Neurophysiological and Kinematic Predictors of Response in Chronic Stroke
Phase: NA
Conditions: Stroke, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Cardiovascular Diseases
Sponsor: VA Pittsburgh Healthcare System

Date: Wednesday, April 21, 2021 10:51:23 AM
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ID: Pro00003161
View: 0.0 Type of Submission Entry
Study Identification Information
This is the first step in your Human Research Application.  You will automatically be guided to the 
appropriate forms needed to complete your submissions.
1.0
* Study Name:
Neurophysiological and Kinematic Predictors of Response in Chronic Stroke (SRT5)
2.0
* Brief Description (using layman's terms) - 500 words or less:
Stroke is the leading cause of neurological disability in the veteran population and upper extremity 
dysfunction is a major cause of functional loss. The costs of rehabilitation are significant and 
practically limits therapy to the first few months after stroke onset. Recent results show clearly 
that patients with chronic stroke benefit from rehabilitation and robot assisted therapy offers a 
more cost effective approach to this patient group. In this study, we are validating a predictive 
model that uses demographics, functional status, genomics, neurophysiology, neuroanatomy, and 
other potential biomarkers to predict the likelihood of a clinically significant change in impairment 
at the end of a robot assisted therapy intervention.
3.0
* Is this research study a Greater than Minimal Risk Clinical Trial?
Yes
No
4.0
* Is this study a Greater than Minimal Risk Comparative Effectiveness research?
Yes 
No
5.0
* Principal Investigator:
George Wittenberg
  5.1
* VA hours per week the PI is devoted to project:
10
  5.2
* Is the PI working with ionizing radiation?
Yes 
No
  5.3
* Is the PI working with biological hazards?
Yes 
No
  5.4
* Is the PI shipping biological hazards?
Yes 
No
A completed and signed Research Financial Conflict of Interest Statement is required for all 
investigators (including Principal Investigators, Co-Principal Investigators, and Co-
Investigators) listed on the study application. Financial Conflict of Interest Form-Nov. 
2013
5.5
Upload Financial Conflict of Interest Statement:
GW FCOI(0.01)
6.0
Research Staff:
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Researcher Role in Project
Hours per 
Week 
devoted to 
project
Administer 
Informed 
Consent
Working 
with 
Ionizing 
Radiation
Working 
with 
Biologicial 
Hazards?
Shipping 
biological 
hazards?
FCOI 
Form
Kasey 
Stepansky
Research 
Staff
2
no
no
no
no
Amy Boos
Research 
Staff
Coordinator
30
yes
no
no
no
Stacy 
Eckstein
Coordinator
1
no
no
no
no
Jennifer 
Collinger
Co-
Investigator
1
no
no
no
no
Collinger 
FCOI
(0.01)
7.0
Type of Submission:
Description
This is a new study. This has not previously been submitted to the IRB.
This is a new paper conversion. This study has been previously approved by the IRB.
If this is a 'New Paper Conversion' please include the MIRB Number:
Please upload a letter certifying that you have made no modifications or amendments in 
converting this research study from paper to electronic:
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ID: Pro00003161
View: 1.0 Study Identification Information
Study Identification Information (Continued)
1.0
* Do you certify that all research staff administering informed consent are 
knowledgeable about the study?
yes 
2.0
* To the best of your knowledge do you, or any member of your research staff, have any 
potential, actual or perceived conflict of interest of a professional or personal nature 
that may affect any aspect of the research, including, but not limited to, the review 
and/or conduct of this study?
Yes 
No
If yes, provide a description, including name of study team member with conflict:
3.0
* Qualifications of the Investigators:
Dr. George Wittenberg, MD, PhD, FASNR, is a clinician-scientist at the VAPHS and University of 
Pittsburgh. He has an A.B. degree in Engineering and Applied Sciences from Harvard College, and 
both doctoral degrees from UCSD. He was trained in transcranial magnetic stimulation at NINDS 
by Leonardo Cohen. He has extensive experience since 1996 as an investigator in 
neurorehabilitation clinical trials, and has been a principal investigator on many of them. He was 
site principal investigator for VA CSP #558, which involved robotic rehabilitation.
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ID: Pro00003161
View: 1.2 VA Involvement
VA Involvement
1.0
Does the proposed research involve any of the following?:
Name

VA Funding

VA Personnel Funded Effort

VA Patients or their Private Health Information
Other VA Resources: Central IRB

Other VA Resources: VA Equipment

Other VA Resources: VA Property (Including space leased to, or used by VA)
Other VA Resources: VA Databases
None of the Above apply to this research
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ID: Pro00003161
View: 1.3 Study Funding Information
Study Funding Information
1.0
* Funding Sources:
Funding Source
(Other)
Code
View Merit Review (CC 103)
9003
2.0
Upload Grant Application, if applicable (If NIH, VA, voluntary agency, must upload):
Name
Modified Date
Grant Application
7/12/2019 1:45 PM
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ID: Pro00003161
View: 1.4 Resources
1.0 
* Do you currently have adequate resources (e.g., staff, physical space, information 
technology, etc.) to protect the safety of participants, staff, and the confidentiality of 
subjects’ data during the conduct of this study?
Yes
No
If yes, include a listing of the VAPHS resources that will be used for this study and are 
necessary to protect participants. 
The main laboratory area is the Laboratory for Research on Arm Function and Therapy (RAFT) 
which is located in the Keystone building, a commercial building leased by the University of 
Pittsburgh, with a pending Memorandum of Understanding regarding its use as VA Research 
Space. There is an off-site waiver for the current study-related activities in RAFT, which is part 
of the Rehab Neural Engineering Labs (RNEL.) The laboratory contains a variety of devices 
designed around upper extremity motor function. This includes transcranial magnetic 
stimulation (TMS) equipment (a rapid stimulator capable of modulating brain activity for
several minutes, standard TMS stimulators and Bistim device), and Brainsight Neuronavigation 
systems. There is a unimanual exoskeleton robot (Armeo Power) and a bimanual KINARM 
exoskeleton robotic system (B·Kin / KINARM, Kingston, ON.)
University Drive VAPHS: All veterans will have their functional evaluations in the occupational 
therapy area at this facility.
Human Engineering Research Laboratories (HERL) are a part of the U.S. Department of 
Veterans Affairs as the Center for Wheelchairs and Associated Rehabilitation Engineering. Dr. 
Wittenberg has office space in this facility and receives administrative and scientific support 
from its faculty and staff. Sensitive data will be stored within its VA resources.
If no, please describe the resources that will be needed and explain how the resources will be 
obtained before the study is initiated:
2.0 
* VAPHS requires that either the PI or co-PI have a physical presence at VAPHS. 
Please describe the role the PI and/or co-PI have at VAPHS with respect to clinical 
responsibilities or in relation to other research activities.
The P.I. is a 5/8 part-time employee of VAPHS, with an appointment as Neurologist in the 
Medicine Service. He has 2/8 of clinical effort, which is on the Outpatient Neurology service, 
seeing consultations and follow-up patients preferentially with stroke and movement disorders, 
as well as other general neurological disorders. The remainder of his effort is devoted to VA 
specific research.
3.0 
* Will off-site ancillary service facilities (e.g., radiology services, central labs, non VA 
space, etc) be used for this study?
Yes
No 
If yes, please provide the location and a brief description of the project activities to be 
conducted at the off-site ancillary facilities:
MRI scans will be conducted at the Magnetic Resonance Research Center, which houses and 
operates two 3T Siemens Prisma systems and has research staff and technologists to support 
our project.
The Main Laboratory Area is the Laboratory for Research on Arm Function and Therapy (RAFT) 
part of the Rehab Neural Engineering Labs (RNEL.) The laboratory is in the Keystone Building, 
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second floor, in one suite that contains a variety of devices designed around upper extremity 
motor function. This includes transcranial magnetic stimulation (TMS) equipment (a rapid 
stimulator capable of modulating brain activity for several minutes, standard TMS stimulators 
and Bistim device), Brainsight Neuronavigation systems. There is a bimanual KINARM 
exoskeleton robotic system (B·Kin, Kingston, ON.).
4.0 
* Will a firm be contracted to obtain consent from subjects, collect private 
individually identifiable information from human subjects, or be involved in activities 
that would institutionally engage the firm in human subjects’ research?
Yes 
No
If yes, please provide a description of the contracted service(s):
* Please specify the IRB that has oversight of the firm's activity(ies):
Name of Site / Institution
IRB Approval Document
FWA Number
There are no items to display
5.0
Collaborations
Please list any non-VAPHS institutions or individuals (i.e. co-authors, mentors, etc.) that you 
will collaborate with and describe their specific role in the research:
Dr. Amit Sethi will supervise the clinical evaluations of upper extremity function and TMS 
studies. As Assistant Professor in the Department of Occupational Therapy at the University of 
Pittsburgh, he is a clinical investigator who is experienced in the assessment of upper 
extremity function and the training of stroke survivors in upper extremity functional use.
Dr. Tae Kim’s specific role is designing acquisition and analysis methods for the MRI portion of 
the proposed work. He is an Assistant Professor in the departments of Radiology and 
Bioengineering at the University of Pittsburgh. Research interests include brain perfusion 
modeling, cerebrovascular regulation mechanisms, and technical development and 
quantification of functional MRI, all relevant for this study.
5.1
If this is not Multi-Site Research, please upload the appropriate written agreement(s) here:
Name
There are no items to display
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ID: Pro00003161
View: 1.5 Project Information
1.0 
Does the project involve any of the following (check all that apply):
Type
Biological Hazards (including human biological specimens)
Chemicals 
Ionizing radiation or use of radioactive materials 
Drug, Biological, or Nutritional (e.g. herbal or dietary) Supplement
2.0 
Project Focus (check if applicable):
Type
Traumatic Brain Injury (TBI)
Post Traumatic/Post Deployment Stress Disorder (PTSD/PDSD)
Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF)
3.0 
KEYWORDS
Please provide a minimum of 3, maximum of 6 keywords.  Please use MeSH terms.
* stroke
* rehabilitation
* robotics
4.0
* Please describe the type of study:
one-arm, multiple baseline sequential, cohort study
5.0
* Will any of the research being conducted as a part of this study be used to fulfill 
academic requirements (e.g., master’s thesis, dissertation, or other academic 
program requirements necessary to obtain a degree/certification, etc.)?
Yes 
No
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ID: Pro00003161
View: 1.6 (CR) Study Locations
Study Locations
1.0
* Please add the local sites where this study will be conducted:
Location
View VAPHS University Drive Division
View Other
If Other, Please Specify:
The Laboratory for Research on Arm Function and Therapy (RAFT).
The Human Engineering Research Laboratories (HERL), part of the U.S. Department of Veterans 
Affairs as the Center for Wheelchairs and Associated Rehabilitation Engineering.
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ID: Pro00003161
View: 1.6.1 (CR) Multi-Site Study
1.6.1 Multi-Site Study
1.0
* Is this a multi-site study:
Yes
No
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ID: Pro00003161
View: 1.6.1.1 (CR) Multi-Site Study
1.6.1.1 Type of Multi-Site Research 
1.0
* Type of Multi-Site Research:
Research NOT Conducted Under a Cooperative Research and Development Agreement (CRADA) 
with a Pharmaceutical Company or other Non-Federal Entity ("Collaborative Research"). 
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ID: Pro00003161
View: 1.6.1.1.2 (CR) Multi-Site Not Conducted Under CRADA
1.6.1.1.2 Multi-Site Not Conducted Under CRADA
1.0
* Status of the PI in Proposal (check all that apply):
Coordinating Investigator in multi-site study (includes studies conducted both at VAPHS and Pitt)
Provide Further Details (if needed):
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ID: Pro00003161
View: 1.6.1.1.2.1 (CR) Coordinating Investigator
1.6.1.1.2.1 Coordinating Investigator
1.0 
* Number of currently participating institutions/sites (including VAPHS and 
international sites, if applicable):
2
2.0
* Does this study involve international/transnational research?
Yes 
No
Please answer the questions below for all research conducted within the United States, its territories, 
or Commonwealth:
3.0
* Specify other research sites where this research will be conducted:
Name of Site / Institution
IRB Approval Document
University of Pittsburgh
4.0 
Provide details with regards to coordinating center responsibilities:
As both sites in the study are the RAFT Lab and the research is being overseen by identical study 
staff, once the VA protocol is approved, the University of Pittsburgh protocol will be modified to 
reflect the coordinating site protocol. The study coordinator will ensure that all study documents 
and amendments are performed to reflect the coordinating site. The PI and study coordinator will 
assure that the University of Pittsburgh will safeguard VA data as required by VA information 
security policies. The study coordinator will communicate to engaged participating sites SAEs that 
have the potential to affect of the study and study events and interim results (if appropriate). The 
study coordinator and PI will report all non-compliance with the study protocol or applicable 
requirements is reported in accordance with VHA Handbook 1058.01. 
5.0 
Please upload the study-wide sample informed consent form(s), protocol, and another 
other relevant documents, as applicable.
Name
There are no items to display
6.0 
Upload applicable agreement(s) with non-VA collaborators (e.g., Research Data Use 
Agreement) that address such issues as the responsibilities of each party, the 
ownership of the data, and the reuse of the data for other research and any other 
relevant documents.
Name
VA MRI contract
RDUA with MRRC
Provide further details (if necessary):
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ID: Pro00003161
View: 1.7 Section Chief and Service Line VP approvals
Please upload the approval of the Section Chief, if applicable and the Service Line VP.
1.0 
* Institutional Approval Document:
Institutional Approval Document(0.02)
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ID: Pro00003161
View: 2 Study Objectives & Design
Study Summary
1.0
Funding End Date:
2.0 
* Abstract.  Please provide a brief description of the study.
Stroke is the leading cause of neurological disability in the veteran population and problems 
with arm movement are a major cause of loss of functional ability. The costs of rehabilitation 
are significant and effectively limit therapy to the first few months after stroke onset. Recent 
results show clearly that patients with chronic stroke (> 6 months) benefit from intensive arm 
practice. Robot assisted therapy followed by task related training offers a cost-effective 
approach to this type of practice that also results in better arm function in daily life. A 
previous study has shown that it is possible to predict who will benefit from this kind of 
treatment, specifically what individual characteristics are related to a clinically meaningful 
improvement in arm movement. This next phase of the study will test whether the prediction 
method is reproducible and independent of the type of robot being used. It will also expand 
knowledge of how the brain area most important for movement changes its connections with 
other brain areas and the muscles in the arm.
3.0
* Describe the study objectives. Please include primary aim and hypothesis, if applicable 
any secondary aims and hypotheses. 
Chronic upper extremity dysfunction after stroke is a leading cause of disability and 
has been the target of many therapeutic methods that involve repetitive task 
practice. Clinical trials of intensive practice-based interventions have demonstrated 
significant changes in mean impairment in a group, but variable effects among 
individuals, with clinically significant improvements in only a fraction of the 
population. This is true of our previous Merit Review study, which showed good 
mean gains in several areas, and about half of participants having clinically 
significant changes in the primary outcome of motor impairment. The basis for these 
variable responses is not known, i.e. we do not know the biological mechanisms that 
moderate response to these standardized interventions. And while recovery of 
function is associated with normalization of brain network interactions and task-
related brain activation, the causal role of these changes is not well understood. In 
our current project period, we are continuing to address both issues with 
construction of a predictive model that uses demographics, functional status, 
genomics, neurophysiology, neuroanatomy, and other potential biomarkers to 
predict the likelihood of a clinically significant change in impairment at the end of 
the intervention. 
Our long-range goal is the prescriptive application of intensive task practice to 
veterans who have suffered a stroke, maximizing the cost-benefit ratio. We therefore 
plan to externally validate the predictive value of biomarkers as incorporated in the 
model resulting from our previous chronic stroke robotic rehabilitation trial. We will 
not only validate the predictive model in a new cohort, we will now quantify the 
changes in functional connectivity of the affected hemisphere’s primary motor cortex 
with other brain areas and with the spinal cord, in order to uncover the mechanisms 
by which intensive task practice leads to increased motor ability. We will continue to 
use an effective intervention for individuals with chronic stroke, robotic training 
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with  transition to task practice (Robot + TTT,) now focusing on use of an exoskeleton 
platform, which has already been part of our intervention. We propose the following 
two specific aims in the proposed renewal of this award:
1. To validate a predictive model based on baseline measures of biological and functional 
biomarkers. Working hypothesis: Baseline factors that include functional and physiological 
status will predict clinically significant responses to therapy. Change from use of end-
effector and exoskeleton robots to solely exoskeleton will not significantly affect the 
prediction model. The rationale for the hypothesis is that the effects of assisted repetitive task 
practice is not dependent on a particular technology but does depend on a biological 
substrate. Expected outcomes: The predictive model will be externally validated, a 
receiver operating curve described, and the intervention and model validated on an 
exoskeleton platform for delivering therapy.
2. To identify the changes in the input and output of the affected primary motor cortex 
associated with change in motor impairment. Working hypothesis: Increased input into 
the motor cortex, increased output from the motor cortex, or both, underlies the 
treatment effect of repetitive task practice. Normalization (increase) in connectivity 
of affected primary motor cortex to other motor brain areas of both sides of the brain 
will be associated with reduction of motor impairment. In a subpopulation of 
treatment responders an increased effectiveness of the motor cortex in directly 
activating muscles will be demonstrated. Expected outcome: The causal role of task 
practice in changing a brain region’s connectivity will be known, with potential uses 
as a surrogate measure of outcome in rehabilitation trials. Resting state BOLD MRI, 
transcranial magnetic stimulation, and clinical electrophysiology will be used to 
provide data regarding the mechanisms of training-related gains.
When we have completed the above aims, we will have a validated algorithm by 
which a set of baseline variables (biomarkers) can be used to inform both the 
clinician and patient regarding the likelihood of successful training, in an appealing 
exoskeleton robotic rehabilitation platform, for upper extremity disability in the 
chronic period after stroke. This algorithm can be modified to consider those 
biomarkers that are more practical in VA clinical settings. We will also extend 
mechanistic knowledge about the response to intensive training on brain 
connectivity, which has been noted to be altered after stroke and which may relate to 
learned non-use of the affected limb and loss of spinal response to descending input. 
We will have new efficacy data on the use of assisted mass practice followed by 
assisted task practice on multiple dimensions of functioning and disability, including 
use of the arms in daily life.
4.0
* Provide a summary of the background of the study, and explain how this research will 
contribute to existing knowledge.  Describe previous studies that provides a basis to 
show that the proposed research can be carried out without undue risk to human 
subjects.  
Stroke is the leading cause of long-term disability [1] costing an estimated $38.6 
billion a year [2] and stroke-related disability is becoming more prevalent [3], even 
as overall rate of stroke is in slight decline. Recent evidence indicates that the brain 
can remodel after stroke, even years later, through neuroplasticity (including 
changes in excitability and synaptic strength) and synaptogenesis [4-6]. Behavioral 
remodeling also occurs and allows compensatory movement patterns to accomplish 
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task goals [7-9]. Interventions incorporating strategies of task specificity, challenge, 
and repetition appear to be key factors in promoting these two types of remodeling 
and are central elements in rehabilitation of motor weakness following stroke [11]. 
Since our initial project period, the value of robot-assisted therapy to improve upper 
extremity function has become more established but there are still questions about 
many aspects of  implementation, including patient selection, dose, and type of 
treatment [12]. There are two basic types of rehabilitation robots, endeffector, in 
which the patient engages with the tip of the limb, and exoskeleton, in which a 
powered framework encloses the limb. Both types have demonstrated efficacy [13] 
with some potential advantage in full use of exoskeleton capabilities in training joint 
coordination [14], and we have used both types in our ongoing study. Robot-assisted 
and other types of upper extremity treatment studies in chronic stroke 
report relatively modest average gains in motor function that typically fail to 
translate into meaningful change in everyday use of the paretic arm [15]. This has 
prompted us to directly address issues of predicting response, promoting and 
measuring translation to daily use and determining optimal scheduling for that 
therapy. Therefore, there is now a critical need for research that: 1. predicts response 
to hybrid robotic and functional task oriented therapies in chronic stroke and 2. determines 
the brain mechanisms of response to such therapies so that we better understand why such 
therapies work for some, but not all, stroke survivors.
5.0 
* Describe the overall significance of the research in terms of the problem to be studied 
and potential findings, as well as its relevance to the care of veterans, the VAPHS, and 
the VHA:
Importance and Impact
The primary purpose of the current proposal is to externally validate predictors of response to 
Robot + TTT (transition-to-task) therapy in the chronic stroke population. By doing so, we 
will validate biomarkers and algorithms for a predictive model to guide matching of  
patients to a therapy based on residual neural and motor function and other 
measurable factors. We have been contributing to understanding the mechanisms of 
recovery specifically by relating baseline clinical, neurophysiological and kinematic 
markers to functional outcomes. We are now proposing to go beyond this contribution by 
measuring specific changes in connectivity of the primary motor cortex, the hub of voluntary 
movement function in the human brain.
While we, and others, have as a goal personalized treatment during the sub-acute 
period when spontaneous recovery, optimal neuroplasticity and available 
rehabilitation coincide, the field has been turning to chronic populations for a few 
reasons. First, doing so addresses the problem of an exponential growth in 
individuals aging with disabilities from stroke. Strokes are occurring earlier in the 
lifespan [16] and individuals live longer with stroke [17] therefore causing increased 
costs to society as a public health concern as well as increased costs to the 
individuals who face more years with a lower quality of life. Since it is known that 
neuroplasticity continues across the lifespan [18] and that rehabilitation can be 
effective years after the stroke e.g. [19], validating biomarkers and algorithms that 
best match individuals with a specific therapy will maximize recovery of function and reduce 
health care resource utilization over the long term. Second, providing further evidence 
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for optimal use of robotic therapy in the chronic period may provide an impetus for 
the installation of robots and other arm exercise programs into health clubs and veteran’s 
service organizations where rehabilitation and exercise can usefully combine.
Impact on Health Care Delivery for Veterans:
The long-range goal of the proposed work is to meet the Department of Veterans Affairs 
Strategic Plan 2014-2020 listed objective 1.1 and create evidence-based rehabilitation 
methods for veterans with stroke related upper extremity hemiparesis that focus resources 
more efficiently. Prevalence of stroke-induced disability in our veteran population 
is expected to rise since 64% of the population is aged 55 or older [20]. Robotic 
devices provide a cost-effective method to automate parts of therapeutic practice, 
allowing more efficient use of therapist time while providing high doses of training 
[21]. We expect that the results from this study will validate and possibly refine our 
method for choosing the Robot + TTT rehabilitation technique during the long 
period following sub-acute recovery. It will also bring insights for the science of 
predicting outcomes and optimally matching therapeutic techniques in this period. 
While use of robotic training is a key part of the treatment in this trial, we take steps toward 
generalization with the use of an advanced robotic rehabilitation system piloted in the 
current study. Inclusion of an exoskeleton robot is also in line with the RR&D service’s call 
for studies of such devices.
6.0
Please upload any additional documents:
Name
Version
There are no items to display
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ID: Pro00003161
View: 2.1 Required Reviews
Required Reviews
1.0
Type of Submission:
New study 
If this is a 'New Paper Conversion' please include the MIRB Number:
Please upload a letter certifying that you have made no modifications or amendments in 
converting this research study from paper to electronic:
2.0
* Requested Review Type:
Name
Exempt
Expedited
Full IRB Review
Not Human Subject Research
3.0 
Please check which of the following Service 
Lines/Departments/Entities
will be impacted or used in the conduct of this study
Upload 
Letter 
of Support
Clinical Support
Medical Specialty
Investigational Drug Service
Imaging
Community Based Care
Patient Care Services
Behavioral Health
Primary Care
Surgical Specialty
Critical Care
Clinical Trials Center
Regulatory Coordinator Support Core
Clinical Coordinator 
Support Core
 Ancillary Support Core
 Data Support Core
Research Registry
Registry Number:
Other
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If Other, please specify:
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ID: Pro00003161
View: 3 Research Design
Methods & Procedures 
1.0 
* Does this research study involve any of the following: 
Name
Deception
Interview/Focus Groups
Use of Drug, biological, or nutritional (e.g., herbal or dietary) supplement (investigational or 
FDA approved)?

Use of medical devices
Prospective Analysis of Specimens
Banking of Specimens-Data
Retrospective use of specimens
Audio/Video Recordings or Photographs 
Honest Broker or other similar service
None of the Above
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ID: Pro00003161
View: 3.4 Use of Medical Devices
Medical Devices
1.0
* Specify all devices used on this study:
Device 
Name
Manufacturer Use of Device
IDE Number
(if Applicable)
Device 
Brochure
Description 
of Use
Risk Level 
Determined by 
Sponsor
The 
MagStim 
200
MagStim
FDA Approved but 
used in 
unapproved way
Non-Significant 
Risk
2.0
* Describe your plan for storage and control of devices:
The device will be stored in a secure laboratory environment only accessible by research study 
staff. Use is restricted to individuals who have been educated and trained.
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ID: Pro00003161
View: 4 Research study methods
Research Study Methods
Describe all study related procedures following enrollment of a subject in this study.
Please see Section 6 for where the study team defines when a subject will be considered enrolled in the 
study.
1.0 
* Research Procedures/Interventions:
After obtaining informed consent and a review of medical records, participants will be seen for 
a neurological exam visit by the PI and initiation of study evaluations.
All baseline testing will occur within a 6 week time frame and will include 2 separate baseline 
functional upper extremity outcome evaluations and one baseline robot evaluation with the 
rehabilitation robots in measurement mode for quantitative measures of upper extremity 
kinematics and strength. If participants have differences in Fugl-Meyer scores greater than 2, 
one additional baseline may be administered to establish the more stable result with only two 
baseline datasets used for analysis. On all participants who do not have any TMS or MRI 
medical exclusion criteria one baseline TMS evaluation and one baseline MRI will occur.
After completion of the baseline evaluations, the intervention phase of the study will begin. 
During this time, participants will complete a total of 36 intervention sessions of Robot +TTT 
training. These will occur 3 times per week for 12 weeks. If scheduling conflicts arise, changes 
will be allowed with sessions occurring up to 4 times per week but will not exceed 18 total 
weeks. The intervention sessions will be one hour in duration. During each session, participants 
will complete 45 minutes of robotic intervention followed by 15 minutes of TTT.  Participants 
will progress through 3 robot programs sequentially with 12 sessions focused on distal upper 
extremity function, 12 sessions focused on proximal upper extremity function and the final 12 
sessions alternating between a distal and proximal focus. Functional outcome and robot 
evaluations will occur after each robot block, at final training, and at a 12 week retention 
follow-up. On all participants who do not have any TMS or MRI exclusion criteria one TMS 
evaluation and one MRI will occur after final training.  Also, one TMS evaluation and one MRI 
will occur at the 12 week retention follow-up. The retention follow-up visit must occur within 4 
weeks of when it is due. All procedures are routinely done within clinical practice.
Baseline/Outcome evaluations:
Upper extremity measures and evaluations will consist of: the Fugl-Meyer Upper Extremity 
Motor Assessment (FMA), the Wolf Motor Function Test (WMFT), Stroke Impact Scale (SIS), 
Action Research Arm Test, isometric strength and range of motion evaluations of the 
shoulder, wrist, thumb, and grip. The Activity Monitor wearing schedule will occur at baseline 
(3 days), and post-training.
The Fugl-Meyer Upper Extremity Motor Performance Section Test:
Selected because it assesses impairments and has been shown to be valid and has high inter-
rater reliability and test/retest reliability [46]. In particular, it correlates well with interjoint 
coordination measures in the UE of stroke patients [47]. The Fugl-Meyer [48] has been shown 
to be both internally and externally valid. According to Duncan et al., it is probably the most 
widely known scale of motor recovery after stroke and can be considered a gold standard for 
motor impairment measures [49] but its relationship to task performance is not clear. It is a 
primary outcome variable because it measures impairment and we can it compare to other 
studies.
The Wolf Motor Function Test:
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Selected because it measures functional capability in terms of performance time, quality of 
movement, and ability to hold weight. The test appears to be more sensitive than other UE 
tools such as the Frenchay Arm Test and is commonly used in the CI studies of UE 
rehabilitation. It has high interrater reliability, high test-retest reliability and good concurrent 
validity with the Fugl-Meyer with patients who have mild deficits [50]. It has been modified for 
use with moderate to severely impaired patients [51] and streamlined to reduce testing time 
[52]. The time measure is the primary variable used because it continuously measures 
functional ability and we can compare to our previous work and other studies.
Stroke Impact Scale (disability):
The short version of this test contains 50 questions and is designed to assess changes in 
impairments, disabilities and handicaps following stroke [53]. This tool assesses physical, 
mental, and emotional changes that occur as a result of stroke and that can contribute to a 
change in quality of life. The Stroke Impact Scale has been tested for and found to be reliable, 
valid, and sensitive to change in the stroke population. The hand domain is a primary variable 
because it measures participation in daily life and captures the addition of TTT to robot 
training.
Action Research Arm Test:
This has been suggested to be more responsive in chronic stroke than the Fugl Meyer and is 
also more rapid to administer [54, 55]. It is included for comparison to other studies and 
because we expected it to have neither floor nor ceiling problems in the target study 
population. Our experience so far has confirmed this. However, it is not the primary outcome 
variable because it has not been as sensitive to change as the FMA.
Isometric strength and range of motion:
Manual muscle testing is done for finger extension and shoulder abduction and grip strength is 
measured with a Dynamometer. The hand-held dynamometer has been validated for use on 
stroke patients. Active and passive range of motion is collected using standard goniometry. 
Shoulder (flexion/abduction), wrist (extension), and thumb opposition are tested. 
KINARM and finger load cell evaluations.
A set of standard sensory, motor, and cognitive-motor evaluations will be performed. These 
tests, which have been normed, will provide multiple secondary outcomes. They will relate 
connectivity measures and unimanual function to bimanual sensorimotor function. Since the 
KINARM only allows shoulder-elbow movement, finger movements will be evaluated using a 
custom-made load-cell array developed by Dr. Collinger. Due to altered finger biomechanics, 
we may not be able to collect data from a subject's impaired hand with the custom load-cell 
device at baseline.  For these individuals, we will not collect this data at future testing time 
points. 
Physical Activity Monitors of arm use:
To complement the self-report measures of using the paretic arm in daily life, we will continue 
to use low cost, portable 3D accelerometers (ActiGraph, Pensacola, FL) to objectively quantify 
arm movement. Such accelerometers have good rater and test-retest reliability [56, 57] as 
well as sensitivity to change and convergent validity with standardized measures of 
impairment, performance and activity (see [58, 59] for recent reviews). We will coach the 
participant and caregiver on how to attach and detach a sensor to each arm before allowing 
them to leave our facility and return in 3 days at baseline, after training and at retention. The 
schedule will be Monday-Thursday or Tuesday-Friday to avoid the weekend (potentially more 
variable within/between participants). Arm use will be collected and classified in 1-second 
epochs, summed over 24 hours and averaged over the three days using an established 
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software program. Reporting a ratio of paretic to non-paretic arm use will reduce the effect of 
mobility activity such as walking that provides common kinematic drive to both arms. The 
results of accelerometry analysis will be correlated with the measures of functional assessment 
using the Fugl-Meyer, WMFT and SIS-hand domain.
TMS Outcomes
Transcranial magnetic stimulation of the motor cortex is performed using a MagStim 200 
Magnetic Stimulator (MagStim Ltd., Wales, UK) to assess changes in brain physiology and MEP 
in arm muscles. Surface electromyography (B&L Engineering, Santa Ana, CA) is used to record 
muscle activity from three muscles (first dorsal interosseous [FDI], extensor carpi radialis 
[ECR], the anterior deltoid [AD]) on both the paretic and non-paretic arms. SIGNAL (CED, 
Oxford, UK) scripts are used to drive single pulse TMS and collect simultaneous EMG data 
through a Power 1401 (CED) system. TMS sessions are completed at three time points: 
baseline, post-training, and at the 12-week follow-up visit. Soft foam earplugs are inserted into 
each ear canal for hearing protection. 
Prior to the initial TMS session, a skin and whole-brain reconstruction are created from the 
participant’s high resolution anatomical MRI scan, using neuronavigation software (BrainSight, 
Rogue Research, Montréal, QC, Canada). The hand knob in each hemisphere is identified from 
the anatomical scan and used as the center point for hotspot grid (described below). The 
neuronavigation software records three-dimensional coordinates of each TMS stimulation site, 
measured using an optical digitizing device (Vicra, Northern Digital Inc.). Thus, this technique 
ensures reproducible locations at each session.
MRI Evaluation:
Participants will lay down and be positioned in the scanner by MRRC staff with 
supervision from study staff. They will be given a device to communicate any discomfort 
to staff and the procedure can be  paused or discontinued at any time. The MRI 
procedure will take approximately 1.5 hours.  The MRI facility is located at the UPMC MR 
Research Center. It consists of two 3T Siemens Prisma scanners.  
A high resolution MPRAGE (TE 3.44 ms, TR 2250 ms, T1 900 ms, flip angle 9°, 1.5 mm 
isotropic voxels) will be obtained. Two resting state BOLD (T2*) scans will be obtained, 
with TE=30 ms, TR = 2000 ms, FOV=220mm, resolution=64X64 with 36 4 mm axial slices 
over 10 min to yield 380 volumes each.  Diffusion tensor images for fractional isotropy 
(FA) analysis will be obtained using the most up to date Siemens protocols to maximize 
resolution and will be optimized for determination of FA rather than  tractography. An 
ROI and seed based method will be used to determine the FA value for the posterior  
limb of the internal capsule on each side and a voxel -based correlation of a seed in the 
arm area of the primary motor cortex with the rest of the brain. A Z transformed score 
for mean correlation of the seed ROI with the rest of the brain will be obtained and will 
serve as a variable for the prediction model. This will also lead to an exploration of the 
relationship of this connectivity measure with lesion and function. Volumetric data will 
be normalized and right hemisphere strokes mirrored so that all images are in the same 
space, with the affected hemisphere on the left. But the ROI and seed-based approaches 
will be carried out in individuals to avoid most of the blurring effects of normalization. 
The spatial normalization itself will be purely linear affine transformations, with masking 
of large lesions to reduce normalization  error. An atlas- based approach to the internal 
capsule and primary motor cortex UE representation will be used (e.g. WFU Pick-atlas, 
Maldjian et al., 2003, NeuroImage 19, 1233 9.) In general we will use a combination of 
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public domain tools for image analysis, include AFNI, SPM, FSL, and MRIcron, all listed at 
http://www.nitrc.org.
INTERVENTION (Robot + TTT)
All participants will be enrolled in the same intervention: Robot + TTT. The intervention 
proposed will be completed 3x/week for 12 weeks. The training progression will be 
sequential with 12 sessions focused on distal upper extremity function, 12 sessions 
focused on proximal upper extremity function and the final 12 sessions alternating 
between a distal and proximal focus. Participants will perform robot training on an FDA-
approved robot for 45 minutes followed by 15 minutes of TTT practice to complete their 
60 minute intervention session.
Transition to Task Training (TTT):
Participants will receive robotic training in the sequence described above. The 
intervention session will be 60 minutes long; however, 15 minutes will focus on TTT. This 
transition to task training is functionally based within four domains of real world tasks: 
homemaking, hygiene, feeding and dressing skills. Two tasks are designed for each 
session and they are matched to the patient’s type of robot therapy (wrist or 
shoulder/elbow) as well as to their severity level. 
The task design is progressive in nature with difficulty added by changing the parameters 
and demands to promote generalization. The tasks are performed with the participant 
sitting for tabletop activities with therapist supervision to prevent substitution and 
promote the use of available arm motor control and motion for a more normal reaching 
pattern. The minimization of compensatory trunk movements during reach-to-grasp 
movements has been shown to improve inter-joint coordination and active arm joint 
ranges in patients with hemiparesis due to chronic stroke The TTT activities proposed 
include tasks that promote both stabilizing and active use of the hemiparetic upper 
extremity. Active arm tasks however will be emphasized more than stabilizing tasks.
Please upload a table of procedures if applicable.
The study procedures table must be completed for: 
   - All Greater than Minimal Risk (GTM) studies; and 
   - All Minimal Risk studies that use Standard of Care or Usual Care/Interventions.
Name
Modified Date
Study Procedures Table
7/15/2019 1:19 PM
2.0 
* Will Usual Care Procedures/Interventions be used?"
Yes 
No
If yes, please specify and include a description of what the usual care or expected level of care 
is at VAPHS (e.g., medications, testing, timing, etc.) for patients, similar to those individuals 
that meet the inclusion/exclusion criteria for this research study:
2.1 
If Usual Care Procedures/Interventions will be used, who is the individual or entity responsible 
for relevant aspects of the usual care (i.e., which of the above usual care activities will the 
research study team be responsible for)?:
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2.2 
Does the usual care at VAPHS for the condition of interest in this research study differ from 
national guidelines/recommendations (i.e. standard of care)?
Yes 
No
If yes, please describe the differences:
2.3 
Are any procedures that are considered standard for this patient population performed more 
frequently than usual care?
Yes 
No
If yes, please indicate which time points are considered usual care and which are considered 
research.
2.4 
If there is more than one standard, does VAPHS limit which one is followed (e.g. warfarin use 
for atrial fibrillation vs. one of the newer anticoagulants).
Yes 
No
If yes, please explain:
3.0 
* Does clinical expertise need to be enlisted?
Yes 
No
If yes, please provide the provisions for enlisting the services of a clinician with appropriate 
expertise and privileges to perform duties, if the investigator is not a clinician [i.e. reviewing 
the data, adverse events, and new study findings; also making required decisions to protect 
the health of the subject (e.g., stopping the participant’s involvement in the study or 
determining when to notify the subject or the subject’s health care provider of information that 
may affect the health of the subject)]:
4.0 
Please upload any surveys, questionnaires, and data collection forms.
Document
Description
Version Number
View ARAT Scoring(0.01)
0.01
View Demographics(0.01)
0.01
View Dynamometry and ROM Scoring(0.01)
0.01
View Finger Assessment Form(0.01)
0.01
View Fugl-Meyer Scoring(0.01)
0.01
View Inclusion Exclusion Checklist(0.01)
0.01
View Medical History Form(0.01)
0.01
View Stroke History Form(0.01)
0.01
View Stroke Impact Scale(0.01)
0.01
View Wolf Scoring(0.01)
0.01
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ID: Pro00003161
View: 4.1 Research study methods: analysis Plan 
1.0 
* Please describe the analysis plan for the study (it is acceptable to refer to the 
sponsor/multi-site protocol for section if applicable):
Analysis Plan for Aim #1.
We will determine the receiver operating curve (ROC, sensitivity vs 1-specificity) of the 
predictive model for the primary outcome, a (positive) change in FMA of greater than 
four points at 12 weeks. (A five-point change in FMA is a MCSD [34].) The ROC will be 
compared to the SRT4 model [35]. With our proposed sample size of 64 subjects and 
12% attrition rate, we expect to have 57 subjects completing the study, a validation set 
of similar size to the original set from which the model was derived.
Further analysis, validation and refinement of the predictive model will be performed 
using the random decision forest technique [36]. This would also result in an algorithm 
like the PREP [30] that can be used for step-wise decision-making about embarking on 
the 12-week program of robot+TTT.
Analysis Plan for Aim #2.
The primary analysis with be correlation between change in physiological parameters 
(e.g. affected M1 connectivity, recruitment curve slope) and change in FMA. Analysis of 
H-reflex changes will be compared to recruitment curve changes to rule out a general 
change in lower motor neuron excitability. Secondarily, there will be correlations of 
these parameters at baseline with baseline motor function measures. A more detailed 
analysis of the MRI data will also examine individual interregional connections to 
determine whether any of them are more sensitive to the intervention than others. 
There will be exploration of whether the predictive model also predicts changes in 
physiological measures, which could lead to more efficient studies in the future.
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ID: Pro00003161
View: 5 Sub-Studies
1.0 
* Is there a sub-study or are there sub-studies associated with this study?
There is no sub-study associated with this study. 
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ID: Pro00003161
View: 6 Study Population Summary
Study Population Summary
1.0
* What is the maximum number of subjects you plan to enroll at VAPHS?
80
2.0
* Do you plan on enrolling patients into different categories:
Yes 
No
If yes, please explain:
3.0
If this is a multi-site study, indicate the projected total subject accrual:
70
4.0
* Please provide a justification for the sample size:
Based on our record of recruitment and design feasibility, we propose to enroll 64 participants. 
Our current 12-week study has an attrition rate after enrollment of 12% so we anticipate 
completing about 57. We verify that with our sample size of 57, we will be able to estimate the 
area under the Receiver operating characteristic (ROC) curve (AUC) with an adequate precision 
(that is, the standard error is reasonably small). The AUC is an important measure to describe the 
performance of a predictive model for a binary outcome such as the change in FMA of greater than 
4. The table below displays the standard error (SE) of the estimated AUC for several values of the 
true AUC and different prevalence of responders [10]. The SE is less than 0.07 in all cases except 
when AUC is 0.7 and the proportion of responders is only 33%. (This is the current situation in the 
preliminary analysis, providing an upper bound on our AUC measure.) 
For Aim #2, which is based on correlations, a sample size of 57 would allow detection of Pearson 
correlations r > 0.365, which is comparable to individual correlations found in the Robot Biology 
study, assuming alpha = 0.05, beta = 0.2 [41]. This was confirmed by the Statistics Core using 
that data and PASS (v14.0) software.
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ID: Pro00003161
View: 6.1 Study Population
Study Population
1.0
* Check all that apply to describe your study population:
Study Population

Non-Veterans
Special Populations

Veterans
Vulnerable populations
Other
2.0
* Indicate the inclusion criteria for enrollment:
1. Clinically defined, unilateral, hemiparetic stroke with radiologic exclusion of other possible
diagnosis
2. Stroke onset at least 6 months before enrollment
3. Present with Mild/Moderate to Severe arm dysfunction (based on Fugl-Meyer scores of 10 to
45)
4. Be medically stable to participate in the study
5. Be English speaking
3.0
* Indicate exclusion criteria for enrollment:
1. Unable to give informed consent
2. Have a serious complicating medical illness that would preclude participation.
3. Contractures, orthopedic problems, or other impairments that would interfere with the
interventional training or limit the range of joint motion in the potential study arm
4. Visual loss such that the subject would not be able to see the test patterns on the robot
computer monitor
5. Botulinum toxin to study arm within four months of baseline testing or if received during the
study period
6. Unable to comply with requirements of the study
7. <21 years of age
8. Enrollment in another greater-than-minimal risk study
9. Presence of medical condition or implant that prevents safe administration of TMS
(history of seizures, and/or currently taking any of the following medications: lamotrigine
(Lamictal), levetiracetam (Keppra), oscarbazepine (Trileptal), topiramate (Topamax),
phenytoin (Dilantin), arbamazepine (Tegretol), valproic acid (Depakote), phenobarbital
(Barbita, Luminal, Solfoton) and/or metallic implant in the head and/or neck area including
aneurysm clips or coils, stents, deep brain stimulators, electrodes, shrapnel/bullets, facial
tattoos with metallic or magnetic-sensitive ink) or MRI. If participants have a medical
condition or implant mentioned above, this only makes them ineligible for TMS and/or MRI,
not for other parts of the study.
10. Pregnancy
4.0
If there are any age, ethnic, language, or gender-based exclusion criteria, including the 
exclusion of any pregnant or lactating women, or those of child-bearing potential, 
please provide justification:
Participants must be English speaking to ensure that all study procedures and interventions are
understood and performed safely.
5.0
Please specify why vulnerable subjects and/or special populations will not be enrolled: 
6.0
With some exceptions as listed in VHA Handbook 1200.05, incompetent subjects cannot 
be enrolled in VAPHS approved research. Specify that you will not enroll incompetent 
subjects and the general rules to be used in making that determination:
Incompetent subjects will not be enrolled in this study because they would not meet the 
inclusion/exclusion
criteria for the study.
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ID: Pro00003161
View: 6.1.1 Non-Veterans
Non-Veterans
1.0
* Target number of participants:
25
2.0
* Describe why you cannot complete enrollment in this study without the use of Non-
Veterans:
As stated in our study objectives, our long-range goal is the prescriptive application of intensive 
task practice to individuals who have suffered a stroke, maximizing the cost-benefit ratio. Our 
predictive model must be validated with a large and heterogeneous group of subjects having 
varied demographics, functional status and neurophysiology. Considering the inclusion/exclusion 
criteria, it is possible that we would not recruit a sufficient number of veteran subjects required to 
complete the proposed study in accordance with 38 CFR 17.45 and 38 CFR 17.92. For eligible 
subjects, their stroke must be their main health deficit. Participants may be excluded from the 
study if they have orthopedic and/or joint problems in the arm affected by their stroke. They 
cannot have any other injuries to the brain such as traumatic brain injury diagnosis. Therefore, we 
will recruit non-veteran subjects in order to achieve our goal of validating our predictive model. 
Nearly 40 subjects have completed the previous version of the study without any major study-
related adverse events, therefore we expect future participants will have a low likelihood of injury 
from the study procedures. 
According to the CDC, 795,000 Americans have a stroke every year. Only 15,000 of those are US 
Veterans. This is 1.89% of the total number. During recruitment for other studies in our lab, only 
one individual out of the 19 screened was a veteran. Stroke research is, however, very relevant to 
present and former military personnel and should be pursued. By including nonveterans, this will 
allow for a larger subject pool which will increase the strength of the study statistically speaking. 
We will make every effort to actively recruit veterans into this study, including posting of approved 
advertisements at VAPHS, staffing recruitment tables at VA Research Week events and requesting 
direct referrals from VA staff. The PI of the study is a practicing neurologist at VAPHS and may 
provide information about the study to patients.
The long-range goal of the proposed work is to meet the Department of Veterans Affairs Strategic 
Plan 2014-2020 listed objective 1.1 and create evidence-based rehabilitation methods for veterans 
with stroke related upper extremity hemiparesis that focus resources more efficiently. By 
increasing our sample size, the inclusion of non-veterans will help us to validate evidence-based 
treatment methods for the veteran population. 
The goal of our study is the prescriptive application of intensive task practice to individuals who 
have suffered a stroke. Once we have validated this predictive model, it can be directly utilized in 
the rehabilitation plans for veterans who have had a stroke. By establishing a larger, more 
heterogeneous subject pool with the inclusion of non-veterans, the statistical strength of the study 
will increase, which will improve the prediction ability of the model. 
Please upload the Inclusion of Non-Veterans Worksheet here:
3.0
* If your study is a clinical trial, please indicate where the VHA Notice of Privacy 
Practices (VA Form 10-0483) will be stored once signed:
This form will be stored in the secured file room in the VA Human Engineering Research
Laboratory at Bakery Square.
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ID: Pro00003161
View: 7 Risk/Benefit Assessment-Risks
Risk/Benefit Assessment-Risks
1.0
* Risk classification for this study (select one).
Name
Minimal Risk
Greater than Minimal Risk
2.0
* Basis for making the above recommendation:
Transcranial Magnetic Stimulation is categorized as a greater than minimal risk procedure by the 
VAPHS.
3.0
* Describe the safety precautions that will be taken to minimize risks/harms:
There are potential risks associated with some of the procedures included in this study. However, 
the procedures have been planned by the investigators to minimize the danger of any major 
complications. All study procedures will be supervised by qualified personnel who will carefully 
monitor the participants. All participants will undergo a medical and history interview with the PI 
at entry into the study to assure that it is safe for them to participate.
1. Risk of injury by the robot. The possible injuries from a malfunctioning robot include bruises, 
pinching, strain, lacerations, dislocations, or bone fractures. The robot has not caused dislocation 
or bone fracture in any of our ongoing robot studies. The risk of injury is minimized by the design 
of the robot allowing the participant to stop it as well as oversight by a staff member who can also 
stop the robot if there is any potential for injury.
2. Risk of injury from TTT. The is minimal risk of muscle fatigue and/or soreness, and joint pain, 
from the repetitive exercise. In order to minimize this risk the participant will be supervised 
throughout the activity and given rest breaks as needed. The participant will be made aware that 
they can stop the task at anytime.
3. Seizures. Transcranial magnetic stimulation at low frequency (< 1 Hz) has been used for over 
30 years in a variety of normal subjects and in subjects with neurological conditions and has 
generally been found to be safe. In a review of 38 studies involving 850 subjects, there were no 
seizures or other major adverse events (Gilbert et al. 2004). For non-neurologically impaired 
subjects and for subjects with stroke, the risk is considered minimal. Although TMS is not used in 
subjects with implanted metallic devices, it is thought to be safe in patients with hydrocephalus 
and ventricular shunts. Although high-rate, repetitive TMS has the potential to induce seizures 
(Wassermann et al. 1996), TMS rates of 0.2 Hz or less are safe in epileptic patients and even
higher rates may have a protective effect in the case of intractable seizures (Tergau et al. 1999).
ONLY rates < 0.2 Hz will be used in this study.
4. Discomfort. 1000 TMS stimuli are an upper limit that will not be exceeded during any session. 
Usually, it will be far fewer stimuli provided. But in any case, this number (1000) of stimuli not 
likely to be stressful or uncomfortable, as they are spread out over time. There is no cumulative 
effect, besides potentially a slight headache. The participant may always ask for a break, and if 
this is done in between mapping different locations, causes no loss of validity of data collection. 
Since the investigator is literally inches away from the participant, participant comfort is 
monitored closely.
5. The risk of hearing loss from the MRI scanning is minimized by having the subject wear 
earplugs or headphones. If a subject feels anxiety in the scanner, they will be removed from the 
scanner. For those participants who have an MRI that reveals a potential condition, previously 
unknown, having the MRI may lead to further medical work up. This is likely beneficial, as a 
condition may be revealed earlier in its course than it otherwise would have been, but may cause 
psychological distress to the participant. The MRI will be reviewed by the PI, a neurologist 
experienced in reading brain MRI, and any need for follow up will be communicated directly to the
participant.
7. Breach of confidentiality. To minimize risk all files and information is maintained in a locked file 
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cabinet in the study coordinator's locked office or the Principle Investigator's office.
8. There are also general risks associated with using any piece of equipment and with any exercise 
involving moving, standing, sitting, or lying in place for prolonged periods of time. These risks 
include skin wounds like abrasions, bruises, or irritations; body stiffness, soreness, aches, and 
trembling; and general symptoms like upset stomach, chills, fatigue, mood changes, 
lightheadedness, and dizziness. The subject will be monitored by a staff member while using any 
equipment and will be encouraged to voice any discomfort or fatigue to the study staff to take 
appropriate breaks and precautions as needed.
4.0
* Provide details regarding the nature of each risk using the area provided below:
Risk Name
View Intervention and Testing
View Data Collection -Confidentiality
5.0
* Do you plan on using the research answering service:
Yes
No
If yes, please Upload the research answering service form:
Answering Service Form(0.01)
6.0
If your study involves a treatment or intervention, please upload the Patient ID Card:
Subject ID Card(0.01)
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ID: Pro00003161
View: 7.1 Risk/Benefit Analysis-Potential Benefits and Alternatives
Risk/Benefit Analysis-Potential Benefits and Alternatives
Describe any potential for benefits to participants in this study:
1.0
* Direct and Indirect Benefits to Subjects:
There may be no direct benefit from participation in this study but they will receive many sessions 
of arm rehabilitation that has previously been shown to be effective in improving arm function. 
Subjects may receive indirect benefit given that they are contributing to medical science or 
helping to advance future understanding of rehabilitation after stroke.
2.0
* Describe alternatives (research or non-research) that are available to subjects if they 
choose not to participate in this study:
Participation is voluntary and the alternative is not to participate.
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ID: Pro00003161
View: 8 Methods of Recruitment and Retention
Recruitment Methods and Materials used for Retention
1.0
* Select recruitment methods used on this study:
Name
Mail Campaign

Referral by independent source

Advertising such as fliers, letters, or ads (newspaper, TV, radio)
Web Site

Research registry

Selected from pre-existing records

Pre-existing relationship with participants
Other
If Other Methods Specify:
2.0
* Specify how subjects will be identified and how study eligibility will be determined:
Recruitment will occur from within the VAPHS through the neurology and rehabilitation clinical 
services as well as the University of Pittsburgh Medical Center (UPMC). Two primary mechanisms 
will be used:
1. The Western Pennsylvania Patient Registry (Pitt IRB# PRO07080061) will be used as a 
recruitment mechanism. This registry draws from patients admitted to the UPMC Stroke Institute, 
and area rehabilitation hospitals plus ongoing contact from Stroke Survivor Support Groups. The 
purpose of the database is to provide a way to contact appropriate patients to discuss possible 
inclusion in research projects. Our investigators will inform the database coordinator of any 
recruitment through the database and of any requests to opt out. All information will be kept 
confidential. The database is maintained by the Co-Directors who are University of Pittsburgh and 
Carnegie Mellon University professors.
2. UPMC Department of Physical Medicine and Rehabilitation (Pitt IRB #12030122). All registry 
participants have provided informed consent to be contacted for future research studies. The IRB 
approved flyer for this study will be provided to the registry investigators to distribute to potential 
subjects according to the procedures established in the registry IRB approved protocols. In 
response to the flyer, potential subjects will directly contact the research team if interested in 
participating.
Veteran participants may also be identified through screening medical records in CPRS and/or 
VISTA. To identify potential participants, we would do a search for a diagnosis of stroke over 6 
months ago and identify which VA clinics the individual attends. We may then contact providers so 
that information about the study can be passed along to the potential subjects. We will also 
regularly provide study pamphlets to VAPHS rehab supervisors for electronic distribution on their 
“Rehab Recap” email listserv. Physical and occupational therapists can then identify appropriate 
Veteran patients that may be candidates for the study and provide them with information. In 
addition we may staff recruitment tables at VAPHS Research Week events, providing written and 
verbal study information directly to Veterans. VA researchers who attend Stroke Rehabilitation 
Research Network quarterly meetings may also be approached directly regarding potential 
participants appropriate for this study. Study pamphlets will also be placed at the University Drive 
campus registration desk area.
Potential participants will receive the study pamphlet where brochures are displayed at the VA 
Human Engineering Research Laboratories, and areas where brochures are displayed at the Rehab 
and Neural Engineering Labs on the University of Pittsburgh campus. The study pamphlet may 
also be distributed at local stroke support groups. 
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A phone pre-screening will be administered to determine potential study eligibility. After written 
consent is obtained, eligibility will be formally determined based upon the inclusion/exclusion 
criteria. 
3.0
* Provide the location (or locations) of the sites where participants will be recruited:
VPAHS, HERL- Bakery Square, UPMC, RNEL/ RAFT Labs, University of Pittsburgh, off-site 
recruitment events (stroke support groups, public speaking events by staff, etc.)
4.0
Please include information regarding any advertisements (print, TV, radio, etc) that will 
be used to recruit subjects including a general description of where this information will 
be posted:
Our approved study pamphlet has been uploaded in question 5.0. This will be posted at VPAHS, 
the VA Human Engineering Research Laboratories, and areas where brochures are displayed at the 
Rehab and Neural Engineering Labs on the University of Pittsburgh campus. The study pamphlet 
may also be distributed at local stroke support groups/events to provide information to individuals 
interested in research participation.
5.0
Please UPLOAD the documents that will be used for recruitment and an introductory 
statement or letter to accompany consent for those studies obtaining written informed 
consent using methods such as fax, email or mail (if applicable). Please also upload any 
screening/recruitment questions that will be verbally asked of potential research 
subjects.  Also, if you will be providing any retention materials, please upload them 
here.
Name
Reviewer
Modified Date
Version Number
Public Affairs email
Boos, Amy
9/20/2019 10:09 AM
0.02
Study Pamphlet
Boos, Amy
9/20/2019 10:09 AM
0.02
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ID: Pro00003161
View: 9 Informed Consent
Informed Consent
1.0
* Indicate the types of consent that will be involved in this study (check any or all that 
apply):
Informed Consent Category
Written/signed consent by subject
Waivers are being requested.
2.0
* Waivers: If you are applying for any waivers of consent (check any or all that apply):
Name
Waiver of Informed Consent

Waiver of HIPAA Authorization

Waiver of Documentation of Informed Consent ( telephone consent, verbal script)
No Waiver at all
3.0
* Will this study include non-English speaking participants?
Yes 
No
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ID: Pro00003161
View: 9.1 Waiver of HIPAA
You have indicated you are requesting a waiver of HIPAA. 
1.0
* Is the request only for Screening/Recruitment purposes?
Yes
No
If yes, please describe your screening/recruitment method:
We will use a phone screening script to explain the study and ask eligibility questions over the
phone. The waiver is for the verbal screening and review of medical records after verbal consent.
If no, the request is for the full study (e.g. retrospective chart reviews and certain observational 
studies)
Please describe the types of records and/or databases to be accessed:
We will access the discharge summary and MRI report from when an individual had their stroke 
relating to the current study. 
THE IDENTIFIABLE INFORMATION BEING REQUESTED:
Note: If participants will be receiving payment and HIPAA Authorization is not being obtained, you 
must select Names, Addresses and Social Security Numbers as that information will be disclosed for 
payment purposes.
2.0
* Identifiable Information per HIPAA Definition
Name
None
Account numbers
Biometric identifiers, including finger and voice prints
Certificate/license numbers
Device identifiers and serial numbers

Elements of dates (except year, for example, date of birth, admission date, 
discharge date, date of death, date of procedures; and all ages over 89)
Email Address
Fax Numbers
Full-face photographic images or any comparable images

Geographical subdivisions smaller than a State (street address, city, county, 
precinct, zip code, and their equivalent geocodes, except for the initial three digits 
of a zip code)
Health plan beneficiary numbers
Internet Protocol (IP) address numbers
Medical Record Numbers

Name or any derivative of name such as initials
Social Security Numbers

Telephone Numbers
URLs (Web Universal Resource Locators) 
Vehicle identifiers and serial numbers, including license plate numbers
Any other unique identifying number, characteristic, or code (Note: The study ID number, 
code or other means of record identification is not considered one of the identifiers that must 
be excluded for de-identification)
3.0
* Patient Protected Health Information:
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Name

Demographic Information (e.g., Name, Address, Phone Number, Social Security 
Number
Billing and Payment Information

Hospital or Medical Records
History and Physical Exam Notes
Mental Health Records
Data Previously Collected for Research Purposes
Progress Notes
Consultation Reports
Laboratory Test Results
Operative Reports

Other
Please indicate the 'Other' Patient Protected Health Information:
Answers to phone screen 
4.0
Other Health Information:
Name
There are no items to display
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ID: Pro00003161
View: 9.1.1 Waiver of HIPAA - More Information
Waiver of HIPAA- More Information 
1.0
* Describe how the identifiable information is to be used and/or disclosed only by 
members of the research team and the following persons (identify with specificity and 
justify the need to disclose the information to anyone outside the VHA.) Note: If 
participants will be receiving payment and HIPAA Authorization is not being obtained, 
you must also describe this disclosure to representatives of the VA for administrative 
purposes here. 
Also describe how this activity meets the “minimum necessary standard” described in 
the HIPAA Privacy Rule:
All registry participants have provided informed consent to be contacted for research studies. 
Individuals will be contacted according to the procedures established in the registry IRB approved 
protocols. Research staff will be provided with contact information for individuals from the registry 
who may be eligible for the study. Recruitment materials will be sent to individuals from the 
registry.
Identified information will be used to screen prospective subjects for eligibility. Subjects can 
choose to answer the phone screening questions with a yes or no. The phone screen is performed 
in an effort to reduce the burden of travel on individuals who may not be eligible for the study. If 
an individual agrees to schedule a consent visit, then their name and contact information will be 
recorded.
The proposed study poses minimal risk to the privacy of the subjects because...
2.0
* Describe how the identifiable information will be protected from improper use or 
disclosure by (detail how this will be accomplished including the limitations of physical 
or electronic access to the information and other protections):
Registry information will not be shared with anyone not involved in the recruitment process. 
Information will be recorded on the phone screening paper form and stored in a locked file room 
with other identifiable data.
3.0
* Describe how the identifiers will be destroyed at the earliest opportunity consistent 
with the research (discuss the timeframe or the reasons the identifiers must be 
retained, including health or research justifications or any legal requirement to retain 
them) (Note: At this time, identifiers used for research screening and all other screening 
records must be retained indefinitely and this must be documented by checking “Other” 
below):
All research records will be maintained in accordance with the Veterans Health Administration 
(VHA) Records Control Schedule. Paper records will be disposed of using methods deemed 
appropriate by the VAPHS Privacy Officer, and all electronic data will be sanitized using methods 
rendered appropriate by the VAPHS ISO.
* When will screening data be de-identified or destroyed:
Name
Other
If Other, please describe:
All research records will be maintained in accordance with the Veterans Health Administration 
(VHA) Records Control Schedule. Paper records will be disposed of using methods deemed 
appropriate by the VAPHS Privacy Officer, and all electronic data will be sanitized using methods 
rendered appropriate by the VAPHS ISO.
4.0
* Describe how the identifiable information will not be reused or disclosed to any other 
person or entity outside the VHA other than the manner described in the protocol, 
except as a required by law, for authorized oversight of this research study, or as 
specifically approved for used in another study by an IRB:
Information (including any medical records) will remain in locked file storage as described in our 
protocol along with other identifiable study information. It will not be reused or disclosed to any 
other person or entity not directly involved in the study, except as required by law, for authorized 
oversight of this research study, or as specifically approved for use in another study by an IRB.
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5.0
* Describe why the proposed study cannot be practicably conducted  without a waiver of 
authorization: (discuss reasons why it would not be possible to obtain authorization 
from individual subjects.  Time constraints themselves are generally not considered 
adequate for this justification:
The phone screening is conducted to minimize the burden of travel for people who may not be 
eligible for the study. Since initial screening is conducted over the phone, providing written 
authorization prior to asking the screening questions is not practical. Verbal authorization also 
allows medical record screening which will help identify participants who may not be eligible for 
the study. The anticipated discomfort in answering the screening questions is not greater than 
what is encountered in daily life. People can choose not to answer the questions in the phone 
screening. If they choose not to answer these questions, we will inform them that eligibility criteria 
will be verified after informed consent.
6.0
* Describe why the proposed study cannot be done without the specified identifiable 
information: Discuss reasons why it would not be possible to conduct the research 
without the identifiable information being collected.
The phone screening is conducted to minimize the burden of travel for people who may not be 
eligible for the study. Since initial screening is conducted over the phone, providing written 
authorization prior to asking the screening questions is not practical. The anticipated discomfort in 
answering the screening questions is not greater than what is encountered in daily life. People can 
choose not to answer the questions in the phone screening. If they choose not to answer these 
questions, we will inform them that eligibility criteria will be verified after informed consent.
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ID: Pro00003161
View: 9.3 Waiver of Documentation of Informed Consent
Waiver of Documentation of Informed Consent
You have selected a waiver of Documentation of Informed Consent
1.0
This is a request for Waiver of Documentation of Informed Consent because this 
research study conforms to either A and/or B (Check if ‘yes’ and provide the verifying 
information requested): 
* A: The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality.  Each subject will 
be asked whether the subject wants documentation linking the subject with the research, and the 
subject's wishes will govern.    
Yes 
No
AND/OR
* B: The proposed study poses minimal risk to the subjects.   
Yes
No
If yes, please explain why the proposed study poses minimal risks to the subjects.  (Outline the 
subject’s involvement in the project and why the study poses minimal risk) :
The anticipated discomfort in answering the screening questions is not greater than what is 
expected to be encountered in daily life.
2.0
*  The research involves no procedures for which written consent is normally required 
outside of the research context. Research procedures include:
Questions will be asked over the phone to determine if the potential participant meets the 
eligibility criteria for this study.
3.0
* Explain how whenever appropriate, the subjects will be provided with additional 
pertinent information (e.g. an information sheet):
If the subject is interested in participating in the study after screening, then they will be scheduled 
for an in-person consent process.
4.0
Please upload SCRIPT here:
Document
Description
Version Number
View Phone Screening Script(0.04)
0.04
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ID: Pro00003161
View: 9.4 Consent Forms & Process of Consent
Consent Forms & Process of Consent
1.0
Upload the completed forms into the correct lists below.
1.1
Informed Consent Form (clean copy):
Document
Modified Date
Version Number
View Consent Form(0.09)
12/3/2019 12:00 AM
0.09
1.2
Provider Behavior Informed Consent Form (clean copy):
Document
Modified Date
Version Number
There are no items to display
1.3
Screening Informed Consent Form (clean copy):
Document
Modified Date
Version Number
There are no items to display
2.0
Consent Forms (modified copy):
Document
Modified Date
Version Number
View ICF with tracked changes(0.05)
1/29/2020 10:45 AM
0.05
3.0
* Describe how, where, when, and by whom the consent process will be initiated:
Potential subjects will be provided an explanation of the purpose of the research, why they are 
being asked to participate, and the duration of the study. In addition, the potential participant will 
be made aware of any foreseeable risks associated with the study as well as any potential 
benefits. Potential participants will be made aware of the alternative to participation in the study 
and the methods used to protect the confidentiality of the records during the study. Also, subjects 
will be told that their participation in this study is completely voluntary and that they can withdraw 
at any time. Information on who to contact if they were to have any questions, concerns, or
complaints about this research will also be provided. Subjects will also be asked if they understand 
the purpose, risks and benefits, procedures, and their rights as a research subject. Any questions 
the subjects have at any time will be answered by one of the listed study team members. The 
entire process will occur prior to obtaining written informed consent. The principal investigator or a 
team member of this study will be involved in the consent process described above. The consent 
process will take place in a private location.
4.0
* Will you be maintaining a Master List of Subjects?
Yes 
5.0
* Describe when the subject’s name will be added to the master list and how the list will 
be maintained in a secure fashion.  
Only once informed consent has been obtained from the subject and it has been documented 
using an IRB approved consent form, will the study subject’s name be added to the master list of 
subjects. The electronic master list will be secured in compliance with all VA confidentiality and 
information security requirements at \\vhapthmulherl07.v04.med.va.gov\herl\HERL Projects 
Wittenberg\3161.SRT5.
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ID: Pro00003161
View: 10.0.0 Data Security and Privacy: Data Types Storing
10.0 Data Types Collecting and Storing
1.0
Click the add button (below) to open an entry form to indicate the types and/or sources 
of the data that will be collected/stored as part of the project. 
Instructions: For each type/source of data that will be collected as part of the project, 
this includes screening data, click the add button to open an entry form that lists the 
types and/or sources of data. Select a source/type of the data that will be 
collected/stored. Then indicate what, if any, identifiers or sensitive information will be 
collected/stored from the source/type (None is an option). To add another source/type 
click “OK Add Another” button to open up a new entry form to repeat the process.
Example 1: You are collecting data from VA Medical records including names, last 4 of 
SSN, and addresses. Therefore, you would select “VA medical record data” as the 
source, and then select in the identifiers: “Name or any derivative of name, such as 
initials,” “Social Security Numbers,” and “Geographical subdivisions smaller than a 
State (street address, city, county, precinct, zip code, and their equivalent geocodes, 
except for the initial three digits of a zip code)” as the identifiers being collected.
Example 2:  You are screening VA Medical Records and recording the information you 
use to screen (i.e.: names, last 4 of SSN, and addresses, etc.)  Note: This information 
must be treated as a Source document, please select “Screening” as the source and then 
select the identifiers “Name or any derivative of name, such as initials,” “Social Security 
Numbers,”, as applicable.
* 
Data Type/Source
Collection Details
Identifiers
View Other
Robotic Quantitative 
Measures
The Armeo Power robot has the 
ability to precisely record a 
subject's performance during 
assisted and unassisted modes. 
We may use this data to 
provide an objective motor 
performance measure to 
augment the clinical 
evaluations. The KINARM robot 
may also be used to perform a 
set of standard sensory, motor, 
and cognitive-motor 
evaluations. 
None
View Questionnaires/Surveys, 
paper
Demographic and questionnaire 
data will be recorded on the 
attached data collection sheets 
by approved research staff. 
Subjects will be assigned a 
subject number for labeling the 
data collection sheets. Prior to 
data entry, all data will be 
reviewed for inconsistencies 
and checked for missing 
values.
Telephone 
Numbers
Geographical 
subdivisions 
smaller than a 
State (street 
address, city, 
county, 
precinct, zip 
code, and their 
equivalent 
geocodes, 
except for the 
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Data Type/Source
Collection Details
Identifiers
initial three 
digits of a zip 
code)
Name or any 
derivative of 
name such as 
initials
View Other
TMS
Magnetic stimulation will be 
performed at each examination 
according to the following 
general experimental 
procedure: The target muscle 
will be at rest during the entire 
procedure with the participant 
resting on a pillow in the lap. 
Audio monitoring of muscle 
activity is performed during the 
study through the EMG 
amplifier to ensure that 
muscles are at rest. Soft foam 
earplugs are inserted into each 
ear canal for hearing 
protection. The three 
dimensional coordinates of 
each TMS stimulation site will 
be measured using an optical 
digitizing device (Vicra, 
Northern Digital Inc.) with 
localization software 
(BrainSight, Rogue Research, 
Montreal, Canada.) This 
technique ensures reproducible 
locations at each session, 
without having to search for 
the hotspot each time.
None
View Other
MRI 
The data will be collected and 
recorded at the MRRC by 
research staff and study staff. 
Data will be transferred via a 
VA-encrypted hard drive to the 
VAPHS server.
None
View Other
Social Security Number
Social Security numbers will be 
collected and then destroyed 
after creation of the VA CPRS 
health record, which is required 
for study enrollment and 
progress notes for this 
intervention study. 
Social Security 
Numbers
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ID: Pro00003161
View: 10.0.1 Data Security and Privacy: Social Security Numbers
10.0.1 Data Security and Privacy: Social Security Numbers
1.0
You indicated that you will be using all or some part of the research subjects' SSNs as 
part of this study.  Which of the following will you be using:
Real Social Security numbers 
* 
Yes
No
Scrambled Social Security numbers
* 
Yes 
No
Last 4 digits of Social Security Number * 
Yes
No
Other (some derivation of the SSN)
* 
Yes 
No
If other, please explain:
2.0
* Please describe how subjects’ Social Security numbers will be used in this study:
The SS number is required for CPRS documentation in this intervention study as well as for 
processing payment. The last 4 digits are required on the HIPAA form, which will be stored in a 
secure file room with other paper documents at the Human Engineering Research Laboratories. 
HERL is located at Bakery Square, 6425 Penn Avenue, Pittsburgh, PA 15206. The secure file room 
is Suite 401, Room 4103. This is a locked room inside a locked office, inside a locked suite. 
Documents are transported under an approved Authorization to Transport and Utilize VA Sensitive 
Information Outside Protected Environments form. 
3.0
* Please describe the security measures that will be taken to protect SSNs.
The SS number will be destroyed after the CPRS record is created. 
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ID: Pro00003161
View: 10.1.0 Data Security and Privacy: Incoming Data
10.1.0 Incoming Data 
1.0
* Will data be transferred into VAPHS?
Yes. Data is being obtained from a non-VA source and will be transferred to VAPHS
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ID: Pro00003161
View: 10.1.1 Data Security and Privacy: Incoming Data - Identifiable Data
10.1.1 Incoming Data - Identifiable Data
1.0
* Is any of the data being transferred into VAPHS identifiable?
Yes 
No
If yes, please describe what the identifiable data is and where it is coming from:
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ID: Pro00003161
View: 10.2.0 Data Security and Privacy: Outgoing Data
10.2.0 Outgoing Data 
1.0
* Will any of the data being collected/stored be transferred outside of VAPHS?
Yes. The data will be transferred to a non-VA entity.
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ID: Pro00003161
View: 10.3.0 Data Security and Privacy: Local Data Storage Types
10.3.0 Local Data Storage Types 
1.0
* How will data be stored on this project? (Select all that apply)
On Paper
Electronically
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ID: Pro00003161
View: 10.3.1 Data Security and Privacy: Local Data Storage Types - Paper
10.3.1 Local Data Storage Types - Paper 
1.0
* All VA research data collected in paper must be stored in a locked room at VAPHS. 
List the room number(s) and the campus(es) where data will be stored in the text box 
below.
Paper documents will be stored in a secure file room at the Human Engineering Research 
Laboratories. HERL is located at Bakery Square, 6425 Penn Avenue, Pittsburgh, PA 15206. The 
secure file room is Suite 401, Room 4103. This is a locked room inside a locked office, inside a 
locked suite. 
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ID: Pro00003161
View: 10.3.2 Data Security and Privacy: Local Data Storage Types - Electronic
10.3.2 Local Data Storage Types - Electronic
1.0
* Where is the electronic data being stored? Select all that apply.
VAPHS Network (shared drive)
VA Encrypted VA external drive or thumb drive
Other
If "Other" please describe OR if you would like to provide additional information for 
clarification, please elaborate in the text box below.
Non-identifiable data may be collected and analyzed using a non-VA (Pitt) computer with any 
identifiable data being stored on the VAPHS shared drive. The equipment used in this study may 
require specific software that is available on non-VA (Pitt) computers. All data will ultimately be 
transferred and stored on the VAPHS network using an encrypted hard drive. All data being 
transferred will be non-identifiable. Access will be restricted to only those associated with this 
research study. Data may include kinematic, neurophysiological and robot-generated metrics. 
If you selected VAPHS or VA Network (Shared Drive), please provide the name of the 
drive (i.e. "MySharedDriveName (\\vapthshsare) (X:)"):
\\oitpthhsmsvm200.v04.med.va.gov\Research\Wittenberg_Pro3161_PSRT5
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ID: Pro00003161
View: 10.4.0 Data Security and Privacy: Reusing Data
10.4.0 Data Security and Privacy: Reusing Data
1.0
* Will the data collected in this study be reused in other studies?
Yes 
No
If yes, please describe where the data to be reused will be stored and how access to 
that data will be provided and monitored:
2.0
If this research is part of a grant, please upload the Data Management Access Plan 
(DMAP) or Resource Sharing Plan for this study.
Name
Modified Date
DMAP
7/15/2019 1:59 PM
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ID: Pro00003161
View: 10.5.0 Data Security and Privacy: Off-Site Storage and Transfer of Data
10.5.0 Off-Site Storage and Transfer of Data
1.0
* You indicated that data collected as part of this study will 
be transferred outside of VA/VAPHS. Please provide a 
justification for why the data must be stored, transmitted, 
and/or transferred off-site:
Data may be transferred to the Magnetic Resonance Research 
Center, where MRI scans will be performed. 
Click here for Research 
Data Security and 
Privacy Frequently 
Asked Questions 
Specify in detail how data 
will be collected, entered, 
and analyzed. For multisite 
studies, if no data entry 
and/or analysis will occur on 
site, this should be specified. 
Specify how long each phase 
of the study will take to 
complete and provide a time 
line for each aspect of the 
study ending with the final 
analyses and projected 
publication/presentation 
timeframe. If you are 
seeking exempt status on 
the basis of retrospective 
medical records review, 
please include the start and 
end dates (dates of creation) 
of the medical records you 
wish to use (Note: In order 
for the study to be granted 
exempt status the data must 
have already been collected 
prior to the date of 
submission of the application 
for exempt status)   Also, 
provide all data entry forms 
or a complete list of the 
variables you will be 
collecting.
2.0
Please list all locations or individuals who will receive/be 
provided with the data, including sponsor, site monitors, 
coordinating center, University of Pittsburgh, non-VA 
investigators/collaborators, reading centers, core 
laboratories, other research laboratories, data monitoring 
committee, etc.
* Data Recipients and Identifiers:
Recipient 
and 
Description
Identifier
Identifier 
Description
Transfer 
Methods
University 
of 
Pittsburgh
Magnetic 
Resonance 
Research 
Center 
(MRRC)
Elements of 
dates 
(except 
year, for 
example, 
date of 
birth, 
admission 
date, 
Date of 
Birth
Direct entry into electronic 
website (Provide URL 
Below)
mrctr.upmc.edu/mrsched/
Any identifiable information 
that is being shared with 
these individuals/entities 
must be described in the 
HIPAA authorization (in the 
disclosure section). 
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Recipient 
and 
Description
Identifier
Identifier 
Description
Transfer 
Methods
discharge 
date, date 
of death, 
date of 
procedures; 
and all 
ages over 
89)
Telephone 
Numbers
Telephone 
number
Direct entry into electronic 
website (Provide URL 
Below)
mrctr.upmc.edu/mrsched/
Name or 
any 
derivative 
of name 
such as 
initials
First 
name, 
Last name
Direct entry into electronic 
website (Provide URL 
Below)
mrctr.upmc.edu/mrsched/
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ID: Pro00003161
View: 10.5.1 Data Security and Privacy: Keeping a Copy of the Data
10.5.1 Data Security and Privacy: Keeping a Copy of the Data
1.0
* How will the study team keep a copy of the data at VAPHS that is being transferred?
Name
Paper (copies of CRFs, questionnaires, etc.)
Specify other method of maintaining a copy of the data being transferred:
The data will be stored on the subject demographic forms, which will be stored in a secure file 
room with other paper documents at the Human Engineering Research Laboratories. HERL is 
located at Bakery Square, 6425 Penn Avenue, Pittsburgh, PA 15206. The secure file room is Suite 
401, Room 4103. This is a locked room inside a locked office, inside a locked suite. 
2.0
* Upload the VA Data Storage and Retrieval Worksheet:
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ID: Pro00003161
View: 10.6.0 Data Security and Privacy: HIPAA
10.6.0 Data Security and Privacy: HIPAA
The Healthcare Insurance Portability and Accountability Act (HIPAA) prohibits the use of a person's 
Protected Health Information without a valid authorization.
1.0
* Select the option which fits this study:
Name
Not applicable: No PHI is being used or disclosed by VAPHS
Not applicable: Waiver has been requested
HIPAA Authorization (Combined Consent and HIPAA Authorization)
HIPAA Authorization (Standalone)
Upload HIPAA authorization (Standalone) here:
Document
Modified Date
Version Number
View Placeholder Document(0.02)
8/2/2019 3:14 PM
0.02
2.0
At screening will clinical personnel be asked to share potential participants PHI:
Yes 
No
 If yes, please upload the 10-5345:
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ID: Pro00003161
View: 10.7.0 Data Security and Privacy: Additional Information
10.7.0 Data Security and Privacy: Additional Information
1.0
Does this research involve...
* ...specially obtained software?
Yes
No
If yes, please describe the software and what it is being used for:
Actilife software is the proprietary software associated with the Actigraph activity monitors. It is 
the only software that can export the data from the monitors and convert it to a .csv or .dat file 
that can then be used for majority of the analysis.
SIGNAL is required to administer Transcranial Magnetic Stimulation according to the study 
protocol. MATLAB is required for data analysis.
The Armeo Power and KINARM robots run on proprietary software that allows safe use with human 
subjects.
The ActiLife software license was previously purchased from the company ActiGraph. A SIGNAL 
software license has also been purchased from the company A-M Systems. Only coded data will be 
stored in temporary files on the computer’s hard drive as data is collected. 
The Armeo Power robot runs on proprietary software that was included in the original purchase of 
the robotic system from the company Hocoma. The KINARM robot runs on proprietary software 
that was included in the original purchase of the robotic system from the company BKin / KINARM. 
The robot computers will not be connected to the VA or Pitt networks. MATLAB software will only 
be used for analysis and is licensed through the RNEL.
* ...one or more Web-based applications?
Yes 
No
If yes, please describe the application and what it is being used for:
* ...mobile devices?
Yes 
No
If yes, please describe:
2.0
* Will a Certificate of Confidentiality be obtained for this study?
Yes 
No
If yes, please attach the Certificate of Confidentiality:
3.0
* Will VA sensitive information be transported and utilized outside protected 
environments?
Yes
No
If you answered yes above, please upload a fully executed VAPHS Memo to Take VA Sensitive 
Information Outside a Protected Environment by following these instructions .
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ID: Pro00003161
View: 10.8.0 Data Security and Privacy: Certifications
10.8.0 Certifications
1.0
* I certify that all study staff are up-to-date and will remain up-to-date with 
Information Security Awareness Training, Rules of Behavior, and VHA Privacy Training.
Yes
No
2.0
* I also certify that when an individual is no longer part of the study team, access will 
be removed to research study data.
Yes
No
3.0
* I certify that all research records will be maintained in accordance with the Veterans 
Health Administration (VHA)Records Control Schedule. Paper records will be disposed of 
using methods deemed appropriate by the VAPHS Privacy Officer, and all electronic data 
will be sanitized using methods rendered appropriate by the VAPHS ISO. 
Yes
No
4.0
* I certify that any loss or compromise of any VA sensitive information (including 
research data), VA equipment or device, or any non-VA equipment or device that is used 
to transport, access, or store VA information will be reported in accordance with the 
reporting requirements outlined in VA Handbook 6500.
Yes
No
5.0
* I certify that, in accordance with VA Handbook 6500, no personal laptops will be used  
for official VA business in conjunction with this study.
Yes
No
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ID: Pro00003161
View: 11 Local Data Safety Monitoring Plan
Local Data Safety Monitoring Plan
 For local studies, a data and safety monitoring plan (DSMP) must be established.
1.0
* Please describe how the study procedures and data being collected will be 
continuously monitored so that changes in the risk/benefit ratio can be determined in a 
timely fashion during the course of the study:
A data and safety monitoring plan will be implemented to insure that there are no changes 
in the benefit/risk ratio during the study and that confidentiality of research data is 
maintained. These meetings are overseen by the Directors of HERL or their designees. Any 
instances of adverse events will be reported immediately using the standard forms and/or 
procedures set forth by the Institutional Review Board. In addition, clinical coordinators 
from HERL may periodically review study documentation and/or consent forms to ensure 
that subject’s confidentiality is maintained. Reporting of adverse events will be done as 
outlined by the VAPHS IRB. A data safety and monitoring report will be sent to the IRB at 
the time of renewal.
2.0
* Describe how frequently Investigators, study personnel, and the clinical coordinators 
involved in the study will meet and/or review study data.
Investigators, study personnel, and the clinical coordinators involved in the study will meet 
quarterly to discuss the study (e.g. study goals, progress, modifications, documentation, 
recruitment, retention, data analysis, and confidentiality) and address any issues or 
concerns at this time.  
3.0
* Will this study use a Data Safety Monitoring Board or Data Monitoring committee? 
Yes 
No
4.0
* Will this study use a Medical Monitor?  
Yes 
No
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ID: Pro00003161
View: 12 Costs and Payments
Costs and Payments
1.0
* Does this study have a budget?:
Yes
No
If yes, please upload the current budget:
Budget(0.01)
2.0
* Will patients receive payments for this study?
Yes
No
If yes, please upload the financial letter of support (either from the Business Service line or the 
Veterans Health Foundation) or documentation waiving the requirement of a letter of support:
Financial LOS Memo
0.01
3.0
* Are you paying patients using the WePay system?
no 
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ID: Pro00003161
View: 12.1 Costs
Costs 
1.0
* Will subjects be required to pay for any services outside of the VHA that may be 
required as part of participating in this research study?
No.
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ID: Pro00003161
View: 12.2 Participant Payments
Participant Payments 
1.0
* Please explain how the proposed payments are reasonable and commensurate with 
the expected contributions of the subject:
Participants will receive payment for time and effort for their study participation, commensurate 
with their expected contributions to the research study. Participants will be attending over 40 
sessions that involve attention and effort, especially during the exercise sessions. They will be 
contributing a significant amount of time and the information gathered from each individual 
contributes to the validation of the predictive model and is therefore very valuable to the study 
outcomes. 
2.0
* Please provide information on how the subject payments are fair and appropriate, and 
that they do not constitute (or appear to constitute) undue pressure or influence on the 
prospective research subjects to volunteer for, or to continue to participate in, the 
research study. In additional the payments do not constitute (or appear to constitute) 
coercion to participate in, or continue to participate in, the research study:
The payment is a small amount and as such does not appear to constitute coercion to participate 
in the research study. Payments are approximately the same as that of other researcher studies in 
the building and area where the study is conducted. Payment is designed to approximate the cost 
of transportation plus time and effort of the participants. 
3.0
* Specify the amount, form of payment and the specific disbursement schedule of 
payments:
Payment of $20 per visit will be made once a month while participants are enrolled in the study. 
Except in limited circumstances, payments issued through VA are generated by Electronic Funds 
Transfer (EFT). If participants are not able to receive payment through EFT, the Direct Express 
Debit MasterCard may be issued. The Direct Express Debit MasterCard is a prepaid debit card.
4.0
* Are the subjects being paid employees?
no 
If yes, please describe how it will be in accordance with the SOP:
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ID: Pro00003161
View: 14 References
References:
1.0
* Please provide a list of references (Multi-site protocols: You may reference the page 
numbers in the original protocol):
1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. Heart Disease and Stroke 
Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135
(10):e146-e603.
2. Go A, Mozaffarian D, Roger V, Benjamin E, Berry J, Borden W, et al. Heart disease and stroke 
statistics--2013 update: a report from the American Heart Association. Circulation. 2013;127
(1):e6-e245.
3. Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global 
and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings 
from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(5):e259-81.
4. Gauthier L, Taub E, Perkins C, Ortmann M, Mark V, Uswatte G. Remodeling the brain: plastic 
structural brain changes produced by different motor therapies after stroke. Stroke. 2008;39
(5):1520-5.
5. Wittenberg GF, Chen R, Ishii K, Bushara KO, Eckloff S, Croarkin E, et al. Constraint-induced 
therapy in stroke: magnetic-stimulation motor maps and cerebral activation. Neurorehabil Neural 
Repair. 2003;17(1):48-57.
6. Wittenberg G, Bastings E, Fowlkes A, Morgan T, Good D, Pons T. Dynamic course of intracortical 
TMS pairedpulse responses during recovery of motor function after stroke. Neurorehabil Neural 
Repair. 2007;21(6):568-73.
7. Raghavan P, Santello M, Gordon A, Krakauer J. Compensatory motor control after stroke: an 
alternative joint strategy for object-dependent shaping of hand posture. J Neurophysiol. 2010;103
(6):3034-43.
8. Boyeson M, Jones JL, Harmon RL. Sparing of motor function after cortical injury: a new 
perspective on underlying mechanisms. Archives of Neurology. 1994;51:405-14.
9. Kwakkel G, Meskers C, van Wegen E, Lankhorst G, Geurts A, van Kuijk A, et al. Impact of early 
applied upper limb stimulation: the EXPLICIT-stroke programme design. BMC Neurol. 2008;8:49.
10. Hanley J, McNeil B. The meaning and use of the area under a receiver operating characteristic 
(ROC) curve. Radiology. 1982;143(1):29-36.
11. O'Dell M, Lin C, Harrison V. Stroke rehabilitation: strategies to enhance motor recovery. Annu 
Rev Med. 2009;60:55-68.
12. Mehrholz J, Pohl M, Platz T, Kugler J, Elsner B. Electromechanical and robot-assisted arm 
training for improving activities of daily living, arm function, and arm muscle strength after stroke. 
Cochrane Database Syst Rev. 2018;9:CD006876.
13. Colombo R, Pisano F, Delconte C, Mazzone A, Grioni G, Castagna M, et al. Comparison of 
exercise training effect with different robotic devices for upper limb rehabilitation: a retrospective 
study. Eur J Phys Rehabil Med. 2017;53(2):240-8.
14. Brokaw EB, Holley RJ, Lum PS. Comparison of joint space and end point space robotic training 
modalities for rehabilitation of interjoint coordination in individuals with moderate to severe 
impairment from chronic stroke. IEEE Trans Neural Syst Rehabil Eng. 2013;21(5):787-95.
15. Kwakkel G, Kollen BJ, Krebs HI. Effects of Robot-Assisted Therapy on Upper Limb Recovery 
After Stroke: A Systematic Review. Neurorehabil Neural Repair. 2008;22(2):111-21.
16. Kissela B, Khoury J, Alwell K, Moomaw C, Woo D, Adeoye O, et al. Age at stroke: temporal 
trends in stroke incidence in a large, biracial population. Neurology. 2012;79(17):1781-7.
17. Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, et al. The state of US health, 
1990-2010: burden of diseases, injuries, and risk factors. JAMA. 2013;310(6):591-608.
18. Rothman S, Mattson M. Activity-dependent, stress-responsive BDNF signaling and the quest 
for optimal brain health and resilience throughout the lifespan. Neuroscience. 2013;239:228-40.
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19. van der Lee JH, Wagenaar RC, Lankhorst GJ, Vogelaar TW, Deville WL, Bouter LM. Forced use 
of the upper extremity in chronic stroke patients: results from a single-blind randomized clinical 
trial. Stroke. 1999;30(11):2369-75.
20. Westat. National Survey of Veterans, Active Duty Service Members, Demobilized National 
Guard and Reserve Members, Family Members and Surviving Spouses. 2010. p. Contract GS-23F-
8144H.
21. Wagner TH, Lo AC, Peduzzi P, Bravata DM, Huang GD, Krebs HI, et al. An Economic Analysis 
of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke. Stroke. 2011;42
(9):2630-U422.
22. Wittenberg G, Bastian A, Dromerick A, Thach W, Powers W. Mirror movements complicate 
interpretation of cerebral activation changes during recovery from subcortical infarction. 
Neurorehabil Neural Repair. 2000;14(3):213-21.
23. Wolf S, Winstein C, Miller J, Taub E, Uswatte G, Morris D, et al. Effect of constraint-induced 
movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE 
randomized clinical trial. JAMA. 2006;296(17):2095- 104.
24. Lo A, Guarino P, Richards L, Haselkorn J, Wittenberg G, Federman D, et al. Robot-assisted 
therapy for long-term upper-limb impairment after stroke. N Engl J Med. 2010;362(19):1772-83.
25. Kwakkel G, Winters C, van Wegen EE, Nijland RH, van Kuijk AA, Visser-Meily A, et al. Effects 
of Unilateral Upper Limb Training in Two Distinct Prognostic Groups Early After Stroke: The 
EXPLICIT-Stroke Randomized Clinical Trial. Neurorehabil Neural Repair. 2016;30(9):804-16.
26. Sawaki L, Butler A, Xiaoyan L, Wassenaar P, Mohammad Y, Blanton S, et al. Constraint-
induced movement therapy results in increased motor map area in subjects 3 to 9 months after 
stroke. Neurorehabil Neural Repair. 2008;22(5):505-13.
27. Sawaki L, Butler A, Leng X, Wassenaar P, Mohammad Y, Blanton S, et al. Differential patterns 
of cortical reorganization following constraint-induced movement therapy during early and late 
period after stroke: A preliminary study. NeuroRehabilitation. 2014.
28. Wittenberg GF, Richards LG, Jones-Lush LM, Roys SR, Gullapalli RP, Yang S, et al. Predictors 
and brain connectivity changes associated with arm motor function improvement from intensive 
practice in chronic stroke. F1000Res. 2016;5:2119.
29. Frohlich H, Balling R, Beerenwinkel N, Kohlbacher O, Kumar S, Lengauer T, et al. From hype to 
reality: data science enabling personalized medicine. BMC Med. 2018;16(1):150.
30. Stinear C, Barber P, Petoe M, Anwar S, Byblow W. The PREP algorithm predicts potential for 
upper limb recovery after stroke. Brain. 2012;135(Pt 8):2527-35.
31. Stinear CM, Byblow WD, Ackerley SJ, Barber PA, Smith MC. Predicting Recovery Potential for 
Individual Stroke Patients Increases Rehabilitation Efficiency. Stroke. 2017;48(4):1011-9.
32. Connell LA, Smith MC, Byblow WD, Stinear CM. Implementing biomarkers to predict motor 
recovery after stroke. NeuroRehabilitation. 2018;43(1):41-50.
33. Gauthier L, Taub E, Mark V, Perkins C, Uswatte G. Improvement after constraint-induced 
movement therapy is independent of infarct location in chronic stroke patients. Stroke. 2009;40
(7):2468-72.
34. Lin K, Hsieh Y, Wu C, Chen C, Jang Y, Liu J. Minimal detectable change and clinically important 
difference of the Wolf Motor Function Test in stroke patients. Neurorehabil Neural Repair. 2009;23
(5):429-34.
35. DeLong ER, DeLong DM. Comparing the areas under two or more correlated receiver operating 
characteristic curves: A non-parametric approach. Biometrics. 1988;44:837-45.
36. Breiman L. Random forests. Mach Learn. 2001;45(1):5-32.
37. Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated 
and anticorrelated brain networks. Brain Connect. 2012;2(3):125-41.
38. Busan P, Barbera C, Semenic M, Monti F, Pizzolato G, Pelamatti G, et al. Effect of transcranial 
magnetic stimulation (TMS) on parietal and premotor cortex during planning of reaching 
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movements. PLoS One. 2009;4(2):e4621.
39. Procacci NM, Stanford TR, Wittenberg GF. The relationship between visual orienting and 
interlimb synchrony in a patient with a superior parietal infarction: A case study. Neurocase. 
2009;15(2):73-88.
40. Schieppati M, Trompetto C, Abbruzzese G. Selective facilitation of responses to cortical 
stimulation of proximal and distal arm muscles by precision tasks in man. J Physiol. 1996;491 ( Pt 
2):551-62.
41. Hulley SB. Designing clinical research. 4th ed. Philadelphia: Wolters Kluwer/Lippincott Williams 
& Wilkins; 2013. p. p.
42. Roger V, Go A, Lloyd-Jones D, Benjamin E, Berry J, Borden W, et al. Heart disease and stroke 
statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125
(1):e2-e220.
43. CDC. Summary Health Statistics for U.S. Adults. 2011.
44. O'Brien S, Xue Y. Predicting goal achievement during stroke rehabilitation for Medicare 
beneficiaries. Disabil Rehabil. 2013.
45. Levin M, Desrosiers J, Beauchemin D, Bergeron N, Rochette A. Development and validation of 
a scale for rating motor compensations used for reaching in patients with hemiparesis: the 
reaching performance scale. Phys Ther. 2004;84(1):8-22.
46. Gladstone D, Danells C, Black S. The fugl-meyer assessment of motor recovery after stroke: a 
critical review of its measurement properties. Neurorehabil Neural Repair. 2002;16(3):232-40.
47. Levin M. Interjoint coordination during pointing movements is disrupted in spastic 
hemiparesis. Brain. 1996;119(Pt 1):281-93.
48. Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 
1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31.
49. Duncan P, Bode R, Min Lai S, Perera S. Rasch analysis of a new stroke-specific outcome scale: 
the Stroke Impact Scale. Arch Phys Med Rehabil. 2003;84(7):950-63.
50. Morris D, Uswatte G, Crago J, Cook E, Taub E. The reliability of the Wolf motor function test 
for assessing upper extremity function following stroke. Arch Phys Med Rehabil. 2001;in press.
51. Liu W, McCombe Waller S, Kepple T, Whitall J. Compensatory arm reaching strategies after 
stroke: induced position analysis. J Rehabil Res Dev. 2013;50(1):71-84.
52. Bogard K, Wolf S, Zhang Q, Thompson P, Morris D, Nichols-Larsen D. Can the Wolf Motor 
Function Test be streamlined? Neurorehabil Neural Repair. 2009;23(5):422-8.
53. Duncan PW, Wallace D, Lai SM, Johnson D, Embretson S, Laster LJ. The stroke impact scale 
version 2.0. Evaluation of reliability, validity, and sensitivity to change. Stroke. 1999;30
(10):2131-40.
54. van der Lee J, Beckerman H, Lankhorst G, Bouter L. The responsiveness of the Action 
Research Arm test and the Fugl-Meyer Assessment scale in chronic stroke patients. J Rehabil Med. 
2001;33(3):110-3.
55. Van der Lee J, De Groot V, Beckerman H, Wagenaar R, Lankhorst G, Bouter L. The intra- and 
interrater reliability of the action research arm test: a practical test of upper extremity function in 
patients with stroke. Arch Phys Med Rehabil. 2001;82(1):14-9.
56. Uswatte G, Taub E, Morris D, Vignolo M, McCulloch K. Reliability and validity of the upper-
extremity Motor Activity Log-14 for measuring real-world arm use. Stroke. 2005;36(11):2493-6.
57. Welk G, Schaben J, Morrow JJ. Reliability of accelerometry-based activity monitors: a 
generalizability study. Med Sci Sports Exerc. 2004;36(9):1637-45.
58. Gebruers N, Vanroy C, Truijen S, Engelborghs S, De Deyn P. Monitoring of physical activity 
after stroke: a systematic review of accelerometry-based measures. Arch Phys Med Rehabil. 
2010;91(2):288-97.
59. Lang C, Bland M, Bailey R, Schaefer S, Birkenmeier R. Assessment of upper extremity 
impairment, function, and activity after stroke: foundations for clinical decision making. J Hand 
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Ther. 2013; 26(2):104-14;quiz 15.
60. Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and 
cytoarchitectonicatlas-based interrogation of fMRI data sets. NeuroImage. 2003;19(3):1233-9.
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ID: Pro00003161
View: 15 Miscellaneous Documents
Miscellaneous Documents
If you have any documents that need to be included in this submission, but do not fit in any of the 
previous sections please upload them here.
Document
Description
Version Number
There are no items to display
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ID: Pro00003161
View: SF - Final Page
Final Page
You have completed your application!
Please hit "Finish" to save and exit the application.  Doing so will NOT submit the application for 
review.
Please note that a submission may only be forwarded to the IRB by the Principal Investigator.  To 
do this, the Principal Investigator must press the "SUBMIT STUDY" button in My Activities for this 
Study ID:Pro00003161.
You can track the ongoing status of your submission by logging into the study workspace.
Please feel free to contact the IRB with any questions or concerns.
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ID: Pro00003161
View: Create/Edit
Study Funding Source
1.0
* Funding Source Name:
Merit Review (CC 103)
If you can't find the Funding Source above, choose "Other" and enter it here:
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ID: Pro00003161
View: Print View
Name of Site / Institution:
University of Pittsburgh
Are the study-related research activities at this site defined as engagement? 
Yes
Investigator Name:
George Wittenberg
Investigator Address:
3520 Fifth Ave, Suite 201, Pittsburgh, PA 15213
Investigator Email:
george.wittenberg@va.gov
Investigator Phone:
412-648-4178
IRB-of-Record Contact Name:
Contact Address:
Contact Email:
Contact Phone:
FWA:
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ID: Pro00003161
View: VA Create-Edit
* Device Name:
The MagStim 200
* Use of Device:
FDA Approved but used in unapproved way
Manufacturer:
MagStim
IDE Class:
IDE Number(if Applicable):
Risk Level Determined by Sponsor: Non-Significant Risk
Upload Device Brochure
Provide any other notes about how this device will be used or justification for lack of IDE number
Is the investigator hold the IDE for this device?
Yes 
No
If yes please provide a basis for risk level. 
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ID: Pro00003161
View: Risk Detail Entry
Address for each screening procedure, research intervention/interatction, and follow-up/monitoring procedure: 
* Research Activity:
Intervention and Testing
Common Risks: 
Infrequent Risks:
Risk of injury by the robot. The possible injuries from a malfunctioning robot include bruises, pinching, 
strain, lacerations, dislocations, or bone fractures. The robot has
not caused dislocation or bone fracture in any of our ongoing robot studies. The risk of injury is minimized 
by the design of the robot allowing the participant to stop it as
well as oversight by a therapist who can also stop the robot if there is any potential for injury.
Risk of injury from TTT. The is minimal risk of muscle fatigue and/or soreness, and joint pain, from the 
repetitive exercise. In order to minimize this risk the participant
will be supervised throughout the activity and given rest breaks as needed. The participant will be made 
aware that they can stop the task at anytime.
Seizures. Transcranial magnetic stimulation at low frequency (< 1 Hz) has been used for over 20 years in a 
variety of normal subjects and in subjects with neurological
conditions and has generally been found to be safe. In a review of 38 studies involving 850 subjects, there 
were no seizures or other major adverse events (Gilbert et al.
2004 - attached). For non-neurologically impaired subjects and for subjects with stroke, the risk is 
considered minimal. Although TMS is not used in subjects with
implanted metallic devices, it is thought to be safe in patients with hydrocephalus and ventricular shunts. 
Although high-rate, repetitive TMS has the potential to induce
seizures (Wassermann et al. 1996),TMS rates of 0.2 Hz or less are safe in epileptic patients and even 
higher rates may have a protective effect in the case of intractable
seizures (Tergau et al. 1999). ONLY rates < 0.2 Hz will be used in this study.
Some people experience anxiety (claustrophobia) when they get in the MRI. The MRI may pose a risk to 
certain metallic or implanted electronic devices (pacemaker) or identify problems that will require follow 
up. Risk of hearing loss from the scanning. For those participants who have an MRI that reveals a potential 
condition, previously unknown, having the MRI may lead to further medical work up. This is likely 
beneficial, as a condition may be revealed earlier in its course than it otherwise would have been, but may 
cause psychological distress to the participant.
Discomfort. 1000 TMS stimuli are an upper limit that will not be exceeded during any session. Usually, it 
will be far fewer stimuli provided. But in any case, this number
(1000) of stimuli not likely to be stressful or uncomfortable, as they are spread out over time. There is no 
cumulative effect, besides potentially a slight headache. The
participant may always ask for a break, and if this is done in between mapping different locations, causes 
no loss of validity of data collection. Since the investigator is
literally inches away from the participant, participant comfort is monitored closely.
Other TMS risks. There is no known risk to participating in multiple low-frequency TMS studies. There are 
no known adverse effects of TMS in pregnancy, but studies
have been limited to a single case report in which there were no adverse effects of high-rate stimulation. 
There is also the risk of skin irritation at the site of the EMG
electrodes used for TMS data collection and the chance of electrical current (DC) less than what would be 
experience with a nine-volt battery.
Other Risks:
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ID: Pro00003161
View: Risk Detail Entry
Address for each screening procedure, research intervention/interatction, and follow-up/monitoring procedure: 
* Research Activity:
Data Collection -Confidentiality
Common Risks: 
Infrequent Risks:
Breach of confidentiality. To minimize risk all files and information is maintained in a locked file cabinet in 
the study coordinator's office or the Principal Investigator's office in the Keystone Building. All sensitive 
documents are stored at HERL in a secure file room. 
Other Risks:
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