document and I have approved the scientific and ethical 
aspects of the project.   
• 
I will supervise the above listed student and ensure compliance with applicable Federal and State research 
regulations and Marquette University policies applicable to this project. 
• 
I acknowledge that I am ultimately responsible for the conduct of this research project, including ensuring 
that all study procedures are followed as written, and that a Final Report, Study Complete or Study Closed 
Form is completed in a timely fashion after study completion. 
I understand that this project cannot begin until an official approval letter has been received. 
 
 
 
 
 
 
      
      
Faculty Supervisor Name 
Date 

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A. OVERVIEW 
 
1. Indicate what level of risk you believe the study involves based on the following definition of minimal risk: 
 
“Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not 
greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine 
physical or psychological examinations or tests”   
 
 
 
[x  ] Minimal Risk 
 
 
[  ] Greater than Minimal Risk 
 
 
1b. Please explain why you feel your study involves minimal risk or greater than minimal risk:  
All procedures are non-invasive, have been safely and reliably been performed in the laboratory for several 
years, and are encountered in routine daily life or routine physical testing.  
 
B. STUDY BACKGROUND 
Instructions: For the following questions, try to use non-technical language that provides a first time reader 
from any discipline with a clear understanding of the research, and avoid abbreviations. Do not cut and paste 
text from the grant proposal, and do not refer to the grant proposal page numbers or include literature 
citations.  Focus your answers on the involvement and treatment of human subjects. 
 
2. Provide a short, non-technical summary (abstract) of the study including a summary of the scientific 
background and existing knowledge on the subject:   
 
The purpose of this study is to examine if a safe and non-invasive intervention, called ischemic 
conditioning (IC), can improve gait speed, neural activation of leg muscles, and cardiovascular function 
when combined with traditional treadmill training in individuals with chronic stroke.  Briefly, IC is a non-
invasive stimulus which is triggered by using a blood pressure cuff to briefly occlude blood flow to the 
tissue of interest (the paretic leg) in 5-minute bouts, done a total of 5 cycles per session, making the 
tissue transiently ischemic.  In individuals without stroke, the IC stimulus is known to increase the 
excitability of motor systems and improve local regulation of blood, but the positive effects of IC on 
motor tasks such as walking in individuals with stroke are unknown.  It is proposed that IC engages 
the autonomic nervous system, causing the release of neurotransmitters that increase the excitability 
of the nervous system. IC has been safely used many special populations to improve blood flow, such 
as critically ill patients, individuals with chronic kidney disease, and individuals recovering from acute 
myocardial infarction (heart attack). We propose to investigate the effects of IC on walking speed and 
paretic leg function with two Specific Aims.  In Aim 1, we will demonstrate the benefit of combined IC 
and treadmill training on walking speed post stroke.  We will use a randomized, blinded, controlled 
design with three groups of individuals with chronic stroke (15 per group) for four weeks (12 total 
sessions) of training: IC+Treadmill Training, IC Sham+Treadmill Training, and IC only. Walking speed 
will be measured at baseline, after 6 sessions, 12 sessions, and 2 weeks post-intervention.  We 
anticipate the largest gains in walking speed in the IC+Treadmill Training group after 12 sessions. In 
Aim 2, we will quantify the effects of IC and treadmill training on improvements in motor unit firing 
behavior and whole muscle activation. Due to enhanced neural activation of motoneuron pools, we 

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anticipate that IC on the paretic leg will decrease recruitment thresholds and increase motor unit firing 
rates during sub-maximal isometric contractions. We also anticipate increased maximal voluntary force 
generation. Similar to Aim 1, we expect that the largest gains in strength and task duration to occur in 
the stroke IC+Treadmill group after 12 sessions. In Aim 3 we will establish that ischemic conditioning 
and treadmill training improve endothelial function and cardiorespiratory fitness.  We hypothesize that 
IC + Treadmill Training will result in increased flow mediated dilation in the popliteal artery of the paretic 
leg (improved local endothelial function) and the brachial artery of the non-paretic arm (remotely 
improved systemic endothelial function). Compared to the other groups, we also predict that the IC + 
Treadmill Training group will have the largest increase in maximal aerobic capacity as assessed by a 
graded exercise test to measure peak oxygen uptake (VO2 Peak).  These studies will be the first to 
quantify the effects of IC, a non-invasive, easy to administer, cost-effective intervention, on walking 
speed, motor function and cardiovascular health in chronic stroke.  Future studies will investigate the 
molecular mechanisms of IC, the effects of IC on acute stroke populations, and the efficacy of IC 
compared with other walking adjuncts. 
 
3. List the specific research aims of this project: 
 
Aim 1: Demonstrate the benefit of IC and treadmill training on walking speed post stroke. 
A randomized, double-blinded, control design will be used with three groups of individuals with 
chronic stroke training for four weeks (12 sessions): IC + Treadmill Training, IC Sham + Treadmill 
Training, and IC only. Walking speed will be measured at baseline, after 6 sessions, 12 sessions, 
and 2 weeks post-intervention. We hypothesize the largest gains in walking speed will be in the 
IC + Treadmill Training group after 12 sessions. Interpretive measures of gait kinematics, 
kinetics, and EMG will also be assessed to understand how IC improves the quality of walking. 
 
Aim 2: Determine the excitatory effects of IC on the activation of paretic motoneurons. 
Using novel high-density surface EMG arrays, we will quantify changes in paretic motor unit 
recruitment thresholds and firing rates. We hypothesize that IC will decrease paretic motor unit 
recruitment thresholds and increase peak firing rates. Interpretive measures of paretic muscle 
voluntary activation (assessed by electrical stimulation), maximal strength, muscle contractile 
properties, and changes in muscle oxygen consumption will be measured at similar time points 
as Aim 1. If IC enhances the excitability of motoneuron pools, we anticipate changes in voluntary 
activation will positively correlate with changes in walking speed more than correlations with 
resting twitch responses of the muscle. 
 
Aim 3: Establish that ischemic conditioning and treadmill training improve endothelial 
function and cardiorespiratory fitness.  We hypothesize that IC + Treadmill Training will result in 
increased flow mediated dilation in the popliteal artery of the paretic leg (improved local endothelial 
function) and the brachial artery of the non-paretic arm (remotely improved systemic endothelial 
function). Compared to the other groups, we also predict that the IC + Treadmill Training group will 
have the largest increase in maximal aerobic capacity as assessed by a graded exercise test to 
measure peak oxygen uptake (VO2 Peak). 
 
 
C. SUBJECTS  
 
4. What is the requested total number of subjects?  
(Note: this number should include subjects who later will be determined ineligible or who may 
be lost to attrition): 
54 
5. Check any of the following special populations that will be targeted for enrollment in the study: 
 
[  ] Pregnant Women/Fetuses 
[  ] Children (minors under 18) 
[  ] Prisoners 

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[  ] College Students* 
[  ] Institutional Residents 
[  ] Cognitively Impaired 
[  ] Physically Disabled 
[  ] Terminally Ill 
[  ] Subordinates or students of the PI
 
 
[  ] Economically or educationally disadvantaged populations  
[ x ] None of These 
 
*If using Marquette students, please consult HRP Policy 98.102 Participation of Students and Employees in 
Research available on the IRB website  
 
6. Provide the inclusion and exclusion criteria for study subjects. 
 
Inclusion Criteria: 
Exclusion Criteria: 
Inclusion criteria include that subjects must: be 
at least 18 years of age, be able to give 
informed consent, ≥6 months post diagnosis of 
unilateral cortical or sub-cortical stroke, and 
have residual lower limb paresis.   
Exclusion criteria: 1) history of chronic low 
back or hip pain, 2) history of substance 
abuse, 3) history of head trauma, 4) comorbid 
neurological disorder, 5) any uncontrolled 
medical condition, 6) pacemaker, 7) unable to 
follow 2 step commands 8) history of any 
condition where resisted leg contractions are 
contraindicated, 9) inability to walk for 5 minute 
bouts at least 80% of their comfortable over 
ground walking speed  
 
 
D. RESEARCH ACTIVITIES 
*If any of these steps will be conducted in languages other than English state this in your responses and make 
sure to submit both English and non-English versions of appropriate materials. 
**If study involves the use of pre-existing data or specimens, complete this section as much as possible 
and make sure to also complete Appendix E** 
 
RECRUITMENT  
 
REMINDER: If verbal announcements will be made please submit the script for the announcement. Also, make 
sure to submit copies of all recruitment flyers, advertisements, recruitment emails and other materials 
7. Describe how and where/when subjects will be recruited for 
the study.   
 
A registry maintained in the Hyngstrom 
Laboratory (HR 2987). 
Word of mouth- frequently individuals will 
call the laboratory or the physical therapy 
department interested in participating in 
studies who have heard about the studies 
through friends/etc. 
 
An online stroke subject recruitment 
database (MCW PRO00026783) which 
contains the names and medical 
information of stroke survivors interested 
in participating in stroke research.   
 
 
 

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8. State who will be doing the recruitment. 
Dr. Hyngstrom PT PhD (PI), Stephany 
Raab MS (graduate student in Hyngstrom 
Lab) or Saad Alqahtani PT (graduate 
student in Hyngstrom Lab) 
 
 
9. Are there any pre-existing relationships that may influence 
a research subject’s decision to participate in the project?  
(for example, a student being recruited by an instructor who 
controls his or her grade, or a healthcare provider recruiting 
his or her own patients)   
[  ] Yes    [ x ] No     
9b. If Yes- explain what steps researchers will take 
during the recruitment process to minimize the 
potential for undue pressure, influence, or coercion.  
 For example, having a third party consent or collect 
data, having researchers contact subject directly, 
postponing data analysis until grades have been 
submitted, etc… 
 
SCREENING 
10. State how and when subjects will be 
screened for study eligibility. 
 
Individuals will be screened by phone by Dr. Hyngstrom or study 
personnel (Stephany Raab MS or Saad Alqahtani PT) prior to 
consent process. Screening will follow a script  and individuals will 
be questioned with respect to the exclusion/inclusion 
criteria(attached). 
 
 
 
11. State if the data from ineligible 
subjects will be discarded and how.  
If data from ineligible subjects will be kept 
then they are considered study subjects 
and should consent before the screening 
process 
 
Data from ineligible participants will be shredded immediately 
upon determination that they are ineligible. 
 
 
 
CONSENT PROCESS  
 
REMINDER: Submit copies of any consent/assent/parent permission documents that will be used 
12. Describe the consent process- state 
who will be obtaining consent as well as 
when and where.   
 
Either Dr. Hyngstrom or Stephanie Raab will consent the 
participants. Upon determination that the participants are 
eligible,the consent process will occur privately in the 
Hyngstrom Laboratory (Cramer Annex 138).  Study 
personnel will go through the consent form and allow time for 
the participant to read the consent on their own and ask any 
questions. No testing procedures will occur until after the 
consent has been signed. 
13. If minors will be enrolled, please 
describe both the minor assent and parent 
permission process. 
 
N/A 

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14. Will subjects be signing a consent 
form?   
[ x ] Yes 
[  ] No – please complete Appendix A, Section 1 to      
request a waiver of documentation of consent 
 
15. Will any of the required elements of 
consent be altered or removed (this is 
common in studies involving deception) or 
is there a request to waive consent 
altogether?  
[  ] Yes—please complete Appendix A, Section 2 to request a 
waiver or alteration of consent 
    [x  ] No 
 
 
STUDY PROCEDURES 
16. Describe any interventions or activities 
the subjects will be asked to perform. 
 
Experimental Protocols 
 
The following clinical, motor and blood flow testing protocols 
will be performed at baseline and after ischemic conditioning 
sessions 6 and 12, and 2 weeks post intervention. 
 
Gait Assessments and Clinical Testing: Clinical testing and 
measurements of gait velocity, as described below, will be 
performed prior to motor testing.  
Following gait and clinical testing, participants will then 
undergo motor and blood flow testing. 
 
Motor Testing: The knee extensors and plantar flexors will be 
tested separately, and the order will be counterbalanced.   
 
1)Maximal Voluntary Contraction Protocol: Maximal 
voluntary contractions will be the first procedure performed by 
each subject. Individuals will be assisted in to a seated position 
in a Biodex Dynamometer. The baseline maximal voluntary 
contraction task will involve an increase in force from zero to 
maximum over 2-3 s. Subjects will be able to observe the 
exerted force on a monitor and will be verbally encouraged to 
achieve maximal force. Subjects will rest for 60s between 
trials. Trials will be repeated until peak forces from two of the 
three trials are within 5% of each other (usually 3-4 trials). The 
peak force generated will be used as the maximal voluntary 
contractions.  
 
2)Voluntary activation, Muscle Contractile Properties: 
Voluntary activation measurements will be made concurrent 
with maximal voluntary contraction measurements. During the 
2nd and 3rd maximal voluntary contractions, the quadriceps or 
gastrocnemius muscle will be electrically stimulated (Digitimer 
North America, FL). Electrodes will be placed over the 
quadriceps muscle. The stimulation intensity will be set to 
supramaximal levels (10% above resting maximal twitch) for 
both stimulations.  Individuals will be stimulated during a 
maximal effort (superimposed twitch) and then at rest(resting 
twitch). This measurement will be done before and after 
ischemic conditioning. The ratio of the superimposed twitch 

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torque (SIT) and the resting twitch (RT) will be used to quantify 
voluntary activation will with the following: 100* [1-(SIT/RT)]24. 
The superimposed twitch will be used as a measure of 
voluntary activation. A decrease in the superimposed twitch 
amplitude across ischemic conditioning  session time points 
will indicate an increase in voluntary activation. Following the 
2nd and 3rd maximal voluntary contractions, resting twitch 
responses of the muscle will be elicited. Changes in the rate 
of relaxation of the twitch response will indicate an effect of 
ischemic conditioning on muscle contractile properties.  
 
3)Sub-maximal Ramp Contractions: To measure motor 
unit firing behavior, subjects will perform 2 isometric knee 
extensor and plantar flexor contractions ramping from 0% to 
50% maximal effort. 
 
4)Sub-maximal Fatiguing Contraction: Using visual 
feedback and receiving verbal feedback, individuals will 
maintain a 30% maximal voluntary contraction until they can 
no longer maintain with a ± 5% error window.  
 
5)Hyperemic Blood Flow in Response to Muscle 
Contractions:  Measurements may be performed and would be 
made using a General Electric Vivid i ultrasound equipped with 
a 13.0 MHz probe designed for vascular imaging.  Superficial 
femoral artery diameter and blood flow will be measured at the 
same site 4-5 cm distal to the bifurcation of the common 
femoral artery as previously described.1-4  Resting blood flow, 
and the hyperemic response to muscle contractions will be 
measured before and immediately after each contraction and 
after muscle fatigue and averaged over 3 cardiac cycles.5  
Blood flow will be quantified using the software on the Vivid i 
ultrasound.   
 
Maximal voluntary contraction, voluntary activation, and 
ramp contractions measures will then be repeated on the non-
paretic leg during the same session after at least 30 mins of 
rest to understand ay systemic effects. Order of paretic and 
non-paretic leg testing will be counterbalanced. 
 
 
ISCHEMIC CONDITIONING Intervention: Subjects will 
undergo a total of 12 sessions (3/week for 4 weeks) of 
ischemic conditioning (cuff inflation to 225 mmHg) or ischemic 
conditioning Sham (cuff inflation to 10 mmHg).  The participant 
will be positioned in supine on a therapy table.  A rapid inflation 
cuff (Hokanson, Bellevue WA) will be placed around the 
proximal thigh of the paretic leg.  The cuff will be inflated to 
225 mmHg for 5 minutes, then released for a 5-minute 
recovery period.  5 cycles of inflation/recovery will be 
performed (total of 50 mins). For the separate group receiving 

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the sham ischemic conditioning, this will consist of the same 
physical set-up, but the cuff will only be inflated to 10 mmHg.  
Participants will be blinded to the sham or typical ischemic 
conditioning protocol.  During the first and last ischemic 
conditioning sessions, oxygen saturation of the tibialis anterior 
muscle of the test leg will be measured using the near infrared 
spectroscopy during the occlusion protocol to monitor the 
tissue response to occlusion (Fig. 6).  Near infrared 
spectroscopy measurements will be made from the tibialis 
anterior during occlusion because the occlusion of the thigh 
would cause a mechanical artifact in a quadriceps 
measurement.   
 
Treadmill Training Protocol: The participants will perform 3 
treadmill training sessions/week for a 4 week period (12 
sessions total). During each session, treadmill training will 
immediately follow ischemic conditioning or ischemic 
conditioning Sham. To ensure safety, all subjects will be 
assisted into a fall arrest harness and instructed to use 
handgrips during walking.  Subjects will walk on a treadmill for 
six, 5-minute intervals. Walking speed will be continuously 
adjusted to maintain heart rate between 50% and 60% of age-
adjusted maximal heart rate to minimize the confounder of 
intensity.8 Participants will be asked to log daily physical 
activity.  
 
Flow mediated dilation of the Popliteal (Paretic) and 
Brachial (non-paretic) Artery:  **Only performed at baseline, 
after 12 sessions, and 2 weeks post-intervention** Study 
participants will be required to fast for 8 hours, but medications 
will not be withheld and if necessary may be taken with food.  
After 15 minutes rest, the participant’s leg will be slightly 
elevated or their arm will be extended and a pneumatic cuff 
will be placed around the calf, 5-7 cm distal to the popliteal 
fossa, or the forearm, immediately distal to the antecubital 
fossa. Baseline artery diameter and blood flow velocity will be 
measured. After baseline images have been captured using 
Vascular Imager (Medical Imaging Applications), the cuff will 
be inflated to 225 mmHg for five minutes to occlude blood flow 
to the lower leg or arm. Immediately after cuff release, artery 
diameter will be continuously captured for 3 minutes (EKG 
gated) post cuff release and measured off-line using Brachial 
Analyzer (Medical Imaging Applications).  A greater flow 
mediated dilation response would be consistent with improved 
endothelial cell function. Study personnel will perform all flow 
mediated dilation and hyperemic blood flow measurements 
and analysis.  Study personnel will be blinded to the treatment 
condition. 
 
VO2 Max Test:  **Only performed at baseline, after 12 
sessions, and 2 weeks post-intervention** Under the 

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supervision of Toni Uhrich, MS (Director of the Human 
Performance Assessment Core at Marquette University), 
subjects will begin an exercise test pedaling at a workload of 
10 Watts on a recumbent bicycle.  Pedaling resistance will be 
increased by 15 watts every 2 minutes until (1) subjects 
report they are fatigued and do not feel they can continue, (2) 
the participant's VO2 peak plateaued or decreased despite 
continuation of exercise, (3) the participant was unable to 
maintain a steady cadence, or (4) at the discretion of the 
study team based on the American College of Sports 
Medicine Guidelines for Exercise Testing (see attached 
ACSM Exercise Guidelines). Heart rate and pulse oximetry 
will be measured throughout the test, as will exhaled air 
using a metabolic cart. Subjects will also be asked to rate 
their perceived level of effort using the Borg Scale of 
perceived exertion (a scale of 6-20 commonly used for 
graded exercise tests). The subjects are free to stop the test 
at any time they choose. 
 
17. Describe what data will be collected 
from subjects and how.  Include 
descriptions of any equipment that will be 
used. 
 
Note: Data will be collected for motor testing aims on the same 
test session days(pre intervention, and after 6 sessions, 12 
session and 2 weeks post intervention). VO2 Max testing and 
flow mediated dilation testing will occur on testing sessions 
separate from the motor test sessions at baseline, after 12 
sessions, and 2 weeks post intervention. 
Aim 1 
Gait Speed: Self-selected walking speed will be 
quantified using the valid and reliable Ten Meter Walk Test9.  
Self-selected walking speed is a primary determinant in daily 
ambulatory activity10,11.   
Bipolar Surface EMG Measurements: Bipolar surface 
EMG recordings may be used to interpret changes in strength 
in response to ischemic conditioning and treadmill training.  
Wireless bipolar surface EMG may be measured using 
Ag/AgCl electrodes placed on the following muscles: rectus 
femoris, vastus medialis, medial hamstrings, tibialis anterior 
and medial gastrocnemius.  EMG signals will be amplified (x 
1,000-10,000) and bandpass filtered (10-500 Hz) (Delsys 
Trigno; Natick, MA).  Signals will be sampled at 1 kHz using a 
data acquisition card (National Instruments Corp.).   
Clinical Measurements of Leg and Walking Function: 
The following clinical metrics will be interpretive measures to 
understand 
how 
ischemic 
conditioning 
affects 
motor 
impairments that contribute to movement dysfunction post 
stroke:  Functional Gait Assessment (dynamic walking 
balance)12, the 6 minute walk test (walking endurance)13, 
Lower Extremity Fugl-Meyer (coordination)14, manual muscle 
tests (strength), the Ashworth Scale (spasticity)15, and 
maximal walking speed.  At baseline and at the 2 week follow 
up, participants will be asked to complete the Physical Activity 
Questionnaire (PAQ) index16 which estimates activity levels 

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and approximates the calorie expenditure above basal 
metabolic rate.  We have used the PAQ in previous 
studies17,18.   
Near infrared Spectroscopy (NIRS) Measurements of 
Leg Muscle Oxygen Saturation: A 4-channel INVOS™ 
(Somantics, Troy, MI) cerebral/somatic oximeter may be used 
to  continually measure regional oxygen saturation of the 
vastus lateralis and tibialis anterior muscles of the test leg (Fig. 
6) during the ischemic conditioning protocol.  NIRS 
measurements will be made during the first and last sessions 
of ischemic conditioning and maximal voluntary contraction 
testing (Aim 2).  Based on previous near infrared spectroscopy 
studies19-23 the rate of oxygen de-saturation of the muscle 
groups during muscle contraction will be calculated, as well as 
the time to peak re-saturation and time to return to baseline.   
 
Aim 2 
Surface 
EMG 
Motor 
Unit 
Measurements 
and 
Decomposition: Surface motor unit potentials will be recorded 
from the vastus lateralis and gastrocnemius muscles using a 
non-invasive, multi-channel linear array of 64 EMG electrodes 
(OT Bioelectronnica, Torino, Italy).  The 64 channel linear 
array will be placed between the innervation zone and tendon 
and oriented with muscle fiber direction using hypoallergenic 
paste (similar to EEG Cap) and tape.   We propose that 
ischemic conditioning will enhance motoneuron excitability 
and responsiveness to descending commands through the 
release of brainstem neuromodulators.  As our preliminary 
data support, ischemic conditioning decreases the force 
recruitment thresholds.   
Knee Extension and Plantarflexion Torque: A Biodex 
dynamometer (Biodex Medical Systems, New York) will be 
used to measure isometric knee extension and may be used 
to measure plantar flexion torques during MVCs (strength) and 
during a sub-maximal contraction fatiguing protocol (task 
endurance). For knee extension trials, subjects will be 
positioned with the hip and knee at 90 degrees. For plantar 
flexion trials, the knee will be adjusted to 20 degrees of flexion. 
Custom-written LabVIEW (National Instruments Corp., Austin, 
TX) programs will be used to acquire all data. Torque signals 
will be low-pass filtered and sampled at 1000 HZ using a data 
acquisition card (National Instruments Corp.) and PC. The 
MVC will be defined as the peak torque generated during a 
given 2-3 s effort. Knee extension and plantarflexion torques 
provide an objective, high resolution measurement of motor 
output. 
Voluntary Activation (see Fig. 1 for example): Voluntary 
activation (neural drive to the muscle) may be assessed by 
stimulating the muscle with a brief stimulus (superimposed 
twitch) while the subject performs during a maximal voluntary 
contraction (MVC).  Immediately after the MVC (within 5 s) a 

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twitch contraction will be performed at rest (resting twitch). The 
stimulation intensity will be set to supramaximal levels (10% 
above resting maximal twitch) for both stimulations.  This will 
be done before and after ischemic conditioning. The ratio of 
the superimposed twitch torque (SIT) and the resting twitch 
(RT) will be used to quantify voluntary activation will with the 
following: 100* [1-(SIT/RT)]24. Reductions in voluntary 
activation are due to failure in pathways upstream of the 
neuromuscular junction24,25. We expect voluntary activation 
will increase in the paretic leg after ischemic conditioning 
treatment. 
Perceived Exertion: We will be monitoring the 
individuals subjective perception of exertion which may differ 
from their cardiovascular response to exercise. Individuals will 
rate their exertion using the 6-20 Borg Rate of Perceived 
Exertion Scale.  
Heart Rate: Heart rate will be continuously monitored 
using a 4 lead EKG. EKG and blood pressure electrodes 
(Finapres Nova, purchased 2016) to make non-invasive 
measurements of heart rate and blood pressure. In addition, 
to using heart rate data to monitor the response to exercise, 
variability in heart rate will be analyzed off line to examine the 
effects of ischemic conditioning on the relative contributions of 
sympathetic/parasympathetic drive to control of heart rate. 
Hyperemic Blood Flow in Response to Muscle 
Contractions:  Measurements may be performed and would be 
made using a General Electric Vivid i ultrasound equipped with 
a 13.0 MHz probe designed for vascular imaging.  Superficial 
femoral artery diameter and blood flow will be measured at the 
same site 4-5 cm distal to the bifurcation of the common 
femoral artery as previously described.1-4  Resting blood flow, 
and the hyperemic response to muscle contractions will be 
measured before and immediately after each contraction and 
after muscle fatigue and averaged over 3 cardiac cycles.5  
Blood flow will be quantified using the software on the Vivid i 
ultrasound.   
 
Aim 3 
Percent FMD: Artery diameter will be recorded 
continuously onto a laptop using Vascular Imager and percent 
FMD will be calculated offline using Brachial Analyzer 
software. 
VO2 Peak:  Exercise capacity and VO2 peak will be 
measured using a metabolic cart and standard procedures. 
 
18.  State who will be collecting the data, 
where data collection will occur and any 
steps taken to maintain subjects’ privacy 
during data collection. 
Study personnel, Stephanie Raab and/or Saad Alqahtani will 
be collecting the data. Data will be collected in the Falk 
Laboratory, Cramer Annex room 138A. Although the Falk 
Laboratory is a shared space, only on study session is 
allowed at any given time. Thus, only study personnel from 
this protocol will be in the laboratory during a study session.  

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14  
 
All documents used during the studies will be de-identified 
and stored in a locked cabinet in Dr. Hyngstrom dedicated 
lab space adjacent to the Falk laboratory, Cramer Annex 
138.  
19. Describe the length of study visits and 
total number of study visits.  Include any 
follow-up data collection time points and 
what data will be collected at these follow-
ups. 
Participation will include at least four test sessions (pre, after 
6 and 12 IC sessions and 2 weeks post IC). Participation will 
include at least 12 training sessions. Because of the time 
dependency of the effects of IC, there may be some 
variability in the number of test/training sessions if make up 
sessions need to be performed in case of illness, etc.  Aim 3 
testing procedures will occur in separate test sessions at 
baseline, after 12 sessions, and two-weeks post intervention. 
 
20. Will data be collected or analyzed using an internet-based application such as Qualtrics, Survey Monkey, 
RedCap or Dedoose?   [  ] Yes 
[ x] No  
 
a. If yes, please state the program(s) that will be used and the security features: 
 
 
b. Will subject identifiers such as email address, name, IP address, etc… be associated with the data at any 
point?  
 
 
[  x ] No- State the specific steps taken to anonymize data: 
At time of consent, participants will be given a unique code 
 
[ ] Yes- List the identifiers that will be recorded and the justification for doing so i.e, sending reminders, 
linking to  other data, etc…: 
 
 
21. Will any social media platforms (Twitter/Facebook/Instagram, etc…) be used for recruitment, communication 
with subjects or data collection?   
 
[ x ] No   
 [  ] Yes- please explain which platforms, how they will be used and provide the text for review: 
 
 
22. Does this study have a data safety monitoring plan?  A data safety monitoring plan is a common requirement 
in federally funded studies that collect clinical data.      
 
 [ x ] No   
 [  ] Yes, Please describe or attach plan: 
 
 
E. RISKS AND BENEFITS 
 
BENEFITS 
23. List any anticipated direct benefits to 
the subject from participation in the 
research.   
If none, state this here and, if applicable, 
in the consent form.   
Individuals in all groups may benefit. Individuals in two of the 
groups will receive four week of treadmill training which may 
result in increased over ground walking speed and endurance. 
Supported by recent evidence in our laboratory, individuals 
receiving IC alone may also have increased over ground 
walking speed. 
24. State any benefits to society from this 
research study. 
Results from the study could help the development of 
rehabilitation therapies that improve walking and quality of life 
in individuals with chronic stroke. 
RISKS 

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15  
 
25. Describe any reasonably anticipated 
risks, harms or discomforts from all study 
procedures.   
*Make sure to consider risks involved with 
recruitment and screening as well as risks 
associated with interventions and data 
collection. 
*Include physical risks as well as 
psychological, social, legal and other 
related risks 
1. Adverse cardiovascular response to exercise: 
According to the American Heart association, 
reoccurrence of stroke during exercise is extremely rare, 
but is a possible risk26.  
2. Muscle Fatigue: We will be measuring the effect of 
fatigue on patterns of muscle activation. Subjects may 
experience transient feelings of tiredness or weakness 
due to fatigue in their leg musculature. 
3. Exercise Induced Muscle Soreness: Because we will 
be asking participants to maximally contract muscles in 
legs, some soreness in the muscles may appear after the 
muscle testing. 
4. Skin Irritation: Participants may experience some mild 
skin irritation from the surface EMG or NIRS electrodes. 
5. Discomfort from Electrical Stimulation: Subjects may 
experience some discomfort from the electrical 
stimulation to their leg.  
6. Discomfort Due to Cuff Inflation: Subjects may 
experience some discomfort during the brief periods of 
cuff inflation of the ischemic conditioning protocol. The 
cuff will be inflated to super systolic level. The sensation 
is similar to what is experienced when standard blood 
pressure measurements are made. The difference will be 
how long the cuff is inflated. Here the cuff will be inflated 
for 5 minutes at a time.  
7.  Light Headedness.  There is a risk the subject may 
become fatigued or light headed due to the 8-hour fasting 
period prior to the FMD study (Aim 3). 
 
MINIMIZING RISKS 
26. Explain what steps are being taken to 
minimize the risks described above. 
1. Adverse cardiovascular response to exercise: As 
recommended by the American Heart Association, the 
guidelines used most often for monitoring a person with 
stroke’s response to exercise are consistent with patients 
post myocardial infarction26. Per the American Heart 
Association’s guidelines, if  prior to any testing or 
familiarization procedures, resting blood pressure is 
greater than 180 mm Hg systolic or 110 mmHg diastolic 
or resting pulse is greater than 110 beats per minute, 
subjects will not be allowed to participate in any 
procedures that day. If during the course of the testing a 
subject’s blood pressure is greater than 240 mmHg 
systolic or 115 mmHg diastolic their session will be 
terminated. Because some subjects may be taking 
medication that affects heart contractility or rate, study 
personnel will ask subjects to report their perceived 
exertion (Borg scale27,28).   If subjects report a number 
equal to or higher than 16 we will terminate testing for that 

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day. This scale is sensitive to strain on the cardiovascular 
system in chronic stroke that may not be reflected in 
changes in blood pressure, heart rate, and respiration 
rate.  All study personnel will be certified in CPR and AED 
training. 
 
If a cardiovascular emergency should occur during any of 
the study sessions, study personnel would immediately 
call Public Safety as they are the campus first 
responders. As physical therapists, we are trained to 
recognize the signs and symptoms of a cardiovascular 
emergency.  As the designated first responders, Public 
Safety would coordinate with emergency services (call 
911) and provide immediate first aid including the use of 
an AED if needed. Public Safety is able to respond to our 
location within minutes and EMT response is under 5 
minutes.  This protocol was jointly established between 
the Department of Physical Therapy and Public Safety in 
2010. 
 
2. Muscle Fatigue: To prevent any prolonged feeling of 
neuromuscular muscular fatigue (i.e. more than 15-20 
minutes) the fatigue protocol will only be performed one 
time and the subject will be allowed to recover before 
leaving. Study personnel will monitor blood pressure, 
pulse and heart rate before, during, and after the fatigue 
task.  
3. Muscle Soreness: This soreness will be slight, will in no 
way impede normal daily activity and if present will be 
expected to subside within a few days.  Participants will 
be instructed to notify their physician as well as Dr. 
Hyngstrom if muscle soreness persists beyond a few 
days.  
4. Skin Irritation: This irritation involves redness of the 
skin and usually subsides within a few hours. In the last7 
years of testing using the electrodes, no individuals have 
reported skin irritation following the study. 
5. Discomfort from Electrical Stimulation: Participants will 
be instructed to tell study personnel present during testing 
if they are experiencing any discomfort and the level of 
stimulation will be adjusted to a comfortable level.  
6. Discomfort from Cuff Inflation: Participants will be 
instructed to tell study personnel present during testing if 
they are experiencing discomfort and the level of inflation 
will be adjusted to a comfortable level. To date, we have 
tested over 40 participants (stroke and control) using the 
cuff inflation protocol and all participants have tolerated 
well (none withdrew themselves or requested to stop 
protocol). 

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7.  Light Headedness:  An 8-hour fast is common when 
conducting FMD and blood flow studies. Most subjects 
will be arriving in the morning; therefore, fasting for 8 
hours during the nighttime hours should not have a 
substantial effect on the subjects. The subjects will be 
given a snack and something to drink when they are 
complete with the study. 
 
RISK/BENEFIT RATIO 
27. Describe how the risks to subjects are 
reasonable compared to the benefits to 
the subjects or society in general. 
 
Due to the non-invasive and routine nature of proposed 
study procedures and the potential for an increase in 
walking function, the benefits outweigh the potential risks. 
 
 
DECEPTION: 
28. Does the study involve deception 
(providing false information) or incomplete 
disclosure (withholding information about 
study purposes or activities)?     
[  ] Yes 
[ x ] No 
 
If yes, answer the following 
a. What information will be withheld from 
the subject? 
N/A 
b. Why is deception or incomplete 
disclosure necessary? 
N/A 
c. Describe how and when subjects will 
be debriefed. 
 
REMINDER: Submit a copy of your 
debriefing sheet or script 
N/A 
 
INCENTIVES 
29. Will an incentive be offered to 
subjects? 
[  x] Yes                        [  ] No 
a. If yes, please describe the 
incentive including dollar amounts 
and/or monetary value. 
$450.00 total if individuals participate in all four test sessions and 
twelve treatment sessions.  If subjects choose to participate in 
Aim 3, which requires 3 additional visits, they will receive $50 per 
visit and be paid a grand total of $600. 
30. State when subjects will receive the 
incentive.  Describe any pro-rating based 
on amount of study completed. 
Participants will receive 50.00 in cash at the end of the 
familiarization session and each test sessions. Participants will 
receive 100 dollars in cash after 6 treatment sessions and 
additional $100 in cash after completing the twelfth treatment 
session.  Subjects will receive $50 after each session in Aim 3. 
31. Will extra-credit be offered to students 
as an incentive? 
[  ] Yes                           [x  ] No 
a. If yes, please state the amount of 
extra credit being offered  
 

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b. If yes, state the non-research 
alternative for extra credit that 
students will be offered.   
REMINDER: This alternative must be 
equivalent in duration and effort to 
the study activities and should be 
included in consent forms and 
recruitment materials 
 
 
 
F. DATA HANDLING 
 
Direct Identifiers 
32. If you will be collecting any direct identifiers such as name, date of birth, address or telephone number, 
with the research data, please state what identifiers will be collected, why it is necessary and how the data 
containing identifiers will be secured. 
Name, date of birth, email address and telephone number will be collected to contact if needed. Age is needed 
to be used as part of sample description in manuscripts. Subjects will be identified by an alphanumerical 
code. A spreadsheet will be kept that links the participants name to their study code on a password 
protected computer in Dr. Hyngstrom’s office (Cramer 346). 
 
 
 
 
Data Security 
33. Complete the following table to provide details on the procedures in place to maintain the confidentiality 
and security of the study data. 
Data type 
Who will have access? Where will they be 
stored?  What security measures are in 
place? 
When and how will 
they be 
deidentified? 
When and how 
will they be 
destroyed? 
Signed consent 
forms 
Signed consent forms will be kept in 
locked cabinet in Schroeder Complex 
346 (Dr. Hyngstrom’s office). Only Dr. 
Hyngstrom will have access to the 
documents. 
 
 
After 10 years, 
paper records will 
be shredded and 
all computer files 
will be deleted. 
No data will be 
used for future 
research 
purposes. 
 
 
Hard copy data 
(questionnaires, 
etc…) 
Data sheets will be kept in a locked 
cabinet in Dr. Hyngstrom’s laboratory 
(Cramer Annex 138). Only study 
personnel will have access to the 
documents. 
At time of consent. 
Subjects will be 
identified by an 
alphanumerical 
code. A 
spreadsheet will 
be kept that links 
the participants 
name to their 
study code on a 
password 
After 10 years, 
paper records will 
be shredded and 
all computer files 
will be deleted. 

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19  
 
protected 
computer in Dr. 
Hyngstrom’s office 
(Cramer 346). 
 
Electronic 
datasets 
Data sets will be kept on password protected 
computers in Dr. Hyngstrom’s laboratory and 
Dr. Hyngstrom’s office, and on the laptops of 
study personnel. All data sets will have de-
identified data. 
At time of consent. 
Subjects will be 
identified by an 
alphanumerical 
code. A 
spreadsheet will 
be kept that links 
the participants 
name to their 
study code on a 
password 
protected 
computer in Dr. 
Hyngstrom’s office 
(Cramer 346). 
 
After 10 years, 
computer files will 
be deleted. 
Key linking 
names to study 
IDs (if data are 
coded) 
A spreadsheet will be kept that links the 
participants name to their study code on 
a password protected computer in Dr. 
Hyngstrom’s office (Cramer 255c). 
 
 
After 10 years, 
computer files will 
be deleted. 
Audio or video 
recordings 
n/a 
 
 
Other (add rows 
as needed for 
your study) 
n/a 
 
 
 
34. Indicate if data will be stored at any time (even temporarily) on electronic portable devices such as laptops, 
digital recorders, or flash drives. 
 
[  x ] Identifiable data WILL NOT be stored on portable devices 
[  ] Identifiable data WILL be stored on portable devices (NOTE: PHI and sensitive data stored in this 
manner must be encrypted) 
 
 
a. Rationale for storage of personal/private identifiable data on these devices: N/A 
 
b. State the security measures in place and where devices will be stored: N/A 
 
35. Will study data be shared outside of the study team or with non-local team members?  
[  ] Yes  
 
[ x ] No 
 
a. If yes, describe with whom, for what purposes, and how the sharing will take place and the security 
measures in place to protect data during transfer: 
 
 
36. Will data or specimens (identifieable or deidentified) be stored for future use?  
 [ x ] Yes  
[  ] No 

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20  
 
 
 If yes, please describe and make sure to include in consent form:  
Name and contact information (phone number and email address) will be stored to contact participants to 
participate in future studies. 
 
37. Breaking confidentiality: Will any information, such as abuse of a child or elder, be collected that is subject to 
mandated reporting requirements?  Or, will any data be collected that would require study staff to report results to 
medical professionals to ensure the safety of the subject?   [  ] Yes  
 
[ x ] No 
If yes, please describe the circumstances under which this could happen below and make sure to notify subjects of 
this in the consent form:N/A 
 
 
G: DISSEMINATION AND OTHER STUDY INFORMATION 
38. Describe your plans for disseminating the results of the study (include educational products such as 
dissertations/masters theses as well as academic products such as publications or presentations).  Make sure 
to state if identifiers will be used in any research products and if data will be presented in the aggregate or 
individual level.  If direct quotes will be used, please state this and include in the consent form: 
Results may be disseminated in the following forms: manuscripts, oral presentations, poster presentations, 
dissertations, and future grant applications. 
 
 
39. Have you registered your project with the Office of Research and Sponsored Programs (ORSP)?  [  ] Yes    [  ] 
No 
 
 
If Yes, Please list your Marquette ORSP Institutional Proposal # (XXXXXXXX), which can be found in 
Kuali: 00032902 
  
40. Is this project funded by NIH, HHS, Dept of Education, NSF or any other federal agency? 
  
 
 [ x ] No**            [  ] Yes*   If so, which agency? :  
              
 
*If your project is federally funded, you must also submit a copy of the proposal to the IRB. 
 
**If your project receives funding in the future you are required to notify the IRB of this via an amendment 
process 
 
 
Does the investigator or key personnel have a potential financial conflict of interest in this study that should 
be  
disclosed? 
 
[ ] Yes    [  x] No     If Yes, Please explain: 
 
 
 
H: STUDY PERSONNEL 
Provide the names, titles and affiliations of all investigators (include PI, faculty advisor, co-PIs, and investigators 
from outside institutions) in the table below.  Please add lines as needed   
To minimize future amendment submissions, non-key personnel roles such as student or graduate 
student “research assistant” do not require those individuals to be individually named.  Consider entering 
“research Assistants” in the name field and “n/a” in the contact email field. 
 

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21  
 
*Human subjects training is required for all human subject investigators.  See 
http://www.marquette.edu/orc/irb/training-education.shtml for more information on this requirement. 
 
 
I. 
Is this study… 
 
Submission directions 
Resources 
...accessing or using protected 
health information (PHI) from a 
HIPAA-covered entity? 
[  ] Yes 
[  x]  No 
Also complete Appendix B and 
provide any supporting 
documentation such as a draft 
authorization form or a request 
to waive authorization 
HIPAA Privacy Rule 
 
HIPAA and Research 
 
Covered Entities on 
MU Campus 
…using student educational 
records/data including GPA, course 
documents, etc…? 
[  ] Yes 
[ x ] No 
Also complete Appendix C 
FERPA regulations 
 
MU FERPA policies 
…collecting data through electrical 
powered equipment that comes in 
contact with subjects (excluding 
computers and battery –operated 
devices)? 
[  x] Yes 
[  ] No 
Make sure to describe the 
device in Section II.D, 
complete Appendix D and 
submit a copy of the purchase 
receipt or last safety testing 
record 
MU’s Electrical Safety 
Testing Policy 
… testing the safety and/or efficacy 
of a new medical device or drug? 
[  ] Yes 
[ x ] No 
FDA regulations may apply- 
please contact the ORC to 
discuss click here to email the 
ORC) 
Also see MU’s device 
safety in research 
website 
… using secondary data or 
biospecimens collected outside of 
this research study? 
[  ] Yes 
[ x ] No 
Also complete Appendix E 
 
 
 
Submission Instructions: Email this completed form and any supporting documents including consent 
forms, information sheets, surveys, interview questions, etc. as attachments to orc@mu.edu with the following 
subject line:  
Name 
Institution 
Status 
(Faculty, Grad., 
Undergrad., 
etc.) 
Contact e-mail 
Allison Hyngstrom 
MU 
Faculty 
Allison.hyngstrom@
marquette.edu 
Saad Alqahtani 
MU 
Grad student 
Saad.alqahtani@ma
rquette.edu 
Stephanie Raab 
MU 
Grad student 
Stephanie.raab@m
arquette.edu 
Brian.schmit@marquette.edu  
MU 
Faculty 
     Brian.schmit 
@marquett.edu 
Matthew Durand 
MCW 
Faculty 
Mdurand@mcw.edu 
Jennifer Nguyen 
MCW 
Staff 
Jnguyen@mcw.edu 
Zhilun Zhou 
MU 
Grad student 
Zhilun.zhou@marqu
ette.edu 
Ashley Dejaco 
MU 
Undergrad 
student 
Ashley.dehaco@ma
rquette.edu 
Toni Uhrich 
MU 
Staff 
Toni.uhrich@marqu
ette.edu 

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22  
 
New Study Submission for [first and last name of PI] or 
Amendment Submission for [first and last name of PI], HR-[XXXX] 
• 
In the body of e-mail, include the title of the study and an itemized list of attachments. 
• 
The email address of the sender must be the Principal Investigator’s Marquette email. 
• 
If the PI is a student, the faculty advisor must be cc’d. 
 
Once submitted, the IRB will e-mail back a response of receipt. If you do not receive an e-mail confirmation of 
submission within 3-5 days of submission, please contact the IRB by phone (288-7570) or email (orc@mu.edu) to 
verify receipt. 
 
 

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23  
 
Appendix A: Consent 
 
**COMPLETE ONLY IF REQUESTING TO WAIVE, ALTER, OR WAIVE DOCUMENTATION OF CONSENT** 
 
Section 1. WAIVER OF DOCUMENTATION OF CONSENT (not requiring subject to sign the consent form) 
 
Complete either Option A, B or C questions 
OPTION A 
 
OPTION B 
 
OPTION C 
Would the signed consent 
document be the only record 
linking the subject to the 
study? 
 
     [  ] Yes            [  ] No 
OR 
Does the research pose no 
more than minimal risk? 
 
    [  ] Yes 
[  ] No  
 
OR 
Is it NOT the cultural 
norm for subjects to sign 
these type of 
documents? 
 
  [  ] Yes 
[  ] No 
Is breach of confidentiality 
the principal risk to the 
subjects? 
 
 
    [  ] Yes 
    [  ] No 
 
Does the research include 
any activities that would 
require signed consent in a 
non-research context? 
 
 [  ] Yes 
 
[  ] No  
 
Is an alternate 
mechanism of 
documenting consent 
being included in the 
protocol? 
 
  [  ] Yes 
[  ] No 
 
Provide a justification/explanation for the responses above: 
 
 
Section 2. WAIVER OR ALTERATION OF CONSENT 
 
Are you requesting: 
 
 
[  ] Waiver of consent  
 
 
[  ] Alteration or removal of required elements of consent- State what will be altered or removed:  
 
Respond to the following questions: 
1. Does the research pose more than minimal risk to the 
participants? 
 
2. Will the waiver adversely affect participants’ rights and 
welfare? 
 
3. Why would it be impracticable to carry out the research 
without the waiver or alteration? 
 
4. When appropriate, how will pertinent information be 
returned to or shared with participants? 
 
5. Explain why the study cannot be conducted using de-
identified datasets (if appropriate). 
 
6. Is this study approved by governmental officials, designed 
to evaluate public service programs and is impracticable to 
be carried out without the waiver? 
 
Appendix B: HIPAA 
 

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24  
 
**COMPLETE ONLY IF REQUESTING TO USE PROTECTED HEALTH INFORMATION IN THE 
STUDY** 
Protected Health Information (PHI) = Health information + identifiers 
 
Will the project require the use or disclosure of PHI? 
 
] YES  
[ x] NO (If NO, you do not need to fill out the rest of this appendix). 
 
If the answer is YES, indicate the source of protected health information: 
Marquette University Sources 
Non-Marquette University Sources 
[  ] 
School of Dentistry 
[  ] 
College of Health Sciences 
[  ] 
College of Nursing 
[  ] 
Dental Hygiene 
[  ] 
Speech Pathology and Audiology 
[  ] 
Counseling and Educational Psychology 
[  ] 
Clinical Psychology 
[  ] 
MU Medical Center 
[  ] 
Intercollegiate Athletics 
[  ] 
Other (describe): 
[  ] 
Hospital medical records (in- and /or outpatient) 
[  ] 
Health professional/Clinic records 
[  ] 
Health professional/Office records 
[  ] 
Laboratory, pathology and/or radiology results 
[  ] 
Biological samples 
[  ] 
Interviews/questionnaires 
[  ] 
Mental health records 
[  ] 
Billing records 
[  ] 
Data previously collected for research purposes 
[  ] 
Decedent information 
[  ] 
Other (describe):  
 
A. Nature of Request: 
 
 [  ] Authorization (Also submit draft authorization form) 
 
 [  ] Waiver of authorization (Also submit completed request to waive authorization) 
 
 [  ] Limited data set agreement  
 
B. Details 
 
1. 
Identify all individuals who will have access to data and PHI: 
 
 
2. 
Describe the PHI that will be gathered, used or disclosed as part of this research project: 
 Age, date of stroke, type of stroke, and reported medical history including current medications. These data 
are important for describing participant characteristics and assisting with the interpretation of the results. 
 
3. 
Describe the identifiers that will be gathered, used or disclosed as part of this research project:  
 
 
4. 
Explain why the research cannot practicably be conducted without requested PHI: 
 
C. Data Security: explain safeguards and how data will be stored. 
 
 
1. 
Electronic (check all that apply) 
[  ] Secure network  
 
[  ] Password access  
[  ] Coded, with master list kept as a hard copy or on a secure network, separate from PHI/data    
[  ] Other (explain): 
 
2. 
Hard copy (check all that apply) 
[  ] Locked suite  [  ] Locked filing cabinet 
 [  ] Locked office  
[  ] Data de-identified with master list secured and kept separately   
[  ] Other (explain): 
 
D. Sharing of PHI 
1.  Will the PHI be removed from the entity that owns the PHI? 

HR-1812027206 
 
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25  
 
[  ] YES  
 
[  ]NO 
 
2. 
Will the PHI be shared/used by others than P.I. and research staff? 
[  ] NO 
[  ] YES (mark all that apply below) 
 
[  ] Statistician 
 
 
[  ] Colleagues 
[  ] Other research laboratories 
[  ] Publications 
[  ] Data & Safety monitoring committees 
[  ] Sponsor  
 
[  ] Consultants 
[  ] Participants (Subjects) 
[  ] Other(s) – explain  _______________________________________  
 
a. If data will be shared, which of the following apply? 
 
[  ] With identifiers   [  ] Without identifiers   [  ] With a linkage code  
[  ] As a Limited Data Set (Requires data use agreement) 
 
E.  Retention of PHI 
 
1. 
How long will the information be retained? 
[  ] End of study   [  ] A set date (provide date):  
 
 
 
[  ] When data analysis is complete 
[  ] Other (explain):  
 
2. 
How will the information be destroyed? 
a. Electronic (explain):  
 
b. Hard copy (explain):  
 
 
3. 
Is there a justification for retaining the identifiers? 
 
[  ] YES   
 
[  ] NO 
 
If YES, what is the justification? 
[  ] Health reasons (explain): 
[  ] Scientific (explain): 
[  ] Legal (explain): 
[  ] Other (explain):  
 
 
4.     Will the stored PHI be reused or disclosed to any other person or entity except as required by law, for 
authorized  
oversight of the research project, or for other research for which the use or disclosure of PHI 
would be permitted? 
 
[  ] NO 
 
[  ] YES- explain: 
 
 
 
 

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26  
 
Appendix C: FERPA 
 
**COMPLETE ONLY IF USING STUDENT EDUCATIONAL DATA FOR RESEARCH PURPOSES** 
 
 
1. Are you accessing individual student educational data including course documents, GPA, registry information, 
or grades? 
 
[  ] YES  
 
 
[  ] NO 
 
 
2. List the specific student educational data you are accessing: 
 
 
 
 
3. Will you be recording student identifiers (name, MU ID#, etc…) with the educational data? 
 
[  ] YES  
 
 
[  ] NO 
 
 
4. How will you gain access to the educational data (i.e., will the registrar be providing it to you, will you be pulling 
it from your own students’ records, etc…)? 
 
 
 
 
5. Is any use of individual-level, identifiable student data clearly stated in a consent form that students will be 
signing? 
 
[  ] YES  
 
 
[  ] NO 
 
 
 
Please contact the registrar’s office with any questions about FERPA permissions and requirements 
http://www.marquette.edu/mucentral/registrar/  
 
 
 
 
 
 

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27  
 
Appendix D: Electrical Safety Testing 
 
**COMPLETE ONLY IF ELECTRICAL EQUIPMENT WILL COME IN CONTACT WITH SUBJECTS** 
 
 
*Note- this policy does not apply to devices that are battery-operated or computers used for data collection 
 
Office of Research Compliance policy #98.106 requires that electrical equipment that comes in contact with 
research subjects is required to pass electrical safety testing every three years starting from the date of purchase.  
If this study uses electrical equipment, please list it below, describe what it is and provide the most recent testing 
date or date of purchase.  Note that custom modified devices must undergo testing prior to use in human subjects 
research. 
 
 
Name of device 
Description 
Date of testing or date of 
purchase (indicate which) 
GE Vivid I ultrasound 
 
12/2018 
Delysis wireless EMG 
 
Measures muscle activity 
2018, battery operated 
OT AMplifier 
Measures muscle activity 
12/2018 
Biodex 
Measures strength of different 
muscle groups 
12/2018 
Bertec Treadmill 
Treadmill with embedded force 
sensors  
Uses 220 power supply 
Near Infrared Spectroscopy 
Machine 
Infrared light used to 
noninvasively measure oxygen 
saturation to the muscle 
12/2018 
 
 
 
 
 

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28  
 
Appendix E- Pre-existing data or specimens 
 
**COMPLETE ONLY IF USING PRE-EXISTING DATA OR SPECIMENS FOR RESEARCH PURPOSES** 
1. Answer the following: 
 
Yes 
No 
n/a 
a. Will the data or specimens include identifying information? 
 
 
 
b. Does the data include ONLY information protected under 
HIPAA? 
 
 
 
c. Will you be attempting to re-identify or contact subjects? 
 
 
 
 
2.  Describe the data or specimens that will be used in this study.  Include where they are coming from, how/why 
they were originally collected, and list the specific data fields (if applicable).   
 
 
3. What is the total number of existing records or specimens that will be used in this study? 
 
 
 
4.  Describe the plan to obtain consent for use of the data/specimens in this study or complete Appendix A to 
request a waiver of consent.  If the data or specimens were collected in a previous study, please state if subjects 
were made aware that their specimens or data would be stored and used in future studies.  
 
 
 
 
5. How will data or specimens be transported to research team and what security measures are in place during 
transit?   
 
 
 
 
6. Make sure you have described data storage and security in Section V of the protocol form or describe it here:  
 
 
 

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