Multimodal Treatment for Hemiplegic Shoulder Pain
Phase: NA
Conditions: Stroke, Shoulder Pain
Sponsor: MetroHealth Medical Center

Clinical Trials Cover Page: Study Protocol and Statistical Analysis Plan 
Document Date: 11/5/2021 
Multimodal Treatment for Hemiplegic Shoulder Pain 
NCT02893267 

Date: Friday, November 05, 2021 2:47:55 PM
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View: 01-00 Study Information
  1.0 Study Information:
  1.1  * Short Title: PNS+PT for HSP
The Short Title Should be the sponsor protocol number. If there is no sponsor protocol, then enter 3-5
words or numbers that capture the important study characteristics and help identify the study. 
 
  1.2
* Full Title of Research Project:
Multimodal Treatment for Hemiplegic Shoulder Pain
  Enter the Full
Title of the
study. 
  1.3  Principal Investigator: Richard Wilson
HSR Certification Status:   Certified   HSR Certification Expiration Date:   8/10/2022 ;
COI Expire Date: 7/3/2022 ; COI Yes or No: No ; COI Management Plan: No ; PI Non-
Compliance:   
 
  The PI must
be a
MetroHealth
Staff person or
have privileges
to practice at
MHS. The PI 
must assume
full
responsibility
for the conduct
of the study.  
   
  
 
  1.4
Key Personnel:
 
Name
CREC
Status
CREC
Expiration COICOI
Expire
Management
Plan?
Study
Roles
Employer
Name
Non-
Compliance
View Shannon
Hogan
Certified2/23/2023 no
6/4/2022 
Research
Support
Staff
Obtaining
Informed
Consent
The
MetroHealth
System
 
View John Chae Certified9/1/2022
yes 7/2/2022yes
Co-
investigator
The
MetroHealth
System
 
View Kristine
Hansen
Certified4/6/2023
no
7/7/2022 
Research
Support
Staff
Interviewer
(Survey,
Focus
Group)
Study
Coordinator
Obtaining
Informed
Consent
DRA (only
one)
Physical
Medicine and
Rehabilitation
 
View Amy
Friedl
Certified3/16/2023 no
7/2/2022 
Research
Support
Staff
Obtaining
Informed
Consent
The
MetroHealth
System
 
View Terri
Hisel
Certified10/18/2022no
6/5/2022 
Research
Support
Staff
Physical
Medicine and
Rehabilitation
 
 
 
 
 
Add
additional Staff
as needed.
Update to add
Study Roles
If using Epic,
add role of
DRA to one
person

 
Name
CREC
Status
CREC
Expiration COICOI
Expire
Management
Plan?
Study
Roles
Employer
Name
Non-
Compliance
View Nathaniel
MakowskiCertified6/16/2022 no
6/2/2022 
Research
Support
Staff
The
MetroHealth
System
 
View Victoria
Whitehair Certified4/11/2022 no
7/2/2022 
Research
Support
Staff
The
MetroHealth
System
 
View Douglas
Gunzler
Certified12/1/2022 no
7/2/2022 
Research
Support
Staff
The
MetroHealth
System
 
 
 
 
  1.5
Type of Research:
Clinical Device Trial
 
  1.6
If "Other" Type of Research Please Explain:
 
View: 01-01 Study Information
 
  1.1    Study Information:
  1.7
* Department-What Department approvals are required?
Name
Physical Medicine and Rehabilitation
 
   
   
 
  1.9 
Definitions to keep in mind when selecting the degree of risk:
Minimal Risk is defined in 45CFR46 and in FDA regulations 21CFR50.3 as: 
Minimal risk means that the probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of themselves than those ordinarily
encountered in daily life or during the performance of routine physical or
psychological examinations or tests.
   
 
 
* Degree of Risk: (This is the investigator's assessment of the risks involved in
the research which will informed the IRB Decision but which will not
automatically be accepted. The Board is the final arbiter of risk. The risk level
will be set by the IRB staff at the time of approval.)
 
Name
Risk
Not Greater Than Minimal Risk
 
 
 
 
 
 
Select most appropriate one.
  1.10
 
 
 
 
 
* Type of IRB Review Requested:
Full Board
 
 
 
Select one. If you select Exempt
or Expedited you will be taken
to that section when you hit
continue.
View: 01-02 Study Information

  1.2 Study Information:
  1.11 
Will you require access to Epic to conduct this study?   
Yes 
No
 
***The DRA's employee number must be listed on their registration form.***  
  If you answer this question yes
you will need to identify a
Designated Records
Administrator one person only.
 
 Please add the role of "DRA" to one study staff member on page 1 of the
application.
 
  1.12  Is the Principal Investigator a resident or trainee?
  
Yes 
No
 
  Please check yes or no. 
   
NOTE: Residents, Fellows, and non-MHS Personnel cannot be listed as the Principal
Investigator
 
 
   
 
 
 
View: 01-03 Study Information
 
  1.3    Study Information:
 
 
  1.13   * Will CRU Be Used:
Yes  If you answer yes to this question this application will be sent to the CRU for
review after departmental review and before it is submitted to the IRB.
  Will the CRU be used?  
  1.14
* Has this research protocol ever been submitted to another CASE
affiliated IRB (i.e. UH, CCF, VA or CASE)?
No
 
  If this study has been reviewed
at another CASE affiliated IRB
you should answer yes.
  1.15 
 
If yes, was it:
 
  Select one from drop down
menu.
  1.16
 
 
 
 
 1.17
Please supply the following information: At which institution was it approved?
If it was disapproved, why was it disapproved?
Please attach the Approval letter/letters from other IRBs (i.e. UH, CCF, VA or
CASE):
Name
Description
There are no items to display
 
 
What institutions have approved
this study. If it has been
disapproved, please give a brief
explanation of why study was
disapproved.
 
Please attach approval
letter/letters.
View: CRU 01-01 Application
  Please Note: If you are using the CRU you must adhere to the following New NIH Public Access Policy: 
Please review the information provied by theis link regarding enforcement of the NIH Public Access Policy  that will begin on
April 1, 2013.  The most recent changes to the NIH Public Policy are explained in the attached Power point presentation from the
NIH (January 15, 2013) and the attached MS-Word document, "Manuscript Submission to PubMed Central for a PMCID".
 
All studies that utilize the MetroHealth CRU resources (space, nursing, lab, bionutrition) that are non-industry funded, are
required be NIH Public Access Policy compliant by obtaining a PMCID number.  The PMCID number is an separate index from
the PMID - the PMCID number indexes the entire publication while the PMID indexes the abstract, only.  In addition to the
PMCID number, investigators are required to post their publications on 'My Bibliography' and link their publications to grant
numbers.
 

Attention to this policy is important because the NIH will halt the process of renewals, re-submissions and certain progress
reports if relevant publications are non-compliant with the PMCID number and My Bibliography.  Continued use and funding of
the CRU may be jeopardized if appropriate publications are not fully compliant. 
 
In addition, please ensure that studies utilizing the CRU also acknowledge the CTSC grant in their publications and cite the
CTSC grant number, UL1TR000439.  This is a NEW NIH CTSC grant number that went into effect on June 1, 2012. The
acknowledgment and grant number can also be found by going to the Cleveland CTSC website acknowledgments page. (This
page also has information about the NIH Public Access Policy.)
 
Thank you in advance for ensuring that all publications from studies utilizing CRU resources (that are not-industry supported) are
compliant with these requirements as soon as possible.
 
1.00 CRU Application [Since you have indicated in your application that you want to utilize the resources of the CRU Please
complete the following pages of the IRB Application. Hit the continue button to move from page to page  in that way you will
be able to take advantage of the built in branching logic to complete your CRU application.]
  1.01 Is this an HIV/AIDS Project:   
Yes 
No
  HIV/AIDS?
  1.02 Are you currently Funded by NIH?    
Yes 
No
 
  If yes please add grant or
contract number.
  1.03 Would you like to conduct your study on the CRU? 
  
Yes 
No
  Yes or No
  1.04 What is your eRA Commons Name?
RDWILSON
  eRA Commons Name required
for all non- industry studies
  1.05 Anticipated Start Date:
9/1/2016
Anticipated End Date:
5/31/2021
  Anticipated Date Study to
Begin (1st Patient)
Anticipated End Date
  1.06
 
Approximate Inpatient Days Per Subject:
0
Approximate Outpatient Visits Per Subject:
18
  Enter approximate numbers
  1.07
 
After August 2010 this is a read only copy of the paper CRU Resource Application:
Name
Version
There are no items to display
  Old CRU Application forms
  1.08
These are your target enrollment numbers for the ethic and racial categories
below:
 
Ethnic Category
 
 
 
 
 
  Sex/Gender
 
 
 
 
 
Ethnic Category
Females 
Males
  Total
 
 
Hispanic or Latino
  4
4
  8
 
 
Not Hispanic or Latino
  44
44
  88
 
 
Ethnic Category Total of All Subjects
  48
48
  96
 
 
 
 
 
 
 
 
Racial Category
 
 
 
 
 
Females
Males
  Total
 
 
American Indian/Alaska Native
0
0
  0
 
  Enter anticipated numbers for
this protocol

 
Asian
6
4
  10
 
 
 
Native Hawaiian or Other Pacific
Islander
0
0
  0
 
 
Black or African American
15
15
  30
 
 
 
White
27
29
  56
 
 
Racial Categories Total of all Subjects
48
48
  96
 
 
View: CRU 01-02 CRU Resource Needs
 
 
 
2.00 CRU: Resource Needs
 
Hospital Lab Tests:   
Yes 
No
 
  Hospital Lab Tests = CRU draws
blood and send it to Hospital Lab
or forwards blood already drawn
to Hospital Lab
 
Human Performance Lab Tests and Measurements:
  
Yes 
No
 
  Human Performance Lab Tests
and Measurements
 
Research Nutrition Services:   
Yes 
No
 
  Research Nutrition Services
 
CRU Laboratory Services:   
Yes 
No
 
  Core Laboratory Services (7:00
am to 5:30 pm, weekdays)
 
Use of CRU Facilities or Equipment Only:   
Yes 
No
 
  Use of CRU Faciities or
Equipment Only
   
 
 
 
 
 
 
 
Nursing Resources:   
Yes 
No  
 
Spanish Translation Services:   
Yes 
No  
 
Spanish Interpertation Services:   
Yes 
No
  Use CRU Nurses
 
Translation is the rendering of a
written text in one language in a
comparable written text in
another language
Interpreting is the oral rendering
of spoken or signed
communication from one
language into another.
 
 
 
 
View: CRU 01-05 Hospital Lab Tests
  1.05 CRU: Hospital Lab Tests

 
Required for research purposes.  Include Standard of Care test to be drawn and sent
to the MHMC central lab here.
 
  5.01 CRU Hospital Lab Tests:
 
EPIC Order Code
Hospital Lab Test Name
Number Of Tests Per Subject
View 81025
Urine hCG
1
View 85610
INR/PT
1
  Please give the details of any
Lab tests needed.
   
 
 
View: CRU 01-08 Use of CRU Facilities or Equipment Only
  8.00 CRU: Use of CRU Facilities or Equipment Only
  8.01 Use Of Equipemnt:   
Yes 
No
 
  8.02 Use Of Equipment List:
 
  8.03 Use Of Space:   
Yes 
No
 
  8.04 Use Of Space Description:
Lab space at Old Brooklyn Health Center routinely will be used.
 
  8.05 Other (Specify):
 
 
 
View: CRU 01-09 Additional Notes or Requests
  1.09 CRU: Additional Notes or Requests
   9.01 If you have any additional notes or requests from the Clinical Research Unit that have
not been covered, please describe them here:
 
 
   
View: 01-04 Study Information
  1.4 Study Information
These Questions are specifically about the adequacy of resources, are there the necessary resources to
complete this study? There are two questions which focus on nursing resources. If this research will require
the use of nursing resources then the Nursing Resources Form found on the IRB Home Page under forms and
templates will need to be completed and attached to this research application.
     
  1.18  Can you assure the IRB that there are adequate numbers of qualified staff to
conduct this research?
  
Yes 
No
  Please answer yes or no. This is
an assurance to the IRB.
  1.19
How will the investigator ensure that persons assisting with the research were
adequately informed about the protocol and their research-related duties and
functions and requirements for maintaining the confidentiality of all data?
Meeting between PI and participating staff will take place to ensure that all are
appropriately informed of their roles and responsibilities. Parties will meet
regularly after the initiation of the protocol to maintain communication and
ensure proper equipping and training of persons assisting with the research.
  i.e. investigator meeting, formal
protocol review with PI,
monitor, sponsor. 
  1.20  Will the PI and study staff have sufficient time to conduct and complete the
research?
  
Yes 
No
  Please answer yes or no. This is
an assurance to the IRB.
  1.21
What facilities are available to conduct the research? Are they adequate? Please
describe.
Visits will take place in our labs in PM&R at OBHC.
Some visits may be completed via phone, email or telehealth
Nursing Resources:
  Please describe the facilities, i.e.
lab, procedure room, chemo
treatment room.

  1.22
Is this study using MetroHealth staff nurse time or labor ? (i.e. giving
medcations, teaching, or additional documentation)  
  
Yes 
No
  This is in addition to the time of
the study/research nurse.  
  1.23
Attach Nursing Resources Form here:
  Click here for Nursing
Resources form 
Open the form, Complete the
form and save it to your files
then attach it to the study by
hitting the browse file and
selecting the file and hitting OK.
Click here for the MHS Policy
 
 
 
 
   
   
 
View: 04-00 Scientific Review
  4.0 Scientific Review:
All Studies need a Science Review. Has your study been reviewed by any of the following?
  4.1  Please Check all that Appy to this study so that the IRB may make a
determination if there needs to be further scientific review: 
 
Review Type
Initiated and sponsored by industry under an IND, IDE, HDE, or 510K
exemption issued by the FDA for which no scientific integrity concerns were
identified during the FDA review process
Trial initiated and sponsored by industry that has undergone a scientific merit
review by the sponsoring agency, but is not being conducted under an IND, IDE,
HDE, or 510K exemption
Sponsored by a Cooperative Group
Proposed research has been awarded funding by a federal agency
Peer reviewed by a federal funding agency and received a favorable funding
score
Peer reviewed by a federal funding agency with the acknowledgment of
scientific merits, but not likely to be funded for reasons unrelated to scientific
merit
Sponsored by a foundation or a private agency that requires a separate scientific
merit review process at the sponsoring agency
No Science Review
  Select all that apply. Note FDA
Approval does not equal science
review.
  4.2
Do any of the following apply to your study? Please check all that apply:
Additional Reasons Why Science Review May Be Required
Investigator-initiated study
  Check all that apply your
answers will assist the IRB in
deciding if further science review
is necessary.
  4.3  Does this study require review by the Biosafety Committee?
No
  All studies involving
vaccines, potentially hazardous
materials or genetic research
must go to the biosafety
committee at CASE.

  4.4
Does this study require review by the Radiation safety committee?  No
  If a study involves more than
routine exposure to radiation on
the part of subjects the study
must go to the radiation safety
committee.
  4.5
Does this study require Review by the Nursing Committee?
No
  The nursing committee must
review all studies where the PI is
a nurse, and all studies which
have as the primary objective to
contribute to nursing
knowledgebase, and/or have
implications for nursing practice.
View: 05-00 Funding Information I
  5.0   Funding Information I:
All Research Projects must have an identified funding source! 
  5.1  Is this research externally funded? Yes  
Research can be both externally and internally funded so you can answer yes to both
5.1 and 5.6. 
  Check one
  5.2
Types Of External Funding:
Name
Government / Federal
  Check all that apply.
  5.3  If other, external funding please explain:
  If other please describe.
  5.4
Sponsor Information:
Name Sponsor/Agency
Address
Telephone FAXContact
Person
NIH: National Institute of
Child Health and Human
Development
6710B Rockledge Drive
Room 2161C, MSC 7002,
Bethesda, MD 20817
301-435-
6838
 
Susan
Marden
  Please supply this information
as your application can not be
processed without it.
  5.5
Have you received and/or submitted a Notice of Award or Contract?
Yes
 
If yes, attach your Notice of Award letter here (not your grant):
Name
Version
PNS+PT NOA
0.01
Summary Statement 1R01HD084564-01A1 2016_04_14 (Scientific Review)
0.01
  Select one from drop down
menu.
Attach notice of award.
View: 05-01 Funding Information II
  5.1  Funding Information II
  5.6 
Is Research Internally Funded (internal funding is any
MetroHealth System or MetroHealth Foundation funds):
 
  
Yes 
No
 
 
Check one, research can be both externally and internally
funded so you can answer yes to both 5.1 and 5.6.
  5.7
Internal Funding Sources List:
Internal Funding Source
There are no items to display
  Check all the apply.
  5.8 
If a MetroHealth Foundation funds or any MetroHealth
System funds are being used, has department approval been
  Check yes or no.

received?
  
Yes 
No  
  5.9
If a MetroHealth Foundation funds or any MetroHealth
System funds are being used indicate the Account Number:
  Please enter the account number if this applies.
  5.10
* Are there current Conflict of Interest Forms for all Key
Personnel? [It is the responsibility of the Principal
Investigator to ascertain this information and check this box.]
  
Yes 
No
This question is not asking if there are COI forms for all Key Personnel it is
asking if all Key Personnel have current COI forms so that any SFI is reported
and can be dealt with if a management plan is need or reporting to NIH is
required.
 
In order to submit a new protocol all COI Forms for key
personnel and investigators must be current = provide up to
date information.
  5.11 
Please check below any Conflicts of Interest (Financial) you as
Principal Investigator or your study staff [Co-Investigator,
Coordinators, Other Study Staff] may have on this Study:
Potential Conflict of Interest
You or your co-investigators have a significant financial interest
in the sponsor of this research, the manufacturer of the drug or
device being tested, or in the drug or device itself, including any
share of potential future profits or royalties.
 
This question pertains to this study and is not a general
question. Check all that apply.
You and/or your study staff will need to file a Conflict of
Interest Disclosure Form annually.
If anyone working on this study has a Conflict of Interest or a
perceived conflict. This information will need to be included in
the consent form i.e. company is paying MHS to do this study. 
  5.12  Please attach a copy of your grant application here:
Name
Description
PNS and PT for HSP Grant
 
 
You must attach a copy of your grant application here (i.e.
NIH Grant Application).
You have the option to attach a copy of the budget, clinical
trial account authorization form, contract and Approval
letter(s) now or you can email them to your grants
management specialist in the RABO office.
Copies of all RABO forms are available at:
http://www.metrohealthresearch.org/raboforms.html
 
 
View: 06-00 Performance Site Information
  6.0 Performance Site Information:
  6.1  At what sites will the study team be performing this research, (please enter 
information about all non-MHS sites in 5.2):
Name
The MetroHealth System
FES Center
If this study is being done at MetroHealth where is it being done give the
physical location (i.e. 8B, ED, Broadway, Old Brooklyn, PICU, Cath Lab):
Visits will take place in our labs in PM&R at OBHC.
If immediate hazard to subject to come to the labs in PMR at OBHC the visit will be
completed via telephone, email or telehealth.
 
  Select all that apply. If  you select
other please enter information
about that site in question 6.2.
 
 
 
 
 
 
Where is the research going to be
done? What physical location on
the Main campus or the
community health centers?

  6.2
Please provide information about other external sites here:
Name of Site
Address
Telephone Number
There are no items to display
 
  Please enter contact
information. Please include name
of facility, address and
department.
  6.3  If you are doing this research at an external site does this site have an IRB?
  
Yes 
No
  Select yes or no. 
  6.4
If the External Site has an IRB will that IRB defer review to the MHS IRB?
  
Yes 
No
 
  This  only applies if there is no
IRB or if there  is  a legal 
agreement between
institutions permitting a
reciprocal review, i.e. CASE.
  6.5
Attach letter from external site agreeing to permit the MHS to review this
protocol:
Name
Description
There are no items to display
  
  Attach letter.
  6.6
Has the external site granted permission for the research to be conducted?
  
Yes 
No
 
  This applies to sites where there 
is no IRB and
the investigator must get  a  letter 
from the site that gives
permission to conduct the
research  at the site.
  6.7
Attach letter from external site granting permission for the research to be
conducted:
Name
Description
There are no items to display
 
  Attach letter of support. 
 
View: 06-01 Performance Site Information
  6.1 Performance Site Information
  6.8 
 Is MHS the lead institution of a multi-site study?   
Yes 
No
 
  Please answer yes or no. 
  6.9
If yes, is there a plan to communicate information obtained through research
that might be relevant to the protection of human subjects, including a plan to
provide the IRB with information on unanticipated events, interim results, and
protocol modifications.
  
Yes 
No
 
  Please answer yes or no.
  6.10  Please give a detailed explanation of the above plan:
The Shirley Ryan Ability Lab(SRAL) formally Rehabilitation Institute of Chicago
(RIC) will serve as a second performance site.
The Investigators and respective project staff will meet or confer at least semi-
annually to review all adverse events and study data collected since the previous
meeting. All adverse events will be reviewed to determine a course of action. Events
are categorized according to severe/not severe, expected/unexpected, and
related/unrelated.
IRBs at each participating institution will be informed of progress, AEs, unanticipated
events and protocol modifications per their policies.
Carolinas Rehabilitation will serve as a third performance site.
  This plan must give the IRB
enough information to decide if
the plan is appropriate and
adequate. 

The Investigators and respective project staff will meet or confer at least semi-
annually to review all adverse events and study data collected since the previous
meeting. All adverse events will be reviewed to determine a course of action. Events
are categorized according to severe/not severe, expected/unexpected, and
related/unrelated.
IRBs at each participating institution will be informed of progress, AEs, unanticipated
events and protocol modifications per their policies.
 
  6.11
Will the Principal Investigator conduct this study at any location outside the
United States of America?
  
Yes 
No
 
  Answer these questions only if
there are research sites outside
the USA.
  6.12
Country, City, and address:
Country
Address of Research Facility
There are no items to display
 
  Give country and location.
 
 
View: 07-00 Research Objectives and Background
  7.0 Research Objectives and Background:
  7.1  * ABSTRACT: Please give the IRB a 500 word Abstract that contains
the specific objectives of the study.
Hemiplegic shoulder pain (HSP) affects up to 60% of moderate to severely
impaired stroke survivors. [12] HSP is associated with poor rehabilitation
outcomes, including interference with activities of daily living (ADLs) [13] and
poor quality of life (QoL). [14] While many treatments for HSP have been
proposed, most do not result in long-term relief of pain.
Our team developed the use of intramuscular peripheral nerve stimulation (PNS)
for the treatment of HSP, which involves the temporary placement of a
percutaneous intramuscular electrode to stimulate the axillary nerve motor points to
the deltoid muscle. [8, 15-22] The deltoid muscle is stimulated for 6 hours per day
for 3 weeks, causing comfortable, non-fatiguing contractions. This treatment, which
occurs in the community setting, results in pain relief for up to 12 months when
compared to treatment with a hemisling. [21] A systematic review of randomized
controlled trials (RCT) concluded that intramuscular PNS was the only treatment to
provide long-term relief of pain for those with HSP. [23] However, physical therapy
(PT), which focuses on correcting biomechanics, is the most commonly prescribed
treatment for HSP [24] and is recommended by multiple practice guidelines. [5-7]
Prior to acceptance by the clinical community, the superiority of PNS to a course of
PT must be demonstrated. We completed a pilot RCT comparing PNS to PT and
67% vs. 25% of participants experienced successful pain relief (i.e., ≥ 2-pt or 30%
reduction [25]) from PNS and PT, respectively. [8] Thus, the primary objective of
this 3 site RCT is to confirm the findings of this preliminary pilot RCT.
Consistent with prior studies, only 2/3 of PNS participants in our preliminary RCT
experienced clinically important pain relief. And among these, only a third
experienced complete pain relief. Unfortunately, for those with HSP, the altered
shoulder biomechanics associated with hemiparesis provides a risk for reinjury
even if pain is improved at the end of treatment; this may require co-treatment with
PT. There is an opportunity to refine the PNS treatment regimen and thereby
increase the magnitude of the response and the number of responders. Consistent
with clinical practice, participants in the PT group in our preliminary RCT
  This is your abstract also known as
a synopsis from an industry
sponsored study.  Please
limit to 500 words.

experienced an average pain reduction of 33% by the end of treatment. Combining
PNS and PT, which may be how PNS is actually implemented in clinical practice,
may have a synergistic therapeutic effect. Thus, the second objective of this
multisite RCT is to determine if multimodal treatment of HSP with PNS + PT is
more efficacious for pain relief than PNS alone or PT alone.
The mechanisms behind PNS and PT for the treatment of HSP are not known. The
onset of HSP is associated with the severity of hemiparesis and the resultant
biomechanical impairment of the shoulder. [12, 26-28] Our team and others have
found that in the chronic stage central mechanisms may also have a role in
perpetuating pain, [10, 29-32] as it does in other forms of chronic shoulder pain. [9]
Thus, our third objective is to explore mechanisms of PNS and PT for the treatment
of HSP. PNS and PT may reduce chronic HSP via central mechanisms, or by
improving shoulder biomechanics, or both. These mechanisms will be explored via
measures of sensory and pain perception (mechanical pain thresholds, secondary
hyperalgesia, and temporal summation) and clinical measures of impairment
(shoulder abduction torque, shoulder kinematics, Fugl-Meyer score.)
This pilot-phase II device trial will advance the knowledge about chronic HSP
treatment by testing single and multimodal treatments to produce greater pain
reduction and increase the number of responders. Information regarding mechanism
of action that may lead to future treatment improvements will also be generated.
The collaborators involved in this project are leaders in utilizing PNS to reduce
pain and disability after stroke and are well positioned to carry out this trial.
  7.2
* What are the specific aims of this study i.e. what are the question(s) this
research intends to answer? Provide at a maximum 3 primary and 3 secondary
aims.
AIM 1. Compare the efficacy of PNS vs. PT in reducing HSP.
Hypothesis 1. The reduction in HSP and associated improvements in upper
limb related ADLs and QoL will be greater with PNS alone versus PT alone.
AIM 2. Compare the efficacy of PNS + PT, PNS + ShamPT, and PT +
ShamPNS in reducing HSP.
Hypothesis 2. The reduction in HSP and associated improvements in upper
limb ADLs, and QoL will be the greatest with PNS + PT, followed by PNS +
Sham PT, and finally PT + Sham PNS.
AIM 3. Explore the roles of central and biomechanical mechanisms in pain
reduction by PNS and PT.
Hypothesis 3. Improvement in measures of central sensitization (mechanical
pain thresholds, secondary hyperalgesia, and temporal summation) will be
greatest in those who receive PNS whereas improvements in biomechanics
(shoulder abduction torque, shoulder kinematics, and Fugl-Meyer score) will
be greatest in those who receive PT; and the PNS+PT group will have
improvements in both.
   This is your Hypothesis also know
as your aims (NIH) or safety and
efficacy aims (industry). Please list
no more than 3 primary and 3
secondary clearly label these aims
primary and secondary.
  7.3
Please provide a summary of the present knowledge relevant to the research
and make citation to any applicable scientific literature:
See attached.
  This is your literature search and
bibliography. Also known as
Background and significance
(NIH) or Introductory Section from
industry sponsored trial.  
  7.4
Option to Upload Documents related to question 7.3:
Name
Description
Background | History
 
References | History
 
  If it is easier to attach your
response to question 7.3 please do
so here. Please limit to three pages.
View: 08-00 Methods and Procedures I
  8.0 Methods and Procedures I:
  8.1  Will this research involve the following Social-Behavioral Procedures:
  Check all that apply.

Name
Psychological Testing
Surveys/Questionnaires
  8.2
Will this research involved any of the following Medical
Procedures/Considerations:
Name
Collection of Biohazardous Substances
Study of Human Biological Materials (i.e. Urine Collection)
Investigation/Approved Devices
Study of Existing Data
Medical Tests, Comparisons, Evaluations
Clinical Assessments (EEG, EKG, SCID, etc.)
Venipuncture (Blood Draw)
Use of investigational devices
Psychological testing
  Check all that apply.
  8.3  Identify Data Collection types for this study:
Name
Audio-Recording/Video-Recording/Photographs
Chart Review - Prospective
Existing/Retrospective Data/Specimens
Interviews, questionnaires or psychological tests
  Check all that apply.
Note if you are doing,
recordings, Video-
Recording/Photographs then
subjects will need to sign the
MetroHealth Audio-Video
Consent form. See the IRB
Forms and Templates.
View: 08-01 Methods and Procedures II
  8.1 Methods and Procedures II:
  8.4  * Please specify in detail the methods and procedures that are involved in this
research:
Study Summary: This is a multi-site, placebo controlled, double-blinded RCT to
confirm the superiority of PNS over PT in reducing HSP, and to determine if
multimodal treatment of HSP with PNS + PT is more efficacious than PNS or PT
alone. The standard of care for treating shoulder pain is to try several options, most
commonly including medications, injections and therapy. Candidates considering this
study likely have tried some treatments but without lasting success. Ninety-six
participants will be randomized to receive PNS + PT, PNS + sham-PT, or sham-PNS
+ PT. The PNS + PT group will receive active PNS therapy for 6 hours per day for 3
weeks along with 8 sessions of PT to improve biomechanics of the affected shoulder.
The PNS+ sham-PT group will receive active PNS therapy and sham-PT, consisting
of placebo ultrasound, application of inert gel, lower limb strengthening, and walking
exercises. The sham-PNS + PT group will receive a percutaneous lead in a similar
manner as the active therapy groups, but with sham-stimulation, along with 8 sessions
of PT. Measures of pain, pain interference with ADLs, QoL, shoulder biomechanics
(shoulder abduction torque, shoulder kinematics, and Fugl-Meyer score), and
measures of central sensitization (pain thresholds, secondary hyperalgesia, and
temporal summation) will be assessed at baseline and at weeks 4 (end of treatment),
8, 12, 16, 20, 24, and 28.
Baseline Variables and Randomization: Baseline data will be collected so that the
balance of covariates across the three groups can be evaluated. Each participant will
be characterized with respect to demographics, comorbidities, and medication use.
Study outcome measures (see Outcomes Assessment) will be administered to
establish baseline levels. Participants are assigned to treatment groups using an
adaptive randomization algorithm [90-92] to minimize group imbalances on key
patient characteristics: baseline pain (>6 or <=6) [93], duration of pain (>=18 months
or <18 months) [15], age (>=55 years or <55 years) and study site. For each
assignment, the algorithm calculates the balance of these variables across the groups
and makes an assignment that would result in greater balance in the variables across
groups.
  If this field is not completed your
protocol will not be reviewed.
Do not enter N/A. Please
describe what methods and
procedures will be involved in
this research.

Percutaneous PNS System: The Sprint PNS System (SPR Therapeutics, Cleveland,
OH), also known as the Smartpatch System, will be used to deliver the PNS therapy.
The System consists of a small external stimulator, percutaneous lead, and pad. The
external stimulator “snaps” on to the pad. The pad has an embedded power source for
the System but also serves as the anode. The pad is replaced regularly. The single-
channel stimulator outputs a biphasic current waveform with current pulse parameter
ranges that are suitable for PNS. These electrodes have been used extensively to
deliver percutaneous PNS to shoulder muscles. [16-22, 85, 86]
Lead Placement Procedure:
Active PNS Groups: The procedure will be performed under a sterile condition. The
location and depth of the electrode implant site are determined by monopolar needle
stimulation with demonstration of strong contraction of both the middle and posterior
deltoid muscles. [16, 19, 71, 86] The introducer loaded with the lead is inserted
perpendicular to the skin surface and advanced to the depth (3-4 cm) defined by the
monopolar test stimulation. The introducer is then withdrawn with the electrode
retained in the muscle by a barb at its tip. The subject will be provided the option of
subcutaneous lidocaine infiltration prior to placement of the electrode lead.
Sham-PNS Group: In order to facilitate blinding, sham-PNS participants also will
receive a percutaneous electrode. The sham-PNS group will not require localization
with monopolar needle electrodes.
PNS Treatment Protocol:
Active PNS Groups: After one week for lead stabilization [95], the Sprint PNS
System will be programmed for stimulation. Based on over 30-yrs of experience, the
Cleveland FES Center established parameters for safe and effective delivery of PNS
(pulse frequency = 12 Hz; pulse amplitude = 20 mA; pulse duration = 5-200 usec (set
by clinician); duty cycle = 5-sec ramp-up, 10-sec plateau, 5-sec ramp down, 10 sec
off; daily dose = 6 hrs/day). [96] These parameters provide strong fused comfortable
muscle contraction with minimal fatigue. [16-22, 59, 85, 86, 94, 97, 98] Stimulation
frequency and amplitude are fixed. The pulse duration is set to produce strong,
comfortable contraction of both the middle and posterior deltoids. A balanced
biphasic waveform allows an equal amount of current to flow in either phase, creating
a safe net zero charge. [99] Participants receive 6-hrs of stimulation per day in their
home. The stimulator keeps an electronic log for compliance monitoring. There are
no formal dose response studies to provide guidance on the optimal dose of PNS;
however, the selected duty cycle and daily dose of 6-hrs were used in our prior
studies [8, 16-21, 86] and by others with robust results. [85]
Sham-PNS Group: Control participants will not receive active stimulation. The
stimulator will be placed in non-stimulation mode by a study team member. In this
condition, the stimulator appears to function normally, and the battery will drain,
though no stimulation will be delivered.
All participants are queried at their final visit to determine the success of blinding.
The implanted electrode poses minimal risk to control participants. The probability of
serious adverse event (e.g. infection) due to electrode fragments in this study is 0.1%
per electrode. The implantation of electrodes is no more painful than subcutaneous
infiltration of lidocaine.
Electrode and Electrode Site Surveillance and Electrode Removal: All caregivers and
participants will be trained in the assessment of electrode site and the daily placement
of the Sprint Pad. The caregiver conducts daily inspections to detect complications.
The nurse coordinator inspects the site for infection and performs motor/sensory
threshold testing for lead migration and lead integrity, respectively, at the following
times: within 48-72 hrs of lead placement, at the beginning of PNS treatment, and at
the end of treatment. Inspection and testing of motor/sensory thresholds and
impedance may also occur anytime during the 3-wk PNS treatment period as deemed
necessary. At the end of treatment, the electrode is removed by gently pulling on the
external portion. All participants undergo radiographic surveillance for retained

electrode fragments.
Physical Therapy:
Active PT Groups: The Active PT Groups will receive Shoulder Therapy Treatment.
Participants will receive eight 60-minute sessions of outpatient therapy over a 4 week
period concurrent with PNS or sham-PNS treatment. Proper Positioning and
Handling: Little evidence supports specific positioning or handling of the hemiparetic
upper limb to prevent the development or worsening of HSP [5]; however, there is
consensus that proper positioning and handling are necessary elements of best
practice. [6, 7, 47] Therapists will practice proper positioning and handling of the
hemiplegic upper limb and provide training to participants and their caretakers. [100,
101] Based on guidelines and clinical judgement, humeral cuff slings may be issued
to reduce the risk of trauma to the hemiparetic upper limb. [6] Chair-bound
participants may be provided arm troughs or lap trays as needed. [102] Ambulatory
participants may be issued a humeral cuff sling. [103] Therapeutic Positioning and
Strengthening Exercises: Therapeutic positioning exercises will be provided by
trained therapists, with primary focus on humeral external rotation. [1] Therapists will
ensure that the shoulder is moved with appropriate rotation of the scapula and
humerus to avoid impingement or damage to the rotator cuff during all ROM. [1,
104] Prior to abduction, the scapula will be rotated upward and the shoulder will be
externally rotated to avoid impingement beneath the acromion. [47] Similarly, the
subluxed shoulder will be manually reduced prior to any movement to avoid traction
damage. [105] Overhead pulleys will not be used. [104] Mirror Therapy: For those
with severe hemiplegia, a standardized protocol requiring arm, hand, and fingers will
be utilized. [106] Subjects will sit at a table with their affected arm placed in a
triangle mirror box so that the mirror image of the unaffected arm appears to be the
affected one. Subjects will be asked to move their affected limb as well as possible
while watching the reflected image of their unaffected limb. [107] Task-Specific
Therapy: High repetitive task-specific therapy will be provided for participants with
residual hand function. [1] Sessions will include functional training in basic and
instrumental ADLs and active repetitive movement training of the paretic upper limb.
The incorporation of the impaired upper limb to carry out specific functional tasks
will be emphasized, and traditional compensatory strategies such as singlehanded
techniques will be avoided. Home Exercise Program: Except on days they are in
outpatient therapy, participants will participate in a daily home exercise program
throughout the length of the study. For those without residual motor ability, the home
exercise program will exclude ROM exercises for the hemiparetic shoulder due to
risk for injury when not conducted with a trained therapist. [5, 6, 47, 108] Exercise
will be provided for ROM exercises for the hand, wrist, and elbow. For those with
residual shoulder motor ability, active ROM exercises within the limits of pain-free
range will be prescribed. Use of these hemiparetic upper limb for functional tasks as
much as safely possible will be encouraged for those able. All participants will be
provided instructions guiding through a Mental Practice program. [109] Subjects will
receive an audio-recorded intervention that begins asking patients to imagine
themselves in a warm, relaxing place, and asking them to contract and relax their
muscles. This portion is followed by mental practice of internal, cognitive
polysensory images related to using the affected arm in one of four functional tasks.
The final minutes will allow patients to refocus into the room. Subjects will complete
this twice per week. Participants will be asked to self-report compliance with home
program at each visit.
Sham PT Group: The Sham PT Group will receive Stroke Therapy Treatment.
Participants randomized to sham-PT will receive eight 60-minute sessions with
therapists with the goal of controlling for the effect of regular contact with a therapist
and study staff in a therapeutic environment. Therapists will provide sham ultrasound
therapy and light application of inert gel to the shoulder for 10 minutes. Pre-Gait
Training or Gait Training: Pre-Gait training focuses on trunk and balance control and
mastery of specific gait components to walk safely and efficiently. The amount of
Pre-Gait Training required before proceeding to Gait Training depends on the
individual and will be determined by the therapist. Exercise therapy could include
weight shifting exercises, balance training, walking exercises, weight shifts,
strengthening exercises, and listening session regarding stroke education, relaxation

and coping. While it is possible that the sham-PT might alter lower limb impairment,
it will not affect outcomes related to shoulder function. Aspects of this sham-PT have
been used in prior RCTs of shoulder interventions with moderate to high degree of
blinding. [110, 111] Participants will be asked to self-report compliance with home
program at each visit.
Outcomes Assessment: The primary outcome measure is the worst pain in the prior 7-
days (BPI SF-3). Secondary measures include pain interference with ADLs (BPI SF-
9); QoL (SF-36); shoulder impairment (isometric voluntary abduction shoulder torque
(IVAST), shoulder kinematic analysis, optional Fugl-Meyer Motor Assessment (upper
limb)); and measures of central sensitization (mechanical pain thresholds for
hyperalgesia, optional pinprick pain thresholds for hyperalgesia, temporal summation
of repetitive pin-prick stimuli). Details for each measure are presented below. The
outcomes are administered face-to-face in a blinded manner.
Brief Pain Inventory SF-3 (Aims 1 and 2): The BPI has excellent psychometrics [112-
118] and is recommended by the IMMPACT group for the assessment of pain in
clinical trials. [89] The developers of the BPI recommend BPI SF-3, the “pain worst”
rating, as the primary response metric. The question asks participants to rate their
worst pain in the prior 7-d on a 0 to 10 NRS, where “0” indicates “No pain” and “10”
indicates “Pain as bad as you can imagine.” In order to gain a more comprehensive
assessment of participants’ pain experience, daily least pain (BPI SF-4), daily average
pain (BPI SF-5) and daily present pain (BPI SF-6) after morning ADLs are also
collected. To analyze successful treatment, responders will be defined as those who
have a clinically meaningful 30% reduction of pain [25] at end of treatment and at the
conclusion of the trial. The investigative team has extensive experience with the BPI.
[8, 13, 15, 18, 20, 21, 71, 85, 119, 120]
Pain interference with ADLs – BPI SF-9 (Aim 2): BPI SF-9 specifically evaluates the
impact of pain on ADL performance within 7 domains of daily activity over a 7-day
period: general activity, mood, walking ability, normal work, relations with other
people, sleep and enjoyment of life on a 0-10 NRS, where 0 indicates “does not
interfere” and 10 indicates “completely interferes.” [121] The BPI SF-9 score is the
average of the scores for the 7 domains. Psychometrics have been evaluated as part of
the BPI battery. [112-115] BPI SF-9 has been used to evaluate the impact of
percutaneous PNS mediated pain reduction on ADLs. [8, 16, 18, 21, 71, 86]
QoL – SF 36 (Aims 1 and 2): SF-36 is a health related QoL measure that assesses
physical functioning, role limitation because of physical health problems, bodily pain,
social functioning, general mental health, role limitations because of emotional
problems, vitality (energy/fatigue), and general health perception. [122] It is the only
reliable and valid measure previously used to assess change in QoL associated with
the treatment of shoulder pain with PNS. [8, 16, 19, 85]
Isometric Voluntary Abduction Shoulder Torque (IVAST, Aim 3): IVAST is an
objective predictor of strength which is an important factor in ability to complete
functional tasks in older adults. [123] IVAST will be measured in an established
protocol [82] with a Biodex Biomechanical Measurement System (Biodex Medical
Systems, Shirley, NY). Participants will be seated and fastened securely with the
abduction axis of the shoulder aligned with the rotational axis of the dynamometer.
The arm will be attached to the dynamometer by a strap just above the elbow. The
arm will be held at 30 degrees of shoulder abduction and neutral rotation. Participants
will be asked to abduct their arm in response to an audio tone. The duration of the
audio tone randomly varies between 3 and 5 seconds to prevent the anticipation of the
start or end of the cue. The average torque during the last second of the audio tone
will be calculated and those values will be averaged over three trials, with 1-minute
rest between trials. Abduction torque measurement via Biodex shows high intra – and
interrater reliability. [124]
Shoulder Kinematic Analysis (Aim 3): An objective measure of glenohumeral and
scapular range of motion will be obtained using an optical tracking system (Optotrack
Certus, NDI Measurement Science, Ontario, Canada) during the performance of

passive and active pain-free shoulder abduction rotation while seated. Active LED
markers will be mounted on the sternum, scapula, upper arm, and forearm.
Digitization of bony landmarks on the thorax, scapula, and humerus permit
transformation of sensor data into local segment coordinates according to standard
protocol. Custom software will be used to extract angular data from the sensors and
calculations will be made following the recommendations of the International Society
of Biomechanics, Shoulder Group. [125] The extracted angular data includes: 1) peak
humeral elevation and 2) Peak scapular tilt. Analysis in post-stroke shoulders is a
reliable and valid measure of impairment. [126, 127]
Fugl-Meyer Motor Assessment, upper limb (Aim 3) (optional): If PNS reduces HSP
by reducing motor impairment, then Fugl-Meyer Motor Assessment (FMA) scores
should improve. The FMA was derived from the Brunnstrom Stages [128] of post-
stroke motor recovery. Each test element will be graded on a 3-point ordinal scale and
summed to provide a maximum upper limb score of 66. Reliability and validity have
been demonstrated. [129-131] The FMA will be administered while the subject was
seated.
Mechanical Pain Thresholds for Hyperalgesia (Aim 3): The Pressure Pain Thresholds
(PPTs) will be measured with a hand-held Wagner Instruments FPIX Digital
dynamometer (Wagner Instruments, Greenwich, CT) with 1 sq-cm rubber tip. The
PPT is defined as the amount of force (applied at a rate of 1 kg per second) required
to produce a sensation of pain distinct from pressure or discomfort. The 3 sites are the
mid-belly of the deltoid muscle of the affected and non-affected limb and the mid-
belly of the tibialis anterior of the contralateral limb. Three readings will be averaged
at each site. The reliability and validity of the pressure algometry to evaluate deep
somatic tissue sensitivity have been demonstrated [132-134], and the method has
been used to evaluate central sensitization in numerous pain conditions [135-145],
including chronic shoulder pain. [9, 10]
Pinprick pain thresholds for Hyperalgesia (Aim 3) (optional): Pinprick thresholds will
be measured at the same sites using weighted pinprick stimuli that exert forces of 8,
16, 32, 64, 128, 256, and 512 mN (PinPrick Stimulators, MRC Systems GmbH,
Heidelberg). [146, 147] The stimulators will be applied at a rate of 2 s on, 2 s off in
an ascending order until the first percept of sharpness is reached. The final threshold
will be the geometric mean of five series of ascending and descending stimuli.
Pinprick pain threshold has been used to evaluate central sensitization in numerous
conditions [148-151], including chronic shoulder pain. [9, 10]
The perceived magnitude of a single pinprick stimulus will be compared with that of
a train of 10 pinprick stimuli of the same force (256mN OR 512mN) repeated at 1/s
rate at the same sites. The use of the larger stimuli will be made if, when presented at
the first test site, the perceived pain rating is “0” for the lesser of the two. Thus, a
greater differentiation of response may be possible, but will not present a significant
discomfort to the subject. In all tests, the subject can stop the testing procedures.
Single pinprick stimuli will be alternated with a train of 10 stimuli until both are done
at three different sites: affected shoulder, unaffected shoulder, and unaffected tibialis
anterior (lower leg). The mean pain rating of trains divided by the mean pain rating to
single stimuli will be calculated as wind-up ratio (WUR). [116] [147]
Other: Five other surveys also are collected once each for either eligibility
determination or potential correlative data analysis. These are the Mini Mental State
Exam (MMSE), the Beck Depression Inventory (BDI), the Pain Catastrophizing
Scale (PCS), the Fear Avoidance Beliefs Questionnaire (FABQ) and a Patient Global
Impression of Change (PGIC) Assessment.
Concomitant Therapies: Participants may receive additional PT or OT during the
treatment period or during follow-up as long as the therapy is not directed at shoulder
pain. Subjects may not receive any injections, or any other forms of electrical
stimulation, including TENS or surface PNS, to the affected shoulder. Due to ethical
considerations, use of non-opioid and opioid analgesics for pain management will be
allowed. Participants may adjust dosing of these medications, but it is preferred that
they not change or add medications during the protocol. Participants will maintain

their dosage during the week prior to each visit to match the recall period for
assessment of BPI SF-3 and 9. Medication use is monitored via diary.
  8.5
Does this study only involve the use of existing/retrospective data/specimens?
No
  Check yes or no.
  8.6  Describe in detail the study design also known as the experimental flow.
Include all study procedures a subject will go through, in order of sequence and
timing, including frequency of visits, duration of visits, length of subject
participation etc. Please Note this needs to be written for an educated person who
is not an expert in the field, do not exceed 300 words:
The duration of each subject's participation will be ~7 months.
Visit 1 – Consent/Eligibility: Consent form signed; assessed for eligibility per
inclusion/exclusion criteria; MMSE administered; BDI, PCS & FABQ administered;
medical history, demographics, comorbidities, and medication use recorded; blood
drawn for INR (in applicable subjects); pregnancy test (in applicable subjects). (~3.5
hrs)
Visit 2 – Baseline Outcomes Assessment: Study outcome measures (see Outcomes
Assessment) administered to establish baseline levels. (~3 hrs)
Visit 3 - Sprint MicroLead (Electrode) Implant Procedure: Testing of muscle response
with Sprint Test Needles; Implantation of percutaneous Sprint MicroLead. Subject
given instructions on care of Lead exit site. Skin checked, subject queried for
medication usage. Randomization to treatment group. Subset of study outcome
measures (questionnaires only) administered. (~2 hrs)
Visit 4 - PT #1 (1.25 hr)
Visit 5 - PT #2 (1.25 hr)
Note: A 48-72 hour Post-Implant Safety Check (Check the Lead exit site within 48-72
hours of the Implant procedure) can occur during Visit 4 and/or Visit 5. (Add 15 min)
Visit 6 - PT #3 & Start of Stimulation: Collection of parameter data; programming of
external stimulator (Sprint Stimulator). Subject given instructions on use of System
and care of Lead exit site. Skin checked, subject queried for medication usage and
adverse events. Subset of study outcome measures (BPI-SF only) administered. (~2
hrs)
Visit 7 - PT #4 (1 hr)
Visit 8 - PT #5: Subject also queried for medication usage and adverse events. (1.5 hr)
Visit 9 - PT #6 (1 hr)
Visit 10 - PT #7: Subject also queried for medication usage and adverse events. (1.5
hr)
Visit 11 - PT #8 (1 hr)
Visit 12 - EOT Outcomes Assessment & Explant Procedure: Study outcome measures
administered (4 weeks post-Implant). PGIC administered. Skin checked, subject
queried for medication usage and adverse events. Lead Removed. X-rays performed
(may be done as separate clinical visit). (~4 hrs) (Note: This visit optionally could be
split into two visits (12A, 12B) based on scheduling and subject tolerance
considerations.)
Phone Call - 1 week Post-Explant Safety Check: Subject queried on condition of
Lead exit site. (15 min)
Visit 13 - 8-wk Outcomes Assessment: Subset of study outcome measures
  This is also known as NIH
Experimental Procedure
section or Clinical Trial
Procedure/Experimental Flow
section. Do not just attach
documents in response to this
question you must do a study
design summary for IRB
Review.

(questionnaires only) administered (8 weeks post-Implant (4 weeks post-EOT)).
Subject queried for medication usage. (~1 hr)
Visit 14 - 12-wk Outcomes Assessment: Subset of study outcome measures
(questionnaires only) administered (12 weeks post-Implant (8 weeks post-EOT)).
Subject queried for medication usage. (~1 hr)
Visit 15 - 16-wk Outcomes Assessment: Study outcome measures administered (16
weeks post-Implant (12 weeks post-EOT)). Subject queried for medication usage. (~3
hrs)
Visit 16 - 20-wk Outcomes Assessment: Subset of study outcome measures
(questionnaires only) administered (20 weeks post-Implant (16 weeks post-EOT)).
Subject queried for medication usage. (~1 hr)
Visit 17 - 24-wk Outcomes Assessment: Subset of study outcome measures
(questionnaires only) administered (24 weeks post-Implant (20 weeks post-EOT)).
Subject queried for medication usage. (~1 hr)
Visit 18 - 28-wk Outcomes Assessment: Study outcome measures administered (28
weeks post-Implant (24 weeks post-EOT)). Subject queried for medication usage. (~3
hrs)
Provision for lead replacement: If, in the judgement of the Investigator, the Sprint
MicroLead becomes significantly displaced or fully dislodged, it is possible that the
Investigator may elect to place another lead which would require an unscheduled visit
and additional 48-72 hour safety check. Other visits may be repeated as appropriate.
*Any visit may be completed via telephone, telehealth or email as determined by the
principle investigator in case of immediate hazard to the subject
*Visits 13,14,16,17: These visits include questionnaires only and can be completed
via telephone, telehealth or email at the discretion of the Research coordinator or PI
  8.7
 
Please attach study design/subject visit schedule here:
Name
Description
PNS+PT Visit Schedule Table (06-14-2017) | History
 
  If you have an
electronic schedule of study
visits and/or procedures please
attach here.
View: 09-00 Inclusion/Exclusion Criteria
  9.0 Inclusion/Exclusion Criteria:
  9.1  What are the inclusion criteria? Put this information in bullet form:
• shoulder pain localized to the glenohumeral joint, subacromial area or deltoid
insertion associated with: a) rest; b) passive abduction or external rotation range of
motion (ROM); c) active abduction ROM; or, d) manual palpation;
• shoulder pain onset or worsening after the most recent stroke;
• weakness of shoulder abductors (≤4/5 on MRC if isolated movement is present);
• ≥ 21-yrs old; < 90-yrs old;
• time of stroke ≥ 3-mo;
• duration of HSP ≥3-mo;
• HSP with moderate to severe pain (BPI SF-3 ≥ 4);
• cognitive and communication ability to fulfill study requirements (cognitive ability
based upon a score of ≥24 on the Mini Mental Status Exam (MMSE));
• availability of reliable adult who can assist with study procedures if necessary;
• willing and able to report shoulder pain and other conditions and complete study
visits throughout the 7 month study period.
  Please list inclusion criteria.
  9.2
What are exclusion criteria? Put this information in bullet form:
• joint or overlying skin infection or history of recurrent skin infections;
• insensate skin;
• need to take > 1 opioid and > 1 nonopioid analgesic medication for HSP;
• regular intake of pain medications for another chronic pain;
• botox injection or subacromial steroid injections to the shoulder within the past
  Please list exclusion criteria.

12 wks;
• receiving OT or PT for HSP;
• bleeding disorder or INR > 3.0;
• sensitivity to skin surface electrodes and/or medical-grade adhesives, gels, tapes;
• medical instability;
• pregnancy;
• uncontrolled seizures (>1/mo for 6-mo);
• history of cardiac arrhythmia with hemodynamic instability;
• history of lidocaine allergy;
• history of Parkinson’s disease, SCI, TBI, MS, or ipsilateral UE lower motor
neuron lesion;
• history of complex regional pain syndrome, myofacial pain syndrome, other
pain conditions (investigator discretion);
• cardiac pacemaker or other implanted electronic device;
• history of valvular heart disease (artificial valves, requiring antibiotics for
procedures, etc.);
• severely impaired communication;
• history of compromised immune system (i.e., recently or actively taking
immunosuppressive therapies, AIDS) congenital immunodeficiency, or any other
cause for compromised immune system with which participation would pose
excessive risk.
  9.3  How will subject eligibility be determined and by whom?
Subject eligibility will be initially assessed by the study coordinator and will be
confirmed and reviewed by the Investigator. Eligibility will be determined from:
• review of medical history available in the chart;
• completion of the Brief Pain Inventory Short Form (to confirm baseline degree of
pain of ≥ 4);
• bloodwork (to confirm suitable coagulation levels in patients on anticoagulants) or
pregnancy urine or serum test in applicable female subjects;
• physical examination of shoulder.
  Please describe in detail.
  9.4
Will you exclude women and minorities, or persons under 21 from enrollment?
Yes  
  Check yes or no.
  9.5
If yes, which groups are you excluding? Provide justification for your decision.
Pregnant women: Pregnant women will be excluded since the effect of electrical
stimulation on the fetus is not known.
Persons under 21: Children are excluded based on scientific considerations as they
represent a fundamentally different population with chronic post-stroke shoulder pain
etiologies and substantially different from the adult population. Individuals that are at
least 21 years of age possess additional maturity beyond those that are 18. The study
involves the use of an external stimulator and requires the maintenance of a
percutaneous exit site. As such, we believe that this additional level of maturity is a
valid reason to extend the minimum age of enrollment to 21.
  List groups to be excluded then
provide justification.
 
  9.6
Attach Documents:
Name
Description
There are no items to display
  If you are unable to fit your
answers in the text boxes
provided please attach as a
word document.
View: 10-00 Risk/Benefits
  10.0 Assessment of Risk I:
  10.1
Identify and distinguish between those procedures that are standard versus those
that are experimental. Include the frequency and duration of each activity and
the total length of subject participation:
• Physical Exam and Range of Motion of shoulder (standard): A physical exam and
range of motion assessment is standard for patients with shoulder pain and will be
done at Visit 1. The shoulder will be physically inspected during each visit.
• Collection of bloodwork (standard): The blood test (INR score) is standard for
patients taking anticoagulants. This test will be collected in applicable subjects at
Visit 1. A pregnancy test will also be administered in applicable subjects and can
either be urine or serum pregnancy test.
  Please distinguish between
those procedures that are
standard versus those that are
experimental. Describe in detail
all experimental procedures.

• EMG needle electrode testing (experimental ): EMG needles are commonly used to
evaluate muscle physiology and strength of muscle contractions. In this study,
however, EMG needle (Sprint Test Needle) testing will be used to deliver test
stimulation during the lead implant procedure.
• Placement of Percutaneous Fine Wire Intramuscular Lead (experimental): The
placement of the lead during the lead implant procedure and the use of stimulation
during the treatment phase are experimental. Local anesthetic will be used.
• X-rays (standard): One 2-view (AP/Lateral and Scapular Y) shoulder x-ray will be
conducted following the removal (explant) of the electrode lead, to determine and
document the presence of any retained fragments.
• Physical Therapy: Standard PT (standard) will be used during the treatment phase
for the active PT groups. For the sham PT group (experimental), sham ultrasound
therapy and light application of inert gel to the shoulder will be utilized, but standard
PT not expected to affect outcomes related to shoulder function will be utilized as
well. There are 8 PT Visits.
• Collection of surveys and questionnaires - BPI, SF-36 (standard): These surveys are
used for research, but are commonly used in pain patients. These surveys will be
collected as defined elsewhere in this protocol for 9 Outcomes Assessments Visits; the
BPI additionally is collected at the Start of Stimulation Visit. The Mini Mental Status
Exam (MMSE, also standard) will be collected at Visit 1. The BDI and PCS (also
standard) are used for research, but are commonly used in pain patients. They will be
collected at Visit 1. The FABQ (experimental) will be collected at Visit 1. The PGIC
(experimental) will be collected at Visit 12.
• Fugl-Meyer Motor Assessment (upper limb): The FMA (standard) will be used as
defined elsewhere in this protocol for 4 Outcomes Assessments Visits.
• Other outcomes measures (experimental): Isometric voluntary abduction shoulder
torque (IVAST), shoulder kinematic analysis, and measures of central sensitization
(mechanical pain thresholds for hyperalgesia, pinprick pain thresholds for
hyperalgesia, temporal summation of repetitive pin-prick stimuli) are used for
research but some also are used in clinical practice as well. They will be used as
defined elsewhere in this protocol for 4 Outcomes Assessments Visits.
  10.2
Describe any therapeutic alternatives to the research that may exist. How are
they different from those procedures that subjects would normally undergo?
Numerous interventions exist for the treatment of shoulder pain following stroke.
This is due to the large number of possible etiologies, the diversity of clinicians
that treat stroke patients, and the lack of consensus regarding a standard of care.
None of the following interventions have been shown to reduce pain reliably in
randomized controlled trials.
Slings and other supports: Arm slings and other mechanical supports, such as
wheelchair trays, are often used to support the forearm and distribute its weight
to one or both shoulders in an effort to prevent or reduce subluxation. Although
slings may reduce subluxation, they often fail to reduce shoulder pain as
subluxation recurs once they are removed and may slow rehabilitation by
reducing arm mobility.
Strapping: Strapping is the application of non-stretch tape to the affected limb to
support the glenohumeral joint while allowing free movement of the arm. In a
randomized controlled study of 33 patients, those who received strapping
reported reduced average pain compared to those who received no therapy
(inactive control group). However, strapping fails to produce a significant benefit
compared to active control groups, who received either sham strapping or
standard physiotherapy without strapping. In addition, the tapes must be
replaced at least every three days, and skin irritation is common.
Local Injection Techniques: Corticosteroid injections address pain by treating
inflammation. Approximately 50% of clinicians who treat patients with
poststroke shoulder pain believe that steroid injections are effective. However,
there are only two randomized controlled trials of corticosteroid injections for
the treatment of post-stroke shoulder pain and they have mixed results. A recent
trial of subacromial injections reported significant benefit over placebo.
However, an earlier placebo controlled trial of intra-articular injections showed
no benefit. Post-stroke shoulder pain has a variety of possible etiologies and does
  Describe any therapeutic
alternatives. Can subjects
receive this drug or device
outside of a research study?  

not always arise from inflammation, explaining why steroid injections do not
consistently outperform placebo in stroke patients. In addition to uncertain
efficacy, repeat corticosteroid injections are associated with frequent adverse
events, making them a poor treatment option.
Botulinum toxin causes local paresis of muscles by blocking cholinergic
transmission at the neuromuscular junction. It has been widely used to treat
spasticity and some data suggest that it may also help to relieve pain. Six of nine
patients in a small uncontrolled study receiving an injection of botulinum toxin
to the affected limb reported pain reduction. However, the effect of botulinum
toxin is known to diminish after 3-4 months, making repeated injections
necessary. Little data exist regarding the repeated use of botulinum toxin for
shoulder pain relief.
Oral analgesic medications: The use of opioid and nonopioid analgesics,
including nonsteroidal anti-inflammatory drugs (NSAIDs) to manage shoulder
pain is common practice. Unfortunately, extended use of opioids can lead to
dependence and side effects such as headache, skin rash, dizziness, and
gastrointestinal symptoms. Though NSAIDs may reduce shoulder pain in the
general population, their efficacy has not been demonstrated in the stroke
population.
Therapeutic exercises: Therapeutic exercises under the supervision of a trained
professional are generally considered to be an important part of poststroke
rehabilitation. Although they prevent immobility and improve the range of
motion (ROM) of the hemiplegic arm, studies have found that some exercises,
such as the use of an overhead pulley, can cause soft tissue damage and thereby
worsen shoulder pain. In fact, exercises are generally associated with a
worsening of pain or no change, rather than an improvement. In a study
investigating static positional stretches, the treatment group showed increasing
levels of pain.
Acupuncture/Electroacupuncture: Acupuncture has been used for centuries to
treat various types of pain and is believed to improve cutaneous and muscle
blood flow and to increase pain thresholds. Electroacupuncture, a therapy in
which traditional acupuncture needles are used in conjunction with electrical
stimulation, has been evaluated as a therapy for shoulder pain in post-stroke
subjects in a randomized study comparing electroacupuncture plus
occupational/physical therapy to therapy alone. Although statistically significant
improvements in pain reported via a Visual Analog Scale were observed in the
treatment group, the study did not follow the group beyond the conclusion of the
treatment. Thus it is not clear how often the therapy must be reapplied. In
addition, electroacupuncture requires repeated clinic visits (at least 3 visits per
week for 1 month). Traditional acupuncture has also been evaluated as a
treatment for shoulder pain; however subjects in these studies had non-stroke
shoulder pain etiologies.
Surface electrical stimulation: Surface electrical stimulation uses skin surface
electrodes applied to the shoulder to deliver stimulation from an external
stimulator. Baker and Parker published the first results from a randomized
controlled trial of surface electrical stimulation for the treatment of poststroke
shoulder pain. The authors found a treatment effect for subluxation but
inconclusive results regarding pain relief. The investigators of a later study
hoped to obtain more conclusive results than Baker and Parker by enrolling a
larger population of 120 and following the subjects for two years. Pain was noted
as present or absent at rest during passive motion and during active motion.
Subjects were also asked to rate their pain using a visual analogue scale (VAS).
For a subject to be classified as having no pain, all four variables had to be
negative. A significantly higher proportion of subjects receiving electrical
stimulation had no pain at 3, 6, 12, and 24 months compared to the control group
(80.7% vs. 55.1%, p<0.01). The treatment subjects also showed a greater
reduction in subluxation and a significant improvement in the recovery of arm
motion.

The results of four additional studies investigating surface electrical stimulation
are summarized in a Cochrane review. Although the authors found a significant
improvement in pain-free range of motion (ROM) in the treatment groups, the
data did not support a significant reduction in pain intensity or incidence. The
authors concluded that larger randomized controlled studies would be necessary
to fully examine the effects of electrical stimulation in the post-stroke shoulder
pain population.
Another literature review including six trials found that electrical stimulation
paired with conventional therapy is not superior to conventional therapy alone
for pain prevention. However, they noted that this may be due to the indirect
way in which most studies measured pain (as “pain-free range of shoulder
external rotation”). When pain was measured directly, using a VAS, electrical
stimulation was found to be more effective in preventing pain than conventional
therapy.
The results regarding the efficacy of surface electrical stimulation as a treatment
for post-stroke shoulder pain have been promising, leading to its
recommendation by several recently published guidelines. In addition, a
literature review proposed that surface electrical stimulation combined with
gentle clinician guided exercises should be considered the “best practice” for
acute stroke survivors. However, several authors have noted that even with
further evidence of the efficacy of surface electrical stimulation, it is unlikely
that it will ever be the standard of care due to the discomfort caused by
stimulation of cutaneous pain receptors, the potential for skin irritation under
multiple surface electrodes, the need for skilled personnel to place the surface
electrodes on a daily basis, and muscle fatigue that commonly occurs due to the
high frequency of stimulation. Baker and Parker noted that either an
implantable or a percutaneous system would have to be developed before
electrical stimulation could become the preferred treatment. For these reasons,
researchers have turned their attention to the use of intramuscular electrical
stimulation.
bion® microstimulator (investigational): Due to the effectiveness of electrical
stimulation but the difficulties associated with surface electrical stimulation,
researchers have begun to investigate direct muscle and nerve stimulation. The
bion® microstimulator used by Bioness, Inc. (Valencia, CA), is currently being
investigated for the treatment of post-stroke shoulder pain and subluxation.
Although the bion has technical advantages, including its small size and self-
contained electrode, it also suffers from considerable disadvantages. First, the
device does not utilize a trial stage to evaluate whether a candidate is likely to
experience pain relief from long term use prior to implantation. Second,
implantation of the bion requires fluoroscopy and precise placement in close
proximity to the deep axillary nerve trunk. Third, the device must be recharged
daily using a large, stationary charging apparatus, to which the patient must be
tethered during the recharging session. In addition, the bion’s extraction
requires open surgery. Finally, the bion requires precise placement due to its
bipolar configuration, as the stimulus current density (and efficiency of nerve
recruitment) drops off rapidly with distance from the target nerve. Even a small
migration of the bion could significantly diminish its effectiveness. Data
regarding the safe and effective use of the bion for post-stroke shoulder pain
have not yet been published.
  10.3
  
What are the outcome variables and how will they be analyzed? What are the
statistical and analytical methods that will be used? Note this section can be
copied from the NIH Grant Application or from the Statistical and Analytical
Methods section of the industry trial protocol.
See attachments below.
 
  Define outcomes and describe
data analysis, please include a
power calculation.
   10.4 If the above requested information does not fit in the text box please attach a
word document here:
  If the  requested information
does not fit in the text box
please attach a word document.

Name
Description
Data Analysis (inc. Sample Size Calculation under Expectations and
Analysis, Aim 1) | History
 
Outcomes Measures | History
 
Revised Sample Size Wilson PNS+PT R01 (2016_10_12) | History
 
View: 10-01 Risk/Benefits
  10.1 Assessment of Risk II:
  10.5
List and quantitate the risks involved for each experimental procedure in bullet
form. Identify risks as common (greater than 10%) uncommon (greater than
1% up to and including 10 %) rare (1% or less). This must match the risks
listed in the Consent Form:
1) Risks associated with needle insertion for Sprint MicroLead placement
There are minor risks associated with inserting a Lead through the skin with a
needle. These risks are similar to the risks of any needle injection including the
possibilities of puncturing a blood vessel, irritating a nerve, and temporary
bruising or pain at the insertion site. The risks of puncturing a blood vessel and
irritating a nerve are uncommon, but the risks of temporary bruising and pain
at the insertion site are common.
Some participants may experience a vasovagal (“fainting”) response due to the
discomfort or anxiety associated with of the procedure, especially among those
with prior history of “fainting.” This risk is rare and may be associated with
symptoms of lightheadedness, dizziness and or diaphoresis with concomitant
reduction in blood pressure and heart rate. For those with prior history of
“fainting” the procedure will be performed with the subject in the lateral
decubitus position.
To minimize the risks associated with percutaneously placing fine wire leads,
only appropriately trained physician investigators will perform the procedure.
In addition, the risk of excessive bleeding will be reduced by excluding
candidates who are taking warfarin with an INR > 3.0 and by placing manual
pressure on the implantation site until hemostasis is achieved. Finally, the risk
of discomfort during the procedure will be reduced by the use of an appropriate
amount of local anesthetic.
It is possible that, in some cases, multiple attempts may be required to achieve
appropriate placement of the Lead during the procedure. Each additional
attempt at Lead placement carries the same risks as the initial attempt
described in this section.
2) Risk of skin irritation, infection, or inflammation at the Sprint MicroLead
exit site
There are risks of leaving a Sprint MicroLead in place for 4 weeks, including
skin irritation, infection, and granuloma formation (mild tissue inflammation)
at the Lead exit site. Symptoms include redness, swelling, or pain. The risk of
skin irritation is common while the risks of infection and granuloma formation
are rare.
These risks will be minimized by using sterile Leads and thoroughly cleansing
the insertion site with antibacterial solution at the time of insertion. The
insertion site will be covered with a dressing to keep it clean and dry, and the
subjects and their caregivers will be instructed to inspect the site for signs of
infection or irritation regularly and to inform the Investigator if they occur. If
infection or skin irritation occurs, the Investigator will administer an antibiotic
and/or remove the Lead. Infections are rare and typically resolve after Lead
removal and antibiotic treatment.
It should be noted that in a completed clinical trial of percutaneous
intramuscular electrical stimulation, one patient death occurred. The subject
did not follow the instructions for the care of the Lead exit site and also did not
  Select all that apply.

return for his scheduled follow-up visit following electrode placement. He
developed an electrode related infection and was hospitalized. The cause of
death is thought to be a myocardial infarction or a pulmonary embolus, but the
exact cause of the death and its relationship to the infection are not known. To
mitigate the potential risk of serious infection, a 48-72 hour safety check will be
performed after the procedure. Participants will return to the clinic and the exit
site will be evaluated for signs of infection.
3) Risk of the Sprint MicroLead breaking beneath the skin
There is a possibility of a Lead breaking beneath the skin either during the
course of the study or during the procedure to remove Lead. This risk is
uncommon. However, when a Lead breaks, one or more Lead fragments
usually remain in the body. The Investigator will use clinical judgment to
determine if the removal of such fragments is necessary. Visual inspection of the
Lead after it has been removed as well as x-rays will be used to determine if any
Lead fragments remain. The risk associated with the x-rays is no greater than
that associated with conventional clinical x-rays. If the Investigator determines
a Lead fragment has been retained in the body, he/she will determine what is
medically required to further evaluate and treat this retained fragment.
Typically, no treatment is required unless there are further sequelae, such as an
infection or granuloma, associated with the fragment.
The risk of leaving a Lead fragment is minimized by reducing the amount of
time the Lead remains implanted and the number of Leads implanted. In this
protocol, a single Sprint MicroLead will be implanted for just 4 weeks.
4) Risk of infection associated with retained Sprint MicroLead fragments
A Lead fragment could result in the formation of a granuloma or infection.
Although the occurrence of a fragment-related infection or granuloma is
uncommon an infection may require removal of the Lead fragment and/or
treatment with antibiotics. Investigators at the Cleveland FES Center and Case
Western Reserve University have over 30 years of experience with dozens of
research participants and hundreds of implanted leads like those used in this
study. Infections and granulomas of leads or lead fragments have been
uncommon, which is attributed to the materials and procedures that have been
developed as well as the extensive experience of the Investigators..
5) Risks associated with lead fragment removal
It is possible that a Lead fragment or fragments may be retained in the body
following removal of the Sprint MicroLead. If the Investigator determines that
a lead fragment has been retained, the Investigator will instruct the subject and
his/her caregiver to carefully inspect the Sprint MicroLead exit site and the
surrounding skin in the weeks subsequent to Lead removal. Subjects will be
instructed to contact the Investigator if there are any signs of pain, redness,
swelling, discharge, or the appearance of a pimple-like mass (skin abscess).
Such signs indicate that the fragment has migrated to the skin surface. At that
time, if clinically warranted, the fragment may be removed via an outpatient
procedure which involves lancing the abscess and removing the fragment and
application of a topical antibiotic.
The risks associated with the Lead fragment removal procedure include
discomfort during the procedure and skin irritation or infection in the area of
the retained fragment. These risks are rare. The risk of infection is mitigated by
instructing the subject and/or his caregiver to carefully monitor the site and
immediately report any signs of infection.
6) Risk of Lead Replacement due to Lead Migration or Lead Becoming
Dislodged
It is possible that the Lead may migrate from its original intended location or

that the Lead may become dislodged (i.e. come out completely) during the
treatment phase. This risk is rare. If lead migration occurs, it is possible that
the subject may experience discomfort during stimulation (described further
below under “risk of discomfort with electrical stimulation”). If the Lead has
migrated substantially or has come out, it may be necessary to place another
Lead. Each time an additional lead is placed, the subject has an additional
exposure to the same risks of lead placement described above in “risk of needle
insertion for Sprint MicroLead placement”.
This risk of lead migration or the becoming dislodged is mitigated by
instructions to the subject and their caregiver, as appropriate, to ensure careful
handling of the Lead and Lead Connector during bandage changes. In
addition, the risk of placing a new lead is further mitigated by ensuring that
Investigators are trained in the lead placement procedure, ensuring that the
shoulder tissue appears healthy prior to placing a new lead, and collecting an
additional INR blood sample for subjects who are taking warfarin.
7) Risk of skin irritation under the Sprint Pad or bandages
It is possible that the skin could become irritated under the Sprint Pad.
Additionally, there may be skin irritation in the area surrounding the Lead
insertion site, where an adhesive bandage is taped to the skin. This risk is
common; however, the bandages can be changed to prevent the irritation from
returning.
The risks of skin irritation under the Sprint Pad (a modified surface electrode)
and under the bandages surrounding the Sprint MicroLead exit site will be
reduced by excluding patients with known sensitivity to skin surface electrodes
and/or medical-grade adhesive tapes. Subjects and their caregivers will be
advised to examine the electrode exit site at regular intervals to look for any
signs of irritation. To avoid irritation under the Sprint Pad, subjects will be
advised that the Sprint Stimulator and Sprint Pad may be moved to slightly
different locations near the Lead insertion site throughout the treatment phase.
In addition, subjects will be instructed to avoid placing the Sprint Pad or
bandages on unhealthy skin.
8) Risk of mechanical or electrical failure of the Sprint Stimulator
There is a rare chance that the Sprint Stimulator may malfunction. It is very
unlikely that a stimulator malfunction will be harmful. If there is a problem
with the Sprint Stimulator or the Sprint MicroLead, the Stimulator will reset
itself such that no stimulation is delivered.
The Sprint Stimulator will not deliver stimulation if it detects a high impedance
level indicating a broken lead wire or a faulty lead connection. Subjects will be
instructed to contact study staff in the event that an error message is displayed.
9) Risks for pregnant women
The risk of harm to a pregnant woman or fetus is unknown. The device will not
be used in any subjects known to be pregnant. If a subject is known to become
pregnant during the treatment phase, stimulation will be stopped and the
Sprint MicroLead will be removed.
Potential risks of pregnancy will be reduced by administering a pregnancy test
in females of reproductive potential at study enrollment. Additionally, the
Informed Consent form will advise subjects that the risks of electrical
stimulation during pregnancy are unknown and that they should immediately
notify the Investigator if they suspect they have become pregnant during the
study.
10) Risk of discomfort due to electrical stimulation

Intramuscular electrical stimulation may be perceived by the subject as a
tingling or vibrating sensation, which may feel uncomfortable or painful. The
risk of discomfort due to stimulation is uncommon. At high stimulation
intensities, shoulder pain may worsen.
To minimize the risk of increased shoulder pain as the result of high intensity
stimulation, the Investigator will set an appropriate intensity for the
stimulation. Should a subject feel pain as the result of stimulation, he or she will
be able to turn off the stimulation using the Sprint Stimulator controls.
Although muscle fatigue is unlikely with six hours of daily stimulation therapy,
subjects may also feel some discomfort if muscle fatigue occurs. If muscle
fatigue is observed, the Investigator is able to prescribe several shorter
stimulation sessions totaling six hours per day.
Discomfort or pain due to stimulation may occur if the Sprint MicroLead
migrates from its original location. Stimulation near the skin surface may be
perceived as a “pins and needles” or stinging sensation and may be
uncomfortable.
The risk of pain due to a migrating electrode will be minimized by leaving
stimulation off until the Sprint MicroLead has had time to stabilize. The Sprint
MicroLead has a fine wire barb. In addition, the proximal portion of the Lead
exits the skin which makes this Lead more susceptible to becoming dislodged
during bandage changes. As a conservative measure, we allow one week for
encapsulation of the Sprint MicroLead to ensure stability. Data on the Lead has
shown that electrodes are fully encapsulated by the surrounding tissue.
A tingling sensation may be felt under the Sprint Pad but this sensation is not
expected to be uncomfortable. If discomfort or pain is felt at the Sprint Pad
site, the subject will be instructed to turn off stimulation and move the Sprint
Pad and Stimulator to a different location.
11) Risks associated with Diathermy
There is a risk of tissue damage if a subject undergoes diathermy. Shortwave or
microwave diathermy is a therapy that may be used to apply deep therapeutic
heat for the treatment of selected medical conditions such as relief of pain,
muscle spasms, and joint contractures. Diathermy can cause excessive heating
of any implanted metal part (including Leads), resulting in serious injury. The
risk of tissue damage associated with diathermy is rare.
The risk of diathermy will be reduced by informing subjects that diathermy
must not be used. In addition, subjects will be informed to never undergo
diathermy if a Sprint MicroLead fragment remains in the body.
12) Risks associated with MRI
Tissue damage may occur if a subject undergoes an MRI procedure while the
Sprint MicroLead, or a fragment of the Sprint MicroLead, is in the body. The
risk of tissue damage associated with MRI use is rare.
Should a subject require a scheduled MRI during the treatment phase, the
Sprint MicroLead will be removed. The decision to remove any remaining
fragments will depend on a careful assessment of the benefits of the MRI, risks
of MRI with retained fragments and risks associated with removing of
electrode fragments.
13) Risk of allergic reaction to local anesthetics and/or risk of accidental
injection of local anesthetic into a vein
There is a risk that the subject may have an allergic reaction to the local
anesthetic used during the treatment phase prior to insertion of the Sprint
MicroLead. If the subject were to have an allergic reaction, it would usually

happen while the subject was still in the clinic. If a subject complains of itching,
difficulty breathing, lightheadedness and dizziness, or a swollen tongue
(common signs of an allergic reaction), appropriate medical treatment will be
administered. The risk of allergic reaction to local anesthetics is rare. In
addition, there is a risk of adverse central nervous system and/or
cardiovascular effects (including a rare risk that the subject’s heart can stop
beating or that they could stop breathing) if the local anesthetic is administered
improperly.
The risks of allergy to local anesthetic agents will be reduced by excluding
subjects with a prior known history of allergy or sensitivity to local anesthetic
agents. In addition, prior to the procedure, subjects will be advised of the signs
and symptoms of an allergic reaction. Because subjects will be awake during
this procedure, they will be able to verbalize any itching or other signs of
allergy to the local anesthetic. The risks of accidental intravascular injection of
local anesthetic will be reduced by careful administration of the local
anesthetic. Careful administration includes ensuring that a vein has not been
punctured by the syringe prior to injecting the anesthetic and observing the
subject after the injection. In addition, the physical location of the anesthetic
injection (in the deltoid) combined with the injection technique would rarely
result in an accidental intravascular injection.
14) Risk associated with venipuncture (if applicable)
The risks of drawing blood from a vein include discomfort at the site of
puncture, possible bruising and swelling around the puncture site, an infection,
and faintness from the procedure. The risks of discomfort, bruising, and
swelling around the puncture site are common while the risks of infection and
fainting are rare. Blood sample collections are only required in subjects taking
warfarin.
Subjects taking warfarin are at greater risk for developing bruises following
venipuncture. However, the risk of discomfort and bruising at that puncture
site will be reduced by applying gentle pressure following venipuncture as is the
standard practice for collection of blood samples. The rare risk of infection due
to venipuncture will be reduced by using proper blood collection technique
including wiping the puncture site with an appropriate cleansing solution.
Some subjects may experience a vasovagal (“fainting”) response due to the
discomfort of needle insertion or anxiety associated with the procedure. The
risk of fainting will be reduced by observing subjects during and following
venipuncture to ensure that they feel comfortable rising from their seated
position. Subjects with a history of vasovagal responses will be supine during
venipuncture.
15) Risk of worsening of pain symptoms
It is possible that the subject may have a worsening of pain symptoms or that
they may not obtain any therapeutic benefit from the treatment. The risk of
worsening pain symptoms is uncommon. In addition, subjects will have the
opportunity to discontinue treatment if their stimulation is too uncomfortable.
These risks are mitigated by clinical training on the safe limits. Subjects do not
have access to make changes to the programming controls and thus could not
advertently change the value.
16) Risks of Physical Therapy and Performing Shoulder Exercises
Shoulder pain may worsen during outpatient therapy or during home exercises.
To minimize this risk, all exercises will be performed under the supervision of a
trained therapist during outpatient therapies. Participants will be trained to
perform their home exercise program to minimize the risk of further injuring
the shoulder. The proper implementation of the home exercise program will be

reinforced at each outpatient therapy visit. However, if shoulder pain persists
during the home exercises, the home exercise program will be terminated.
17) Risks of Outcomes Assessments
The questionnaires and Fugl-Meyer Assessment present no risks. The
assessments of shoulder torque and kinematics may be slightly uncomfortable.
The measures of central sensitization (mechanical pain thresholds for
hyperalgesia, pinprick pain thresholds for hyperalgesia, temporal summation
of repetitive pin-prick stimuli) may be slightly uncomfortable and may cause
brief skin irritation.
18) Other
When using a sham group there is always the rare risk of psychological harm.
Some of the survey questions present a rare risk of psychological harm.
When PHI is involved there is the rare risk of a privacy breach.
There may be other risks as yet unknown.
 
  10.6 
Are there defined stopping rules?   
Yes 
No
What are the stopping rules for the study? What are the conditions under
which a subject will be withdrawn from the study for safety reasons, i.e. disease
progression?
The study could be terminated at any time for valid scientific reasons or reasons
related to the protection of subjects participating in this study. A reason for study
termination includes but is not limited to the discovery of an unexpected, significant,
or unacceptable risk to the participants enrolled in the study.
What findings, events, or conditions would require a research subject to be
removed from the study? (i.e. disease progression)
The research subject may be removed if they develop any condition during the
course of the study which would preclude the safe use of stimulation or otherwise
impair their safe participation in any study activity.
 
  Describe in enough detail for
the IRB to assess safety. 
  10.7   
 
 
What Category of risk will study participants be exposed too?
Name
Psychological
Physical
Privacy
 
  Should be consistent with risks
listed in the Consent Form.
  10.8
 
 
10.9
If Other listed above please specify:
Describe the availability of medical or psychological services that participants
might require as a consequence of participation in this the research:
It is not expected that participants would require medical or psychological services
as a consequence of participation in this research. If that were to occur, appropriate
referrals would be made for the subject.
  A text box is provided for
further explanation.
A text box is provided for
further explanation. 
  10.10
Describe in detail any measures in place to minimize or protect against the
exposure of study subjects to these risks:
1) Risks associated with needle insertion for Sprint MicroLead placement
To minimize the risks associated with percutaneously placing fine wire leads, only
  Discuss any provisions for
intervention in the event of an
Adverse Event i.e. stopping
rules.

appropriately trained physician investigators will perform the procedure. In addition,
the risk of excessive bleeding will be reduced by excluding candidates who are
taking warfarin with an INR > 3.0 and by placing manual pressure on the
implantation site until hemostasis is achieved. Finally, the risk of discomfort during
the procedure will be reduced by the use of an appropriate amount of local
anesthetic.
Some participants may experience a vasovagal (“fainting”) response due to the
discomfort or anxiety associated with of the procedure, especially among those with
prior history of “fainting.” This risk is rare and may be associated with symptoms of
lightheadedness, dizziness and or diaphoresis with concomitant reduction in blood
pressure and heart rate. For those with prior history of “fainting” the procedure will
be performed with the subject in the lateral decubitus position.
2) Risk of skin irritation, infection, or inflammation at the Sprint MicroLead exit site
These risks will be minimized by using sterile Leads and thoroughly cleansing the
insertion site with antibacterial solution at the time of insertion. The insertion site
will be covered with a dressing to keep it clean and dry, and the subjects and their
caregivers will be instructed to inspect the site for signs of infection or irritation
regularly and to inform the Investigator if they occur. If infection or skin irritation
occurs, the Investigator will administer an antibiotic and/or remove the Lead.
Infections are rare and typically resolve after Lead removal and antibiotic treatment.
It should be noted that in a completed clinical trial of percutaneous intramuscular
electrical stimulation, one patient death occurred. The subject did not follow the
instructions for the care of the Lead exit site and also did not return for his scheduled
follow-up visit following electrode placement. He developed an electrode related
infection and was hospitalized. The cause of death is thought to be a myocardial
infarction or a pulmonary embolus, but the exact cause of the death and its
relationship to the infection are not known. To mitigate the potential risk of serious
infection, a 48-72 hour safety check will be performed after the procedure.
Participants will return to the clinic and the exit site will be evaluated for signs of
infection.
3) Risk of the Sprint MicroLead breaking beneath the skin
The risk of leaving a Lead fragment is minimized by reducing the amount of time
the Lead remains implanted and the number of Leads implanted. In this protocol, a
single Sprint MicroLead will be implanted for just 4 weeks.
4) Risk of infection associated with retained Sprint MicroLead fragments
Investigators at the Cleveland FES Center and Case Western Reserve University
have over 30 years of experience with dozens of research participants and hundreds
of implanted leads like those used in this study. Infections and granulomas of leads
or lead fragments have been uncommon, which is attributed to the materials and
procedures that have been developed as well as the extensive experience of the
Investigators.
5) Risks associated with lead fragment removal
Subjects will be instructed to contact the Investigator if there are any signs of pain,
redness, swelling, discharge, or the appearance of a pimple-like mass (skin abscess).
Such signs indicate that the fragment has migrated to the skin surface. At that time,
if clinically warranted, the fragment may be removed via an outpatient procedure
which involves lancing the abscess and removing the fragment and application of a
topical antibiotic.
6) Risk of Lead Replacement due to Lead Migration or Lead Becoming Dislodged
It is possible that the Lead may migrate from its original intended location or that
the Lead may become dislodged (i.e. come out completely) during the treatment

phase. Each time an additional lead is placed, the subject has an additional exposure
to the same risks of lead placement described above in “risk of needle insertion for
Sprint MicroLead placement”.
This risk of lead migration or the becoming dislodged is mitigated by instructions to
the subject and their caregiver, as appropriate, to ensure careful handling of the Lead
and Lead Connector during bandage changes. In addition, the risk of placing a new
lead is further mitigated by ensuring that Investigators are trained in the lead
placement procedure, ensuring that the shoulder tissue appears healthy prior to
placing a new lead, and collecting an additional INR blood sample for subjects who
are taking warfarin.
7) Risk of skin irritation under the Sprint Pad or bandages
The risks of skin irritation under the Sprint Pad (a modified surface electrode) and
under the bandages surrounding the Sprint MicroLead exit site will be reduced by
excluding patients with known sensitivity to skin surface electrodes and/or medical-
grade adhesive tapes. Subjects and their caregivers will be advised to examine the
electrode exit site at regular intervals to look for any signs of irritation. To avoid
irritation under the Sprint Pad, subjects will be advised that the Sprint Stimulator
and Sprint Pad may be moved to slightly different locations near the Lead insertion
site throughout the treatment phase. In addition, subjects will be instructed to avoid
placing the Sprint Pad or bandages on unhealthy skin.
8) Risk of mechanical or electrical failure of the Sprint Stimulator
There is a rare chance that the Sprint Stimulator may malfunction. It is very unlikely
that a stimulator malfunction will be harmful. If there is a problem with the Sprint
Stimulator or the Sprint MicroLead, the Stimulator will reset itself such that no
stimulation is delivered.
The Sprint Stimulator will not deliver stimulation if it detects a high impedance
level indicating a broken lead wire or a faulty lead connection. Subjects will be
instructed to contact study staff in the event that an error message is displayed.
9) Risks for pregnant women
The risk of harm to a pregnant woman or fetus is unknown. The device will not be
used in any subjects known to be pregnant. If a subject is known to become pregnant
during the treatment phase, stimulation will be stopped and the Sprint MicroLead
will be removed.
Potential risks of pregnancy will be reduced by administering a pregnancy test in
females of reproductive potential at study enrollment. Additionally, the Informed
Consent form will advise subjects that the risks of electrical stimulation during
pregnancy are unknown and that they should immediately notify the Investigator if
they suspect they have become pregnant during the study.
10) Risk of discomfort due to electrical stimulation
To minimize the risk of increased shoulder pain as the result of high intensity
stimulation, the Investigator will set an appropriate intensity for the stimulation.
Should a subject feel pain as the result of stimulation, he or she will be able to turn
off the stimulation using the Sprint Stimulator controls. Although muscle fatigue is
unlikely with six hours of daily stimulation therapy, subjects may also feel some
discomfort if muscle fatigue occurs. If muscle fatigue is observed, the Investigator is
able to prescribe several shorter stimulation sessions totaling six hours per day.
Discomfort or pain due to stimulation may occur if the Sprint MicroLead migrates
from its original location. Stimulation near the skin surface may be perceived as a
“pins and needles” or stinging sensation and may be uncomfortable.
The risk of pain due to a migrating electrode will be minimized by leaving

stimulation off until the Sprint MicroLead has had time to stabilize. The Sprint
MicroLead has a fine wire barb. In addition, the proximal portion of the Lead exits
the skin which makes this Lead more susceptible to becoming dislodged during
bandage changes. As a conservative measure, we allow one week for encapsulation
of the Sprint MicroLead to ensure stability. Data on the Lead has shown that
electrodes are fully encapsulated by the surrounding tissue.
A tingling sensation may be felt under the Sprint Pad but this sensation is not
expected to be uncomfortable. If discomfort or pain is felt at the Sprint Pad site, the
subject will be instructed to turn off stimulation and move the Sprint Pad and
Stimulator to a different location.
11) Risks associated with Diathermy
The risk of diathermy will be reduced by informing subjects that diathermy must not
be used. In addition, subjects will be informed to never undergo diathermy if a
Sprint MicroLead fragment remains in the body.
12) Risks associated with MRI
Should a subject require a scheduled MRI during the treatment phase, the Sprint
MicroLead will be removed. The decision to remove any remaining fragments will
depend on a careful assessment of the benefits of the MRI, risks of MRI with
retained fragments and risks associated with removing of electrode fragments.
13) Risk of allergic reaction to local anesthetics and/or risk of accidental injection of
local anesthetic into a vein
The risks of allergy to local anesthetic agents will be reduced by excluding subjects
with a prior known history of allergy or sensitivity to local anesthetic agents. In
addition, prior to the procedure, subjects will be advised of the signs and symptoms
of an allergic reaction. Because subjects will be awake during this procedure, they
will be able to verbalize any itching or other signs of allergy to the local anesthetic.
The risks of accidental intravascular injection of local anesthetic will be reduced by
careful administration of the local anesthetic. Careful administration includes
ensuring that a vein has not been punctured by the syringe prior to injecting the
anesthetic and observing the subject after the injection. In addition, the physical
location of the anesthetic injection (in the deltoid) combined with the injection
technique would rarely result in an accidental intravascular injection.
14) Risk associated with venipuncture (if applicable)
Subjects taking warfarin are at greater risk for developing bruises following
venipuncture. However, the risk of discomfort and bruising at that puncture site will
be reduced by applying gentle pressure following venipuncture as is the standard
practice for collection of blood samples. The rare risk of infection due to
venipuncture will be reduced by using proper blood collection technique including
wiping the puncture site with an appropriate cleansing solution.
Some subjects may experience a vasovagal (“fainting”) response due to the
discomfort of needle insertion or anxiety associated with the procedure. The risk of
fainting will be reduced by observing subjects during and following venipuncture to
ensure that they feel comfortable rising from their seated position. Subjects with a
history of vasovagal responses will be supine during venipuncture.
15) Risk of worsening of pain symptoms
It is possible that the subject may have a worsening of pain symptoms or that they
may not obtain any therapeutic benefit from the treatment. The risk of worsening
pain symptoms is uncommon. In addition, subjects will have the opportunity to
discontinue treatment if their stimulation is too uncomfortable.
These risks are mitigated by clinical training on the safe limits. Subjects do not have

access to make changes to the programming controls and thus could not advertently
change the value.
16) Risks of Physical Therapy and Performing Shoulder Exercises
Shoulder pain may worsen during outpatient therapy or during home exercises. To
minimize this risk, all exercises will be performed under the supervision of a trained
therapist during outpatient therapies. Participants will be trained to perform their
home exercise program to minimize the risk of further injuring the shoulder. The
proper implementation of the home exercise program will be reinforced at each
outpatient therapy visit. However, if shoulder pain persists during the home
exercises, the home exercise program will be terminated.
17) Risks of Outcomes Assessments
If the subject feels discomfort, they may request that the outcomes assessments be
paused. Measures will be taken to improve their comfort if possible. Skin irritation,
should it occur, should resolved shortly after the cause is removed.
18) Other
The informed consent process ensures that subjects are aware of multiple treatment
groups but acknowledges that there is a rare risk of psychological harm due to not
knowing which group they are in. Subjects may choose not to answer survey
questions that make them uncomfortable.
Privacy breach precautions are included in Sections 15-17.
There may be other risks as yet unknown.
  10.11
Please add any documents related to the above questions:
Name
Description
There are no items to display
  If your answers to the above
questions are too long for the
space provided please attach
them here. 
View: 10-02 Risk/Benefits
  10.2   Benefits:
  10.12  Describe the potential benefits to the subject as a result of participating in this
research. If there is no direct benefit to subjects please state that as well: Note:
payment or compensation to subjects for participation is not to be considered a
potential benefit.
Participants may experience substantial pain reduction, and all subjects are receiving
active treatment.
  Describe potential benefits to
the study subjects.
  10.13
Describe the potential benefits to society as result of this research:
The primary benefit will be the clinical and scientific knowledge gained.
  Describe potential benefits to
society.
  10.14  What is the risk/benefit ratio of the research?
The primary benefit will be the clinical and scientific knowledge gained as described
above. Participants may experience substantial pain reduction, and all subjects are
receiving active treatment. Due to the need for invasive procedures, participants will
be exposed to greater than “minimal risk.” However, the potential benefits to
participants, other patients with chronic HSP, and the scientific/rehabilitation
community are substantial. Therefore, the risk benefit ratio is acceptable.
  Discuss why the risks are
reasonable in relation to the
anticipated benefits. 
  10.15
Attach Documents:
Name
Description
There are no items to display
  Attach documents here. 
View: 11-00 Study Participant Information I
 
  11.0 Study Participant Information I:

  11.1 
 
 
 
11.2 
How will the Principal Investigator assure he/she has access to a population that
would allow recruitment of the required number of study participants (i.e. prep
for research):
The participants needed for this study at MetroHealth are expected to be recruited
from the clinics of the Investigators and via referral from other PM&R stroke
physicians. Additionally, potential participants may be recruited from the Greater
Cleveland area (as allowed for in the Recruitment section).
Anticipated number of subjects (all sites): [enter a number]
96
Anticipated number of subjects to be enrolled at MHS: [enter a number]
96
Anticipated number of potential subjects to be approached: [enter a number]
400
  How does the PI know he/she
has the required number of
subjects?
Please give the total #of
subjects to be enrolled at all
sites and anticipated subjects to
be enrolled at MHS.   
  11.3
If this is a multi-site study, how many sites will there be? [enter a number]
3  
  How many total sites?
  11.4  Subject Characteristics:
Subject Population Categories
Outpatients
Patients with the "disease in question"
  Check all that apply
  11.5
 
 
 
 
 
 
Subject Source:
Subject Source Characteristics
Subjects from the Practice of the Principal Investigator
Subjects referred or recruited from other physicians practices
Public subject recruitment by advertisement, flyers, websites etc. (Note: required IRB
review and approval)
  Check all that apply
  11.6
If "other" list above in either 11.4 or 11.5 please describe:
 
 
  If applicable please describe. 
 
 
View: 12-00 Study Participant Information II
  12.0  Study Participant Information II:
  12.1  Select age range of study participants:
Subject Age Range
18 - 64
65 - 89
  Check all that apply. 
  12.2
* Will the study enroll vulnerable subject groups?
Yes
* Will you be enrolling Children?
  
Yes 
No
* Will you be enrolling Pregnant Women and/or Fetuses?
  
Yes 
No
* Will you be enrolling decisionally impaired subjects?
  
Yes 
No
* Will you be enrolling Prisoners?   
Yes 
No
  Check yes or no.

  12.3  Please identify any vulnerable populations participating in the study:
Vulnerable Populations
Poor / Uninsured
Elderly
Minorities
Cognitively Impaired
  Check all that apply.
  12.4
 
12.5
If you selected "other" above please describe:
If you are going to enroll any vulnerable populations please describe the
safeguards you will put in place to protect these vulnerable Populations.
All potential subjects will be assured that they may decline participation without
jeopardizing their medical and rehabilitation care or compromising their relationship
with their physician or MetroHealth Medical Center. All subjects have an opportunity
to review the consent forms at home and discuss participation with family, friends,
etc. PHI will remain at Metro, except enrolled research participants will be told that
their names and contact information will be shared with the device manufacturer for
tracking purposes (addressed in HIPAA Authorization). Metro paper records with PHI
are kept in locked cabinets in locked rooms. For PHI stored electronically, password
protected secure MHS network drives will be used for electronic data in folders with
access limited to those who are authorized by this protocol. Any data stored on
portable media and/or removed from Metro would be deidentified.
 
  Please describe other.
Please enter a detailed plan.
 
View: 13-00 Recruitment I
  13.0  Recruitment I:
All external advertisements (for radio, print media or TV) must be approved by MHS Communications Department prior to submission to the IRB so the
IRB can see the final advertisement or script. All Advertisements on the MIV or On Hold messaging must be approved by the IRB before they are placed.
You may not advertise a study which is not approved by the IRB. Please note that all studies which have a contract which an external sponsor must have
that contract signed before any advertising can be done.
  13.1  Recruitment Methods/Sources:
Name
Internet/Web/MetroHealth Intranet
Advertisements-Newspapers/Magazines, Television, Radio
Notices/Posters/Flyers
Letters
Research Match
  Check all that apply. 
  
  13.2
If "Other" checked in 13.1 please explain:
  Please explain what other
means.
  13.3  Describe in detail all recruitment strategies for each subject group (as listed in
Section 11.0) selected for this research:
Subjects will be recruited from the outpatient stroke and brain injury rehabilitation
programs at MetroHealth Medical Center (MHMC), as well as from the Greater
Cleveland area. At MHMC, subjects will be recruited via direct referral from
clinicians within the Department of PM&R, and many will already be Dr. Wilson's or
Dr. Chae's patients.
Study subjects may be recruited from the following additional sources:
• All applicable MetroHealth Medical Center outpatient clinics and clinical
departments (e.g., Family Practice, Internal Medicine, Neurology, Orthopaedics, etc.)
• University Hospitals and affiliate hospitals
• Cleveland Clinic and affiliate hospitals
• Other appropriate area physicians/hospitals/clinics/facilities
• Skilled nursing facilities/units
• Visiting nurse associations
• Nursing homes
• Assisted living facilities
• Stroke support groups or forums
• Senior/community/recreation centers
  Please describe recruitment
strategies in detail.

Study subjects may be recruited using the following additional methods:
• Print advertisements (e.g., newspapers, periodicals, newsletters). May also be used
for radio spots. Metro Communications will have approved.
• Craigslist advertisements. Metro Communications will have approved.
• Flyers and/or brochures.
• MetroHealth Website Stroke Research Information Page. Basic study and contact
information will be displayed on a webpage associated with the MHS website.
Developed in cooperation with Metro Communications.
• MetroHealth Voicemail and On-Hold Messaging. Metro Communications will have
approved.
• Approved recruitment materials placed with permission on Bulletin Boards at
appropriate locations in the MetroHealth System or at other locations (e.g., at other
institutions, at conferences).
• In-service presentations at any of the locales listed above. Approved recruitment
materials may be distributed or displayed.
• Stroke Research Introductory Contact Cards (the size of a business card) will be
made available for inclusion with mailings, distribution by clinicians, distribution at
inservices or other meetings, etc.
• Appropriate Informational Internet Sites (e.g., clinicaltrials.gov, MHS Clinical Trials
Website).
• A recruitment campaign will be commissioned from Splash Clinical.
Initially, candidates who respond will be informally screened (possibly over the
phone). Those who pass the informal screening will be scheduled for a formal, more
detailed assessment of eligibility by the study team, usually including the PI or a
physician co-investigator. An informed consent form will be provided for review,
usually in advance. During the Eligibility visit, the clinical nurse coordinator will
describe the research, review the consent form with the candidate, address all initial
questions (with referral to the PI or a physician co-investigator as per the candidate’s
request and the clinical nurse coordinator’s discretion), and request participation in
the study. Discussion is encouraged during the exchange to gauge subject
comprehension. Candidates are free to take more time to think about it, consult with
family or friends, and have additional questions answered if they wish. If and when a
candidate agrees to participate, they sign the consent form, after which the formal
assessment of eligibility takes place. Subjects may ask questions at any time. All
questions will be answered.
  13.4
What measures will be taken during the recruitment process to safeguard
against the potential coercion or appearance of coercion of human subjects,
particularly vulnerable subject groups?
All potential subjects will be assured that they may decline participation without
jeopardizing their medical and rehabilitation care or compromising their relationship
with their physician or MetroHealth Medical Center. All subjects have an opportunity
to review the consent forms at home and discuss participation with family, friends,
etc.
  Please give an explanation of
safeguards to be used.
  13.5
Incentives to Subjects: Will subjects receive any incentives (payments, free
service, gifts, etc.) for participation in the research?
No
  This information must mirror
the consent form language.
 
   13.6 If yes, please describe these incentives and how they will be disbursed: Note:
payment or compensation to subjects for participation is not to be considered a
potential benefit.
Transportation may be arranged for the study participant and covered by the study
budget. Alternatively, subjects who are able to drive may receive reimbursement for
parking.
  Describe incentives, if they are
to be pro-rated based on visits
completed please give that
information. This information
must mirror consent form
language.
 
  13.7
Please attach copies of all recruitment/advertising materials and verbal scripts:
Name
Version
PNS PT study information sheet(tracked).docx | History
0.01
PNS+PT Brochure (11-Sept-2018) | History
0.06
  Attach copies of all recruitment
and advertising materials.

Name
Version
PNS+PT for HSP Appointment Reminder | History
0.01
PNS+PT for HSP Consent Cover Form Letter | History
0.04
PNS+PT for HSP Evaluation Cover Form Letter | History
0.08
PNS+PT for HSP Evaluation Cover Form Letter- Tracked.doc | History
0.03
Poster - PMR Research (5 versions with varying logos, Sep 2017) | History
0.03
Poster - Shoulder Pain (5 versions with varying logos, Sep 2017) | History
0.03
Research Ad(newsletter) | History
0.01
ResearchMatch Study Contact Message | History
0.01
Shoulder Pain Studies Recruitment Video (21-Jun-2017) | History
0.02
Shoulder Pain Study Flyer | History
0.01
Splash Clinical -- MetroHealth Campus_Stroke Study_Marketing
Materials_10.3.17 | History
0.01
Stroke Research Ad 5.0 for Craigslist (24-Jul-2013) | History
0.02
Stroke Research Ad 6.0 (01-Aug-19) | History
0.03
Stroke Research Metro In-House Messaging 5.0 (24-Jul-2013) | History
0.02
Study Information Sheet | History
0.03
View: 13-01 Recruitment II
  13.1  Recruitment II:
  13.8 
Expense to Subjects: Will subjects incur any expenses as a result of
participation in the study or will they be billed for any study-related
procedures?
No  
  Check yes or no, make sure this
information is in the consent.
  13.9
If yes, please describe the expenses or charges that subjects will be assessed:
  Please provide information
regarding expenses to subjects
and add information to
consent.   
  13.10  Compensation For Injury: If applicable, will funding be available to
compensate subjects for injuries sustained as a result of participation in this
research?
No  
  Check yes or no, make sure this
information is in the consent.  
  13.11
Who will cover the costs related to any injuries sustained due to participation in
the study?
The subject and his/her insurance carrier will be responsible for these costs.
  Please describe in detail.
Examples subjects or their
insurance company, study 
sponsor.
View: 14-00 Data Collection
  14.0 Data Collection:

  14.1  A. What type of data will you be collecting as part of this research?
Will you collect existing data?
 
or
Will you collect prospective data?
  
Yes 
No
or                                 
Will you collect both existing and prospective data?   
Yes 
No
Definitions: Data are considered to be existing data only if they were in place or
"on the shelf" prior to the submission of the research protocol to the IRB.  Data
are considered prospective if they are created and collected as part of the research
i.e. from surveys, questionnaires. 
B. Why are you collecting this data?
What will be the purpose of collecting and/or reviewing the data (new data or
existing data).
The data collected in this study will be used to determine and document eligibility
and suitability for the study, to establish baseline data for the study, to document
status throughout the study, and to determine the effects of the intervention provided
during the study.
 
  Existing data must be in place
or on the shelf prior to the
submission of the research
protocol to the IRB.
Prospective data is collected in
real time.
 
 
 
 
Tell the IRB why you are
collecting this data i.e. to verify
inclusion criteria.
 
14.2
If you are collecting existing data:
Specify the type(s) of existing data sources you will use (medical records, school
records, publicly available records, existing database). If you are collecting data
from an exisitng database and that database contains PHI, you must provide the
IRB Approval letter (attach to Section 27.00 Additional Documents).
During the baseline visit, subjects will be queried for existing medical history,
including medication usage. In addition, data to collect descriptive
characteristics (e.g, age, duration shoulder pain, ethnicity) will be collected from
the medical record.
What is the timeframe of the existing data you wish to review? (i.e. 2000-2006)
The timeframe will be patient-dependent, covering the time since their first
stroke and/or first evaluation for shoulder pain.
  Specify the types of existing
data you will use in this study. 
 
 
Time frame i.e. last 10 years or
from 1990-2000.
  14.3  If you are collecting prospective data:
Where or how will the data be obtained? (i.e. surveys, questionnaires,
psychological tests)
Data will be collected during each visit to MHMC and during phone calls when visits
are not necessary. Data that is collected is described in detail at 8.4, 8.6 and 10.4.
If immediate hazard to subject to come to the labs in PMR at OBHC the visit will be
completed via telephone, email or telehealth
   
Where will data
be obtained? i.e. survey.
  14.4
How will the data you collect be identified?
Types of Data Identification:
Name
Deidentified/Confidential- Data will be linked to subject(s) via a code or indirect
identifier (i.e. study IDs or numbers)
Identifiable- Data will be linked to subject(s) via direct identifier (names, medical
records numbers, etc.)
   
Please select how your subject
data will be identified.

  14.5
 
 
14.6 
 
 
Will the information collected from these records be linked to any research
subjects by identifiers? (i.e. name, MRN#, DOB)
  
Yes 
No
Please answer questions about the security of the data in section 15.00
If subject data will be deindentified using a code will there be a link or a key?
Please describe. Who will have the key and where will the key be kept? 
Data will be maintained by the study coordinator in REDCAP. Data will be
deindentified and labeled with each subject’s ID. The Subject ID Log which provides
a link between the subject ID and patient name will be kept on Redcap, accessible to
study staff.
Under the HIPAA Regulations, deidentified key codes must be stores
separately from data & must not be kept on paper, but electronically. The
MetroHealth Research Informatics Support should be contacted at
REDcap@metrohealth.org for assistance. They will assist personnel in
developing a key in MetroHealth REDcap database. They can also assist with
training & development for your study. REDcap is a free database provided in
part by the Case CTSA.
 
  Will your data be linked to
subjects?
 
 
Explain how Data will be
linked. 
 
  14.7
Data Collection Form(s):
Name
Version
PNS+PT Adverse Event | History
0.01
PNS+PT Assessment CRFs (23-Feb-2017) | History
0.03
PNS+PT Medication Diary | History
0.01
PNS+PT Study Termination (16-Nov-2016) | History
0.02
PNS+PT Survey Outcomes Visits (16-Nov-2016) | History
0.02
PNS+PT Treatment Binder CRFs (07-Jun-2017) | History
0.04
PNS+PT Unscheduled Study Visit (16-Nov-2016) | History
0.02
REDCAP Data Collection Forms(all forms) | History
0.01
  Add data collection forms and
CRFs.
        
View: 15-00 Data Security I
  15.0 Data Security I:
It is imperative that the IRB is proactive and consistent in protecting all research data containing Protected Health
Information(PHI).
15.1 * Are the records for this study (some or all) electronic?   
Yes 
No
What is Protected Health Information? The Privacy Rule protects certain information that covered entities use and
disclose. This information is called protected health information (PHI), which is generally individually identifiable health
information that is transmitted by, or maintained in, electronic media or any other form or medium. This information
must relate to 1) the past, present, or future physical or mental health, or condition of an individual; 2) provision of health
care to an individual; or 3) payment for the provision of health care to an individual. If the information identifies or
provides a reasonable basis to believe it can be used to identify an individual, it is considered individually identifiable
health information.
The following questions must be answered when submitting a new protocol. 
15.2       * Are you collecting PHI?   
Yes 
No            
15.3       Is any PHI going to be stored as paper files?   
Yes 
No
15.4       Is any PHI going to be stored in an electronic file format? (i.e. access, excel)   
Yes 
No
15.5       Is your data being stored on a laptop computer?   
Yes 
No
15.6       Will you be using RedCap to store your data?   
Yes 
No

               Which RedCap Database will you be using?
Name
MetroHealth
Case
15.7       Are you planning to store your data using a portable storage device?(i.e. jump drive, external hard drive, cd)   
Yes 
No
               *Per current MetroHealth Policy PHI may not be stored on portable electronic devices. 
15.8       Are there any circumstances under which you would want to remove data from MHS? (i.e. take data home to
work on it) Give details below. Please note identified data can't be removed from MHS unless there is permission granted
in the HIPAA Authorization. If you are unsure about what is identified data please consult the IRB staff. If you feel you
will need access to your data when you are off campus you should ask the MHS IT Department located in Rammelkamp
room R 134 about VPN access.  
  
Yes 
No
               If you answered yes to question 15.8, please explain?
PHI will remain at Metro. Any data stored on portable media and/or removed from Metro would be deidentified. Such data may
be transported to work on elsewhere.
        
  15.9
Where will the records pertaining to this research be stored? (give the actual
physical location of the paper records i.e building name and room
number); and/or the secure network drive where the data is being stored.
Electronic records (inc. electronic photos & videos): For PHI stored electronically,
password protected secure MHS network drives will be used for electronic data in
folders with access limited to those who are authorized by this protocol. The
Subject ID log will be stored on Metro Redcap. Most study data (deidentified) will
be stored in a database on Case Redcap. For portable media or other computers
such as laptops, only deidentified data will be stored.
Paper records (inc. non-electronic photos & videos): For this study, these records
are stored in the following staff offices which are locked when unoccupied: OBC 2
Main SM2-057. Also, the PI’s office is OBC 2 Main. These records with PHI are
kept in locked cabinets in these rooms.
  State the exact physical
location of paper files and the
network drive for electronic
files.
  
  15.10
How will these records be secured (we are refering to both paper records and
electronic records)? Examples for electronic records (i.e. secure drive,
password protected documents, encrypted jump drive). Examples for paper
records, must be double locked (i.e. locked office and locked file cabinet or a
locked file box inside a locked cabinet).
Offices, Labs and storage cabinets are kept locked. EPIC, which is secured,
also will be used. For PHI stored electronically, password protected secure
MHS network drives will be used for electronic data in folders with access
limited to those who are authorized by this protocol. Only deidentified data
will be stored on portable media. Non-electronic records are kept in locked
cabinets in rooms that are locked when unoccupied.
  i.e. locked cabinet, locked
room.
  15.11     Who will have access to the data?
Non-Metro staff who will have access to at least some PHI as well as deidentified
data include the following study staff: Nathan Makowski (Post-Doctoral Research
Staff). If necessary, representatives of the Metro IRB, NIH, and FDA will also have
access.
Please Note: All study documents must be retained for a minimum of four years
after study completion (even when no subjects have been enrolled), twenty-two
years if study involves children or pregnant women. Records for device studies
must not be assigned a destruction date until the FDA approval status is
determined, at which point records will be retained according to the scheme above
(minimum of four or twenty-two years as appropriate). Under HIPAA regulations
you must keep a record of all medical records where you looked at or recorded PHI
(without a HIPAA Authorization) for 6 years (i.e. prep for research).
  Give name and title exclude
study staff who are MHS
employees.

MHS Record Retention Policy VII-4
  15.12
 
 
15.13
How long will you keep the records pertaining to this research? Where will
these records be stored after the study has been completed?
The PI will store these records indefinitely since it is unknown exactly how long it
will be necessary to maintain the records for possible later review and potential
additional analysis in response to post-publication inquiries from the funding or
scientific communities, or in support of new grant proposals. After completion of
the study, the records will continue to be stored as already described:
Electronic records (inc. electronic photos & videos): For PHI stored electronically,
password protected secure MHS network drives will be used for electronic data in
folders with access limited to those who are authorized by this protocol. The
Subject ID log will be stored on Redcap. For portable media or other computers
such as laptops, only deidentified data will be stored.
Paper records (inc. non-electronic photos & videos): For this study, these records
are stored in the following staff offices which are locked when unoccupied: OBC
2Main SM2-057. Also, the PI’s office OBC 2Main. These records with PHI are
kept in locked cabinets in these rooms.
Offices, Labs and storage cabinets are kept locked. EPIC, which is secured, also
will be used. For PHI stored electronically, password protected secure MHS
network drives will be used for electronic data in folders with access limited to
those who are authorized by this protocol. Only deidentified data will be stored on
portable media. Non-electronic records are kept in locked cabinets in rooms that
are locked when unoccupied.
Where, when, and how will the information be destroyed?
If and when it is determined that the information is to be destroyed, paper and
electronic records will be destroyed in compliance with MHS policies and
methodologies.
*Please Note: There are EPA regulations surrounding the destruction of CDs,
DVDs, Floppy discs and other portable storage media. If you want to destroy
these types of media please contact Ron Wallace in Environmental Services at
778-4776. 
 
 
 
 
  Check the MHS Record
retention policy for guidance.
You must have a plan for data
destruction.
View: 15-01 Data Security II
  15.1 Data Security II:
  15.14
 
 
Who (non-study staff) will have access to the records? Give name and title of
individuals. Where an individual's name is not known give title i.e. monitor
from CRO.
If necessary, representatives of the Metro IRB, NIH, and FDA will have access.
  List all those not study staff who
will see and have access to
data.
  15.15
Will data be transmitted to the sponsor?   
Yes 
No  
  Are you sending CRFs to
sponsor?
  15.16
 
If yes, describe what data will be sent to the sponsor and the provisions that
have been made for preservation of confidentiality in the transmission of data
to the sponsor:
Deidentified information and results will be sent to the funding agency (NIH).
If necessary, FDA is authorized to review information.
  Please describe i.e. will you be
using encryption software?

  15.17
Will the data from this research project be transmitted to anyone other than
the sponsor?   
Yes 
No
  Check yes or no.
  15.18  If yes, to whom will this data be transmitted?
  Please describe organization or
individual.
  15.19
Describe the data that will be sent to entities other than the sponsor and what
provisions have been made for the preservation of confidentiality:
  Please describe data, and
confidentiality provisions.
View: 16-00 Request for a Partial Waiver of HIPAA Authorization
  16.00 Request For a Partial Wavier of HIPAA Authorization
An IRB, under certain circumstances, may allow researchers to forgo obtaining an authorization; this is called a waiver of authorization. A waiver of
authorization may be full or partial:
full waiver: an IRB waives the requirement for authorization for all uses of PHI for a particular research protocol (see Section 16.01 Request for a
Waiver of HIPAA Authorization);
partial waiver: an IRB waives the requirement for an authorization only for some uses of PHI for a particular research protocol. Researchers are
required to obtain subjects' Research Authorizations after recruiting and enrolling subjects via a partial waiver and prior to creating or using PHI
during research procedures.
Partial Waiver for Preparatory for Research Activities:
According to HHS guidance on the Privacy Rule the preparatory to research provision permits covered entities to use or disclose protected
health information for purposes preparatory to research, such as to aid study recruitment. However, the provision at 45 CFR
164.512(i)(1)(ii) does not permit the researcher to remove protected health information from the covered entity's
site. As such, a researcher who is an employee or a member of the covered entity's workforce could use protected health
information to contact prospective research subjects. The preparatory research provision would allow such a researcher to
identify prospective research participants for purposes of seeking their Authorization to use or disclose protected health
information for a research study.
Under the preparatory to research provision, a covered entity may permit a researcher who works for that covered entity to use
PHI for purposes preparatory to research. A covered entity may also permit, as a disclosure of PHI, a researcher who is not a
workforce member of that covered entity to review PHI (within that covered entity) for purposes preparatory to research.
 
  16.1  Are you requesting a Partial Waiver of HIPAA Authorization?   
Yes 
No
Why are you requesting a Partial Waviver?
  Check yes or no. 
  16.2
Is the purpose of the Partial Waiver Recruitment (including screening of Medical
Records)?
  
Yes 
No
Is the purpose of the Partial Waiver to request access to PHI for Non-MetroHealth
personnel?
  
Yes 
No
  Check yes or no.  
  16.3  Will the use of Protected Health Information (PHI) involve more than minimal risk to
the privacy of the patients?
  
Yes 
No
  Check yes or no.  
  16.4
The IRB as part of it's review of this request must have certain reassurances that
Patient Privacy will be protected, please respond to the following questions true or
false.
1.) The PHI will be used solely to facilitate the research protocol as an aid to study
recruitment or to expand the research study. The waiver would allow identification of
prospective research participants for the purpose of seeking authorization to use or
disclose PHI for a research study. Essentially, PHI will be used to identify and contact
potential research participants. Only contact and screening information (race, age,
medications, diagnosis, and primary physician) will be recorded, and no information
will leave the premises of MetroHealth Medical Center. The information will not be
disclosed outside the research group for this study.   
True 
False
2.) Information about potential subjects who are not interested in participating will be
destroyed after the patient declines enrollment. The information of patients choosing
to participate will be further used to schedule an appointment. As soon as the research
  Check true or false. 
 
 

staff sees the participant, a full authorization will be obtained to collect, use and
disclose PHI for the remainder of the study.   
True 
False
3.) The PHI will not be reused or disclosed. Because the PHI belongs to individuals
who are not yet in the study, oversight provisions do not apply. After subjects are
formally enrolled, an authorization will be in effect and the waiver will no longer
apply.   
True 
False
  16.5
If you did not answer true to all three parts of question 16.4 please explain:
  Please explain your response to
any statement where you have
entered false.
  16.6
Please give a detailed explanation as to why this research activity cannot be
practicably conducted without a Partial Waiver or without access to PHI:
While most candidates for the study are expected to be identified via direct referral
from the investigators and their department colleagues, or via means whereby the
candidates initially contact us, some prospective candidates for the study could be
identified via review of the electronic medical record system.
Candidates who agree to an Eligibility visit will be asked to sign a Consent and
HIPAA Authorization.
  Example: our study
population has xxx disease and
we rely on the EMR
information to identify and
contact potential subjects.
  16.7
Who will have access to PHI? Please list below:
Name
Employer
Department
Employer Name
John Chae
Metro
PM&R
The MetroHealth
System
Amy Friedl
MetroHealth
PM & R
The MetroHealth
System
Douglas
Gunzler
MetroHealth
Medicine
The MetroHealth
System
Kristine
Hansen
MHS
Physical Medicine and
Rehabilitation
Physical Medicine and
Rehabilitation
Terri Hisel
MHS
PM&R Research
Physical Medicine and
Rehabilitation
Shannon
Hogan
MetroHealth
PM & R
The MetroHealth
System
Nathaniel
Makowski
Case Western
Reserve University
Physical Medicine and
Rehabilitation
The MetroHealth
System
Richard
Wilson
Metro
PM&R
The MetroHealth
System
  Add the names of persons who
will have access to PHI. 
  16.8
Are you or anyone who assists you Non-MetroHealth Personnel?   
Yes 
No
*Note all Non-MetroHealth Personnel have to go through employee orientation, have
a security clearance and Epic training before they can access the MetroHealth EMR.
Also all all Non-MetroHealth Personnel must work under the control of a member of
the MetroHealth Staff.
 If you have previously completed an MHS Prep for Research form add that form
here: 
Name
Version
There are no items to display
Old Memos Requesting Partial Waivers (prior to 11/26/2010):
There are no items to display
  Check yes or no. 
 
If you filed a Prep for research
form with IT and RABO please
attach it here.
Partial Wavier Memos
completed prior to 11/26/2010
will populate here.
 
View: 16-01 Request for a HIPAA Waiver of Authorization
  16.1 Request For a HIPAA Waiver of Authorization:
  16.9 
Are you requesting a Waiver of HIPAA Authorization?
No
  Check yes or no.

Check one, if you check no then hit continue and go to the next page.
If you are requesting a Waiver In order for the IRB to Grant a Waiver you
must answer questions 16.10-16.16
 
  16.10
Disclosure of Protected Health Information (PHI) will not involve more than
minimal risk to the privacy of the patients/subjects:
  Check true or false.
  16.11  What is the plan to protect patient/subject identifiers from improper use and
disclosure?
  i.e. This unique identifier will
be used on the data collection
form. Only the PI will have
access to the key linking the
unique identifier to
patient/subject names. 
  16.12
What is the plan to destroy the identifiers at the earliest opportunity consistent
with the conduct of the research?
  i.e. The unique identifier key
will be retained in Red Cap and
will be destroyed two years
after the study ends.
  16.13
Will PHI be reused or disclosed to others:  
  Check yes or no.
  16.14
Please complete the following: Data will only be used to analyze...
  i.e. Data will only be used to
analyze...
  16.15
Describe why this research can not be conducted without a waiver:
  i.e because many of the subjects
who participate in this treatment
are dead or have transferred to
other treatment modalities, or
are transient. To obtain HIPAA
Authorization from these
individuals would be a greater
risk to their loss of privacy.
  16.16
Describe why this research could not be conducted without access to and use of
PHI:
  i.e. It would not be possible to
determine linkages between
.......and clinical outcomes
without the use of PHI.
View: 16-02 HIPAA II
  16.2 HIPAA II:
  16.11
 
Which of the following identifiers about subjects will be
collected for this study?
Name
2. Telephone Numbers
3. Address - Street
4. Address - Town or City
5. Address - State
6. Address - Zip Code
8. Names or Initials
11. Full face photographic images or comparable images
15. Medical device identifiers or serial numbers
16. Medical record or prescription numbers
18. Email addresses
20. Social Security Numbers
21. Dates (except year) related to an individual (birth date,
admission date, discharge date, date of death)
       
                      
Check all that apply, your answers
will help the IRB to determine if
your data is a limited data set.

These Questions deal with the collection of data and data use
agreements. If you are not receiving data or sending data out to
another entity this does not apply to you. If you have a signed
contract with a sponsor or are in a cooperative group that has a
signed agreement with MHS this does not apply to you. Data use
agreements specify the conditions under which data can be shared
between MHS and other organizations or individuals.
   16.12 If you have selected only numbers 4, 5, 6, or 22 in question
number 16.11 your research is considered to use a limited data
set. If either of the following conditions apply, you will need to
obtain a Data Use Agreement and complete a waiver of
authorization or obtain a HIPAA authorization from the
subjects. (check one):
Name
There are no items to display
Check one, please read carefully
if you are not receiving data or
sending data out to another
entity this does not apply to you,
move on to 16.14. If you have a
contract with a sponsor or you
are in a cooperative group that
has a signed agreement with
MHS this does not apply to you.
In all other cases please
contact the MHS Legal
Department with questions about
data use agreements.
  16.13
Attach a copy of the Data Use Agreement:
Name
Description
There are no items to display
 
Attach Data Use Agreement.
View: 16-03 HIPAA III
  16.3 HIPAA III:
  16.14  If any other unique identifying number, characteristic or code is selected,
please specify:
  Please specify this question
refers back to the list of 22
identifiers.
  16.15
If a link to an identifier will be used (i.e. code numbers) is selected, please
describe the coding mechanism that will be used:
Coding mechanism will be associated with sequential enrollment at each site.
At Metro, numbers will be preceded by the letter "M". Thus, the enrolled
subjects would be numbered M-01, M-02, etc. (At SRAL, numbers will be
preceded by the letter "R". Thus, the enrolled subjects would be numbered R-
01, R-02, etc.) "CR" will be use for Carolinas Rehabilitation
  Describe the coding
mechanism.
  16.16  Will a certificate of Confidentiality be obtained for this study? No  
  Check yes or no. 
  16.17
If yes, please attach a copy the Certificate of Confidentiality:
Name
Version
There are no items to display
  Attach a copy of the Certificate
of Confidentiality.
   16.18 Describe how you will protect the privacy of participants. Describe specifically
how you will gather information from or about them. Please note while
confidentiality concerns data, privacy concerns people. Example People may be
uncomfortable answering questions about their employer in an open cubicle, so
investigators may arrange for a more private location.
Subject screening, informed consent, and eligibility determination procedures as
well as medical histories will be conducted in a closed room with only the necessary
study personnel present. Device deployment and data collection procedures will be
done in labs with closed doors and only the necessary personnel present.
 
  Please note while
confidentiality concerns data,
privacy concerns people.  
   
   
View: 17-00 Waiver of Informed Consent
  17.0  Request for a Waiver or Alteration of Informed Consent:
             

   17.1 Are you requesting a Waiver of Consent [45 CFR 46.116(d)] OR a Waiver of
Documentation of Consent [45 CFR 46.117 (c)]. 
No  
If no hit continue button and you will go to the next page.
If yes please Note:
Note: Waivers of consent are not applicable if the research is subject to FDA
regulations, except the following.
FDA Exception from general requirements:
1. Emergency Ues: Waivers of Informed Consent in FDA-regulated studies are
permissible in case of life-threatening situations, inability to communicate, not
sufficient time and no alternative method, even if research presents more than
minimal risk [21CFR50.23];
2. Planned Emergency Research: If the study satisfies the requirements under
21CFR50.24 “Exception from Informed Consent Requirements for Emergency
Research.”
 
  Answer yes or no.
  17.2
Waiver of Consent: If you are requesting a waiver of consent, please provide the
justification and address each of the following points for the IRB's
consideration:
This research study involves no more than minimal risk:
The waiver will not adversely affect the rights and welfare of the subjects:
This research could not practicably be carried out without a waiver:
Whenever appropriate, the subjects will be provided with additional pertinent
information after participation:
  
Yes 
No
  Check true or false.
 
Note: practicably does not
mean it would be inconvenient.
 
  17.3  Please explain your answers to the above questions (You must provide the IRB
with enough information to make a decision):
An IRB may waive the requirement to obtain a signed consent form for some or all
subjects if it finds either of the conditions below. In cases in which the
documentation requirement is waived, the IRB may require the investigator to
provide subjects with a written statement regarding the research.
  Please explain in detail.
  17.4
 
 
17.5
(1) 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; OR
(2) The research presents no more than minimal risk of harm to subjects and involves no
procedures for which written consent is normally required outside of the research context.
  
Yes 
No
  Check true or false.
 
Check yes or no.
  17.6
If you are requesting any Alteration to the standard consent form/process
(written long form consent is the standard) please provide a detailed
explanation or plan.
  Example of an alteration:
verbal consent.
View: 17-01 Informed Consent Process I
  17.1  Informed Consent Process I:

  17.7
Who will be approached to obtain consent/assent:
Consent Method
Subjects will be asked to sign a study consent form after receiving a complete
explanation of the study.
  Check all that apply.
   
 Idendtify all Staff obtaining consent on page 1 question 1.4 by selecting the
corresponding role.
 
   17.8
Subject Comprehension: What measures will be taken to ensure that subjects
fully understand the nature of their involvement in the research?
Note to Investigator: 
To address issues of comprehension on the part of the participant or
representative, and who is involved in obtaining consent, the answers to
following questions should be addressed:
1.)  Once a potential participant is identified, what process is
followed to inform the subject of the study prior to obtaining a
signature on the informed consent form?
a.    Who introduces the study to the potential subject?
b.    Who reviews the informed consent document in depth?
c.     Do you require the potential participant to have another person
present during the presentation of the study? 
2.)      Who answers the questions presented by the potential   
participant and/or family? 
3.)      What method is used to determine if the potential participant
fully understands the study, what is required from them, risk and
benefits, and their rights as a participant? 
4.)      Is the principal investigator usually present during the
presentation of the informed consent?
The study is first introduced in general terms by our Metro clinical staff listed on the
study (physicians, nurses, therapists, coordinator). Physicians may cite the study
during a clinical visit if the patient seems appropriate. Clinical Staff(Coordinator)
may then follow-up with the candidate. They also may introduce the study to a
candidate who responds to an ad or makes other inquiries.
Typically the Clinical Coordinator conducts Consent/Eligibility Visits, reviews the
ICF in depth, and answers any questions presented by the candidate and/or their
caregiver(s). Candidates are not required to have another person present during the
presentation of the study, but they often do so. Typically, the PI and Co-Investigators
are not involved in the entire lengthy process but they would be involved for a
portion of eligibility determination and, as necessary, would address questions that
cannot be otherwise addressed.
An ongoing dialogue takes place during the subject's introduction to the study and
the informed consent process to ensure that the candidate fully understands the
study, what is required from them, risk and benefits, and their rights as a participant.
Questions are encouraged and answered. In addition, after consent, only subjects that
obtain a score of ≥24 on the Mini Mental Status Examination will be enrolled as it is
used to determine the subject’s cognitive ability to understand the study
requirements.
See 17.10 for more details.
  Please give brief explaination.
   17.9
Capacity to Consent: How will capacity to consent be assessed? This question is
to be addressed for all subjects not just those with limited decision making
capacity. Identify who will make this assessment? Suggested language....all
subjects will be awake, alert and oriented, be able to read etc. It is important to
address issues like ability to read and understand information in the consent. 
All subjects will be awake, alert, and oriented. Cognitive function is assessed as
described in the inclusion criteria. The PI or physician co-investigator will use their
clinical discretion in making the final determination.
  How will you determine
capacity to consent?
   17.10 Attach a description of the Consent Process: Explain the process of obtaining
consent from subjects. Under what settings and conditions will consent be
  Attach a plan for consenting
subjects. This must give detail

obtained? What will be the timing/waiting period? What measures will be taken
to ensure that subjects will make decisions independently? Note to Investigator: 
The “informed consent process” should include sufficient time for the participant to
review and consider participating with the assistance of family members, research
partners or representative if necessary.  Other items to consider regarding time /
waiting periods are:  Is the potential participant given a copy of the consent form to read
prior to the discussion of the study?  Is it presented in person or mailed (where they can
review it in the privacy of their own home)? How much time elapses between the
presentation of the study and informed consent form and the actual signing of the form?  The
answers to these questions will ensure the PI has considered this component of the process
and will reassure the IRB that the PI is allowing adequate time for the participant to make
an informed decision and minimize the possibility of coercion or undue influence.
Name
Description
Informed Consent Process (01-09-2009) | History
 
about the consent process. 
   17.11
Parental Permission and Youth Assent: Complete this question only if enrolling
minors. How will parental permission and youth assent (if applicable) be
obtained?
  Give details of assent process
and assent form.
View: 17-02 Informed Consent Process II
  17.2 Informed Consent Process II:
  17.12  What method will be used to document the consent process (i.e. a note in EPIC)? Not
how you will get consent only how you will document consent has been obtained, i.e
chart note, note in study file.
Subjects will sign a consent form. The original consent form will be scanned into Epic and
placed in the study file. EPIC will be used to schedule subjects and to document the informed
consent process.
 
   i.e chart note, note in
study file.
  17.13
What type of Informed Consent will be used in this study? (check all that apply):
Consent Type
Written/Signed Consent by Subject
Video/Audio Consent Form
  Check all that apply
A non-return cover
memo applies to a
study in which you are
sending out a
questionnaire with a
memo or letter that
informs participants
about the study but
does not need to be
signed and returned. If
they complete and
return the
questionnaire they
have given consent.
  17.14
If other, please specify:
****Attach all consent forms (Informed Consent, Genetic Consent and HIPAA) here:****
  If other, please give
specifics. 
  17.15
 Please attach a copy of each Informed Consent form(s) and HIPAA Authorization you
are using for this study:
Name
Version
PNS+PT in HSP Consent and HIPAA 2.4
0.18
PNS+PT in HSP Consent and HIPAA 2.4 (tracked)
0.14
PNS+PT in HSP HIPAA Alternative Means 1.3 (30-Jul-2019)
0.04
PNS+PT in HSP HIPAA Alternative Means 1.3 (30-Jul-2019, highlighted)
0.02
PNS+PT in HSP Video-Photo Consent 1.0 (16-May-2016)
0.01
 
  Attach Consent form(s)
and HIPAA
Authorization here

  17.16
Will non-English speaking subjects be enrolled?
Yes  
No        Clear
If the answer to 17.17 is no we will not be enrolling non-English speaking subjects then
tell the IRB why not?


There is a significant amount of patient documentation (consent forms, 
manuals, questionnaires) that would require translation. Also, the research, 
and the necessary interaction with the study team, requires understanding of 
 
  Check one
Please give the IRB an
explanation as to why
non-English speaking
subjects will not be
enrolled.
  17.17
If non-English speaking subjects will be enrolled please provide information about the
person(s) obtaining consent (what language they will speak)and how you will deal with
written translation(s):
  Provide information
about translating
consents and having
interpertative services
available for consent.
View: 18-00 Data Safety Monitoring I
 
Section 18.0 Data Safety Monitoring Plan
DATA AND SAFETY MONITORING PLAN GUIDE
 
WHEN DO YOU HAVE TO COMPLETE A DATA SAFETY MONITORING PLAN? 
 
FOR THE IRB- All interventional studies that are greater than minimal risk should have a Data Safety Monitoring Plan. The IRB reserves the right to
require a Data Safety Monitoring Plan for any study.
 
Archived IRB Data Plans - prior to 9/28/2010
 
 
 
FOR THE CRU-  ALL CRU PROTOCOLS [Recent NIH guidelines stipulate that all protocols that involve human subjects, a
signed consent form and are conducted on, or use the resources of, the CTSA Clinical Research Unit - MHMC
(CRU) are required to have a Data and Safety Monitoring Plan (DSM Plan).] 
 
What is a Data and Safety Monitoring Plan (DSM Plan)?
 
A DSM Plan is a prospectively defined strategy to assess the assumptions made in the trial design while the study is in progress.  Its main purpose is to
ensure the safety of participants in clinical research studies and the validity and integrity of research data collection. A properly designed DSM Plan
improves the scientific quality and yield from a clinical trial and the protection of human subjects.
 
The DSM Plan needs to address the nature of the safety monitoring and who will be conducting that monitoring.  It may be reasonable for a single
individual to perform the monitoring in a small trial with minimal/low risk while a local independent or an external data and safety monitoring board
(DSMB) may be required for more complex/high risk trials.
 
Key elements to be incorporated in a DSM Plan
 
·          Assessment of risks and monitoring level
·          Safety contact: Who is responsible?  
·          Safety monitoring: Who will do it? How often?
·          Informed consent process; consistency with the protocol
·          Data collection process
·          Adverse Events Monitoring: Anticipated and unanticipated
·          Description of anticipated adverse events
·          Grading and attribution method
·          Reporting of unanticipated adverse events
·          Plans for periodic reporting
·          Impact on termination of subjects from the study and study closure
 
 
Step 1 - only for Investigators Using the CRU:
1.A Is your protocol approved  and supported by the Ireland Cancer Center?   
Yes 
No
If Yes - The Comprehensive Cancer Center Data and Safety Moniotoring Plan for Clinical Trials is on file. Proceed to Step 5.1.B If No, Proceed and
complete Steps 2-5
**********
Step 2 - all Investigators - Provide Information in order to determine the level of safety monitoring required
2.A List all data collection types and study procedures (this information will pull from Section 8 Methods and Procedures questions 8.1, 8.2, 8.3)

Data Collection types:
Name
Audio-Recording/Video-Recording/Photographs
Chart Review - Prospective
Existing/Retrospective Data/Specimens
Interviews, questionnaires or psychological tests
Social-Behavioral Procedures:
Name
Psychological Testing
Surveys/Questionnaires
Medical Procedures:
Name
Collection of Biohazardous Substances
Study of Human Biological Materials (i.e. Urine Collection)
Investigation/Approved Devices
Study of Existing Data
Medical Tests, Comparisons, Evaluations
Clinical Assessments (EEG, EKG, SCID, etc.)
Venipuncture (Blood Draw)
Use of investigational devices
Psychological testing
**********
*You must select the risk level Please read the information below, check the applicable boxes and select an appropriate risk level.
Level I: Minimal and Low Risk Studies (examples of studies that are minimal and low risk studies)
Types of Studies:
Name
Chart Review, interview, questionnaire
Level II: Moderate Risk Studies (examples of studies with populations, drugs, and procedures that are moderate risk)
Types of Studies:
Name
Elderly Population
Psychologically or neurologically impaired population
Level III: High Risk Studies (examples of diagnostic procedures and drugs or device studies which are high risk)
Types of Studies:
Name
There are no items to display
2.B If you do not see your study procedures on the above list please add in the procedures being done for research purposes:
 Add additional risk(s):
Procedure
DSMB Risk
Outcomes Assessments (questionnaires, tests of arm and shoulder movement, pain thresholds)
Moderate
Percutaneous electrode implant procedure/short term implant and e-stim
Moderate
Percutaneous electrode removal
Minimal or Low
Physical Therapy
Minimal or Low
Venipuncture
Minimal or Low
X-Ray
Minimal or Low
Select the Appropriate Level of Risk for this study based on the criteria above:
 Level of Risk:
Risk Level II Moderate Risk Studies

     Now Select the appropriate Level of Monitoring and give your justification:
     2.C Rank Level of Monitoring (select one by checking the box)
     Minimal/Low/Moderate Levels of Monitoring 
     Justification for selecting Minimal/Low/Moderate Level of Monitoring Required:
The most notable study procedure is the short-term percutaneous electrode implantation and electrical stimulation. As detailed later in
this application, the device is FDA Cleared via 510(k) and is being used in accordance with its labeling. Also, the researchers have
extensive experience with the associated procedures and risks, which are well tolerated by subjects. The risks are low, well
understood and well managed. Thus, the lower level of monitoring will be sufficient.
         
     High Level of Monitoring 
     Justification for selecting Risk High Level of Monitoring:
    
       
    
    
    
    
    
  
     
    
  
    
    
    
 
   
    
   
 
   
 
 
 
View: 18-01 Data Safety Monitoring II
  18.01 Data Safety Monitoring II

    A designee will perform the safety monitoring:
  
Yes 
No
Identify the designee [provide contact information]:
At the study team level, the PI will have oversight. Safety monitoring at Metro also will
be overseen by: Study Coordinator
 
 
 
A medical monitor or independent individual/safety officer will be performing the
safety assessments.
  
Yes 
No
Identify who will be performing the safety assessments [provide contact
information]:
In addition to PI oversight, medical safety monitoring will be a DSMB role (see below).
 
    Has a Data Safety Monitoring Board or Committee been established for this study?
  
Yes 
No
Identify these members by name, title and qualifications. How often will the DSMB
meet? How frequently will the DSMB report it's findings?) data prior to 9/28/2010
read only.
 
    If there is a DSMB or DSMC is it a nationally constituted Data and Safety
Monitoring Committee?   
Yes 
No
Please enter the Name of Contact or Chair, Address and Phone or E-Mail:
A DSMB has been established consisting of 5 members. Jayme Knutson PhD is ideally
suited to serve as the DSMB Chair based on his years of experience with FES research
and technology, and with the stroke subject population with whom we work.
Chair:
Jayme S. Knutson, PhD
Associate Director of Regulatory Affairs, Cleveland FES Center
Assistant Professor, Department of Physical Medicine & Rehabilitation, School of
Medicine,
Case Western Reserve University, Cleveland, OH
Senior Staff Scientist, Department Physical Medicine & Rehabilitation,
MetroHealth Medical Center, Cleveland, OH
Director of Research, MetroHealth Rehabilitation Institute of Ohio
MetroHealth Medical Center
4229 Pearl Rd.
Cleveland, OH 44109
jsk12@case.edu
216-957-3557
Statistics/Clinician:
Douglas Einstadter, MD, MPH
Professor of Medicine, Epidemiology and Biostatistics
Member, Center for Health Care Research and Policy
Staff Physician, Department of Medicine
MetroHealth Medical Center
2500 MetroHealth Dr.
Cleveland, OH 44109
deinstatadter@metrohealth.org
216-778-3901
Clinician:
Prathap Jayaram, MD; Clinician
Director of Regenerative Sports Medicine
Assistant Professor of Physical Medicine & Rehabilitation
Assistant Professor of Sports Medicine
Assistant Professor of Orthopedic Surgery
 

Baylor College of Medicine
7200 Cambridge St
Houston, TX 77030
prathap.jayaram@bcm.edu
786-427-9174
Clinician:
Christina Oleson, MD
MetroHealth Rehabilitation Institute
MetroHealth Medical Center
4229 Pearl Rd.
Cleveland, OH 44109
coleson@metrohealth.org
216-957-3556
Ethicist:
Nicole Deming JD, MA
Assistant Dean, Faculty Affairs and Human Resources
Case Western Reserve University
10900 Euclid Ave
Cleveland, OH 44106
nicole.deming@case.edu
216-368-2821
The DSMB will convene regularly to review and monitor the progress of the study with
respect to enrollment, drop-outs, outcomes and safety.
    Is there a locally constituted Data and Safety Monitoring Committee or Board
that will perform the safety monitoring. Specify composition and responsibilities in
the box below. Note: Board Members should not have conflicts with this study or with
study personnel.   
Yes 
No
Names of Members of Local DSMB [provide contact information]:
 
 
 
    3.B.1 Description of anticipated adverse events. Pulled from question 10.5.
1) Risks associated with needle insertion for Sprint MicroLead placement
There are minor risks associated with inserting a Lead through the skin with a needle.
These risks are similar to the risks of any needle injection including the possibilities of
puncturing a blood vessel, irritating a nerve, and temporary bruising or pain at the
insertion site. The risks of puncturing a blood vessel and irritating a nerve are uncommon,
but the risks of temporary bruising and pain at the insertion site are common.
Some participants may experience a vasovagal (“fainting”) response due to the
discomfort or anxiety associated with of the procedure, especially among those with prior
history of “fainting.” This risk is rare and may be associated with symptoms of
lightheadedness, dizziness and or diaphoresis with concomitant reduction in blood
pressure and heart rate. For those with prior history of “fainting” the procedure will be
performed with the subject in the lateral decubitus position.
To minimize the risks associated with percutaneously placing fine wire leads, only
appropriately trained physician investigators will perform the procedure. In addition, the
risk of excessive bleeding will be reduced by excluding candidates who are taking
warfarin with an INR > 3.0 and by placing manual pressure on the implantation site until
hemostasis is achieved. Finally, the risk of discomfort during the procedure will be
reduced by the use of an appropriate amount of local anesthetic.
It is possible that, in some cases, multiple attempts may be required to achieve
appropriate placement of the Lead during the procedure. Each additional attempt at Lead
placement carries the same risks as the initial attempt described in this section.
 

2) Risk of skin irritation, infection, or inflammation at the Sprint MicroLead exit site
There are risks of leaving a Sprint MicroLead in place for 4 weeks, including skin
irritation, infection, and granuloma formation (mild tissue inflammation) at the Lead exit
site. Symptoms include redness, swelling, or pain. The risk of skin irritation is common
while the risks of infection and granuloma formation are rare.
These risks will be minimized by using sterile Leads and thoroughly cleansing the
insertion site with antibacterial solution at the time of insertion. The insertion site will be
covered with a dressing to keep it clean and dry, and the subjects and their caregivers will
be instructed to inspect the site for signs of infection or irritation regularly and to inform
the Investigator if they occur. If infection or skin irritation occurs, the Investigator will
administer an antibiotic and/or remove the Lead. Infections are rare and typically resolve
after Lead removal and antibiotic treatment.
It should be noted that in a completed clinical trial of percutaneous intramuscular
electrical stimulation, one patient death occurred. The subject did not follow the
instructions for the care of the Lead exit site and also did not return for his scheduled
follow-up visit following electrode placement. He developed an electrode related
infection and was hospitalized. The cause of death is thought to be a myocardial
infarction or a pulmonary embolus, but the exact cause of the death and its relationship to
the infection are not known. To mitigate the potential risk of serious infection, a 48-72
hour safety check will be performed after the procedure. Participants will return to the
clinic and the exit site will be evaluated for signs of infection.
3) Risk of the Sprint MicroLead breaking beneath the skin
There is a possibility of a Lead breaking beneath the skin either during the course of the
study or during the procedure to remove Lead. This risk is uncommon. However, when a
Lead breaks, one or more Lead fragments usually remain in the body. The Investigator
will use clinical judgment to determine if the removal of such fragments is necessary.
Visual inspection of the Lead after it has been removed as well as x-rays will be used to
determine if any Lead fragments remain. The risk associated with the x-rays is no greater
than that associated with conventional clinical x-rays. If the Investigator determines a
Lead fragment has been retained in the body, he/she will determine what is medically
required to further evaluate and treat this retained fragment. Typically, no treatment is
required unless there are further sequelae, such as an infection or granuloma, associated
with the fragment.
The risk of leaving a Lead fragment is minimized by reducing the amount of time the
Lead remains implanted and the number of Leads implanted. In this protocol, a single
Sprint MicroLead will be implanted for just 4 weeks.
4) Risk of infection associated with retained Sprint MicroLead fragments
A Lead fragment could result in the formation of a granuloma or infection. Although the
occurrence of a fragment-related infection or granuloma is uncommon an infection may
require removal of the Lead fragment and/or treatment with antibiotics. Investigators at
the Cleveland FES Center and Case Western Reserve University have over 30 years of
experience with dozens of research participants and hundreds of implanted leads like
those used in this study. Infections and granulomas of leads or lead fragments have been
uncommon, which is attributed to the materials and procedures that have been developed
as well as the extensive experience of the Investigators..
5) Risks associated with lead fragment removal
It is possible that a Lead fragment or fragments may be retained in the body following
removal of the Sprint MicroLead. If the Investigator determines that a lead fragment has
been retained, the Investigator will instruct the subject and his/her caregiver to carefully
inspect the Sprint MicroLead exit site and the surrounding skin in the weeks subsequent
to Lead removal. Subjects will be instructed to contact the Investigator if there are any
signs of pain, redness, swelling, discharge, or the appearance of a pimple-like mass (skin
abscess). Such signs indicate that the fragment has migrated to the skin surface. At that

time, if clinically warranted, the fragment may be removed via an outpatient procedure
which involves lancing the abscess and removing the fragment and application of a
topical antibiotic.
The risks associated with the Lead fragment removal procedure include discomfort
during the procedure and skin irritation or infection in the area of the retained fragment.
These risks are rare. The risk of infection is mitigated by instructing the subject and/or his
caregiver to carefully monitor the site and immediately report any signs of infection.
6) Risk of Lead Replacement due to Lead Migration or Lead Becoming Dislodged
It is possible that the Lead may migrate from its original intended location or that the
Lead may become dislodged (i.e. come out completely) during the treatment phase. This
risk is rare. If lead migration occurs, it is possible that the subject may experience
discomfort during stimulation (described further below under “risk of discomfort with
electrical stimulation”). If the Lead has migrated substantially or has come out, it may be
necessary to place another Lead. Each time an additional lead is placed, the subject has
an additional exposure to the same risks of lead placement described above in “risk of
needle insertion for Sprint MicroLead placement”.
This risk of lead migration or the becoming dislodged is mitigated by instructions to the
subject and their caregiver, as appropriate, to ensure careful handling of the Lead and
Lead Connector during bandage changes. In addition, the risk of placing a new lead is
further mitigated by ensuring that Investigators are trained in the lead placement
procedure, ensuring that the shoulder tissue appears healthy prior to placing a new lead,
and collecting an additional INR blood sample for subjects who are taking warfarin.
7) Risk of skin irritation under the Sprint Pad or bandages
It is possible that the skin could become irritated under the Sprint Pad. Additionally, there
may be skin irritation in the area surrounding the Lead insertion site, where an adhesive
bandage is taped to the skin. This risk is common; however, the bandages can be changed
to prevent the irritation from returning.
The risks of skin irritation under the Sprint Pad (a modified surface electrode) and under
the bandages surrounding the Sprint MicroLead exit site will be reduced by excluding
patients with known sensitivity to skin surface electrodes and/or medical-grade adhesive
tapes. Subjects and their caregivers will be advised to examine the electrode exit site at
regular intervals to look for any signs of irritation. To avoid irritation under the Sprint
Pad, subjects will be advised that the Sprint Stimulator and Sprint Pad may be moved to
slightly different locations near the Lead insertion site throughout the treatment phase. In
addition, subjects will be instructed to avoid placing the Sprint Pad or bandages on
unhealthy skin.
8) Risk of mechanical or electrical failure of the Sprint Stimulator
There is a rare chance that the Sprint Stimulator may malfunction. It is very unlikely that
a stimulator malfunction will be harmful. If there is a problem with the Sprint Stimulator
or the Sprint MicroLead, the Stimulator will reset itself such that no stimulation is
delivered.
The Sprint Stimulator will not deliver stimulation if it detects a high impedance level
indicating a broken lead wire or a faulty lead connection. Subjects will be instructed to
contact study staff in the event that an error message is displayed.
9) Risks for pregnant women
The risk of harm to a pregnant woman or fetus is unknown. The device will not be used
in any subjects known to be pregnant. If a subject is known to become pregnant during
the treatment phase, stimulation will be stopped and the Sprint MicroLead will be
removed.
Potential risks of pregnancy will be reduced by administering a pregnancy test in females

of reproductive potential at study enrollment. Additionally, the Informed Consent form
will advise subjects that the risks of electrical stimulation during pregnancy are unknown
and that they should immediately notify the Investigator if they suspect they have become
pregnant during the study.
10) Risk of discomfort due to electrical stimulation
Intramuscular electrical stimulation may be perceived by the subject as a tingling or
vibrating sensation, which may feel uncomfortable or painful. The risk of discomfort due
to stimulation is uncommon. At high stimulation intensities, shoulder pain may worsen.
To minimize the risk of increased shoulder pain as the result of high intensity stimulation,
the Investigator will set an appropriate intensity for the stimulation. Should a subject feel
pain as the result of stimulation, he or she will be able to turn off the stimulation using the
Sprint Stimulator controls. Although muscle fatigue is unlikely with six hours of daily
stimulation therapy, subjects may also feel some discomfort if muscle fatigue occurs. If
muscle fatigue is observed, the Investigator is able to prescribe several shorter
stimulation sessions totaling six hours per day.
Discomfort or pain due to stimulation may occur if the Sprint MicroLead migrates from
its original location. Stimulation near the skin surface may be perceived as a “pins and
needles” or stinging sensation and may be uncomfortable.
The risk of pain due to a migrating electrode will be minimized by leaving stimulation off
until the Sprint MicroLead has had time to stabilize. The Sprint MicroLead has a fine
wire barb. In addition, the proximal portion of the Lead exits the skin which makes this
Lead more susceptible to becoming dislodged during bandage changes. As a conservative
measure, we allow one week for encapsulation of the Sprint MicroLead to ensure
stability. Data on the Lead has shown that electrodes are fully encapsulated by the
surrounding tissue.
A tingling sensation may be felt under the Sprint Pad but this sensation is not expected to
be uncomfortable. If discomfort or pain is felt at the Sprint Pad site, the subject will be
instructed to turn off stimulation and move the Sprint Pad and Stimulator to a different
location.
11) Risks associated with Diathermy
There is a risk of tissue damage if a subject undergoes diathermy. Shortwave or
microwave diathermy is a therapy that may be used to apply deep therapeutic heat for the
treatment of selected medical conditions such as relief of pain, muscle spasms, and joint
contractures. Diathermy can cause excessive heating of any implanted metal part
(including Leads), resulting in serious injury. The risk of tissue damage associated with
diathermy is rare.
The risk of diathermy will be reduced by informing subjects that diathermy must not be
used. In addition, subjects will be informed to never undergo diathermy if a Sprint
MicroLead fragment remains in the body.
12) Risks associated with MRI
Tissue damage may occur if a subject undergoes an MRI procedure while the Sprint
MicroLead, or a fragment of the Sprint MicroLead, is in the body. The risk of tissue
damage associated with MRI use is rare.
Should a subject require a scheduled MRI during the treatment phase, the Sprint
MicroLead will be removed. The decision to remove any remaining fragments will
depend on a careful assessment of the benefits of the MRI, risks of MRI with retained
fragments and risks associated with removing of electrode fragments.
13) Risk of allergic reaction to local anesthetics and/or risk of accidental injection of
local anesthetic into a vein

There is a risk that the subject may have an allergic reaction to the local anesthetic used
during the treatment phase prior to insertion of the Sprint MicroLead. If the subject were
to have an allergic reaction, it would usually happen while the subject was still in the
clinic. If a subject complains of itching, difficulty breathing, lightheadedness and
dizziness, or a swollen tongue (common signs of an allergic reaction), appropriate
medical treatment will be administered. The risk of allergic reaction to local anesthetics is
rare. In addition, there is a risk of adverse central nervous system and/or cardiovascular
effects (including a rare risk that the subject’s heart can stop beating or that they could
stop breathing) if the local anesthetic is administered improperly.
The risks of allergy to local anesthetic agents will be reduced by excluding subjects with
a prior known history of allergy or sensitivity to local anesthetic agents. In addition, prior
to the procedure, subjects will be advised of the signs and symptoms of an allergic
reaction. Because subjects will be awake during this procedure, they will be able to
verbalize any itching or other signs of allergy to the local anesthetic. The risks of
accidental intravascular injection of local anesthetic will be reduced by careful
administration of the local anesthetic. Careful administration includes ensuring that a vein
has not been punctured by the syringe prior to injecting the anesthetic and observing the
subject after the injection. In addition, the physical location of the anesthetic injection (in
the deltoid) combined with the injection technique would rarely result in an accidental
intravascular injection.
14) Risk associated with venipuncture (if applicable)
The risks of drawing blood from a vein include discomfort at the site of puncture,
possible bruising and swelling around the puncture site, an infection, and faintness from
the procedure. The risks of discomfort, bruising, and swelling around the puncture site
are common while the risks of infection and fainting are rare. Blood sample collections
are only required in subjects taking warfarin.
Subjects taking warfarin are at greater risk for developing bruises following
venipuncture. However, the risk of discomfort and bruising at that puncture site will be
reduced by applying gentle pressure following venipuncture as is the standard practice for
collection of blood samples. The rare risk of infection due to venipuncture will be
reduced by using proper blood collection technique including wiping the puncture site
with an appropriate cleansing solution.
Some subjects may experience a vasovagal (“fainting”) response due to the discomfort of
needle insertion or anxiety associated with the procedure. The risk of fainting will be
reduced by observing subjects during and following venipuncture to ensure that they feel
comfortable rising from their seated position. Subjects with a history of vasovagal
responses will be supine during venipuncture.
15) Risk of worsening of pain symptoms
It is possible that the subject may have a worsening of pain symptoms or that they may
not obtain any therapeutic benefit from the treatment. The risk of worsening pain
symptoms is uncommon. In addition, subjects will have the opportunity to discontinue
treatment if their stimulation is too uncomfortable.
These risks are mitigated by clinical training on the safe limits. Subjects do not have
access to make changes to the programming controls and thus could not advertently
change the value.
16) Risks of Physical Therapy and Performing Shoulder Exercises
Shoulder pain may worsen during outpatient therapy or during home exercises. To
minimize this risk, all exercises will be performed under the supervision of a trained
therapist during outpatient therapies. Participants will be trained to perform their home
exercise program to minimize the risk of further injuring the shoulder. The proper
implementation of the home exercise program will be reinforced at each outpatient
therapy visit. However, if shoulder pain persists during the home exercises, the home
exercise program will be terminated.

17) Risks of Outcomes Assessments
The questionnaires and Fugl-Meyer Assessment present no risks. The assessments of
shoulder torque and kinematics may be slightly uncomfortable. The measures of central
sensitization (mechanical pain thresholds for hyperalgesia, pinprick pain thresholds for
hyperalgesia, temporal summation of repetitive pin-prick stimuli) may be slightly
uncomfortable and may cause brief skin irritation.
18) Other
When using a sham group there is always the rare risk of psychological harm. Some of
the survey questions present a rare risk of psychological harm.
When PHI is involved there is the rare risk of a privacy breach.
There may be other risks as yet unknown.
Additional Comments on anticipated adverse events:
 
3.B.2 Safety data/procedure used to preform evaluation:
Data to be evaluated:
Name
Subject interview and/or contact
Subject's physical exam
Subject's symptoms or performance status
Interim Assessment of AE (e.g. midway, quarterly, semiannually, etc.)
Who will evaluate safety data:
The Executive Committee (PI and Site PI) and respective project staff meet at least
quarterly (including remotely) to review all adverse events and study data collected since
the previous meeting. The Executive Committee reviews all adverse events to determine
a course of action.
The Data and Safety Monitoring Board will convene semi-annuall to review and monitor
the progress of the study with respect to enrollment, drop-outs, outcomes and safety.(per
DSMB report attached)
Frequency of Monitoring:
Name
6 Months
 3.C. Grading method and attribution for adverse event reporting:  
Grading method and attribution for adverse event reporting
The PI must identify what scale will be used to grade adverse events (AEs) and
indicate his/her attribution/assessment of the relationship between the adverse
event and the protocol/intervention.  Each protocol may have a unique approach
to grading adverse events and the PI should consult the parent protocol and/or
funding source for specific grading scales.  Suggested guidelines for the
grading of adverse events are available below:
 
Example A:        Cancer Therapy Evaluation Program (CTEP) Common Toxicity Criteria (CTC II)
available for viewing at http://ctep.info.nih.gov (see “Reporting Guidelines, Common
Toxicity Criteria”)
 
Example B:  Common grading scale
                                      0              No adverse event or within normal limits or not clinical significant
                                      1              Mild AE, did not require treatment
                                      2              Moderate AE, resolved with treatment
3              Severe AE, resulted in inability to carry on normal activities and
required professional medical attention
                                      4              Life threatening or disabling AE
                                      5              Fatal AE
3.C.1 Identify the scale to be used to Grade AEs in this study:
 

CRU Safety Scale:
Name
AEs will be graded using another system (specify and attach description).
3.C.2 Identify the attribution scale to be used in this study:
CRU Attribution Scale:
Name
The PI will determine the relationships of AEs to test procedure/device/agent as not
related, possibly related, or definitely related, using standard criteria for clinical trials.
3.D. Population being studied: (populated from your answers to Sections 11.00 and
12.00) 
Vulnerable subject groups? Yes
Children? No
Decisionally Impaired Subjects? No
Pregnant Women and/or Fetuses? No
Will you be enrolling Prisoners? No
Other Populations being studied:
Vulnerable Populations
Poor / Uninsured
Elderly
Minorities
Cognitively Impaired
* Note More Frequent monitoring intervals may be needed for vulnerable populations.
4.A. Plan for Adverse Event Reporting:
All Reportable Events (Anticipated and Unanticipated events) from this protocol
must be  submitted using the MHA eIRB Reportable event form in a timely maner
consistent with MHS IRB SOPs.
In addition to the MHS IRB adverse events and Uanticipated problems will be
reported to:
Reporting Institutions (check all that apply):
Name
National Institutes of Health (NIH)
If other has been selected above please specify:
4.B Stopping Rules or Conditions under which Subjects can be removed from the
Study [this information is from Section 10.01 of the Protocol Risks/Benefits
Questions
Are there defined Stopping Rules?   Yes
What are the stopping rules for the study? The study could be terminated at any time
for valid scientific reasons or reasons related to the protection of subjects participating in
this study. A reason for study termination includes but is not limited to the discovery of
an unexpected, significant, or unacceptable risk to the participants enrolled in the study.
What findings, events, or conditions would require a research subject to be removed
from the study? (i.e. disease progression)
The research subject may be removed if they develop any condition during the course of

the study which would preclude the safe use of stimulation or otherwise impair their safe
participation in any study activity.
4.D. Additional Information (if Applicable):
Provide any other information relevant to the data and safety monitoring plan that
was not already incorporated into this form.
Attach A copy of your Data Safety Monitoring Plan or other relevant information
related to this form:
Name
Version
PM&R Research Team Routine Study Safety Review Procedure
0.01
Wilson - DSMB Charter Version 3 - PNS+PT in HSP 2018-Mar 8 APPROVED
0.03
View: 19-00 Use of Human Biological Materials In Research I
  19.0 Use of Human Biological Materials In Research I:
  19.1  Will Human Biological Materials be collected as part of this study? (i.e. blood,
tissue, fluids and substances etc.) 
Yes
If no, hit continue and you will be taken to the next page.
  Check yes or no.
  19.2
Will the storage or transportation of study materials place anyone at a health
risk? In other words, are these biohazardous materials? Will they put the staff
collecting them or transporting them at risk?
No
  Check yes or no. 
  19.3  If yes, please explain:
  Please explain the risks. Above
and beyond universal
precautions.
  19.4
Will information from the materials be stored in an electronic database?
Yes
  Check yes or no.
  19.5
If yes, list the database(s) where the information from the materials will be
stored and who will have access to them:
Blood/urine samples will be collected to confirm eligibility for subjects when
necessary. Samples will be taken and tested at Metro using the standard clinical
procedures and Metro Lab. Results are made available via EPIC.
  List the database(s) and who
will have access to them.
  19.6
Human Biological Material Destruction: please describe the plan for materials
destruction (when, where, how and by whom):
Standard Metro Lab procedure.
  Give the destruction plan i.e.
shipped back to sponsor for
destruction at end of study,
incinerated by Browning Ferris
3 months after study ends.
  19.7
Storage of Human Biological Materials: please describe where, how and for how
long the materials will be stored:
Standard Metro Lab procedure.
  Physical storage of materials
where will it be, how will it be
stored and for how long.
 
 
View: 19-01 Use of Human Biological Materials in Research II
  19.1 Use of Human Biological Materials In Research II:
    
  19.8 
Does this research involve human cell/lines and/or products that are made from
human biological materials?   
Yes 
No
 If yes, please explain:
  Check Yes or No.
 
Please explain. 
  19.9
Will Human Biological Materials (tissue, blood or salavia) be collected in this
study for genetic research?
No
  Check Yes or No. 

If Yes, please provide additional discussion of the genetic testing components
including who will conduct the tests:
  19.10  If yes, can subject(s) decide not to participate in the genetic research and still
participate in the study?
  Check Yes or No. 
 
Please submit the appropriate genetic consent/tissue storage form and attached
at 17.15
A template for this form can be found on the IRB Home Page. Note: if tissue storage
is mandatory for participation in a study the subject consent must be included in the
body of the consent form; if it is not mandatory it can be included as a separate page
at the end of the consent form.  
   
  19.11 
Will NIH Genome-Wide Association Studies (GWAS) be conducted?
  
Yes 
No
  Check Yes or No.
  19.12
Will you be sending samples/data to the NIH GWAS?   
Yes 
No
  Check Yes or No. 
  19.13  Will you be using sample/data obtained frm the NIH GWAS?   
Yes 
No
  Check Yes or No. 
  19.14
Please provide justification for using NIH GWAS:
  Please explain. 
 
   
If this is a GWAS study you will need to submit a Patient Information Sheet (add
at 17.16). This sheet should summarize the Genetic research component of this
study and tell the subjects where their biological materials will be sent, what
analysis they will undergo, who will have control of them and for how long and
who to contact if they want to withdraw their permission. It must be clear to
subjects that these samples will not be housed at MHS nor will the MHS
Investigator retain control over them.
   
   
View: 20-00 Drug Information I
  20.0 Drug Information I:
20.1  * Does this study involve drugs? No
If you are doing a drug study you may be required by law to register that study at
Clinical Trials.gov Section 113 of the FDA Modernization Act mandates registration
with ClinicalTrials.gov of investigational new drug efficacy trials for serious
diseases or conditions.  For more information click on the link below:
http://prsinfo.clinicaltrials.gov/registering.pdf
If you answer no and hit continue you will go to the next section. 
Does this study involve:
Is the study drug(s) FDA approved for this indication?   
Yes 
No
Does this study involve use of a Placebo?   
Yes 
No
Does this study have a drug washout period?   
Yes 
No  
Do you have an IND?   
Yes 
No  
If yes please give the IND: (include a copy of the FDA approval letter at 20.4)
Who is the sponsor or holder of the IND?
Does this study have an IND exemption? (include a copy of the FDA exemption
letter at 20.4)   
Yes 
No  
  If you check no and hit
continue you will go to the next
page.
  20.2  Fill in an entry for all drugs that will be used in the study:
  Please give a complete list.

Drug Name
FDA Approved (yes, no)
IND Number
Supplied By
There are no items to display
 
 
  20.3  Manufacturer (name, address):
  Answer only if produced
commercially.
  20.4
Attach a copy of:
1.) Investigator Brochure and/or Package Insert
2. FDA Form 1571 Investigational new Drug Application Form
3.) FDA Form 1572 Statement of the Investigator Form
4.) FDA Correspondence (i.e. FDA Approval Letter for IND, FDA
Exemption letter)
Name
Description
There are no items to display
  Attach the IB, 1572 and 1571
here.
 
View: 21-00 Medical Device Information I rev
  21.0 Medical Device Information I:
Definition of a Medical Device:
 An instrument, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a
component part, or accessory which is
•          Intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of
disease in man or other animals.
•          Intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of
its primary intended purposes through chemical action within or on the body of man or other animals and which is not
dependent upon being metabolized for the achievement of any of its primary intended purposes.
In short any health care product that does not achieve its primary intended purposes by chemical action or by being
metabolized. Medical devices include, among other things, surgical lasers, wheelchairs, sutures, pacemakers, vascular
grafts, intraocular lenses, and orthopedic pins. Medical devices also include diagnostic aids such as reagents and test kits
for in vitro diagnosis (IVD) of disease and other medical conditions such as pregnancy.
  21.1
Is this a Medical Device Study? Yes
If you are doing a device study you may be required by law to register that
study at Clinical Trials.gov Section 113 of the FDA Modernization Act mandates
registration with ClinicalTrials.gov of investigational new device efficacy trials for
serious diseases or conditions.  For more information click on the link below:
 
http://prsinfo.clinicaltrials.gov/registering.pdf
If you answer no and hit continue you will go to the next section. 
  Answer yes or no.
  21.2 
Medical Device Generic Name:
Peripheral Nerve Stimulator
  Give generic name. 
  21.3
 
21.4
Medical Device Brand Name:
The Sprint PNS System
Medicare Code Number:
N/A
As stated in regulations 21 CFR 812.3(m), a device may be considered a,
Significant Risk Device, if it meets any of the following criteria and a
determination is made by the IRB that the device presents a potential for
serious risk to the health, safety or welfare of a subject.
  Give brand name. 
  21.5 
Is this device intended as an implant? No
  Check one
  21.6
Is device to be used in supporting or sustaining human life? No
  Check one

  21.7
Is the device for use of substantial importance in diagnosing, curing, mitigating,
or treating disease or otherwise preventing impairment of human health?
No
  Check one
  21.8
Does this device present a potential for serious risk to the health, safety, or
welfare of a subject?
No
  Check one
  21.9
If you answered NO to all the above, or if an initial risk assessment has
determined that this is a non-significant risk device (21CFR 812.3), attach the
appropriate documentation for this justification:
Name
Description
There are no items to display
  Attach justification. 
  21.10 What is the regulatory status of the study device?
FDA Cleared via 510(k) and used in accordance with its labeling (thus exempt from
IDE regulation).
  Provide information on the
regulatory status of the device.
  21.11
What is the long term plan for device management once the study closes?
Devices are not retained by subjects beyond the Treatment Phase.
  Provide information such as
how you will communicate
important information to
subject; plan for
maintenance/repairs; contact
information besides the PI.
View: 21-01 Medical Device Information II
  21.1 Medical Device Information II:
  21.12  What is the FDA Approval date?
5/31/2018  
  Please give date. 
  21.13
What is the Premarket Approval (PMA)number? 
N/A
  Please give number.
  21.14  What is the Premarket Notification (510K) number?
K181422  
  Please give number.
  21.15
What is the Investigational Device Exemption (IDE) number?
N/A
Who is the sponsor or holder of the IDE?
 
  Please give IDE number if
applicable.
  21.16
What is the Humanitarian Device Exemption (HDE) number?
N/A  
  Please give HDE number if
applicable.
  21.17
Has this medical device ever been used in animals?
No   
  Check one
  21.18
If yes, please give a brief summary of the results of studies involving animals:
 
  Give a brief summary or attach
one below at 22.16.
  21.19
Please attach supporting documents:
Name
Description
K170902 Documentation | History
 
Sprint PNS System Device Description | History
 
Updated 510K letter | History
 
  Give a brief summary.
View: 21-02 Medical Device Information III
 
  21.2 Medical Device Information III:
  21.20   Has this medical device ever been used in humans? Yes  
  Check yes or no.
  21.21
If yes, please give a brief summary of the results from studies involving
humans:
Note: The Smartpatch System discussed here has been renamed the Sprint PNS
  Give a brief summary.

System subsequent to FDA clearance.
Principals of SPR Therapeutics (a subsidiary of NDI Medical) and NDI Medical
have been involved in the study of peripheral nerve stimulation through
percutaneous lead placement for the treatment of post-stroke shoulder pain for
more than a decade. Current SPR and NDI staff participated in sponsoring and
managing the published studies (led by Dr. John Chae, who continues these
studies and is an advisor to SPR) described below. Using the identical
Smartpatch Lead and identical stimulus parameters, percutaneous peripheral
nerve stimulation for the treatment of post-stroke shoulder pain has been
evaluated in multiple studies at Case Western Reserve University by Chae and
associates.
Yu, Chae, and colleagues conducted a double-blind crossover trial to determine
whether sensation associated with percutaneous electrical stimulation is less
painful than sensation associated with surface electrical stimulation. Subjects
rated the pain of each treatment modality using a VAS and the Pain Rating
Index of the McGill Pain Questionnaire11. The median scores on the VAS and
the Pain Rating Index were lower for percutaneous electrical stimulation than
for surface electrical stimulation (p=0.007 and p=0.018, respectively), indicating
less pain with percutaneous electrical stimulation. In addition, nine out of ten
subjects stated that they would prefer to receive percutaneous electrical
stimulation over surface electrical stimulation.
A case report of a chronic stroke patient suffering from shoulder subluxation
and pain, who was unable to tolerate surface electrical stimulation, suggested
initial clinical feasibility of six weeks of percutaneous peripheral nerve
stimulation for the treatment of post-stroke shoulder pain. The authors,
including current SPR staff, then conducted an exploratory case series in which
eight chronic stroke survivors received six weeks of percutaneous electrical
stimulation to their posterior deltoid and supraspinatus muscles. Subjects
experienced a significant improvement in subluxation and self-reported pain.
Furthermore, this study also demonstrated significant improvement in pain
related quality of life based on the pain domain of SF-36.
Yu, Chae and associates, including current SPR and NDI staff, then went on to
enroll 61 subjects into a multi-center single-blinded randomized controlled
study to assess the safety and effectiveness of percutaneous electrical
stimulation for post-stroke shoulder pain. To qualify for participation in the
study, subjects had to be more than 12 weeks post stroke and rate their shoulder
pain as at least a 2 on the pain intensity question of the Brief Pain Inventory,
which is an 11-point numeric rating scale that asks subjects to rate their worst
shoulder pain in the last week. Treatment subjects had four percutaneous leads
placed in the posterior deltoid, middle deltoid, supraspinatus, and upper
trapezius muscles. They were instructed to keep stimulation ON for a total of 6
hours a day during the 6-week treatment period. Control subjects were given a
cuff type sling to use whenever the hemiplegic arm was unsupported during the
6-week treatment period and permitted to continue other pain therapies such as
PT, OT, and medications.
Subjects were assessed at baseline, at 3-weeks, at EOT, and at 3-, 6-, and 12-
months post-EOT. The primary outcome measure was the same as in the
present study (BPI pain intensity). However, these data were collected on the
BPI form rather than a subject diary. Secondary measures included the same
Pain Interference Question of the BPI (BPI 9) as is planned for use in the
present study and a variety of physical functioning assessments, including pain-
free passive external rotation range of motion (ROM) of the glenohumeral joint.
The group receiving electrical stimulation demonstrated a significantly higher
success rate (as measured by a minimum 2-point reduction on the scale) than
the control group (84% vs. 31%, p=.001 at the end of treatment; and 63% vs.
21%, p=.001 for all follow-up visits). In addition, 34% (11 subjects) of the group
receiving electrical stimulation were pain free (reported “0”, indicating no pain)

at the EOT compared to only 3.4% (one subject) in the control group.
The 32 subjects randomized to the treatment group each had four percutaneous
leads placed that were identical to the Smartpatch Lead. The lead placement
procedure was well tolerated. All leads remained intact and free of infection
during the 7-week indwelling period. Of the 128 leads placed in this study, the
tips of five leads (3.9%) among four subjects (12.5%) broke during removal,
none of which resulted in an adverse event. Granuloma formation defined as
localized tissue inflammation exhibited by redness, swelling, or pain at the lead
exit site was noted for five leads (3.9%) in two subjects (6.3%). All granulomas
resolved after lead removal with no further intervention required.
The authors concluded that percutaneous electrical stimulation is safe and
effective in reducing post-stroke shoulder pain, with sustained pain reduction in
a cohort of subjects to at least 12 months after the end of treatment. Placement
of leads in proximity to peripheral nerves within target muscles bypasses
cutaneous pain receptors, which minimizes the discomfort of stimulation and
ensures stable electrode placement. Further, once placed, skilled personnel are
not needed on a daily basis to place electrodes to ensure effective positioning.
In an IRB approved Non Significant Risk (NSR) study, eight chronic stroke
survivors with post-stroke shoulder pain, five with subluxation and three
without, received three weeks of peripheral nerve electrical stimulation, 6-hrs
daily via a single Smartpatch Lead placed between the motor points of the
middle and posterior deltoids, which produced strong contractions of both
muscles. The primary outcome measure was pain intensity (BPI 3) on the short
form of the BPI. Longitudinal analysis demonstrated that participants
experienced significant reduction in pain intensity. Participants also
experienced significant reduction in pain interference with daily activities based
on BPI 9 (F=5.9, p<0.01), and significant improvement in QoL based on the
bodily pain component of the SF-36 (F=12.8, p<0.001). All 8 participants
exhibited significant pain reduction at EOT. This study indicated that the three-
week, single-lead approach produced pain relief comparable to the more
complex six week, 4-lead approach. The three participants without subluxation
all exhibited substantial pain reduction, which reinforced that pain reduction is
not mediated by improvements in subluxation and that subluxation is the not a
necessary inclusion criterion.
Additional testing was conducted in 5 subjects to validate the design of the
Smartpatch Stimulator and other external components. This design validation
of a non-stimulating Smartpatch System provided evidence that the Smartpatch
System meets user needs regarding usability and comfort. Physical aspects of
system usage, such as making cable connections, attachment between
Stimulator and Pad, and attachment to the skin, were reported as easy and
acceptable. Software aspects of the Smartpatch Stimulator usage, such as
starting and stopping stimulation, identifying the battery level, and adjusting
stimulus intensity were all reported as easy and acceptable.
Furthermore, a stimulating Smartpatch System has been used by 3 subjects to
date in an ongoing IDE study being conducted under G090085. In this protocol,
the system is used in the Trial Stage for determining eligibility for our
implantable system. All three subjects completed the Trial Stage and were able
to use the Smartpatch components successfully to deliver their stimulation
therapy. Subjects completed satisfaction surveys upon completion of
Smartpatch System use. All three subjects reported that it was easy to
understand how to use the Smartpatch System and that the System was easy to
operate. Two subjects reported that the pad wasn’t sticky enough, sometimes
causing them to use more than one Pad per day. Subjects in the proposed study
will be given more guidance on the proper preparation of the skin to ensure pad
adhesion. The subjects reported that the covering bandages used were of an
acceptable adhesion and size, but two subjects reported that the Lead
Connector Tapes were difficult to use. All three subjects reported that the
system as comfortable, “not at all” bothersome to wear, and that they were

comfortable going out in public with the system on. The subjects reported that
they were satisfied with their experience in the study, felt that the study had a
positive impact on their lives, and would recommend participation in the study
to a friend.
  21.22  Please list all research personnel authorized to use the study device:
Name
EmployerDepartment
Employer Name
John Chae
Metro
PM&R
The MetroHealth System
Kristine
Hansen
MHS
Physical Medicine and
Rehabilitation
Physical Medicine and
Rehabilitation
Richard
Wilson
Metro
PM&R
The MetroHealth System
  List all research personnel
authorized to use study device.
  21.23  How will this medical device be used in research?
Percutaneous PNS System: The Sprint PNS System (SPR Therapeutics, Cleveland,
OH) will be used to deliver the PNS therapy. The System consists of a small external
stimulator, percutaneous lead, hand held wireless remote and pad. The external
stimulator “snaps” on to the pad. The pad is replaced regularly based on treatment
parameters, allowing the investigative team to prescribe the total dosage based upon
the number of pads. The single-channel stimulator outputs a biphasic current
waveform with current pulse parameter ranges that are suitable for PNS. These
electrodes have been used extensively to deliver percutaneous PNS to shoulder
muscles. [16-22, 85, 86]
Lead Placement Procedure:
Active PNS Groups: The procedure will be performed under a sterile condition. The
location and depth of the electrode implant site are determined by monopolar needle
stimulation with demonstration of strong contraction of both the middle and
posterior deltoid muscles. [16, 19, 71, 86] The introducer loaded with the lead is
inserted perpendicular to the skin surface and advanced to the depth (3-4 cm) defined
by the monopolar test stimulation. The introducer is then withdrawn with the
electrode retained in the muscle by a barb at its tip. The subject will be provided the
option of subcutaneous lidocaine infiltration prior to placement of the electrode lead.
Sham-PNS Group: In order to facilitate blinding, sham-PNS participants will receive
a percutaneous electrode between the middle and posteriod deltoid muscles. The
sham-PNS group will not require localization with monopolar needle electrodes. The
introducer will be advanced 3-4 cm from the skin surface.
PNS Treatment Protocol:
Active PNS Groups: After one week for lead stabilization [95], the Sprint PNS
System will be programmed for stimulation. Based on over 30-yrs of experience, the
Cleveland FES Center established parameters for safe and effective delivery of PNS
(pulse frequency = 12 Hz; pulse amplitude = 20 mA; pulse duration = 5-200 usec
(set by clinician); duty cycle = 5-sec ramp-up, 10-sec plateau, 5-sec ramp down, 10
sec off; daily dose = 6 hrs/day). [96] These parameters provide strong fused
comfortable muscle contraction with minimal fatigue. [16-22, 59, 85, 86, 94, 97, 98]
Stimulation frequency and amplitude are fixed. The pulse duration is set to produce
strong, comfortable contraction of both the middle and posterior deltoids. A balanced
biphasic waveform allows an equal amount of current to flow in either phase,
creating a safe net zero charge. [99] Participants receive two 3-hr sessions per day in
their home. The stimulator keeps an electronic log for compliance monitoring. There
are no formal dose response studies to provide guidance on the optimal dose of PNS;
however, the selected duty cycle and daily dose of 6-hrs were used in our prior
studies [8, 16-21, 86] and by others with robust results. [85]
Sham-PNS Group: Control participants will not receive active stimulation. The
stimulator will be placed in non-stimulation mode by a study team member. In this
condition, the stimulator appears to function normally, and the battery will drain,
though no stimulation will be delivered. All participants are queried at their final
visit to determine the success of blinding. The implanted electrode poses minimal
risk to control participants. The probability of serious adverse event (e.g. infection)
  Give a brief description.

due to electrode fragments in this study is 0.1% per electrode. The implantation of
electrodes is no more painful than subcutaneous infiltration of lidocaine.
Electrode and Electrode Site Surveillance and Electrode Removal: All caregivers and
participants will be trained in the assessment of electrode site and the daily
placement of the Sprint Pad. The caregiver conducts daily inspections to detect
complications. The nurse coordinator inspects the site for infection and performs
motor/sensory threshold testing for lead migration and lead integrity, respectively, at
the following times: within 48-72 hrs of lead placement, at the beginning of PNS
treatment, and at the end of treatment. Inspection and testing of motor/sensory
thresholds and impedance may also occur anytime during the 3-wk PNS treatment
period as deemed necessary. At the end of treatment, the electrode is removed by
gently pulling on the external portion. All participants undergo radiographic
surveillance for retained electrode fragments.
  21.24
Please list all possible complications:
Complications are addressed in the Risks for the Study (duplicated from 10.5):
1) Risks associated with needle insertion for Sprint MicroLead placement
There are minor risks associated with inserting a Lead through the skin with a
needle. These risks are similar to the risks of any needle injection including the
possibilities of puncturing a blood vessel, irritating a nerve, and temporary bruising
or pain at the insertion site. The risks of puncturing a blood vessel and irritating a
nerve are uncommon, but the risks of temporary bruising and pain at the insertion
site are common.
Some participants may experience a vasovagal (“fainting”) response due to the
discomfort or anxiety associated with of the procedure, especially among those with
prior history of “fainting.” This risk is rare and may be associated with symptoms of
lightheadedness, dizziness and or diaphoresis with concomitant reduction in blood
pressure and heart rate. For those with prior history of “fainting” the procedure will
be performed with the subject in the lateral decubitus position.
To minimize the risks associated with percutaneously placing fine wire leads, only
appropriately trained physician investigators will perform the procedure. In addition,
the risk of excessive bleeding will be reduced by excluding candidates who are
taking warfarin with an INR > 3.0 and by placing manual pressure on the
implantation site until hemostasis is achieved. Finally, the risk of discomfort during
the procedure will be reduced by the use of an appropriate amount of local
anesthetic.
It is possible that, in some cases, multiple attempts may be required to achieve
appropriate placement of the Lead during the procedure. Each additional attempt at
Lead placement carries the same risks as the initial attempt described in this section.
2) Risk of skin irritation, infection, or inflammation at the Sprint MicroLead exit site
There are risks of leaving a Sprint MicroLead in place for 4 weeks, including skin
irritation, infection, and granuloma formation (mild tissue inflammation) at the Lead
exit site. Symptoms include redness, swelling, or pain. The risk of skin irritation is
common while the risks of infection and granuloma formation are rare.
These risks will be minimized by using sterile Leads and thoroughly cleansing the
insertion site with antibacterial solution at the time of insertion. The insertion site
will be covered with a dressing to keep it clean and dry, and the subjects and their
caregivers will be instructed to inspect the site for signs of infection or irritation
regularly and to inform the Investigator if they occur. If infection or skin irritation
occurs, the Investigator will administer an antibiotic and/or remove the Lead.
Infections are rare and typically resolve after Lead removal and antibiotic treatment.
It should be noted that in a completed clinical trial of percutaneous intramuscular
electrical stimulation, one patient death occurred. The subject did not follow the
  List all complications.

instructions for the care of the Lead exit site and also did not return for his scheduled
follow-up visit following electrode placement. He developed an electrode related
infection and was hospitalized. The cause of death is thought to be a myocardial
infarction or a pulmonary embolus, but the exact cause of the death and its
relationship to the infection are not known. To mitigate the potential risk of serious
infection, a 48-72 hour safety check will be performed after the procedure.
Participants will return to the clinic and the exit site will be evaluated for signs of
infection.
3) Risk of the Sprint MicroLead breaking beneath the skin
There is a possibility of a Lead breaking beneath the skin either during the course of
the study or during the procedure to remove Lead. This risk is uncommon. However,
when a Lead breaks, one or more Lead fragments usually remain in the body. The
Investigator will use clinical judgment to determine if the removal of such fragments
is necessary. Visual inspection of the Lead after it has been removed as well as x-rays
will be used to determine if any Lead fragments remain. The risk associated with the
x-rays is no greater than that associated with conventional clinical x-rays. If the
Investigator determines a Lead fragment has been retained in the body, he/she will
determine what is medically required to further evaluate and treat this retained
fragment. Typically, no treatment is required unless there are further sequelae, such
as an infection or granuloma, associated with the fragment.
The risk of leaving a Lead fragment is minimized by reducing the amount of time the
Lead remains implanted and the number of Leads implanted. In this protocol, a
single Sprint MicroLead will be implanted for just 4 weeks.
4) Risk of infection associated with retained Sprint MicroLead fragments
A Lead fragment could result in the formation of a granuloma or infection. Although
the occurrence of a fragment-related infection or granuloma is uncommon an
infection may require removal of the Lead fragment and/or treatment with
antibiotics. Investigators at the Cleveland FES Center and Case Western Reserve
University have over 30 years of experience with dozens of research participants and
hundreds of implanted leads like those used in this study. Infections and granulomas
of leads or lead fragments have been uncommon, which is attributed to the materials
and procedures that have been developed as well as the extensive experience of the
Investigators..
5) Risks associated with lead fragment removal
It is possible that a Lead fragment or fragments may be retained in the body
following removal of the Sprint MicroLead. If the Investigator determines that a lead
fragment has been retained, the Investigator will instruct the subject and his/her
caregiver to carefully inspect the Sprint MicroLead exit site and the surrounding skin
in the weeks subsequent to Lead removal. Subjects will be instructed to contact the
Investigator if there are any signs of pain, redness, swelling, discharge, or the
appearance of a pimple-like mass (skin abscess). Such signs indicate that the
fragment has migrated to the skin surface. At that time, if clinically warranted, the
fragment may be removed via an outpatient procedure which involves lancing the
abscess and removing the fragment and application of a topical antibiotic.
The risks associated with the Lead fragment removal procedure include discomfort
during the procedure and skin irritation or infection in the area of the retained
fragment. These risks are rare. The risk of infection is mitigated by instructing the
subject and/or his caregiver to carefully monitor the site and immediately report any
signs of infection.
6) Risk of Lead Replacement due to Lead Migration or Lead Becoming Dislodged
It is possible that the Lead may migrate from its original intended location or that the
Lead may become dislodged (i.e. come out completely) during the treatment phase.
This risk is rare. If lead migration occurs, it is possible that the subject may

experience discomfort during stimulation (described further below under “risk of
discomfort with electrical stimulation”). If the Lead has migrated substantially or has
come out, it may be necessary to place another Lead. Each time an additional lead is
placed, the subject has an additional exposure to the same risks of lead placement
described above in “risk of needle insertion for Sprint MicroLead placement”.
This risk of lead migration or the becoming dislodged is mitigated by instructions to
the subject and their caregiver, as appropriate, to ensure careful handling of the Lead
and Lead Connector during bandage changes. In addition, the risk of placing a new
lead is further mitigated by ensuring that Investigators are trained in the lead
placement procedure, ensuring that the shoulder tissue appears healthy prior to
placing a new lead, and collecting an additional INR blood sample for subjects who
are taking warfarin.
7) Risk of skin irritation under the Sprint Pad or bandages
It is possible that the skin could become irritated under the Sprint Pad. Additionally,
there may be skin irritation in the area surrounding the Lead insertion site, where an
adhesive bandage is taped to the skin. This risk is common; however, the bandages
can be changed to prevent the irritation from returning.
The risks of skin irritation under the Sprint Pad (a modified surface electrode) and
under the bandages surrounding the Sprint MicroLead exit site will be reduced by
excluding patients with known sensitivity to skin surface electrodes and/or medical-
grade adhesive tapes. Subjects and their caregivers will be advised to examine the
electrode exit site at regular intervals to look for any signs of irritation. To avoid
irritation under the Sprint Pad, subjects will be advised that the Sprint Stimulator and
Sprint Pad may be moved to slightly different locations near the Lead insertion site
throughout the treatment phase. In addition, subjects will be instructed to avoid
placing the Sprint Pad or bandages on unhealthy skin.
8) Risk of mechanical or electrical failure of the Sprint Stimulator
There is a rare chance that the Sprint Stimulator may malfunction. It is very unlikely
that a stimulator malfunction will be harmful. If there is a problem with the Sprint
Stimulator or the Sprint MicroLead, the Stimulator will reset itself such that no
stimulation is delivered.
The Sprint Stimulator will not deliver stimulation if it detects a high impedance level
indicating a broken lead wire or a faulty lead connection. Subjects will be instructed
to contact study staff in the event that an error message is displayed.
9) Risks for pregnant women
The risk of harm to a pregnant woman or fetus is unknown. The device will not be
used in any subjects known to be pregnant. If a subject is known to become pregnant
during the treatment phase, stimulation will be stopped and the Sprint MicroLead
will be removed.
Potential risks of pregnancy will be reduced by administering a pregnancy test in
females of reproductive potential at study enrollment. Additionally, the Informed
Consent form will advise subjects that the risks of electrical stimulation during
pregnancy are unknown and that they should immediately notify the Investigator if
they suspect they have become pregnant during the study.
10) Risk of discomfort due to electrical stimulation
Intramuscular electrical stimulation may be perceived by the subject as a tingling or
vibrating sensation, which may feel uncomfortable or painful. The risk of discomfort
due to stimulation is uncommon. At high stimulation intensities, shoulder pain may
worsen.
To minimize the risk of increased shoulder pain as the result of high intensity

stimulation, the Investigator will set an appropriate intensity for the stimulation.
Should a subject feel pain as the result of stimulation, he or she will be able to turn
off the stimulation using the Sprint Stimulator controls. Although muscle fatigue is
unlikely with six hours of daily stimulation therapy, subjects may also feel some
discomfort if muscle fatigue occurs. If muscle fatigue is observed, the Investigator is
able to prescribe several shorter stimulation sessions totaling six hours per day.
Discomfort or pain due to stimulation may occur if the Sprint MicroLead migrates
from its original location. Stimulation near the skin surface may be perceived as a
“pins and needles” or stinging sensation and may be uncomfortable.
The risk of pain due to a migrating electrode will be minimized by leaving
stimulation off until the Sprint MicroLead has had time to stabilize. The Sprint
MicroLead has a fine wire barb. In addition, the proximal portion of the Lead exits
the skin which makes this Lead more susceptible to becoming dislodged during
bandage changes. As a conservative measure, we allow one week for encapsulation
of the Sprint MicroLead to ensure stability. Data on the Lead has shown that
electrodes are fully encapsulated by the surrounding tissue.
A tingling sensation may be felt under the Sprint Pad but this sensation is not
expected to be uncomfortable. If discomfort or pain is felt at the Sprint Pad site, the
subject will be instructed to turn off stimulation and move the Sprint Pad and
Stimulator to a different location.
11) Risks associated with Diathermy
There is a risk of tissue damage if a subject undergoes diathermy. Shortwave or
microwave diathermy is a therapy that may be used to apply deep therapeutic heat
for the treatment of selected medical conditions such as relief of pain, muscle
spasms, and joint contractures. Diathermy can cause excessive heating of any
implanted metal part (including Leads), resulting in serious injury. The risk of tissue
damage associated with diathermy is rare.
The risk of diathermy will be reduced by informing subjects that diathermy must not
be used. In addition, subjects will be informed to never undergo diathermy if a Sprint
MicroLead fragment remains in the body.
12) Risks associated with MRI
Tissue damage may occur if a subject undergoes an MRI procedure while the Sprint
MicroLead, or a fragment of the Sprint MicroLead, is in the body. The risk of tissue
damage associated with MRI use is rare.
Should a subject require a scheduled MRI during the treatment phase, the Sprint
MicroLead will be removed. The decision to remove any remaining fragments will
depend on a careful assessment of the benefits of the MRI, risks of MRI with
retained fragments and risks associated with removing of electrode fragments.
13) Risk of allergic reaction to local anesthetics and/or risk of accidental injection of
local anesthetic into a vein
There is a risk that the subject may have an allergic reaction to the local anesthetic
used during the treatment phase prior to insertion of the Sprint MicroLead. If the
subject were to have an allergic reaction, it would usually happen while the subject
was still in the clinic. If a subject complains of itching, difficulty breathing,
lightheadedness and dizziness, or a swollen tongue (common signs of an allergic
reaction), appropriate medical treatment will be administered. The risk of allergic
reaction to local anesthetics is rare. In addition, there is a risk of adverse central
nervous system and/or cardiovascular effects (including a rare risk that the subject’s
heart can stop beating or that they could stop breathing) if the local anesthetic is
administered improperly.
The risks of allergy to local anesthetic agents will be reduced by excluding subjects

with a prior known history of allergy or sensitivity to local anesthetic agents. In
addition, prior to the procedure, subjects will be advised of the signs and symptoms
of an allergic reaction. Because subjects will be awake during this procedure, they
will be able to verbalize any itching or other signs of allergy to the local anesthetic.
The risks of accidental intravascular injection of local anesthetic will be reduced by
careful administration of the local anesthetic. Careful administration includes
ensuring that a vein has not been punctured by the syringe prior to injecting the
anesthetic and observing the subject after the injection. In addition, the physical
location of the anesthetic injection (in the deltoid) combined with the injection
technique would rarely result in an accidental intravascular injection.
14) Risk associated with venipuncture (if applicable)
The risks of drawing blood from a vein include discomfort at the site of puncture,
possible bruising and swelling around the puncture site, an infection, and faintness
from the procedure. The risks of discomfort, bruising, and swelling around the
puncture site are common while the risks of infection and fainting are rare. Blood
sample collections are only required in subjects taking warfarin.
Subjects taking warfarin are at greater risk for developing bruises following
venipuncture. However, the risk of discomfort and bruising at that puncture site will
be reduced by applying gentle pressure following venipuncture as is the standard
practice for collection of blood samples. The rare risk of infection due to
venipuncture will be reduced by using proper blood collection technique including
wiping the puncture site with an appropriate cleansing solution.
Some subjects may experience a vasovagal (“fainting”) response due to the
discomfort of needle insertion or anxiety associated with the procedure. The risk of
fainting will be reduced by observing subjects during and following venipuncture to
ensure that they feel comfortable rising from their seated position. Subjects with a
history of vasovagal responses will be supine during venipuncture.
15) Risk of worsening of pain symptoms
It is possible that the subject may have a worsening of pain symptoms or that they
may not obtain any therapeutic benefit from the treatment. The risk of worsening
pain symptoms is uncommon. In addition, subjects will have the opportunity to
discontinue treatment if their stimulation is too uncomfortable.
These risks are mitigated by clinical training on the safe limits. Subjects do not have
access to make changes to the programming controls and thus could not advertently
change the value.
16) Risks of Physical Therapy and Performing Shoulder Exercises
Shoulder pain may worsen during outpatient therapy or during home exercises. To
minimize this risk, all exercises will be performed under the supervision of a trained
therapist during outpatient therapies. Participants will be trained to perform their
home exercise program to minimize the risk of further injuring the shoulder. The
proper implementation of the home exercise program will be reinforced at each
outpatient therapy visit. However, if shoulder pain persists during the home
exercises, the home exercise program will be terminated.
17) Risks of Outcomes Assessments
The questionnaires and Fugl-Meyer Assessment present no risks. The assessments of
shoulder torque and kinematics may be slightly uncomfortable. The measures of
central sensitization (mechanical pain thresholds for hyperalgesia, pinprick pain
thresholds for hyperalgesia, temporal summation of repetitive pin-prick stimuli) may
be slightly uncomfortable and may cause brief skin irritation.
18) Other

When using a sham group there is always the rare risk of psychological harm. Some
of the survey questions present a rare risk of psychological harm.
When PHI is involved there is the rare risk of a privacy breach.
There may be other risks as yet unknown.
  21.25
Please list all precautions, warnings, and contraindications:
Detailed precautions, warnings, and contraindications are detailed in the manuals
attached at 27.1.
  List all precautions, warnings
and contraindications.
View: 21-03 Medical Device IV
  21.03 Medical Device IV     
INVESTIGATOR’S RESPONSIBILITY FOR CONTROL OF THE INVESTIGATIONAL DEVICES:
To protect the rights, safety and welfare of research participants the investigator must ensure control and accountability of
all devices used in conjunction with clinical research protocols. To make certain that investigational devices are used only
on research participant’s who have signed the informed consent form specific for the device and IDE number. 
  21.26 
  The device will not be used on a research participant until FDA(when FDA
regulated investigational device is being studied) and IRB approval has been
obtained and the research participant has signed an informed consent document.
  Please check these boxes
  21.27
  The informed consent document will inform the research participants that
their names and information will be shared with the device company for tracking
purposes.
   
  21.28 
  The investigation will be conducted in accordance with the signed agreement
with the sponsor, the investigational plan, and all applicable laws and regulations.
   
  21.29
  The device will be used only in accordance with the MHS IRB approved
protocol.
 
  21.30
  The Investigator is thoroughly familiar with the appropriate use of the
investigational device, as described in the protocol, in the product information, and
in other information sources provided by the sponsor.
 
  21.31
  All persons assisting with the trial are adequately informed about the protocol
and the investigational product(s).
 
  21.32
  Devices will be properly maintained and cleaned.
   
  21.33
  Research participants will receive adequate instructions about the
investigational device to assure their safe participation in a research study.
 
 
 
 
 
 
 
21.34
Any investigational devices used in conjunction with an investigational protocol must be kept in a locked and
secured area. Access to investigational devices must be limited to personnel designated by the Principal
Investigator. Please describe How you will secure the investigational devices to be used in this study and who
will have access to them.
Device accountability will be maintained by the Investigator and his study staff. All devices that are not deployed will
be secured by the research staff in their offices and/or labs. Dr. Wilson and Krissy Hansen, PT will have primary
responsibility for device accountability, but the other staff listed in this protocol will share responsibility.
 
 
21.35 
Attach copies of device logs, see examples of logs on the IRB Home Page in the IRB Guidelines Section under
MHS Medical Device Guidelines :
Name
Version
PNS+PT Device Inventory Logv3 (11-Nov-2017) | History
0.04
 
 
 
 
 
 
 

 
View: 22-00 Clinical Trials Registration
  22.0   Clinical Trials Registration:
Note: Phase 2 - 4 trials of drugs and biologics (controlled clinical investigations other than Phase 1
investigations of a product subject to FDA regulation) AND trials of devices (controlled trials with health outcomes,
other than small feasibility studies and pediatric post-marketing surveillance) must be registered per the Food and Drug
Administration Act of 2007;  NIH encourages registration of all trials, regardless of whether required under applicable law.
How are study protocols submitted to ClinicalTrials.gov?
The FDA Guidance Document (March 2002) (http://www.fda.gov/cder/guidance/4856fnl.htm) describes the submission criteria.
The NLM has developed the Protocol Registration System (PRS), a Web-based tool for submitting information to
ClinicalTrials.gov. Study sponsors or their representatives may register online to apply for a PRS account
(http://prsinfo.clinicaltrials.gov/).
  22.1  Has this trial been registered on www.clinicaltrials.gov?
  
Yes 
No
  Web link to clinical trails
website. 
  22.2
If Yes, who registered the trial?(i.e. sponsor, investigator)
Investigator
  Please respond 
  22.3 
Please provide ClinicalTrials.gov Identifier (i.e. NCT00391872)
NCT02893267
  The sponsor can provide you
with this information or you can
look it up on the website.
 
 
  22.4
If No, are there plans to register the study?   
Yes 
No
  If you answer No you must
provide an reason why this
study will not be registered.
  22.5
If the answer to 22.4 is No, provide and explanation:
  Provide a response if the
answer to 22.4 is No.
 
   
   
 
View: 23-00 Interview/Focus Groups
  23.0 Interview/Focus Groups:
  23.1  Does this study involve Interviews/Focus Groups? No
If you answer no and hit continue you will go to the next page.
  Answer yes or no.
  23.2
 
Attach copies of any scripts/or questions that will be used to guide the interview
focus/groups:
Name
Version
There are no items to display
Attach scripts or questions.
  23.3
Idendtify all Staff conducting interviews on page 1 question 1.4 by selecting the
correct role.
 
  23.4  Is there any specific training or qualifications needed to conduct the
interviews/focus groups?
  Describe training and/or
qualifications. 
View: 24-00 Psychological Testing
  24.0 Psychological Testing:
  24.1  Does this study involve Psychological testing? Yes   
If you answer no and hit continue you will go to the next page.  
  Answer yes or no.
  24.2  First Please list all Psychological Tests that will be given:
Mini Mental State Exam (MMSE)
  First please list the
test(s)/measures to be used. 

  24.3
Attach copies of all psychological test(s)/measures that will be used for this
study:
Name
Version
MMSE | History
0.02
  Second attach copies of all
test(s)/measures.
 
 
 
  24.4
Is there any necessary training or licenses required of those administering the
psychological testing?
No for MMSE.
Idendtify all Staff Administering tests on page 1 question 1.4 by selecting the
correct role.
  Describe any training or licenses
required to administer test(s).
View: 25-00 Surveys/Questionnaires
  25.0 Surveys/Questionnaires:
  25.1  Does this study involve Surveys/Questionnaires? Yes
If you answer no and hit continue you will go to the next section.  
  Answer yes or no.
  25.2
Please attach all questionnaires and/or surveys to be used in this study:
Name
Version
BDI-2 | History
0.02
BPI-SF Last Week | History
0.02
FABQ | History
0.01
PCS- Pain Catastrophizing Scale | History
0.01
PGIC (Shoulder Studies, Feb-2017) | History
0.01
SF-36 | History
0.02
  Attach
survey(s)/questionnaire(s).
  25.3
Idendtify all Staff conducting Surveys on page 1 question 1.4 by selecting the
correct role.
 
View: 26-00 Deception
  26.0  Deception:
Deception is a research methodology. When deception is used in research the subject is not told, or is misled,
about the true purpose of the research, such as in certain studies of group processes, contextual influences on
cognition, etc.
   26.1  Does this study involve the use of deception as a study design method for the
research?
No  
If you checked no then hit the continue button and you will be taken to the next page.
  Deception is defined as
intentionally misleading or
withholding information about
the nature of the experiment. 
  26.2
Describe in detail the nature of the deception and explain why this is necessary
for the research:
  Please describe the nature of the
deception. 
  26.3 
State how, when and by whom the research subjects will be debriefed:
  Briefly describe your plan to
debrief subjects. 
View: 27-00 Additional Documents
  27.0 Additional Documents:
  27.1  Are there any additional study documents you wish to attach to this
application?  
Name
Version
Bandage Change Instructions | History
0.01
Electrode Fragment Information Sheet 4.0 | History
0.02
Electrode Fragment Wallet Card 2.0 | History
0.03
Instructions for Care of Electrode Exit Site 1st 48 hrs | History
0.03
Instructions for Care of Electrode Exit Site 1st 48 hrs(with Mark
up).docx | History
0.04
PNS PT group assignment letter(tracked) | History
0.01
PNS+PT Group Assignment Letter | History
0.03
  Attach any additional study
documents i.e protocols supplied
by sponsor.

Name
Version
PNS+PT Other Therapy Diary (during treatment) | History
0.01
PNS+PT Other Therapy Diary (outcomes visits) | History
0.01
PNS+PT Phone Log | History
0.01
PNS+PT Screening Form | History
0.01
PNS+PT Subject Schedule | History
0.02
PNS+PT Subject Scheduletrackchange.docx | History
0.01
Quickstart guide: Sprint Clinician Sham Mode: Non-Contracting PNS |
 History
0.03
Sprint Clinician Manual Version 2 | History
0.03
Sprint Patient Manual Version 2 | History
0.03
Sprint Stimulator Set up for subject | History
0.01
View: The End
 
To Finalize this application you must do two things:
1.) As a final step you should click on Hide/Show Errors on the top of this page. If there are any required fields in the Application you
have omitted they will show up in red. If you click on each item you will be taken to that page of the application so you can complete
the question.
Note: Unless all named Co-investigators have agreed to participate you will not be able to submit your study. Co-Investigators have
to press the Co-Investigators agree to participate button. You can send them an email message tellng them to do this by pressing
Notify Co-Investigators of Need to Agree to Participate. The minute you have selected your Co-Investigators you can press this
button it is not advisable to wait until you have completed the application as it may hold up your submission.
When all error messages are gone then... 
2.) Click Finish
Please click on the "Finish" button to finalize and exit the Study application.  Doing so will NOT submit the application for review.  
3.) The PI must press the Submit Study button (when they are ready to submit to the IRB)
Please note that a submission may only be forwarded to the IRB by the Principal Investigator.  To do this, the Principal Investigator
must push " Submit Study" in the blue area on the left hand side of the page under My Activities. Only the PI will have this button
it will not be visible to any other study team members.
You can track the ongoing status of your submission by logging into the study workspace. On the top left hand side of the page in the light
blue area there will be a box labeled with the Current State of your study. 
Please contact the IRB with any questions or concerns. When calling the IRB Office Please direct your questions to the IRB staff
named as the "Owner" of your study.
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Shannon Hogan
Study Role:
Name
Research Support Staff
Obtaining Informed Consent
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  John Chae
Study Role:
Name
Co-investigator
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Kristine Hansen

Study Role:
Name
Study Coordinator
Research Support Staff
DRA (only one)
Interviewer (Survey, Focus Group)
Obtaining Informed Consent
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Amy Friedl
Study Role:
Name
Research Support Staff
Obtaining Informed Consent
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Terri Hisel
Study Role:
Name
Research Support Staff
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Nathaniel Makowski
Study Role:
Name
Research Support Staff
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Victoria Whitehair
Study Role:
Name
Research Support Staff
View: CCF Key Personnel Questions View
* Name of Key Personnel Working on Study:  Douglas Gunzler
Study Role:
Name
Research Support Staff
View: CRU DSMP Data Collection Simple View
Name: Chart Review, interview, questionnaire
Level of Risk: Minimal and Low Risk Studies
Type: Data Collection
View: CRU DSMP Data Collection Simple View
Name: Elderly Population
Level of Risk: Moderate Risk Studies
Type: Study Population
View: CRU DSMP Data Collection Simple View
Name: Psychologically or neurologically impaired population
Level of Risk: Moderate Risk Studies
Type: Study Population
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk

 
*  Outcomes Assessments (questionnaires, tests of arm and
shoulder movement, pain thresholds)
 
* 
 
Name
Minimal or Low
Moderate
High
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk
 
*  Percutaneous electrode implant procedure/short term
implant and e-stim
 
* 
 
Name
Minimal or Low
Moderate
High
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk
 
*  Percutaneous electrode removal
 
* 
 
Name
Minimal or Low
Moderate
High
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk
 
*  Physical Therapy
 
* 
 
Name
Minimal or Low
Moderate
High
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk
 
*  Venipuncture
 
* 
 
Name
Minimal or Low
Moderate

 
Name
High
View: Create CRU Procedure Risk
 
CRU Procedure Risk:
 
 
 Procedure
 
Risk
 
*  X-Ray
 
* 
 
Name
Minimal or Low
Moderate
High