High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Combined With Body Weight Supported Treadmill Training (BWSTT) After Stroke: A Pilot Study
Phase: NA
Conditions: Stroke
Sponsor: Texas Woman's University

If applicable, agency approval letters must be submitted to the IRB upon receipt prior to any data 
collection at that agency.   If subject recruitment is on-going, a copy of the approved consent form 
with the IRB approval stamp is enclosed.  Please use the consent form with the most recent approval 
date stamp when obtaining consent from your participants. A copy of the signed consent forms must 
be submitted with the request to close the study file at the completion of the study. 
Any modifications to this study must be submitted for review to the IRB using the Modification 
Request Form. Additionally, the IRB must be notified immediately of any unanticipated incidents. All 
forms are located on the IRB website. If you have any questions, please contact the TWU IRB.
Dr. Mark Weber, Physical Therapy - Dallas
cc.
January 4, 2021
Physical Therapy - Dallas
Extension for High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Combined 
with Body
Weight Supported Treadmill Training (BWSTT) After Stroke: a Pilot Study (Protocol #: 19883)
Re:
Dr. Hui-Ting Goh
Institutional Review Board
Office of Research and Sponsored Programs
P.O. Box 425619, Denton, TX 76204-5619
940-898-3378
email: IRB@twu.edu
https://www.twu.edu/institutional-review-board-irb/
Institutional Review Board (IRB) - Dallas
DATE:
TO:
FROM:
The request for an extension of the IRB approval for the above referenced study has been reviewed 
by the TWU IRB (operating under FWA00000178). This study was originally approved on January 18, 
2018 and has been renewed. Approval for this study expires on January 17, 2022.

June 2015 (revised Nov 2015) 
1 
Texas Woman's University Institutional Review Board 
Application for Expedited and Full Review 
Name of Principal Investigator (PI):   Hui-Ting Goh 
Phone:   (214)6897723 
Status:  
  faculty 
student 
staff 
other : 
E-mail:   hgoh1@twu.edu
Department: 
  Physical Therapy 
Colleague ID# (this is the 7-digit # on your ID): 
  0598520 
Title of Study: High frequency repetitive transcranial magnetic stimulation (rTMS) combined with body 
weight supported treadmill training (BWSTT) after stroke: a pilot study 
If the PI is a student, provide the following information for the faculty advisor: 
Name of advisor: 
E-mail:
TWU Department: 
Estimated beginning date of study: 
  1/1/2018 
Estimated duration of study   December 2020 
Campus (Denton, Dallas, or Houston) 
  Dallas 
Level of review: 
 expedited 
full 
Type of Project : 
thesis 
professional paper 
dissertation 
class project 
(check all that apply) 
  faculty research pilot 
other 
Has project has been submitted for funding (internal or external)?  
  yes 
no 
If yes, funding source: American Society of NeuroRehabilitation Seed Grant 
Signatures: 
Principal Investigator (PI): Signature certifies that the investigator has primary responsibility for all aspects of the 
research project. 
_Nov 13 2017 
_ 
Principal Investigator 
Date 
Faculty Research Advisor (for student research only): Signature certifies that the faculty member has read, 
reviewed, and approved the content of the application and is responsible for the supervision of this research study. 
_ 
Faculty Research Advisor 
Date 
Academic Administrator: Signature certifies that the administrator has read, reviewed, and approved the content of the 
application. 
_1_1_/_1_5_/2_0_1_7
_ 
Academic Administrator (Department Chair, Program Director, or Associate Dean) 
Date 
For office use only: 
Protocol #:  
_ 

June 2015 (revised Nov 2015) 
2 
 
METHODOLOGY 
 
Please refer to instructions when completing this form. The application must be typed using a font 
no smaller than 11-point. 
 
1.   Describe the purpose of study, including research questions and/or hypotheses. 
 
The purpose of this pilot study is to examine the feasibility and efficacy of 5Hz repetitive 
transcranial magnetic stimulation (rTMS) applied to bilateral motor area as an adjuvant 
intervention to task-specific body weight supported treadmill training (BWSTT) in individuals 
with subacute stroke. The study has two specific aims: 
 
Aim 1: To examine the feasibility and efficacy of 5Hz rTMS applied to bilateral leg motor 
cortices combined with BWSTT in individuals with subacute stroke 
This aim will address the following two research questions: 
1. Is a 5Hz rTMS protocol a feasible adjuvant intervention to BWSTT for individuals with 
subacute stroke? 
2. Is a 5Hz rTMS protocol an effective adjuvant intervention to BWSTT for individuals with 
subacture stroke? 
 
Aim 2: To examine the neurophysiological changes associated with rTMS and BWSTT in 
individuals with subacute stroke 
This aim will address the below research question: 
1. Will 24 sessions of rTMS combined with BWSTT induce neurophysiological changes in 
individuals with subacute stroke? 
 
 
Background: 
Each year, cerebral vascular accidents strike millions of Americans and leave many with 
long-term disabilities.1 Recovering the ability to walk is often listed as the primary goal of 
rehabilitation and has substantial impact on community reintegration.2,3 Extensive resources are 
directed toward gait rehabilitation and various training strategies have been proposed, including 
task-oriented training, robotic assisted gait training, virtual reality, and body weight supported 
treadmill training (BWSTT).4-9 Among these, BWSTT has been studied extensively. A recent 
systematic review concluded that BWSTT improves walking speed and walking endurance.9 
Several studies have suggested that BWSTT improves gait kinematics, such as gait 
symmetry,10 hip extension angle,11 and greater muscle activation.11 Improvement in gait 
kinematics suggests that cortical circuitry involvement might be an important mechanism 
underlying the clinical effect of BWSTT.12 
 
Mechanistic investigations on the benefits of BWSTT revealed significant cortical 
reorganization after training.13-15 In general, increased excitability in the ipsilesional motor 
cortex,13 increased excitability in bilateral motor cortices,14 and increased activation in bilateral 
sensorimotor cortices and cingulate motor areas15 were found to be associated with gait 
improvement after training. Cortical reorganization, a form of neuroplasticity, occurs 
spontaneously after injury and can be augmented by extrinsic factors, such as behavioral 
intervention and brain stimulation. Combining brain stimulation, for example repetitive 
transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS), and 
motor training has been shown to promote neuroplasticity and enhance motor recovery in the 

June 2015 (revised Nov 2015) 
3 
 
affected upper extremity.16-18  However, the application of brain stimulation for the 
promotion of gait recovery is relatively unexplored. 3,19,20 Unlike upper extremity motor 
function, gait control involves complex interaction between the two lower limbs and bilateral 
associated cortices.21 Application of non-invasive brain stimulation (NIBS) for upper extremity 
motor recovery is based on the interhemispheric competition model. In this approach, brain 
stimulation is often structured with the goal to either increase the excitability of the ipsilesional 
hemisphere or decrease the excitability of the contralesional hemisphere. Whether the model is 
suitable for gait recovery remains controversial providing that bilateral control of foot movements 
has been demonstrated in healthy individuals.22 Stimulation models that are optimized for the 
lower extremities and gait are needed. 
 
Preliminary evidence suggests that NIBS, either rTMS or tDCS, might hold promise for 
post-stroke gait rehabilitation.19,20  Most tDCS studies adopted ipsilesional facilitation protocols 
by applying the anode to the ipsilesional motor area with the goal to increase cortical excitability. 
However, the results thus far are conflicting. For example, Danzl et al. and Tahtis et al. reported 
that anodal tDCS applied to the ipsilesional primary motor cortex (M1) increased walking 
speed.23,24 In contrast, other investigations failed to demonstrate such gain in gait outcomes.25,26 
To date, there are only 5 published studies examining efficacy of rTMS on gait recovery after 
stroke. 14,27-30 Wang et al. employed a 1Hz rTMS protocol to the contralesional M1 in chronic 
stroke (> 1 year post onset) and reported that the 1Hz rTMS combined with task-oriented 
training significantly improved gait symmetry, walking speed, and motor function compared with 
sham stimulation. Similarly, Lin et al. applied 1Hz rTMS to contralesional M1 in 31 patients with 
subacute stroke for 15 sessions. They reported a positive effect on balance and activities of dail 
y life (ADL) independence. Other rTMS investigations utilized high frequency rTMS applied to 
bilateral motor cortices in individuals with chronic stroke; all showed a significant improvement 
in walking speed and motor function.27,28,30 The somatotopical location of the legs is adjacent to 
midline and deep in the cerebral sulcus. Application of rTMS to either hemispheric leg area is 
very likely to spread over to the contralateral leg area. In an ongoing project using a figure-of-8 
coil to deliver 5Hz rTMS to ipsilesional M1 over tibialis anterior hot-spot, we observed that this 
method of application increased motor evoked potential (MEP) amplitudes bilaterally. Taken 
together, bilateral stimulation (at vertex) with a facilitatory effect seems to be a more reasonable 
approach given the anatomical location of the leg representation in motor cortex and bilateral 
involvement of motor areas in lower limb control and gait recovery.15,21 Previous bilateral high 
frequency rTMS studies were conducted in individuals with chronic stroke. It is unclear 
whether such benefits would be observed in patients in the acute or subacute phase in 
which neuroplasticity is believed to be more viable compared to the chronic phase. 
 
The primary objective of the proposed study is to examine the feasibility and clinical 
efficacy of using high frequency rTMS applied to bilateral motor area as an adjuvant intervention 
to task-specific BWSTT in a group of patients with subacute stroke. We have previously 
demonstrated the feasibility and efficacy of a gait training protocol incorporated BWSTT in 
individuals with acute stroke (< 6 weeks post-stroke) in an inpatient rehabilitation setting.31 
However, there is a growing trend towards reduced lengths of stay (LOS) in rehabilitation for 
persons with stroke.32,33 For example, from 2000 to 2007 the LOS decreased from a mean of 
19.6 days to 16.5 days.32 The trend towards shorter LOS is particularly concerning given the 
well-established fact the most functional motor recovery happens early after stroke.34,35 There is 
evidence to suggest the period immediately following the stroke up to about 2 months post is 
critical for gait recovery.34,36,37  Baer and Smith, for example, found in a heterogeneous 
population of persons with stroke that 75% of the cohort regained gait function within 25 days of 
stroke onset.36 These studies highlight the reality that walking recovery happens early after 
stroke. Therefore, gait recovery efforts must be focused on this critical period. Given the trend 

June 2015 (revised Nov 2015) 
4 
 
towards shorter LOS in the inpatient rehab setting and less available time to focus on the 
important task of gait recovery, gait training during this critical period will likely occur in the 
outpatient rehabilitation setting. 
 
BWSTT is beneficial in the way that it allows for maximum stepping repetitions and 
focuses on optimum gait kinematics. BWSTT delivered during early recovery period (subacute) 
provides opportunity to promote an optimal gait pattern or to limit abnormal gait patterns 
developed right after stroke. Abnormal compensatory movement patterns are associated with 
maladaptive neuroplasticity that further interfere with recovery.38 Our previous work has shown 
that a BWSTT protocol can be easily implemented in a clinical setting and resulted in favorable 
outcomes.31 Our studies found that persons trained with this approach utilized fewer assistive 
devices, experienced fewer falls, walked faster and further with improved temporal and spatial 
symmetry and experienced less fatigue when compared to published data of patients that 
received traditional rehabilitation.10,31,39-42However, it is unknown whether this body weight 
supported gait training protocol could be augmented with non-invasive brain stimulation. 
Further, our previous investigations did not include neurophysiological measures to demonstrate 
a training-induced neuroplasticity. Thus, the secondary objective of the proposed study is to 
determine the extent to which neuroplasticity could be induced by non-invasive brain stimulation 
and BWSTT. 
This pilot study has been awarded by the American Society of NeuroRehabilitation with a 
seed grant of $4,900. The deposit of the fund is pending upon the IRB approval. The fund is 
provided to collect preliminary data for preparation for extramural fund applications. A larger scale 
randomized controlled trial will be conducted upon securing funding. 
 
2. Participant Information: 
 
a. 
Description of participants in study: 
 
2. 5 individuals (men or women) with a diagnosis of subacute stroke will be recruited. 
 
b. 
Approximate number of participants:   5 
 
c. 
Vulnerable populations as participants (check all that apply): 
 
Prisoners ............................................... 
Pregnant women ................................... 
Fetuses / neonates ................................ 
Minors.................................................... 
 
NOTE: Researchers must comply with the federal mandate to report child abuse. See instructions for 
details. 
 
d. 
Age (or age range) of participants:  18 to 80 years 
 
Provide the rationale for inclusion/exclusion on the basis of age: 
 
Stroke is relatively uncommon in persons younger than 18 years. Further, TMS safety 
data in children and adolescents are less well-established. We exclude individuals 
younger than 18 years for both scientific merit and safety concern. Individuals older than 
80 years often have multiple comorbidities (e.g. cardiac problem, joint pathology) that will 
interfere with their ability to participate in physical exercise. 

June 2015 (revised Nov 2015) 
5 
 
e. 
Sex of participants ............................................................................... 
Male 
Female 
  Both 
 
Provide the rationale for inclusion/exclusion on the basis of sex: 
 
 
 
f. 
Participants will be excluded based on ethnicity:............................................................ 
Yes 
  No 
 
If yes, provide a description of the exclusion criteria and the rationale for using these criteria: 
 
 
 
 
g. 
List and provide rationale for any other inclusion/exclusion criteria: 
 
The inclusion criteria are: 
1) 18-80 years old: This study will not include individuals age below 18 years for a few 
reasons. Stroke is relatively uncommon in persons younger than 18 years. Further, TMS 
safety data in children and adolescents are less well-established. We exclude individuals 
younger than 18 years for both scientific merit and safety concern. Individuals older than 
80 years often have multiple comorbidities (e.g. cardiac problem, joint pathology) that will 
interfere with their ability to participate in physical exercise. 
 
2) < 2 months post stroke at the time of enrollment: the purpose of this study is to 
determine the feasibility and efficacy of high frequency rTMS in gait recovery among 
individuals with subacute stroke. Our rationale to recruit individuals with a recent stroke 
is that neuroplasticity is most evident during early phase of recovery. 
 
3) first time stroke: individuals with a previous history of stroke leaving them with 
significant gait dysfunction are anticipated to respond differently to the training. In order 
to ensure we have a homogenous sample in this pilot study, we will only recruit those 
with a first time stroke. 
 
4) able to walk > 25 feet with or without assistive device and with no more than moderate 
assistance: The training is structured for 2-3 times per week for sessions of 45 minutes 
in duration. To ensure that the participants will be able to tolerate the training in a safe 
manner, we will recruit individuals with the ability to walk at least 25 feet. 
 
5) able to follow 1-step commands: Stroke can lead to significant cognitive impairment 
interfering with training and testing. To ensure participant’s safety and compliance, we 
will only recruit individuals with the ability to follow at least one-step commands. 
 
3. 6) able to communicate verbally  
      
The exclusion criteria are: 
1) severe medical problems (e.g. recent cardiac infarct, heart failure, cancer): Severe 
cardiac problems will forbid participants from any physical exercises. 
 
2) presence of conditions that could affect gait training (e.g. amputation, severe arthritis): 
Individuals with gait dysfunction resulted from other diagnoses will be excluded as they 
will not represent a typical individual post stroke. 

June 2015 (revised Nov 2015) 
6 
 
3) bilateral stroke: Individuals with bilateral stroke often exhibit different clinical 
presentations and recovery pathways than unilateral stroke. Excluding persons with 
bilateral stroke is to make sure that we will have a homogenous sample. 
 
4) non-ambulatory prior to stroke: Individuals who are non-ambulatory before stroke are 
unlikely to become ambulatory and they will not be able to participate in the training 
 
5) BMI > 40: The standardized gait training includes using a harness system to support 
body weight. There is a safety concern of using the harness system in overweight 
persons. 
 
6) any contraindications to TMS (e.g. history of seizure, cardiac pacemaker, metal or 
magnetic implants): The study involves using TMS to facilitate cortical excitability. 
Individuals with contraindications to TMS will not be included. 
 
7) pregnant or potentially to be pregnant: pregnancy is a contraindication to TMS. 
 
 
3. Describe the participant recruitment process in detail. Make sure that you attach any 
recruitment materials or scripts in the attachment section. 
 
The team will recruit potential participants from hospitals in the community. Facilities will be 
provided with information regarding the study by members of the team at the facilities. The 
information will direct participants and/or caregivers to contact the PI or co-I for telephone 
screening before scheduling for consent and testing. Those who are deemed to meet the 
inclusion and exclusion criteria may be scheduled for initial testing. 
 
 
4. Research Procedures: 
 
a. 
In the space below, describe in detail the research procedures (do not use an attachment): 
 
Assessment procedure: Once study eligibility is confirmed, participants will be scheduled for two 
pre-training assessments. The first assessment session will consist of several clinical and 
behavioral outcomes, including the Functional Independent Measure (FIM) locomotion 
subscale, temporal-spatial gait analysis using a GaitRite system, 6 Minute Walk Test, Stroke 
Rehabilitation Assessment of Movement (STREAM), modified Ashworth scale, Stroke Impact 
Scale and Fatigue Severity Scale. The second assessment session will include measures of 
cortical excitability using single pulse MagstimTMS stimulator. Motor threshold (MT) and motor 
evoked potential (MEP) amplitudes will be acquired from bilateral M1 corresponding to the 
respective Tibialis Anterior (TA) muscle. All assessments will take place at The Stroke Center- 
Dallas, Texas Woman’s University. A blinded tester will administer all assessments and will not 
be involved in the rTMS or gait training sessions. 
 
rTMS procedure: After the pre-training assessments, participants will be assigned to either the 
real-rTMS or sham-rTMS group. The real-rTMS group will receive a 5Hz rTMS protocol applied 
to the vertex via a figure-of-8 air-filmed coil that is coupled with a Magstim Rapid2 stimulator. 
Stimulation will be delivered at the intensity of 90% of resting MT of the lesion M1. We have 
previously shown that this stimulation protocol effectively increased cortical excitability in 
persons with stroke.43 For the sham-rTMS group, a figure-of-8 sham coil will be placed at the 
same location on the scalp. The sham stimulation will induce a similar acoustic artifact and 

June 2015 (revised Nov 2015) 
7 
 
some scalp sensation without an effective electrical field. Each rTMS session will last about 30 
minutes. During stimulation, participants will sit in a reclining chair with their arms and legs 
supported. Vital signs (heart rate and blood pressure) will be measured before and after each 
rTMS session. Participants will be asked to report any adverse effects, such as headaches or 
dizziness. All reported adverse effects or measured abnormal responses will be documented. 
The rTMS sessions will be delivered at The Stroke Center-Dallas. The persons administering 
the rTMS sessions will not participate in any other assessment or gait training sessions. 
 
Gait training procedure: After the rTMS session, participants will go to the Gait Disorders Clinic 
at UT Southwestern Medical Center to receive a 45-minute gait training session. The Gait 
Disorders Clinic is approximately 10 minutes (0.5 mile) away from The Stroke Center-Dallas. 
Our previous investigation showed that the effect of the rTMS lasted up to 90 minutes post- 
stimulation.43 We are confident that the distance between the two study sites will not present a 
problem. Gait training will start on a treadmill equipped with an unweighting mechanism. Initially, 
the body weight support will be set between 30-50% of body weight and the starting velocity set 
at 0.7 mph or 1.5 times the velocity of the initial walking speed (whichever is greater). A trained 
therapist will assist participants with weight shift and hemiparetic limb advancement with the 
goal to duplicate typical gait mechanics and optimum kinematics. Upper extremity support will 
not be allowed throughout the training. Participants will walk on the treadmill for 30 minutes with 
a goal of 3-minute minimum bouts. Body weight support will be progressively reduced as 
treadmill speed is increased until participants are able to walk at a speed of 1.8 mph with no 
body weight support, good kinematics and no assistance from the therapist. The remaining 15 
minutes of each session will be spent on over ground walking and/or standing activities. Each 
participant will engage in a home exercise program comprised of home walking and 
standardized exercise. Participants will be prescribed an appropriate walking orthosis or aid 
when the therapist deems it is necessary. The therapist involved in gait training will have no 
knowledge of group assignment or the assessment results with the exception of participant’s 
initial walking speed. 
After participants finish the 24 sessions of training, both assessment sessions 
(clinical/behavioral and neurophysiological) will be repeated. These sessions will be completed 
by the same tester as before training. 
The table below presents the timeline of the study procedure. 
Week 1 
Visit 1: obtain consent, clinical and behavioral outcomes 
Visit 2: TMS assessment 
Week 2 to 
Week 11 
Treatment session 1 to 24 will be scheduled over a 10-week period (2-3 
sessions per week) 
Each session starts at TWU-Dallas campus with a 30 minute brain stimulation 
followed by a 45 minute gait training at the UTSW -Gait Disorder Clinic. 
Week 12 
Visit 1: obtain consent, clinical and behavioral outcomes 
Visit 2: TMS assessment 
 
Data analysis: 
Outcomes used to examine the feasibility include recruitment rate, reasons for declining 
participation, retention rate, compliance to study protocol, time required to conduct the 
intervention (visit duration and actual treatment duration), and number of adverse events. This 
pilot study is a collaboration between two institutes and the participants will travel between the 
two sites to receive the treatments in a timely manner. It is critical for the research team to 
establish the feasibility and a logistic plan before planning for a bigger trial. 
 
Outcomes used to determine clinical efficacy include walking speed, FIM locomotion score, 6 
Minute Walk Test score, STREAM, modified Ashworth scale, Stroke Impact Scale and Fatigue 

June 2015 (revised Nov 2015) 
8 
 
Severity Scale. The walking speed (in m/s) will be the primary outcome to examine efficacy and 
walking speed will be used to calculate effect size for sample size estimation in grant 
preparation. 
 
Outcomes used to examine the effect on cortical excitability (Aim 2) include resting motor 
threshold, motor evoked potential amplitudes, intracortical facilitation and intracortical inhibition. 
Given the small sample, these outcome will be analyzed descriptively and be used to 
demonstrate technical feasibility for future grant submission. 
 
 
b. 
Is video recording a part of the study? 
Yes 
  No 
With sound 
Without sound 
c. Is audio recording a part of the study?............. ............................................................. 
Yes 
  No 
 
If you answered “yes” to question #4b or 4c, describe the 
purpose of the recording and who will have access to these recordings. 
 
 
 
d.  Is internet / email a part of the study? .............. ............................................................. 
Yes 
  No 
If you answered “yes” to question #4d, describe how the internet and/or email 
will be used. 
 
 
 
 
5. What is the time commitment for the participants? Include the number of sessions, 
maximum time commitment per session, and the maximum cumulative time 
commitment. 
 
The study involves 2 assessment sessions (pre- and post-training) and each session is 
estimated to be completed within 3 hours. 
 
The training involves 24 sessions and each session is estimated to take 2 hours including the 
transportation time between two sites and waiting time. 
 
The total time commitment for the participants is 54 hours (2 x 3 hours + 24 x 2 hours). 
 
 
6. Site / location of the study. 
 
a. 
Will participants be affiliated with a specific non-TWU agency, institution, or organization?........ 
Yes 
  No 
 
If yes: 
 
Name of the site(s)? 
 
 
 
Affiliation of the principal investigator to this site(s)? 

June 2015 (revised Nov 2015) 
9 
 
 
 
 
Affiliation of the participants to this site(s)? 
 
 
 
 
Agency approval letters are required by the IRB before data can be collected at a site. If you 
answered “yes” to 6a, attach the signed agency approval letter on letterhead from each agency. If 
agency approval cannot be obtained prior to submitting the IRB application, explain here. 
 
 
 
b. 
Describe the setting of the study (i.e. physical location, surroundings, privacy aspects, etc.) 
 
The study will take place at the TWU – Dallas Campus Neurophysiology Lab and the 
UTSW-Gait Disorder Clinic. The Neurophysiology lab is located on the first floor of the 
Stroke Center-Dallas. The center has an attached parking garage with easy access to the 
lab. The lab is in an independent suite with limited access. Participant interview and data 
collection will be conducted in private. The lab is equipped with all necessary equipment 
to carry out the study. 
 
The gait training will take place at the UTSW-Gait Disorder Clinic. The gait clinic is 
located on the first floor of the School of Health Professions on the campus of the 
University of Texas Southwestern Medical Center campus. The clinic has an attached 
parking garage and easy access to the clinic. The clinic has all the equipment necessary 
to conduct the study including treadmill equipped with a body weigh support unit. 

June 2015 (revised Nov 2015) 
10 
 
POTENTIAL RISKS AND PROTECTION OF PARTICIPANTS 
 
7. 
Explain the potential risks to the human participants involved in this research. All risks 
must be identified and listed on the consent form (if applicable). 
 
 
RISK 
STEPS TO MINIMIZE RISK 
Loss of confidentiality 
The investigators will attempt to maintain 
confidentiality to the extent that is allowed by 
law. The study will take place at Texas 
Woman’s University, School of Physical 
Therapy – Dallas Campus and the University 
of Southwestern Medical Center. Codes, 
rather than names, will be used in the data 
analysis and in the final report. The data will 
be stored in a locked file cabinet. The data 
recorded on papers will be stored for 
approximately 5 years and then will be 
shredded. The data recorded on disks will be 
stored for 5 years and then will be deleted. It 
is anticipated that data will be published in 
books and/or journals. However, names or 
other identifying information will not be 
included in any publication. 
RISK 
STEPS TO MINIMIZE RISK 
Loss of balance /fall 
There is a minimal risk of falling while walking 
after stroke but this risk is small 
Participants will always be closely guarded 
during any gait training and assessment. 
All members of the research team are 
professionally trained to manage individuals 
with balance deficits. 
RISK 
STEPS TO MINIMIZE RISK 
Fatigue 
The participants may experience fatigue 
during the assessment or training sessions. 
The estimated duration of each session 
includes scheduled breaks. 
Participants will be reminded to request 
breaks whenever they feel tired. 
The therapists and testers will also pause or 
stop the procedure when they deem 
necessary. 
RISK 
STEPS TO MINIMIZE RISK 

June 2015 (revised Nov 2015) 
11 
 
Skin irritation or shortness of breath 
There is also a very minimal risk of injury with 
the vest that is worn during the treadmill 
training (such as irritation from the straps that 
secure the harness, shortness of breath if the 
vest is secured too tightly, irritation to 
sensitive skin or tubes such as a feeding tube 
in the stomach. 
Therapists involved in the training will be 
trained to put on the vest and harness 
properly. 
Participants will be instructed to report 
immediately to the therapist if they feel that 
the harness/vest is too tight. 
Therapists will also perform skin check after 
the gait training sessions to detect any skin 
irritations. 
RISK 
STEPS TO MINIMIZE RISK 
Changes in auditory threshold 
There is a minimal risk of alteration in auditory 
threshold after TMS protocols as TMS 
produces loud click when it is charged. The 
changes in auditory threshold are transient 
(lasts about 1 day) and not different from 
going to a music concert. 
To minimize the risk, we will provide earplugs 
during TMS testing. 
RISK 
STEPS TO MINIMIZE RISK 
Headaches 
There is a minimal risk of developing 
headaches during or after rTMS procedure. 
The effect is transient and can be resolved 
with over-the-counter medications. 
The intensity of the procedure is relatively 
low and should reduce the likelihood of 
developing headaches. If participants 
develop a severe headache during the 
testing, we will stop the testing and withdraw 
them from the study. 
RISK 
STEPS TO MINIMIZE RISK 
Seizure 
There is an increased risk of triggering a 
seizure in persons with a history of seizures 
or in persons taking medications that are 
known to reduce seizure threshold while 
receiving TMS. 
In the case of the low frequency and low 
intensity stimulation (as in this study), the risk 
of triggering a seizure is very small. All 
known cases of TMS-induced seizures in 
neurologically normally persons have 
happened at frequencies and intensities 
greater than what will be used in this study. 
The TMS frequencies and intensities will be 
kept within extremely safe limits. Since there 
are no known reports of seizures in 
individuals undergoing TMS without a history 
of seizures, the probability of a TMS-induced 
seizure is extremely rare. 
(Use continuation pages if necessary) 
 
 
8. 
Will participants be told about the intent of the study prior to participating? .. 
  Yes 
No 

June 2015 (revised Nov 2015) 
12 
 
If “no,” provide an explanation of why deception is necessary and the debriefing method to be used to 
fully inform the participants of the study's intent. 
 
 
 
 
9. 
Explain when and how the participants will be given the opportunity to ask questions. 
 
Participants will have the opportunity to ask questions anytime during the initial meeting with 
researchers or throughout the duration of the study. 
 
 
10. Identifiable Data 
 
Outline the steps to ensure the confidentiality of identifiable data. Identifiable data 
includes documents, audio and video recordings, electronic data, and blood or other 
human specimens. 
 
a. 
Explain what identifiable data, if any, will be collected. 
 
Name, date of birth, gender, self and family medical history 
 
 
b. 
Where will identifiable data be stored? (Specify precise location, preferably in a locked file cabinet 
with limited access.) 
 
Identifiable data will be stored in a locked file cabinet in the School of Physical Therapy, 
Dallas Campus research lab room 8811. Access will be limited to the researchers. 
 
 
c. 
Give the date that identifiable data will be destroyed (mm/dd/yy). If identifiable data will be stored for 
an indefinite period of time, please explain. 
 
The identifiable data will be destroyed by 12/31/2024 by shredding all paper documents. 
Electronic data will be destroyed by 12/31/2024 by deleting all files containing identifiable 
data from any and all electronic devices including computers and portable storage 
devices. 
 
 
d. 
Identify specific ways that identifiable data will be destroyed at the end of this period of time. 
 
The identifiable data will be destroyed by 12/31/2024 by shredding all paper documents. 
Electronic data will be destroyed by 12/31/2024 by deleting all files containing identifiable 
data from any and all electronic devices including computers and portable storage 
devices. 

June 2015 (revised Nov 2015) 
13 
 
e. 
Because the academic component of TWU is classified as a non-covered HIPAA entity, identifiable 
health or health-related data cannot be transmitted electronically. You must be able to answer “no”  
to at least one of the following questions in order for your study to be approved. 
 
Does this research involve health or health-related data? .........................................     Yes    No 
If yes, are the data identifiable? ..................................................................................     Yes     No 
If yes, will data be transmitted electronically?  ............................................................     Yes     No 
 
 
BENEFITS/REMUNERATION 
11. What will the participant receive for taking part in the study (i.e., financial remuneration, free 
services, access to information, and access to an intervention)? If there are none, state below that 
there are no direct benefits to the participant. 
 
Each participant will receive $200 in cash upon completion of the last assessment session. Participants 
will receive standarized gait intervention at no cost. Participants will have access to their own data 
upon request. 
 
 
12. What are the generalizable benefits of this study? (e.g., contribution to knowledge in 
field). 
 
There is limited research investigating the effects of non-invasive brain stimulation in gait recovery. 
The findings of this pilot study will allow the research team to develop a larger trial to systematcially 
examine the effects. 
 
 
13. Explain when and how the participants will be provided with the results of the study. 
 
Participants will be provided with the results of the study if they choose to receive one. A copy of 
result summary 3. with aggregate results of all participants will be mailed or e-mailed to them 
when the study is completed. 
 
INFORMED CONSENT PROCEDURES 
 
14. Written Informed Consent 
 
a. 
Explain the PROCESS you will use to obtain informed consent. 
 
Prospective participants will have the opportunity to read a written informed consent form 
describing this study and ask questions regarding this study with research study personnel. Each 
participant will sign the informed consent form in order to participate in this study after Institutional 
Review Board approval. 
 
b. 
Unless there are unusual circumstances, investigators are required to document informed consent  
by obtaining the participant’s signature (or the signature of their parent or guardian) on a written 
consent form. Explain when and how that signature will be obtained. Explain where the signed 
consent forms will be stored (specify precise location, preferably in a locked file cabinet with limited 
access), how long the signed consent forms will be kept, and identify specific ways that the signed 
consent forms will be destroyed at the end of this period of time. Note that a copy of the signed 
consent forms will need to be placed on file with the IRB when the study file is closed. 

June 2015 (revised Nov 2015) 
14 
 
The signature will be obtained after the prospective participant has read the  written  informed 
consent and agreed to participate. The signed consent forms will be stored in a locked file cabinet in 
the School of Physical Therapy, Dallas Campus research lab room 881l where only the researchers 
have access to it. The signed consent forms will be kept until 12/31/2024 and then be destroyed 
using a paper shredder. A copy of the signed consent form will be placed on file with the IRB when 
the study file is closed (estimated closing date December 2020) 
 
c. 
If you will not use a written consent form, provide a detailed rationale and explain how informed 
consent will be obtained 
 
N/A 
 
 
RESEARCH TEAM MEMBERS 
 
15. Provide a list of all research team members other than the investigator and faculty 
advisor. 
 
A current human subjects training certificate (less than 3 years old) must be on file for the 
investigator, advisor, and all research team members before an approval letter will be sent. 
These training certificates may be sent directly to the IRB separately or attached to this 
application in the attachment section. If a current training certificate is already on file with the 
IRB, there is no need to attach another copy. 
 
Name 
Karen McCain 
TWU 7-digit Colleague ID # (if applicable) 
N/A 
Email Address: 
karen.mccain@utsouthwestern.edu 
TWU Department or Name of Other Institution 
The University of Southwestern Medical Center 
Role on Project 
co-Investigator 
 
 
Name 
Vyoma Parikh 
TWU 7-digit Colleague ID # (if applicable) 
0927661 
Email Address: 
vparikh@twu.edu 
TWU Department or Name of Other Institution 
School of Physical Therapy 
Role on Project 
Research Assistant 
 
 
(Attach additional sheets if necessary) 
 
 
ATTACHMENTS 
 
16. List and describe all attachments (Include forms, scripts, flyers, consent forms, agency approval 
letters, human subjects training certificates, signed confidentiality agreement forms, referral lists, 
surveys, questionnaires, or any other instrument used in the study.) Attachments should be listed 
below in the same order in which they are attached. 
 
1. Human subjects training certificates 
2. Consent forms 

June 2015 (revised Nov 2015) 
15 
 
SUBMISSION INSTRUCTIONS 
 
The application should be submitted to the appropriate campus IRB. 
Denton and Dallas 
Mail the signed original to the address below. If electronic submission is preferred, combine all 
parts of application into single .pdf document and email to irb@twu.edu. If the application is 
submitted electronically as a fully signed .pdf, the original copy is not required. 
 
TWU’s Office of Research & Sponsored Programs 
Institutional Review Board 
PO Box 425619 
Denton, TX 76204-5619 
 
Applications may also be hand delivered to the Denton campus ACT 7th floor or the Dallas 
campus Office of Research IHSD 8th floor. 
 
Houston 
 
All parts of the application (including the signed cover page and appendices in order) should be 
combined into one single .pdf or Word document and emailed to irb-houston@twu.edu. The 
original copy is not required. If you have any difficulty with preparing a .pdf file, please contact 
the Houston Office of Research via email for assistance. 
 
 
RESPONSE TIMES 
 
Upon receipt of the application, the investigator will receive an email notifying them that the 
application has been received, the level of review that the application has been assigned, and 
the protocol number that has been assigned. Applicants can expect to receive a response from 
the IRB regarding the review within three weeks for an expedited application and within two 
weeks from the date of the meeting for a full review application. Note that these times are 
estimates and additional time may be required during certain times of the academic calendar 
such as summer, semester breaks, and Holidays. 
 
REFERENCES 
 
 
1. 
Writing Group M, Mozaffarian D, Benjamin EJ, et al. Executive Summary: Heart Disease 
and Stroke Statistics--2016 Update: A Report From the American Heart Association. 
Circulation. 2016;133(4):447-454. 
2. 
Barclay R, Ripat J, Mayo N. Factors describing community ambulation after stroke: a 
mixed-methods study. Clin Rehabil. 2015;29(5):509-521. 
3. 
Rogers LM, Madhavan S, Roth H, Stinear JW. Transforming neurorehabilitation of 
walking following stroke: the promise of non-invasive brain stimulation--a review. Restor 
Neurol Neurosci. 2011;29(6):507-516. 
4. 
An M, Shaughnessy M. The effects of exercise-based rehabilitation on balance and gait 
for stroke patients: a systematic review. J Neurosci Nurs. 2011;43(6):298-307. 

June 2015 (revised Nov 2015) 
16 
 
5. 
de Rooij IJ, van de Port IG, Meijer JG. Effect of Virtual Reality Training on Balance and 
Gait Ability in Patients With Stroke: Systematic Review and Meta-Analysis. Phys Ther. 
2016;96(12):1905-1918. 
6. 
Ferreira LA, Neto HP, Grecco LA, et al. Effect of Ankle-foot Orthosis on Gait Velocity 
and Cadence of Stroke Patients: A Systematic Review. J Phys Ther Sci. 
2013;25(11):1503-1508. 
7. 
Kafri M, Laufer Y. Therapeutic effects of functional electrical stimulation on gait in 
individuals post-stroke. Ann Biomed Eng. 2015;43(2):451-466. 
8. 
Swinnen E, Beckwee D, Meeusen R, Baeyens JP, Kerckhofs E. Does robot-assisted gait 
rehabilitation improve balance in stroke patients? A systematic review. Top Stroke 
Rehabil. 2014;21(2):87-100. 
9. 
Mehrholz J, Pohl M, Elsner B. Treadmill training and body weight support for walking 
after stroke. Cochrane Database Syst Rev. 2014(1):CD002840. 
10. 
McCain KJ, Pollo FE, Baum BS, Coleman SC, Baker S, Smith PS. Locomotor treadmill 
training with partial body-weight support before overground gait in adults with acute 
stroke: a pilot study. Arch Phys Med Rehabil. 2008;89(4):684-691. 
11. 
Mulroy SJ, Klassen T, Gronley JK, Eberly VJ, Brown DA, Sullivan KJ. Gait parameters 
associated with responsiveness to treadmill training with body-weight support after 
stroke: an exploratory study. Phys Ther. 2010;90(2):209-223. 
12. 
Koenraadt KL, Roelofsen EG, Duysens J, Keijsers NL. Cortical control of normal gait 
and precision stepping: an fNIRS study. Neuroimage. 2014;85 Pt 1:415-422. 
13. 
Yang YR, Chen IH, Liao KK, Huang CC, Wang RY. Cortical reorganization induced by 
body weight-supported treadmill training in patients with hemiparesis of different stroke 
durations. Arch Phys Med Rehabil. 2010;91(4):513-518. 
14. 
Yen CL, Wang RY, Liao KK, Huang CC, Yang YR. Gait training induced change in 
corticomotor excitability in patients with chronic stroke. Neurorehabil Neural Repair. 
2008;22(1):22-30. 
15. 
Enzinger C, Dawes H, Johansen-Berg H, et al. Brain activity changes associated with 
treadmill training after stroke. Stroke. 2009;40(7):2460-2467. 
16. 
Graef P, Dadalt ML, Rodrigues DA, Stein C, Pagnussat Ade S. Transcranial magnetic 
stimulation combined with upper-limb training for improving function after stroke: A 
systematic review and meta-analysis. J Neurol Sci. 2016;369:149-158. 
17. 
Klomjai W, Lackmy-Vallee A, Roche N, Pradat-Diehl P, Marchand-Pauvert V, Katz R. 
Repetitive transcranial magnetic stimulation and transcranial direct current stimulation in 
motor rehabilitation after stroke: an update. Ann Phys Rehabil Med. 2015;58(4):220-224. 
18. 
Le Q, Qu Y, Tao Y, Zhu S. Effects of repetitive transcranial magnetic stimulation on hand 
function recovery and excitability of the motor cortex after stroke: a meta-analysis. Am J 
Phys Med Rehabil. 2014;93(5):422-430. 
19. 
Fleming MK, Pavlou M, Newham DJ, Sztriha L, Teo JT. Non-invasive brain stimulation 
for the lower limb after stroke: what do we know so far and what should we be doing 
next? Disabil Rehabil. 2017;39(7):714-720. 
20. 
Chieffo R, Comi G, Leocani L. Noninvasive Neuromodulation in Poststroke Gait 
Disorders: Rationale, Feasibility, and State of the Art. Neurorehabil Neural Repair. 
2016;30(1):71-82. 
21. 
Charalambous CC, Bowden MG, Adkins DL. Motor Cortex and Motor Cortical 
Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial 
Magnetic Stimulation and Animal Models in Our Current and Future Understanding. 
Neurorehabil Neural Repair. 2016;30(1):94-102. 
22. 
Aglioti S, Dall'Agnola R, Girelli M, Marzi CA. Bilateral hemispheric control of foot distal 
movements: evidence from normal subjects. Cortex. 1991;27(4):571-581. 

June 2015 (revised Nov 2015) 
17 
 
23. 
Danzl MM, Chelette KC, Lee K, Lykins D, Sawaki L. Brain stimulation paired with novel 
locomotor training with robotic gait orthosis in chronic stroke: a feasibility study. 
NeuroRehabilitation. 2013;33(1):67-76. 
24. 
Tahtis V, Kaski D, Seemungal BM. The effect of single session bi-cephalic transcranial 
direct current stimulation on gait performance in sub-acute stroke: A pilot study. Restor 
Neurol Neurosci. 2014;32(4):527-532. 
25. 
Chang MC, Kim DY, Park DH. Enhancement of Cortical Excitability and Lower Limb 
Motor Function in Patients With Stroke by Transcranial Direct Current Stimulation. Brain 
Stimul. 2015;8(3):561-566. 
26. 
Leon D, Cortes M, Elder J, et al. tDCS does not enhance the effects of robot-assisted 
gait training in patient with subacute stroke. Restor Neurol Neurosci. 2017. 
27. 
Chieffo R, De Prezzo S, Houdayer E, et al. Deep repetitive transcranial magnetic 
stimulation with H-coil on lower limb motor function in chronic stroke: a pilot study. Arch 
Phys Med Rehabil. 2014;95(6):1141-1147. 
28. 
Kakuda W, Abo M, Watanabe S, et al. High-frequency rTMS applied over bilateral leg 
motor areas combined with mobility training for gait disturbance after stroke: a 
preliminary study. Brain Inj. 2013;27(9):1080-1086. 
29. 
Wang RY, Tseng HY, Liao KK, Wang CJ, Lai KL, Yang YR. rTMS combined with task- 
oriented training to improve symmetry of interhemispheric corticomotor excitability and 
gait performance after stroke: a randomized trial. Neurorehabil Neural Repair. 
2012;26(3):222-230. 
30. 
Kakuda W, Abo M, Nakayama Y, Kiyama A, Yoshida H. High-frequency rTMS using a 
double cone coil for gait disturbance. Acta Neurol Scand. 2013;128(2):100-106. 
31. 
McCain KJ, Smith PS, Polo FE, Coleman SC, Baker S. Excellent outcomes for adults 
who experienced early standardized treadmill training during acute phase of recovery 
from stroke: a case series. Top Stroke Rehabil. 2011;18(4):428-436. 
32. 
Granger CV, Markello SJ, Graham JE, Deutsch A, Ottenbacher KJ. The uniform data 
system for medical rehabilitation: report of patients with stroke discharged from 
comprehensive medical programs in 2000-2007. Am J Phys Med Rehabil. 
2009;88(12):961-972. 
33. 
O'Brien SR, Xue Y, Ingersoll G, Kelly A. Shorter length of stay is associated with worse 
functional outcomes for medicare beneficiaries with stroke. Phys Ther. 
2013;93(12):1592-1602. 
34. 
Duncan PW, Goldstein LB, Horner RD, Landsman PB, Samsa GP, Matchar DB. Similar 
motor recovery of upper and lower extremities after stroke. Stroke. 1994;25(6):1181- 
1188. 
35. 
Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. 
Outcome and time course of recovery in stroke. Part II: Time course of recovery. The 
Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995;76(5):406-412. 
36. 
Baer G, Smith M. The recovery of walking ability and subclassification of stroke. 
Physiother Res Int. 2001;6(3):135-144. 
37. 
Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Recovery of walking function in 
stroke patients: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995;76(1):27- 
32. 
38. 
Xu Y, Hou QH, Russell SD, et al. Neuroplasticity in post-stroke gait recovery and 
noninvasive brain stimulation. Neural Regen Res. 2015;10(12):2072-2080. 
39. 
Ivey FM, Macko RF, Ryan AS, Hafer-Macko CE. Cardiovascular health and fitness after 
stroke. Top Stroke Rehabil. 2005;12(1):1-16. 
40. 
Macko RF, Ivey FM, Forrester LW, et al. Treadmill exercise rehabilitation improves 
ambulatory function and cardiovascular fitness in patients with chronic stroke: a 
randomized, controlled trial. Stroke. 2005;36(10):2206-2211. 

June 2015 (revised Nov 2015) 
18 
 
41. 
Michael K, Goldberg AP, Treuth MS, Beans J, Normandt P, Macko RF. Progressive 
adaptive physical activity in stroke improves balance, gait, and fitness: preliminary 
results. Top Stroke Rehabil. 2009;16(2):133-139. 
42. 
Michael KM, Allen JK, Macko RF. Fatigue after stroke: relationship to mobility, fitness, 
ambulatory activity, social support, and falls efficacy. Rehabil Nurs. 2006;31(5):210-217. 
43. 
Goh HT, Chan HY, Abdul-Latif L. Aftereffects of 2 noninvasive brain stimulation 
techniques on corticospinal excitability in persons with chronic stroke: a pilot study. 
Journal of neurologic physical therapy : JNPT. 2015;39(1):15-22.