Advanced Restoration Therapies in Spinal Cord Injury. AIM1: Patterned FES Ergometry of Arm and Shoulder in Individuals With Spinal Cord Injury
Phase: PHASE1
Conditions: Spinal Cord Injury
Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

 
NOV 2006 
1/33 
 
 
 
 
 
 
 
 
 
Title: Patterned FES Ergometry of Arm and Shoulder in individuals with Spinal Cord Injury 
 
PI: Cristina Sadowsky 
 
IRB Number: NA_00014481 
 
NCT01005615 
 
16-Sept-2013 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
2/33 
 
 
 
 
 
 
 
Advanced Restoration Therapies in Spinal Cord Injury.  Aim1: Patterned FES Ergometry of Arm and 
Shoulder in Individuals with Spinal Cord Injury. 
 
I. 
PROTOCOL INFORMATION 
Title: 
Advanced Restoration Therapies in Spinal Cord Injury.  Aim1: Patterned FES Ergometry of 
Arm and Shoulder in Individuals with Spinal Cord Injury. 
 
Protocol No. 
Sponsor: 
Opportunity#W81XWH-BAA07-1 
 
 
ERMS # 08284002 
 
Sponsor: 
Opportunity #W81XWH-09-2-0186 
 
 
ERMS #09181006 
 
Local IRB: 
NA_00014481 
 
Sponsor: 
Department of Defense (DOD) Telemedicine and Advanced Technology Research Center 
(TATRC) 
 
IRB of Record: 
The Johns Hopkins Medicine Institutional Review Boards (JHM IRBs) 
Reed Hall B-130 
1620 McElderry Street 
Baltimore, Maryland 21205-1911 
Phone: (410) 955-3008 
Fax: (410) 955-4367 or (443) 287-5353 
 
Phase of study: 
randomized, controlled, single-blinded trial 
 
Version/Date: 
11.0, 16-Sept-2013 
 
The protocol will be conducted in accordance with the protocol submitted to and approved by the Office of 
Research Protections (ORP), Human Research Protection Office (HRPO) and will not be initiated until written 
notification of approval of the research project is issued by the ORP HRPO. 
 
II. 
PRINCIPAL INVESTIGATOR’S INFORMATION 
 
PI Name: Cristina Sadowsky, MD 
 
Title: Assistant Professor, Dept. Physical Medicine & Rehabilitation, The Johns Hopkins 
University School of Medicine 
Director,Paralysis Restoration Clinic, Int. Center for Spinal Cord Injury 
Research Institution: Kennedy Krieger Institute 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
3/33 
 
Address: The International Center for Spinal Cord Injury, Room 518 
707 North Broadway 
Baltimore, MD 21205 
 
Phone #: (443) 923-9210 
 
Fax #: (443) 923-9215 
 
Email: Sadowsky@kennedykrieger.org 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
4/33 
III. 
ROLES AND RESPONSIBILITIES 
a. study team members 
All Study Team Members are employed by the International Center for Spinal Cord Injury at the Kennedy 
Krieger Institute (KKI). 
 
1. Principal Investigator: Cristina Sadowsky, M.D. 
The Principal Investigator will be responsible for: 
 Compliance with all the requirements of the IRB on Records and the United States Army Medical Research 
and Materiel Command’s (USAMRMC) Office of Research Protections (ORP), Human Research Protection 
Office (HRPO). 
 Performing screening chart review. 
 Consenting the research subjects. 
 Conducting some of the assessments as listed in section XI. 
 Performing the data analysis. 
 
2. Co-Investigator 1: John McDonald, M.D., Ph.D. 
Title: Associate Professor of Neurology and Physical Medicine and Rehabilitation, The Johns Hopkins 
University School of Medicine 
Executive Vice President and Director, Int. Center for Spinal Cord Injury 
 
The Co-Investigator 2 will be responsible for: 
 Performing screening chart review. 
 Consenting the research subjects. 
 Conducting some of the assessments as listed in section XI. 
 Performing the data analysis. 
 
3. Co-Investigator 2: Albert Recio, M.D. 
Title: Faculty Instructor, Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine 
Physician, Paralysis Restoration Clinic, Int. Center for Spinal Cord Injury 
 
The Co-Investigator 3 will be responsible for: 
 Conducting data analysis for some of the assessments as listed in section XI, specifically the Severity of 
gleno-humeral subluxation. 
 
4. Therapist 1: Rebecca Martin, OTR/L, OTD 
Title: Manager, Clinical Training and Education, Int. Center for Spinal Cord Injury 
 
The Therapist 1 (T1) will be responsible for: 
 Conducting some of the assessments as listed in section XI. 
 . 
 Performing the data analysis. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
5/33 
5. Therapist 5: Marjorie Morgan, AD Physical Therapist Assistant 
Title: Physical Therapist Assistant I, Int. Center for Spinal Cord Injury 
 
The Therapist 5 (T5) will be responsible for: 
 Conducting the treatment. 
 
6. Therapist 6: Kim Perone, OTR/L, M.S 
Title: Occupational Therapist I, Int. Center for Spinal Cord Injury 
 
The Therapist 6 (T6) will be responsible for: 
 Conducting some of the assessments as listed in section XI. 
 Performing the data analysis. 
  
7. Therapist 6: Heidi Nash, OTR/L, M.S 
Title: Occupational Therapist I, Int. Center for Spinal Cord Injury 
 
The Therapist 6 (T6) will be responsible for: 
 Conducting some of the assessments as listed in section XI. 
 Performing the data analysis. 
 
 
8. Therapist 7: Jennifer Silvestri, OTR/L, M.S. 
Title: Occupational Therapist I, Int. Center for Spinal Cord Injury 
 
The Therapist 7 (T7) will be responsible for: 
 Conducting the treatment. 
 
9. Therapist 8: Cara Felter, BS, DPT, MPH 
Title: Physical Therapist IV (Senior), Int. Center for Spinal Cord Injury 
 
The Therapist 8 (T8) will be responsible for: 
 Conducting the treatment. 
 
10. Therapist 7: Scott Meyer. 
Title: Physical Therapist Assistant II, Int. Center for Spinal Cord Injury 
 
The Therapist 9 (T9) will be responsible for: 
 Conducting the treatment. 
 
11. Nurse 1: Charnan Koller, CRRN, AD, BA, MA 
Title: Nurse Clinician, Int. Center for Spinal Cord Injury 
 
The Nurse 1 (N1) will be responsible for: 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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 Conducting  some of the assessments as listed in section XI. 
 
12. Nurse 2: Grethlyn Orr, BSN, MA 
Title: Nurse Clinician, Int. Center for Spinal Cord Injury 
 
The Nurse 2 (N2) will be responsible for: 
 Conducting  some of the assessments as listed in section XI. 
 
13. Nurse 3: Florence Hanssen, RN 
Title: Nurse Clinician, Int. Center for Spinal Cord Injury 
 
The Nurse 3 (N3) will be responsible for: 
 Conducting  some of the assessments as listed in section XI. 
 
14. Study Coordinator 2: Shannon Inches 
Title: Research Assistant I (clinical trial), Int. Center for Spinal Cord Injury 
 
The Study Coordinator 2 (SC2) will be responsible for: 
 Preparing all regulatory documentation. 
 Compliance with all the requirements of the IRB on Records and the United States Army Medical Research 
and Materiel Command’s (USAMRMC) Office of Research Protections (ORP), Human Research Protection 
Office (HRPO). 
 Conducting the screening phone interview. 
 Consenting the research subjects. 
 Coordinating subject visits. 
 Conducting some of the assessments as listed in section XI. 
 Holding the randomization sequence. 
 Maintaining study data. 
 
15. Medical Monitor: Daniel Becker, M.D. 
Title: Assistant Professor, Physical Medicine & Rehabilitation, Johns Hopkins University School of Medicine 
Associate Medical Staff, Paralysis Restoration Clinic, ICSCI 
 
The Medical Monitor(MM) will be responsible for: 
 Providing medical care to research volunteers for conditions that may arise during the conduct of the study. 
 Monitoring the volunteers’ medical status during the conduct of the study. 
 Reviewing all unanticipated problems involving risk to subjects or others, serious adverse events and all 
subject deaths associated with the protocol and provide an unbiased written report of the event. 
 
16. Other Staff 1: Edward Hammond, M.D., M.P.H. 
Title: Research Coordinator II, Int. Center for Spinal Cord Injury 
 
The Other Staff 1 will be responsible for: 
 Performing the data analysis. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
7/33 
 
b. collaborating institutions 
Not applicable 
 
IV. 
SITE INFORMATION 
All the research activity will take place at the Broadway& Fairmount campus of the International Center for 
Spinal Cord Injury (ICSCI) Paralysis Restoration Clinic at the Kennedy Krieger Institute (KKI). 
 
The Kennedy Krieger Institute has a Federal Wide Assurance, FWA00005719, expires 09/26/2016. 
 
The Shoulder X-Ray will be done as fee-for-service at the Radiology Services of the Johns Hopkins Hospital, 
which is accessible through an underground tunnel from KKI.  There is no need for the subjects to organize 
their own transportation and there is no additional travel cost.  A study team member will be available to assist 
the subject if needed. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
8/33 
V. 
TABLE OF CONTENT 
VI. 
STUDY INFORMATION ......................................................................................................................10 
a. 
Type of Research ............................................................................................................................................... 10 
b. 
Abstract .............................................................................................................................................................. 10 
VII. 
STUDY DESIGN....................................................................................................................................10 
a. 
Background ........................................................................................................................................................ 10 
b. 
Study Design, Research Objectives ................................................................................................................... 12 
VIII. 
INCLUSION / EXCLUSION CRITERIA ..............................................................................................12 
a. 
Inclusion criteria: ............................................................................................................................................... 12 
b. 
Exclusion criteria: .............................................................................................................................................. 13 
IX. 
SUBJECT RECRUITMENT & SCREENING .......................................................................................13 
a. 
Subject recruitment & screening: ...................................................................................................................... 13 
b. 
Target Population: ............................................................................................................................................. 14 
c. 
Recruitment Material: ........................................................................................................................................ 14 
X. 
INFORMED CONSENT PROCESS ......................................................................................................15 
a. 
Consent Process: ................................................................................................................................................ 15 
b. 
Subject Identification/Randomization: .............................................................................................................. 15 
c. 
HIPAA Compliance ........................................................................................................................................... 15 
d. 
Pregnancy: ......................................................................................................................................................... 16 
XI. 
DATA COLLECTION and ANALYSIS ................................................................................................16 
a. 
Study Procedures ............................................................................................................................................... 16 
1. 
Study design, including the sequence and timing of study procedures (distinguish research procedures from those 
that are part of routine care). ........................................................................................................................................... 16 
2. 
Study duration and number of study visits required of research participants. ................................................................. 19 
3. 
Blinding, including justification for blinding or not blinding the trial, if applicable. ...................................................... 20 
4. 
Justification of why participants will not receive routine care or will have current therapy stopped. ............................. 21 
5. 
Justification for inclusion of a placebo or non-treatment group. ..................................................................................... 21 
6. 
Definition of treatment failure or participant removal criteria. ....................................................................................... 21 
7. 
Description of what happens to participants receiving therapy when study ends or if a participant’s participation in 
the study ends prematurely. ............................................................................................................................................. 21 
b. 
Devices .............................................................................................................................................................. 21 
1. 
Name of Test Device: ...................................................................................................................................................... 21 
2. 
Schedule/duration/administration of test device: ............................................................................................................. 21 
3. 
FDA Status: ..................................................................................................................................................................... 22 
4. 
FDA approved use description: ....................................................................................................................................... 22 
5. 
IDE Info: ......................................................................................................................................................................... 22 
c. 
Study Statistics .................................................................................................................................................. 22 
1. 
Primary outcome variable. ............................................................................................................................................... 22 
2. 
Secondary outcome variables. ......................................................................................................................................... 23 
3. 
Statistical plan including sample size justification and interim data analysis. ................................................................ 23 
4. 
Early stopping rules. ........................................................................................................................................................ 23 
XII. 
LABELING & STORAGE OF DATA & SPECIMENS ........................................................................24 
XIII. 
RISK AND INJURY...............................................................................................................................25 
a. 
Risks, Risk Management: .................................................................................................................................. 25 
1. 
Assessment Risks: ........................................................................................................................................................... 25 
2. 
Intervention Risks: .......................................................................................................................................................... 26 
3. 
Other Risks: ..................................................................................................................................................................... 26 
b. 
Medical Care For Research Related Injury: ...................................................................................................... 26 
XIV.  BENEFIT(S) ...........................................................................................................................................26 
XV. 
COMPENSATION .................................................................................................................................27 
a. 
Payment and Remuneration: .............................................................................................................................. 27 
b. 
Costs .................................................................................................................................................................. 27 
XVI.  CONFIDENTIALITY.............................................................................................................................27 
XVII.  ADVERSE EVENTS ..............................................................................................................................28 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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XVIII. CHANGES TO PROTOCOL .................................................................................................................28 
a. 
Protocol Modifications: ..................................................................................................................................... 28 
b. 
Protocol Deviations: .......................................................................................................................................... 28 
XIX.  CONTINUING REVIEW & FINAL REPORT ......................................................................................28 
a. 
Continuing Review Reports: .............................................................................................................................. 28 
c. 
Final Study Report: ............................................................................................................................................ 29 
XX. 
LITERATURE REVIEW .......................................................................................................................29 
XXI.  Appendix: Study Related Documents .....................................................................................................32 
a. 
Recruitment forms: ............................................................................................................................................ 32 
b. 
Informed Consent forms: ................................................................................................................................... 32 
c. 
Case Report Forms: ........................................................................................................................................... 32 
d. 
Serious Adverse Event report forms: ................................................................................................................. 32 
XXII.  Appendix: Medical Device Related Documents .....................................................................................33 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
10/33 
VI. 
STUDY INFORMATION 
a. Type of Research 
This is Specific Aim 1 of Proposal 08284002 titled “Advanced Restoration Therapies inSpinal Cord Injury". 
 
Specific Aim 1:  To determine whether functional electrical stimulation promotes neurological and 
physical recovery in patients with Spinal Cord Injury. 
We will investigate the extent of functional recovery in patients with Spinal Cord Injury (SCI) who receive 
Functional Electrical Stimulation (FES) in the upper extremities compared with patients who do not receive 
FES. 
 
b. Abstract 
Background:  Recent evidence suggests that FES can improve certain functions in the Central Nervous System 
(CNS) following injury or disease; it can enhance motor recovery, change H reflex and flexor reflex excitability 
[1-3]and enhance sensory function in chronic SCI [4]. 
Using FES-based therapies in our clinic, we have seen neurological, physical, and functional improvements.  By 
systematically measuring the impact of FES on functional recovery in individuals with spinal cord related 
paralysis, we hope to greatly advance our clinical application of FES. 
 
Objective/Hypothesis:  To test the hypothesis that patterned neural activity induced by FES enhances recovery 
of function in the injured spinal cord patients with paralysis. 
 
Study Design SA1:  A randomized, controlled, single-blinded, in-subject controlled (A-B type) trial will be 
performed in patients with SCI receiving an upper extremities non-FES assisted exercise protocolcompared 
with patients receiving upper extremities ergometry in combination with FES.  Neurological and functional 
outcome measures will be obtained at baseline (time 0), after 1st4 months of intervention (4 months), after 1 
month washout (5 months),after 2nd 4 months intervention (9 months), and 3 month after completing the last 
intervention (12 months). 
 
Relevance:  The studies proposed here will rigorously test the efficacy of FES-based restorative therapies in 
promoting neurological and functional recovery in patients with SCI. These findings will be applied in a clinical 
setting to optimize the FES-based therapies. 
 
VII. 
STUDY DESIGN 
a. Background 
Overview:Spinal Cord Injury and related paralysis imposeamajor socioeconomic burden on those afflicted with 
this devastating neurologic deficit. At the society level, the estimated annual aggregate cost is over 7 billion 
1992 US dollars [5].  There is no cure, but bench research data point to neuro-restorative potential of different 
interventions. Several different reports support the hypothesis that plasticity occurs at the spinal cord level [6-
8], and that maintenance of neural activity in injured areas influences the nervous system modeling and repair 
through different mechanisms: 1) new synapse formation and strengthening of existing ones, 2) re-myelination, 
3) new cell birth. Neuronal activity is necessary for the full development and maintenance of inhibitory circuitry 
[9-21]. Chemical inhibition of neural activity in culture and in animals, results in reduced numbers of inhibitory 
synapse connections and can result in nervous system over-activity (such as spasticity) once the blockade is 
partially removed. New synapse formation and stabilization of excitatory synapses may also require coincident 
neural input to refine connection selectivity and to maintain connections. Re-myelination of axons that have 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
11/33 
been de-myelinated secondary to injury is dependent on optimal electrical activity [22]. The strongest evidence 
is in the peripheral nervous system but strong data also exist in the central nervous system [23-25]. Stem cells 
exist in the ventricle lining of the brain and spinal cord of adults.  These stem cells are capable of birthing new 
neurons, oligodendrocytes and astrocytes [26, 27].  Patterned neural activity created by enhancing walking 
activity in rodents can lead to overall greater production and survival of newly born cells [27]. The survival of 
injured or newly developed neurons and glia has been shown to be partly dependent upon optimal levels of 
neural activity [28]. 
 
Most research groups study the acute phase of injury [29].  ButKennedy Krieger’s International Center for 
Spinal Cord Injury (ICSCI)is developing and applying treatments for long-standing SCI.  Its central focus is 
Activity-Based Restoration Therapies (RT), [30], which have been shown to reduce the risk of cardiovascular 
disease and diabetes and to lower the incidence of the medical complications of SCI [4, 30]. However, recent 
research from our group and others has raised the captivating idea that enhancing activity in regions of the 
nervous system that become dormant after SCI might be critical for spinal cord regeneration [30, 31]. How does 
functional electrical stimulation enhance neuro-recovery is not entirely clear, but there is evidence that 
thesensory afferent input provided by peripheral electricalstimulation provides drive to the spared CNS, altering 
electrophysiologicalparameters of spinal motor pattern-generating circuitry[32-34], altering amino acid 
neurotransmitter levels in the spinal cord (glycine and taurine) [35], and altering blood flow, both peripherally 
and centrally [36,37].Direct electrical stimulation of peripheral neuron cell bodies increasesBDNF and TrkB 
expression and leads to axonal regeneration [38-41]. 
 
To build on our success with clinical trials that combined leg cycle ergometry with FES of paralyzed muscles 
[4, 31, 42], we propose to determine whether FES, a major component of RT, can promote regeneration and 
functional recoveryby enhancing neural activitythrough external electrical stimulation. The studies will be 
performed by field leaders, scientists, clinicians, and therapists in ICSCI’s three major divisions, which are 
housed at the same location. With their collective expertise in clinical care, regeneration research, magnetic 
resonance imaging, and clinical trials, these experts are superbly equipped to perform all of the in vitro, in vivo, 
and imaging studies proposed here and to disseminate RT methodology to military and civilian rehabilitation 
specialists across the United States. 
 
Specific Aim 1:We will test the hypothesis that patterned FES of arm and shoulder muscles, via upper 
extremity FES ergometry, improves physical and neurological function in subjects with chronic tetraplegia 
due to SCI.  We propose a 12-month randomized, controlled, A-B type, single-blinded trial in which we test the 
effect of FES used in combination with an ergometer wheel versus an upper extremities non-FES assisted 
exercise protocol. 
This aim builds on our center’s success with comparing FES cycle ergometry to standard physical therapy for 
chronic SCI.  Our preliminary data suggests clinically relevant physical, functional, and neurological recovery.  
Importantly, we found that FES cycle ergometry 3 hours per week doubled thigh muscle volume, halved thigh 
fat volume, and increased muscle strength while proportionally reducing spasticity.  We also demonstrated 
clinically significant improvements in sensory and motor functions and functional independence. Also, more 
than half the FES subjects were able to stop using Baclofen, an anti-spasmodic, and 90% reduced the dosage or 
switched from polytherapy to monotherapy to control spasticity.  Moreover, 40% of FES subjects converted 
from ASIA A to B, C, or D, despite having injuries more than 2 years old.  In stark contrast, the control group 
exhibited the 4% ASIA A conversion rate that is reported in the literature [42]. 
We now wish to study upper extremity function, which is a major problem for patients with cervical injury and 
cannot yet be reliably treated. We propose to measure a battery of physical, functional, and neurological 
domains that are known to respond to FES cycle ergometry or that relate to the common sequelae of the 
shoulder dysfunction seen in tetraplegia. FDA approval of a recently developed FES/motor ergometer provides 
the first real opportunity to pursue this Aim. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
12/33 
 
Military Significance:Traumatic injury to the Central Nervous System (CNS) is an increasing problem for the 
U.S. military, given the increasing number of soldiers with SCI returning from combat zones.  Our proposed 
project will address this specific need by developing rehabilitative programs and training tools as well as 
advanced technologies for restoring nerve cell function. Understanding the underlying mechanisms that 
promote regeneration and recovery, as outlined in this proposal, will contribute to the knowledge base in the 
field as well as advance current concepts of regeneration.  Overall, the aims of this proposal have direct and 
indirect relevance to military and related civilian populations. 
 
Public Purpose:SCI is a devastating condition that imposes major costs on individuals and society.  Close to 
12,000 traumatic injuries occur each year in the United States, and approximately 1 million people live with 
SCI. Moreover, military personnel have returned from combat zones with SCI in the past years.  Estimates for 
lifetime financial burden per individual range from $500,000 to $2 million, and costs for SCI patient care in the 
United States exceed $7 billion dollars.  Including non-traumatic spinal-cord lesions, such as those associated 
with multiple sclerosis, would quadruple the number and annual cost of U.S. SCI cases [43].  However, 
virtually all current treatments must be applied shortly after the onset of SCI, as there are not yet effective 
treatments for the chronic phase of injury [4]. Effective treatment and therapeutic strategies geared toward the 
chronic injury phase would both improve the lifestyles of people with SCI and decrease their financial burden. 
 
b. Study Design, Research Objectives 
Study Design:A 12 months randomized, controlled, single-blinded, in-subject controlled (A-B type) trial will 
be performed in patients with SCI receiving upper extremity ergometry in combination with FESversus an 
upper extremities non-FES assisted exercise protocol.  Neurological and functional outcome measures will be 
used at 0, 4, 5, 9, and 12 months to test the efficacy of each intervention. 
 
Specific Aim:  Does FES of the upper extremities promote neurological and functional recovery? 
 
Hypothesis 1:  Patterned FES of arm and shoulder muscles, via upper extremity ergometry, will improve 
physical and neurological function in individuals with paralysis resulting from spinal cord injury. 
Expected Result:An FES paradigm involving ergometry of the upper extremities will enhance subjects’ 
functional recovery, as measured in the clinic by neurological and anatomical indices. 
 
VIII. 
INCLUSION / EXCLUSION CRITERIA 
a. Inclusion criteria: 
a. Male, Female, age 18-55, all ethnic groups. 
b. Spinal Cord Injury, traumatic and non-traumatic. 
c. C1-C6 neurological level. 
d. ASIA class A or B. 
e. Chronic injury,>12 months and < 20 years from the injury. 
f. No upper-extremity electrical stimulation in the previous 4 weeks. 
g. Subjects are medically stable, with no recent (1 month or less) inpatient admission for acute 
medical or surgical issues. 
h. Baseline physical activity will be kept stable during the study. 
i. Pain and antispasticity medications dose will be kept stable during the study. 
j. Subjects are legally able to make their own health care decisions. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
13/33 
b. Exclusion criteria: 
a. Associated lower motor neuron/peripheral nerve injury in the C1-C6 levels. 
b. Presence of pacemaker. 
c. Presence of cancer. 
d. History of seizures. 
e. Women who are pregnant. 
 
IX. 
SUBJECT RECRUITMENT & SCREENING 
a. Subject recruitment & screening: 
Recruitment scenario 1: 
Patients of the ICSCI, and prior study participantswill be identified as meeting the inclusion criteria by 
reviewing the medical records held by the ICSCIand filling out a Medical Chart Review Form.  A waiver of 
privacy authorization will be obtained from the local IRB of Record [HIPAA Form4] prior to chart review.  
Patients will be told about the studyduring a clinical visit;they will be given aSubject Recruitment Flyer with 
contact information;  a note of this communication will be made in the patient's medical record.  Those who are 
interested can meet privately with, or contact later the principal investigator or study coordinator who will 
explain in simple terms: 1) the purpose of the research and the procedures involved, 2) potential benefits, 3) 
potential risks, 4) the subject’s right to withdraw at any time without penalty of any sort, and 5) assurance of 
anonymity.If a patient indicates that he/she is no longer interested or is not eligible, the Medical Chart Review 
Form will be shredded. 
 
Recruitment scenario 2: 
Subject Recruitment Flyers will be posted at KKI and outside medical facilities who have agreed to do so.  
Physicians at KKI and these outside facilities will be provided with a guide to inform them generally of the 
exclusion/inclusion criteria for the study, and extra copies of the flyer to give out to potential subjects.  The 
Subject Recruitment Flyer will be posted on the ICSCI website (www.spinalcordrecovery.org) and 3rd party 
websites who have agreed to do so.The Study will also be listed on the newsletter published periodically by 
ICSCI and KKI.  The Study will also be listed on KKI Facebook social networking page 
(http://www.facebook.com/kennedykrieger)and other social network sites as appropriate.This study will also be 
registered onwww.clinicaltrials.gov within one year from initial IRB approval.This study can also be posted on 
and www.centerwatch.com. This study will also advertisedon the KKI on-hold message phone system.  This 
study will be also discussed in an Press Release.  All potential subjects who contact us in respond to the 
recruitment flyers will be called back by the study coordinator to complete a phone screening interview 
todetermine initial eligibility documented in a Phone Screening Form.  A waiver of privacy authorization will 
be obtained from the local IRB of Record [HIPAA Form4] prior to phone screening interview.  The study 
coordinator will explain in simple terms: 1) the purpose of the research and the procedures involved, 2) 
potential benefits, 3) potential risks, 4) the subject’s right to withdraw at any time without penalty of any sort, 
and 5) assurance of anonymity.  If the potential subject is interested in participating, study coordinator will ask 
the potential subject questions about his/her medical history.  The principal investigator or co-investigators will 
review the potential subject’s medical history to ascertain if inclusion criteria are met and that there are no 
obvious exclusions.  The potential subject will be called back to indicate if they are eligible to participate.  If a 
potential subject indicates that he/she is no longer interested or is not eligible, the Phone Screening Form will be 
shredded. 
 
For all recruitment scenarios: 
If the potential subject meets the inclusion criteria and agrees to participate, the subject will receive a copy of 
the Informed Consent Form.  The potential subject will be allowed as much time as needed (up to 1 month) to 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
14/33 
make a decision to participate in the study.  In addition, the candidate will be allowed to discuss the study’s 
appointment logistics with their own care providers.  Any questions the potential subject has about the study 
will answered. Once the potential subject agrees to participate, the subject will be enrolled andan initial visit 
will be set up.  The subject consent will be obtained during this initial visit before the post-consent screening is 
performed. 
 
In the 3 years since opening the International Center for Spinal Cord Injury (ICSCI) in 2005 (05’-08’), we have 
evaluated and treated over 600 new patients with longstanding SCI (White 63.57%, Black 31.69%, American 
Indian 0.91%, Hispanic 0.36%, Asian 0.18%, Other 3.28%).  Currently we evaluate and treat over 250 new 
patients annually.  Of the new patients with long-standing SCI, 50% are ASIA A and B and of this subgroup, 
over 10% have a neurological level between C1 and C6.  Using projections through 08’ and bases of 850 system 
clients, approximately 85 patients will meet the entry criteria of ASIA A-B, neurological level C1-6 proposed in 
our study.  Furthermore, study entry does not have to be limited to clients already within our ICSCI system.  
Therefore, based on this availability, we do not anticipate the recruitment of patients to be a substantive barrier 
to recruitment for this study. 
 
b. Target Population: 
We plan to enroll up to 30 subjects with an expected accrued number of subjects of 24 (screening failure of 6).  
The 24 accrued subjects will be randomized in 2 groups of 12.  We are anticipating an attrition rate of 4 subjects 
maximum. 
 
We plan to enroll both male and female subject, all ethnic groups. 
No specific racial or ethnic groups will be targeted by our recruitment process. 
Non-English speaking subjects will not be targeted by our recruitment process. 
 
No vulnerable population is specifically targeted by our recruitment process. 
Pregnant womenwill be excluded from this study. 
 
c. Recruitment Material: 
Subject Recruitment Flyer: form given to ICSCI patients that fit the study criteria during a clinic visit, and 
posted on the ICSCI website (www.spinalcordrecovery.org). 
Inclusion/Exclusion Index Card: Laminated index cards with inclusion/exclusion criteria that physician can 
carry. 
Inclusion/Exclusion Wall Listing: Laminated listing with inclusion/exclusion criteria posted in ICSCI clinic 
rooms that physician can refer to. 
ICSCI & KKI Newsletter: IRB approved language that will be inserted in the ICSCI and KKI Newsletter. 
KKI Facebook: IRB approved language that will be inserted on the KKI Facebook page. 
KKI On-Hold Phone Message: IRB approved script that will be played on the KKI On-Hold phone system. 
ICSCI Press Release: IRB approved press release. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
15/33 
X. 
INFORMED CONSENT PROCESS 
a. Consent Process: 
For all eligible participants, informed consent will be obtained at the ICSCI by the PI, Co-Investigator 1, or 
Study Coordinator during their initial (screening) study visit.  The meeting will take place privately in one of 
the clinic rooms.  The informed Consent Form will be read to the subject explaining the following in simple 
terms: 
(1) the criteria for participation. 
(2) the purpose of the research and the procedures involved. 
(3) the subject’s right to withdraw at any time without penalty of any sort. 
(4) potential benefits to the subject. 
(5) potential risks. 
(6) assurance of anonymity. 
(7) terms of remuneration. 
 
Questions will be asked about the purpose of the study, procedures, risk and benefits to study participants to 
assess understanding. All participant questions will be answered and he/she will be asked to sign the consent 
document in the presence of one of the study team members. 
 
Only individuals that are legally able to make their own health care decisions will be enrolled. 
 
For individuals that do not speak English, a “short form” consent document will be used in conjunction with an 
oral presentation of the full English version consent form to the subject in his or her language by a translator 
fluent in both English and the subject’s spoken language. 
 
A “short form” is a written document stating that the elements of informed consent required by 45CFR46.116 
have been presented to and are understood by the subject or the subject’s legally authorized representative.  The 
IRB of Record provides an English version of the “short form” and the following approved translations of the 
“short form” (Arabic, Chinese, Haitian, Italian, Korean, Polish, Portuguese, Russian, Spanish, Vietnamese). 
 
b. Subject Identification/Randomization: 
Once consented and qualified, subject will be assigned a study number in the format “14481nnn”, where nnn is 
a sequential 3 digit number starting with 001. 
 
The randomized sequencewill be generated by using the Web site Randomization.com 
(http://www.randomization.com) using the Random Block Size method for 24 subjects in two groups.The 
sequence will be stored electronically in a password-protected document. 
 
The Research Coordinator 1is assigned to: 
 Manage the randomized sequence electronic file. 
 Assign participants to subgroups according to the randomized sequences. 
 
c. HIPAA Compliance 
As per the Local IRB of Record Consent Form Template, the HIPAA compliance/authorization language is 
included in the Consent Form. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
16/33 
d. Pregnancy: 
As per the local IRB of Record, pregnant participants are typically excluded from protocols using ionizing 
radiation.  Also, while there are no known risks to an embryo or fetus associated withFES during pregnancy, 
this research may hurt an embryo or fetus in ways we do not currently know.  For this reason, pregnant women 
cannot take part in this study. If a woman is capable of having children, shemust have a pregnancy test. The 
pregnancy test will be performed during the post-consent screening. If the subject become pregnant (or suspect 
pregnancy) before this study is completed, the subject must inform the study team immediately. 
 
XI. 
DATA COLLECTION and ANALYSIS 
a. Study Procedures 
1. Study design, including the sequence and timing of study procedures 
(distinguish research procedures from those that are part of routine care). 
The study subjects will engage in an A (upper extremities FES assisted ergometry)-B (upper extremities non-
FES assisted exercises) type protocol intervention in which they undergo either 4 months of FES assisted upper 
extremity ergometry followed by 1 month wash out period, then by 4 months of a specific, individualized, non 
FES assisted exercise regimen (strengthening, stretching, splinting) or 4 months of an upper extremities non-
FES assisted exercise protocol followed by 1 month wash out period, then by 4 months of FES assisted upper 
extremity ergometry.  12 subjects randomly selected will start with the FES assisted intervention and the other 
12 subjects will start with the non FES assisted regimen.  FES will be delivered using the RT300-SLSA Cycle 
Ergometer, Restorative Therapies, Inc.The subjects will be assessed using a battery of physical and neurological 
indicators before starting the intervention (time 0), after completing first 4 months of intervention (4 months), 
after the 1 month wash out (5 months), after completing the second 4 month of intervention (9 months) and 3 
months after completing the last intervention (12 months).The evaluator will be blinded to group assignment, 
but we cannot use true blinding due to the intervention’s sensory component.  The Study Time Line is found in 
Figure 1. 
 
 
Figure 1: Study Time Line 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
17/33 
(1) Assessment: 
The tests listed below will be performed for all subjects.The data collection schedule in Table 1. 
 
a) Neurological Exam:  This is a routine exam performed to rule out any associated lower motor 
neuron/peripheral nerve injury in the C1-C6 levels.  Subjects will undergo testing of the deep tendon reflexes at 
the biceps, brachio-radialis and triceps level.  This involves tapping of each specified muscle tendon with a 
neurologic reflex hammer. 
 
b) Fast Urine Pregnancy Test:  This is a routine exam performed for women of child bearing age who do not 
take any birth control prophylaxis. 
 
c) Severity of gleno-humeral subluxation:  This is a routine exam performed to assess shoulder subluxation.  
The space between the glenoid and head of the humerus can be visualized on plain X-rays and measured, in 
centimeters, to grade severity.  This test is done bilaterally. 
 
d) Spasticity measurement:  This is a routine exam performed for people with spinal cord injury.The Modified 
Ashworth Scale assesses muscle resistance to passive movement.  The evaluator moves the joint through the 
available range of motion and assigns a score from 0–4, where 0 is no tone and 4 is fixed limb (ordinal scale, 
[44]).Subjects are tested in a seated position preferably in their wheelchairs.  The subjects’ upper extremity is 
stabilized by the examiner above and below the joint to be tested. Then the joint is quickly moved through the 
previously determined subjects’ maximum range of motion. 
 
e) Capabilities of the Upper Extremity (CUE) test:  This is a routine exam performed for people with spinal 
cord injury.The CUE test is a 32-item interview. It is designed to self-assess upper extremity performance on a 
7-point scale (nominal scale, [45]).Subjects  are questioned while sitting in their wheelchairs.  A brief 
description of the test will be read to the subjects and then questions asked, one at a time.  Subjects will give 
verbal responses on a 7-point likert scale. 
 
f) Jebsen-Taylor Hand Function(JTHF) test:  This is a routine exam performed for people with spinal cord 
injury.The JTHF test is a 7-item test designed to objectively assess various hand functions and speed of 
performance (ordinal scale, [46]).  Subjects are tested in a seated position, preferably from their wheelchairs, in 
front of a table.  Test items will be laid out on the table and the test conducted per the standardized instructions.  
The JTHF requires subjects to reach for, lift, and in some cases manipulate small objects. 
 
g) Box and Blocks (BB) test:  This is a routine exam performed for people with spinal cord injury.The BB 
assesses gross hand function (ordinal scale, [47]).  Subjects are tested in a seated position, preferably from their 
wheelchairs, in front of a table.  Test items will be laid out on the table and the test conducted per the 
standardized instructions.  The BB requires subjects to reach for, lift, and move one inch cubes across a divider 
inside a wooden box. 
 
h) Action Research Arm (ARA) test:  This is a routine exam performed for people with spinal cord injury.The 
ARA test observationally assesses upper extremity function (20 items, ordinal scale [57]).Subjects are tested in 
a seated position, preferably from their wheelchairs, in front of a table.  Test items will be laid out on the table 
and the test conducted per the standardized instructions.  The ARA requires subjects to handle objects differing 
in size, weight and shape. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
18/33 
i) Functional Reach (FR) test:  This is a routine exam performed for people with spinal cord injury to evaluate 
trunk balance. The test is performed by patient reaching forward as far as they can while seated in their 
wheelchair. The distance traveled by the top of the reference shoulder is measured. 2 practice trials and 1 actual 
reach test is performed for the purpose of the study. 
 
j) Range Of Motion (ROM)of the upper extremity joints:  This is a routine exam performed for people with 
spinal cord injury.The Range Of Motion of the shoulder, elbow, wrist, and metacarpal-phalangeal joints will be 
measured via goniometry.Subjects are tested in a seated position, preferably in their wheelchairs.  The desired 
joint is isolated and moved through the maximum available range of motion.  Once the end range is reached, 
joint excursion is measured with a goniometer. 
 
k) Numerical Rating Scale (NRS) for pain:  This is a routine exam performed for people with spinal cord 
injury.Subjects report how much pain they are having by choosing a number from 0 (no pain) to 10 (the worst 
pain imaginable) (ordinal scale, [48]). 
 
l) Pulmonary Function Test (PFTs):  This is a routine exam performed for people with spinal cord 
injury.Three respiratory functions will be measured.  Vital Capacity (VC) is the maximal amount of air that can 
be exhaled after a maximal inhalation.  Negative Inspiratory Force (NIF) is the ability to take a deep breath in 
and to generate a cough strong enough to clear secretions.  Peak Cough Flow (PCF) measures the expiratory 
muscle force and the ability to cough. 
 
m) American Spinal Injury Association (ASIA) exam:  This is a routine exam performed for people with 
spinal cord injury.The ASIA exam assesses motor function at 10 key muscles in the body and light touch and 
pinprick sensation at 28 key points on each side of the body. It is also used to classify injury level and severity 
(ordinal scale, [49]). 
 
n) Pain and Spasticity Medication inventory:  This is a routine exam performed for people with spinal cord 
injury.  Pain and antispasticity medications dose will recorded. 
 
o) FES Evaluation:  This is a routine exam performed for people with spinal cord injury prior to receiving 
FES.Therapist 1 or 6 will test the different muscles that are targeted for this study to achieve the best motor 
response to FES, and maintain subject comfort.  Depending on the neurological level of the subject, the muscles 
are: supraspinatus; infraspinatus; teres major and minor; anterior, middle, or posterior deltoid; biceps; and 
triceps. 
 
(2) Intervention: 
The subjects will be randomly assigned, in a one-to-one ratio, either to group 1, which will first engage in the 
FES assisted ergometry followed by the non-FES assisted exercise, or to group 2, which will first engage in the 
non-FES assisted exercise followed by the FES assisted ergometry. 
 
p) FES Upper Extremity Cycle Ergometry:  While undergoing the FES assisted ergometry intervention, the 
subjects will use an RT300-SLSA upper extremity ergometer configured with FES.  Electrode placement will 
be individually optimized to produce smooth cycling, as measured by crank symmetry, average stimulation 
level, expended energy per hour, and muscle stiffness.  Parameters of stimulation current will also be 
individually optimized to achieve the best motor response (frequency of 10 to 100 Hz, pulse duration of 50 
to500 µs, and amplitude of 10 to140 mA).  Silver mesh self-adhesive surface electrodes will be used to conduct 
the stimulation. They will activate some combination of the following muscles,depending on the neurological 
level at which they are applied: supraspinatus; infraspinatus; teres major and minor; anterior, middle, or 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
19/33 
posterior deltoid; biceps; and triceps.  Target cycling speed will be 20 rpm, with a resistance of0.965Nm.  The 
subjects will warm up between2 and 10 minutes depending on muscle stiffness or spasms, actively cycle with 
FES for 1 hour, and cool down of 2 minutes. The ergometer software will be set to provide motor support once 
muscle fatigue has been reached so the subjects can continue.  The subjects will remain seated in their primary 
wheelchair throughout the treatment.  The subjects will cycle for 60 minutes/session, three times a week for 4 
months. 
 
q)Non-FES Upper Extremity Exercise:  While undergoing the non-FES exercise intervention, the subjects 
will receive a specific, individualized exercise regimen, consisting of strengthening, stretching, splintingand any 
other therapeutic interventions that do not use electrical stimulation..  The subjects will remain seated in their 
primary wheelchair throughout the treatment.  The subjects will exercise for 60 minutes/session, three times a 
week for 4 months. 
 
2. Study duration and number of study visits required of research participants. 
The study will last 12 months.  The Study Time Line is found in Figure 1, and the Data Collection Schedule in 
Table 1. 
(1) Assessment: 
The following post-consent screening will be performed at the Initial visit: 
a. Neurological Exam (about 30 minutes) 
b. Fast Urine Pregnancy Test (about 15 minutes) 
 
The following assessments will be performed at the Initial Visit: 
o. FESEvaluation (about 15 minutes) 
 
The following assessments will be performed at the Initial, 4th month, 9th month, and 12thmonth Visits: 
c. Severity of gleno-humeral subluxation (about 30 minutes) 
 
The following assessments will be performed at the Initial, 4th month, 5th month, 9th month, and 12th month 
Visits: 
d. Spasticity measurement (about 15 minutes) 
e. Capabilities of the Upper Extremity test (about 10 minutes) 
f. Jebsen-Taylor Hand Function test (about 15 minutes) 
g. Box and Blocks test (about 15 minutes) 
h. Action Research Arm test (about 20 minutes) 
i. Functional Reach test (about 5 minutes) 
j. Range Of Motion of the upper extremity joints (about 30 minutes) 
k. Numerical Rating Scale (NRS) for pain (about 1 minutes) 
l. Pulmonary Function Test (PFTs) (about 5 minutes) 
m. American Spinal Injury Association (ASIA) exam (about 60 minutes) 
n. Pain and Spasticity Medication inventory (about 10 minutes) 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
20/33 
 
Initial 
4th Month 
5th Month 
9th Month 
12th Month Test Evaluator*
Blinded
 
5 hours 
4 ½ hours 
3 2/3 hours
4 ¼ hours 
4 ¼ hours 
 
 
Neurological 
Exam 
√ 
 
 
 
 
PI, CoI1 
No 
Fast Urine 
Pregnancy 
√ 
 
 
 
 
N1, N2, N3 
No 
Shoulder 
X-Ray 
√ 
√ 
 
√ 
√ 
PI, CoI3 
Yes 
Modified 
Ashworth 
√ 
√ 
√ 
√ 
√ 
PI, CoI1 
Yes 
CUE 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
JTHF 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
BB 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
ARA 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
FR 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
ROM 
√ 
√ 
√ 
√ 
√ 
T1,T6 
Yes 
Pain NRS 
√ 
√ 
√ 
√ 
√ 
PI, CoI1, SC2 
No 
PFTs 
√ 
√ 
√ 
√ 
√ 
N1, N2, N3 
No 
ASIA 
√ 
√ 
√ 
√ 
√ 
PI, CoI1 
Yes 
Meds 
Inventory 
√ 
√ 
√ 
√ 
√ 
PI, CoI1, N1, 
N2, N3, SC2 
No 
FES Eval 
√ 
 
 
 
 
T1,T6 
No 
* PI: Principal Investigator, CoI1: Co-Investigator 1, CoI3: Co-Investigator 3, T1-7: Therapist 1-7, 
N1: Nurse 1, N2: Nurse 2, N3: Nurse 3, SC2: Study Coordinator2. 
Table 1: Data Collection Schedule 
 
(2) Intervention: 
There are a total of 96 visits: 48 FES assisted intervention visits scheduled 1 hour, 3 times a week for 4 months, 
and 48 non-FES assisted exercise regimen visits scheduled 1 hour, 3 times a week for 4 months. 
 
3. Blinding, including justification for blinding or not blinding the trial, if applicable. 
The evaluator will be blinded to group assignment for the following assessment, but we cannot use true blinding 
due to the intervention’s sensory component: 
c. Severity of gleno-humeral subluxation 
d. Spasticity measurement 
e. Capabilities of the Upper Extremity test 
f. Jebsen-Taylor Hand Function test 
g. Box and Blocks test 
h.Action Research Arm test 
i. Functional Reach test 
j. Range Of Motion of the upper extremity joints 
m. American Spinal Injury Association (ASIA) exam 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
21/33 
4. Justification of why participants will not receive routine care or will have current therapy 
stopped. 
All subjects will continue to consistently perform their usual (“baseline”) amount of physical activity 
throughout the study, including performance of lower extremities assisted FES ergometry, home exercise 
stretching program, cardiovascular conditioning, etc.  “Baseline” activity is defined as amount of physical 
activity performed for at least 1 month prior to enrollment.  Routine care will not be interrupted. 
 
5. Justification for inclusion of a placebo or non-treatment group. 
Both groups will receive some type of intervention: upper extremity passive ergometry or FES assisted upper 
extremity ergometry.  This way, the effect of FES application will be extracted. 
 
6. Definition of treatment failure or participant removal criteria. 
Treatment failure constitutes of: 
 Increased pain (more than 3 points increase on the NRS). 
 Increased shoulder subluxation (more than 1 cm). 
 Decreased range of motion (more than 15 deg). 
 
Subjects will be removed from the study if they: 
 Requires significant hospitalization (that would interfere with physiologic processes proposed to be 
studied through the protocol, i.e. e-stim) – at the discretion of PI. 
 Become pregnant. 
 
7. Description of what happens to participants receiving therapy when study ends or if a 
participant’s participation in the study ends prematurely. 
We will be offering FES assisted upper extremity ergometry through our Open Gym program or, if 
rehabilitative care requires it, though an ongoing, patient tailored program. 
 
b. Devices 
1. Name of Test Device: 
 
RT300-SLSA 
Manufactured by: Restorative Therapies, Inc 
907 South Lakewood Ave 
Baltimore, MD 21224 
Phone:(800) 609-9166 
Fax:(410) 878-2466 
 
2. Schedule/duration/administration of test device: 
The RT300-SLSA Cycle Ergometer is the only device capable of upper extremity cycle ergometry with and 
without FES, for use in the study. 
 
The device will be used for 1 hour, three times a week, for 4 month,, by both the FES and Control group.For the 
Treatment group, the device will be program to delivered synchronized electrical pulses to the upper 
extremities.For the Control group, the device will be programmed to drive thecycling of the upper extremities. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
22/33 
Device Risk Assessment:The RT300-SLSA cycle ergometer is a motorized system that allow for purely 
passive, active, or assisted control over leg or arm cycling. The stimulation system is fully integrated with leg 
and arm motors (“dynamic motor support”) with unilateral or bilateral stimulation option, allowing for 
individualized usage for upper and lower extremities.  The systems allow for the individual to remain in his/her 
wheelchair, insuring easy usage across subjects without transfer of the subjects. The speed of cycling can be 
changed from zero to sixty revolutions per minute (rev/min) and the load (resistance) can be adjusted from zero 
to 17 Newton-meters (Nm). The system has numerous safety features, such as muscle spasm detection and arm 
guides, that make it ideal for use in this study. The system have internet connectivity allowing the retrieval of 
subject settings and the automatic collection of cycling data, ensuring easy use across subjects in this study. 
 
All the ergometers that will be used for this study will be checked and tagged by Johns Hopkins Hospital 
Clinical Engineering Services (CES).  The local IRB of Record does require an approval letter from CES 
regarding the use of the device in the study.  The approval letter is part of the application to the local IRB of 
Record. 
 
3. FDA Status: 
The device is classified as an external functional neuromuscular stimulator (CFR 882.5810).The device is FDA 
cleared under section 510(k).  The device clearance number is K072398. 
 
The device will be used in a research mode that: 
1] allows the stimulation of our proposed list of upper extremity muscles (supraspinatus; infraspinatus; teres 
major and minor; anterior, middle, or posterior deltoid; biceps; and triceps), which is more that the standard  set 
of muscles (bilateral biceps, triceps and supraspinatus). 
2] allows to change the timing of the stimulation (On/Off) to produce a smooth cycling motion. 
 
4. FDA approved use description: 
The device FDA indication for use are: 
1. Relaxation of muscle spasms 
2. Prevention or retardation of disuse atrophy 
3. Increasing local blood circulation 
4. Maintaining or increasing range of motion 
 
5. IDE Info: 
Not applicable 
 
c. Study Statistics 
1. Primary outcome variable. 
Independent Variables 
FES or no FES 
 
Dependent Variables: to be measured at 0, 4, 5, 9 and 12months 
Severity of gleno-humeral subluxation, measured by X-ray (not measured at 5 months). 
Spasticity of the pectoralis, biceps, triceps, and long finger flexor muscles, measured with the Modified 
Ashworth. 
Functional movement of the shoulder, measured with the Capabilities of the Upper Extremity (CUE) test. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
23/33 
Hand function, measured with the Jebsen-Taylor Hand Function (JTHF) and Box and Blocks (BB) tests. 
Upper limb function measured with the Action Research Arm test (ARA) test. 
Range Of Motion of the upper extremity joints (of the shoulder, elbow, wrist, and fingers/thumbs), measured 
with goniometry. 
Pain, measured with the Numerical Rating Scale (NRS). 
Neurological function, measured with the American Spinal Injury Association (ASIA) exam. 
 
2. Secondary outcome variables. 
Not applicable 
 
3. Statistical plan including sample size justification and interim data analysis. 
Data Analysis:  Data will be collected in accordance with each instrument‘s standardized instructions, with the 
evaluator being blinded to group assignment. To obtain consistency and facilitate interpretation of the data, we 
will use means and standard deviations (SDs) to describe normally as well as non-normally distributed 
variables.  Appropriate post-hoc statistical analysis will be used to compare between group means and repeated 
measures.  Baseline tests of homogeneity will be used a priori.  If statistically significant differences are found 
after the subjects are randomized to the two groups, they will be corrected in the post-hoc analysis.  Results will 
be considered significant at P<0.05. 
 
Power analysis:Because upper extremity, FES-assisted ergometry training is a new intervention, we based our 
power analysis on previously completed studies that looked at the effect of FES on muscle mass (50, 51) and 
cardio-vascular conditioning (52-56).  A sample size of 24 will allow us to detect a mean difference between the 
pre- and post-measures.  Some of our outcome measures (CUE, JTHF, BB tests) have been shown to respond to 
many types of rehabilitative interventions, and we believe they will be particularly responsive to the type of 
training used here.  One of our goals is to use the data obtained in this study to determine the magnitude of the 
effect so we can design future trials.  If the magnitude is very small, however, it is unlikely to be clinically 
relevant.  We would then be more likely to propose intensifying the intervention (e.g., by lengthening the 
periods of cycling) than to suggest increasing sample size. 
 
4. Early stopping rules. 
* Subject medical status: 
 Requires significant hospitalization (that would interfere with physiologic processes proposed to be 
studied through the protocol, i.e. e-stim) – at the discretion of PI. 
 Increased pain (more than 3 points increase on the NRS). 
 Increased shoulder subluxation (more than 1 cm). 
 Decreased range of motion (more than 15 deg). 
* Subject not compliant: 
 Fails to follow directions. 
 Become pregnant. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
24/33 
XII. 
LABELING & STORAGE OF DATA & SPECIMENS 
All paper study documents are stored in locked cabinets at the Broadwaycampus of the KKI-ICSCI.  Access to 
the locked cabinets is strictly limited to the study team members listed on this protocol.  The documents with 
identifiers (such as the consent forms, phone screening forms, and the document that links the subject study # to 
the identity of the subject) are stored in a study binder in a separate locked cabinet from hard copy data 
collection forms. 
 
All electronic study documents are saved on KKI-ICSCI departmental shared networked drives, and access is 
strictly limited to the study team members listed on this protocol.  The share drives are managed by KKI’s 
Information Systems Department, and housed in a Data Center at KKI’s Green Spring Campus.  The Data 
Center is all Card Swipe and Key Pad protected.  Access to the Data Center is strictly limited to Director Level 
and System Administrators.  The Data Center is monitored using APC Data Center Monitoring System.  We 
monitor the location with Camera's that store the Video on a Central Server.  We monitor the Data Center for 
Temperature, Humidity and Water as well.  All of the Institute's Data is backed to tape on a daily basis and the 
Tapes are shipped to Iron Mountain, a Data Storage facility.  All of the Data on the tapes is encrypted and very 
secure. All of the Institute Data is also replicated Real Time to our Disaster Recovery site in Baltimore. 
 
All the procedures listed below will be used to protect the confidentiality of data and samples collected and 
stored for research purposes: 
 Only authorized persons will be granted access 
 Only authorized persons may enter and view study data 
 Passwords and system IDs will not be shared 
 Physical security of the workstations/files will be maintained 
 Adequate back-up plan is in effect 
 Staff trained on data entry system and importance of security procedures 
 Workstations with databases will not be left unattended 
 
Authorized persons include: 
 the study team members listed on this protocol. 
 QA/QI and other regulatory personnel at KKI and the local IRB of Record. 
 
For compliance with 45 CFR 164.528, the local IRB of Record requires investigators to retain study records, 
along with records of all disclosures of study information, for the following time periods: 
1) At least 7 years after the last subject has completed his or her participation in the study, or 
2) The date of the last disclosure of identifiable health information from study records, if disclosures continue 
after all subjects have completed the study. 
 
Accurate and complete study records will be maintained and made available to representatives of the U.S. Army 
Medical Research and Materiel Command. These representatives are authorized to review research records as 
part of their responsibility to protect human research volunteers.  Research records will be stored in a 
confidential manner so as to protect the confidentiality of subject information. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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XIII. 
RISK AND INJURY 
a. Risks, Risk Management: 
All assessments and intervention sessions will be supervised by the Principal Investigator. 
 
For all the study procedures, the risks and risk management are defined in the sections bellow. 
 
1. Assessment Risks: 
a) Neurological Exam:  During testing, the subject might experience pain induced by hitting/tapping of the 
arm, but usually, the sensation experienced is a quick, non-painful touching sensation.Tominimize the risk,one 
of the study team member trainedin the procedure will perform the test. 
 
b) Fast Urine Pregnancy Test:  There is the possibility of psychological stress occurring if testing shows that 
the subject may be pregnant.  To minimize the risk in the event that pregnancy test results are positive, the 
result will be disclosed to the subject.  If the subject is uncomfortable with this arrangement, his/her consent to 
participate in this study is not recommended. 
 
c) Severity of gleno-humeral subluxation:  The subjects receive ionizing radiation due to the 
diagnosticbilateral shoulder X-ray procedures they receive at the Initial, 4th Month, 9th Month, and 12th Month 
visit.The Total Effective Dose from the procedures is 0.4 rem.This ismore than the 0.3 rem that the average 
person in the United States gets each year from natural sources like the sun, outer space, air, food and soil.  It is 
less than the 5 rems of radiation that is allowed each year for people who are exposed to radiation in their 
jobs.To minimize the risk,pregnant women are excluded from the study. 
 
d) Spasticity Measurement:  There is a risk of eliciting spasmsduring the test.Subjects will feel a quick pull of 
the muscle, which might be painful at times.Tominimize the risk,one of the study team member trainedin the 
procedure will perform the test. 
 
e) Capabilities of the Upper Extremity (CUE) test:  There are no known risks associated with this test. 
 
f) Jebsen-Taylor Hand Function (JTHF) test:  Patients may feel some discomfort associated with fatigue in 
the shoulder, elbow, wrist or hand.Tominimize the risk,one of the study team member trainedin the procedure 
will perform the test. 
 
g) Box and Blocks (BB) test:  Patients may feel some discomfort associated with fatigue in the shoulder, 
elbow, wrist or hand.Tominimize the risk,one of the study team member trainedin the procedure will perform 
the test. 
 
h) Action Research Arm (ARA) test:  Patients may feel some discomfort associated with fatigue in the 
shoulder, elbow, wrist or hand.  Tominimize the risk,one of the study team member trainedin the procedure 
will perform the test. 
 
i) Functional Risk (FR) test:  Patients may feel anxiety related to loss of balance.  Tominimize the risk, one 
of the study team member trained in the procedure will perform the test and will position themselves in the 
direction of the lean so subject does not fall. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
26/33 
j) Range Of Motion (ROM)of the upper extremity joints:  Subjects may feel a stretch near the end range, 
which could be painful.Tominimize the risk,one of the study team member trainedin the procedure will 
perform the test. 
 
k) Numerical Rating Scale (NRS) for pain:  There are no known risks associated with this measurement. 
 
l) Pulmonary Function Test (PFTs):  The risk is minimal for most people.  Since the test involves some 
forced breathing and rapid breathing, patients may have some temporary shortness of breath or light-
headedness.  Patients breathe through a tight-fitting mouthpiece, and will have nose clips.  Tominimize the 
risk, one of the study team member trained in the procedure will perform the test. 
 
m) American Spinal Injury Association (ASIA) exam:  There is a risk of discomfort at the site of the pin 
prick during the ASIA Exam.Tominimize the risk,one of the study team member trainedin the procedure will 
perform the ASIA exam. 
 
n) Pain and Spasticity Medication inventory:  Aside from the risk associated with disclosing personnel or 
protected health information outside the research study, there are no known risks associated with this 
measurement. 
 
2. Intervention Risks: 
o) FES:  The risk associated with FES is pain at the stimulation site.  To minimize the risk, stimulation will 
only be done to the participant’s tolerance level.There is a minimal risk of skin burn.  To further minimize the 
risk of skin burn, only appropriate size electrodes will be used and they will replaced as per the manufacturer’s 
recommendations. 
 
3. Other Risks: 
p) Time Commitment:  The time commitment to the 3 visits per week for 4 months may be inconvenient.  To 
minimize the risk: 1] The subject should contact the study coordinator if having problems scheduling the visits;  
2] If we feel that the subject can not commit the time and effort, he/she will be excluded from the study; 3] The 
visits may cause moderate social, school and work disruption.  The start of the study will be scheduled to lessen 
the disruption. 
 
b. Medical Care For Research Related Injury: 
For greater than minimal risk studies, the USAMRMC can commit to providing treatment to research volunteers 
free of charge in an Army medical facility, therefore the ORP HRPO mandated language shall be included in 
the consent form. 
 
XIV. 
BENEFIT(S) 
There are no known benefits for those who participate in this study.  The possible benefits to the participant 
from upper extremity FES ergometry include muscle mass and strength increase, muscle tone decrease, 
cardiovascular conditioning. This study may benefit others in the future by helping understand how upper 
extremity ergometry with FES might contribute to an improved quality of life for people with cervical spinal 
cord injuries. 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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XV. 
COMPENSATION 
a. Payment and Remuneration: 
Subjects will be paid a total of $250.00 if they complete the study.  Of this amount, $20.00 is a bonus, which the 
subjects will be eligible to receive if they have shown up on time for all study visits as scheduled, and followed 
the directions of the study staff. 
 
If the subjects do not finish the study, they will be paid only for the amount completed as follows: 
$30.00 for the Initial Visit 
$25.00 for the 1st month of FES treatment 
$25.00 for the 2nd month of FES treatment 
$25.00 for the 3rd month of FES treatment 
$25.00 for the 4th month visit 
$25.00 for the 5thmonth visit 
$25.00 for the 9th month visit 
$50.00 for the 12th month visit 
 
Payment will be made by check at the final visit. 
 
b. Costs 
There is no cost to study participants for any of the study tests.  Subjects will be responsible for the cost of 
travel to and from the Institute (Valet parking is available at no cost to study participant), as well as any 
food/meals purchased throughout the day while engaged in study procedures. 
 
XVI. 
CONFIDENTIALITY 
All the procedures listed below will be used to protect the confidentiality of data and samples collected and 
stored for research purposes: 
 Only authorized persons will be granted access 
 Only authorized persons may enter and view study data 
 Passwords and system IDs will not be shared 
 Physical security of the workstations/files will be maintained 
 Adequate back-up plan is in effect 
 Staff trained on data entry system and importance of security procedures 
 Workstations with databases will not be left unattended 
 
Accurate and complete study records will be maintained and made available to representatives of the U.S. Army 
Medical Research and Materiel Command. These representatives are authorized to review research records as 
part of their responsibility to protect human research volunteers.  Research records will be stored in a 
confidential manner so as to protect the confidentiality of subject information. 
 
 
 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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XVII. ADVERSE EVENTS 
“Unanticipated problems involving risks to participants or others” is defined as: 
 The information is unexpected in terms of nature, severity, or frequency, given: a) the research procedures 
described in the protocol and informed consent document; and b) the characteristics of the subject 
population being studied; and 
 The information indicates that participants or others are at greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized." 
 
All unanticipated problems involving risk to subjects or others, serious adverse events related to participation in 
the study and subject deaths related to participation in the study should be promptly reported by phone (301-
619-2165), by email (hsrrb@det.amedd.army.mil), or by facsimile (301-619-7803) to the USAMRMC, Office of 
Research Protections, Human Research Protection Office.  A complete written report will follow the initial 
notification.  In addition to the methods above, the complete report will be sent to the U.S. Army Medical 
Research and Materiel Command, ATTN: MCMR-ZB-PH, 504 Scott Street, Fort Detrick, Maryland 21702-
5012. 
 
The Medical Monitor is required to review all unanticipated problems involving risk to subjects or others, 
serious adverse events and all subject deaths associated with the protocol and provide an unbiased written report 
of the event.  At a minimum, the medical monitor must comment on the outcomes of the event or problem and 
in case of a serious adverse event or death, comment on the relationship to participation in the study.  The 
medical monitor must also indicate whether he/she concurs with the details of the report provided by the 
principal investigator.  Reports for events determined by either the investigator or medical monitor to be 
possibly or definitely related to participation and reports of events resulting in death must be promptly 
forwarded to the ORP HRPO. 
 
XVIII. CHANGES TO PROTOCOL 
a. Protocol Modifications: 
Major modifications to the research protocol and any modifications that could potentially increase risk to 
subjects must be submitted to the USAMRMC ORP HRPO for approval prior to implementation. All other 
amendments will be submitted with the continuing review report to the USAMRMC ORP HRPO for 
acceptance. 
 
b. Protocol Deviations: 
Any deviation to the protocol that may have an effect on the safety or rights of the subject or the integrity of the 
study must be reported to the USAMRMC ORP HRPO as soon as the deviation is identified. 
 
XIX. 
CONTINUING REVIEW & FINAL REPORT 
a. Continuing Review Reports: 
A copy of the continuing review report for the research study will be submitted to the local IRB of Record. A 
copy of the approved continuing review report and the local IRB of Record approval notification must be 
submitted to the ORP HRPO as soon as these documents become available.  PI will report progress of the 
approved research to the local IRB of Record and the ORP HRPO as often as requested, but not less frequently 
than once per year. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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c. Final Study Report: 
A copy of the final study report will be submitted to the local IRB of Record.  A copy of the approved/accepted 
final study report and the local IRB of Record approval/acceptance notification will be submitted to the ORP 
HRPO as soon as these documents become available.  
 
XX. 
LITERATURE REVIEW 
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Donaldson N, Perkins TA, Fitzwater R, Wood DE, Middleton F. FES cycling may promote recovery of 
leg function after incomplete spinal cord injury. Spinal Cord. 2000;38(11):680–82. 
2. 
Knikou M, Conway BA. Effects of electrically induced muscle contraction on flexion reflex in human 
spinal cord injury. Spinal Cord. 2005;43(11):640–48. 
3. 
Knikou M.  Conway BA. Reflex  effects of induced muscle contraction in normal and spinal cord injured 
subjects. Muscle Nerve 26: 374–382, 2002 
4. 
McDonald, J.W., et al., Late recovery following spinal cord injury. Case report and review of the 
literature. J Neurosurg, 2002. 97(2 Suppl): p. 252-65. 
5. 
Sadowsky CL, Margherita A. The Cost of Spinal Cord Injury Care. 1999. SPINE: State of the Art 
Reviews. 13(3):593-606 
6. 
Wolpaw JR, TennissenAM. Activity-dependent spinal cord plasticity in health and disease. Annu Rev 
Neurosci. 2001;24:807–43. 
7. 
Dobkin BH. Neurobiology of rehabilitation. Ann N YAcad Sci. 2004;1038:148–70. 
8. 
Edgerton VR, Tillakaratne NJ, Bigbee AJ, De Leon RD,Roy RR. Plasticity of the spinal neural circuitry 
after injury.Annu Rev Neurosci. 2004;27:145–67. 
9. 
Hendry SH, Jones EG. Reduction in number of immunostainedGABAergicneurones in deprived-eye 
dominance columns of monkey area 17. Nature. 1986;320(6064):750-3. 
10. 
Simons DJ, Land PW. Early experience of tactile stimulation influences organization of somatic sensory 
cortex. Nature. 1987;326(6114):694-7. 
11. 
Hendry SH, Jones EG. Activity-dependent regulation of GABA expression in the visual cortex of adult 
monkeys. Neuron.1988;1(8):701-12. 
12. 
Ramakers GJ, et al. Development in the absence of spontaneous bioelectric activity results in increased 
stereotyped burst firing in cultures of dissociated cerebral cortex. Experimental Brain Research. 
1990;79(1):157-66. 
13. 
Baker RE, Ruijter JM. Chronic blockade of bioelectric activity in neonatal rat neocortex in vitro: 
physiological effects. International Journal of Developmental Neuroscience. 1991;9(4):321-9. 
14. 
Furshpan EJ. Seizure-like activity in cell culture. Epilepsy Research. 1991;10(1):24-32. 
15. 
Ruijter JM, et al. Chronic blockade of bioelectric activity in neonatal rat cortex grown in vitro: 
morphological effects. International Journal of Developmental Neuroscience. 1991;9(4):331-8. 
16. 
Corner MA, Ramakers GJ. Spontaneous firing as an epigenetic factor in brain development- physiological 
consequences of chronic tetrodotoxin and picrotoxin exposure on cultured rat neocortex neurons. Brain 
Rsearch. 1992;65(1):57-64. 
17. 
Seil FJ, Drake-Baumann R. Reduced cortical inhibitory synaptogenesis in organotypic cerebellar cultures 
developing in the absence of neuronal activity. The Journal of Comparative Neurology. 1994;342(3):366-
77. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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18. 
Seil FJ, et al. Morphological correlates of altered neuronal activity in organotypic cerebellar cultures 
chronically exposed to anti-GABA agents. Brain Research. 1994;77(1):123-32. 
19. 
Benevento LA, et al. gamma-Aminobutyric acid and somatostatinimmunoreactivity in the visual cortex of 
normal and dark-reared rats. Brain Research. 1995;689(2):172-82. 
20. 
Micheva KD, Beaulieu C. An anatomical substrate for experience-dependent plasticity of the rat barrel 
field cortex. Proceedings of the National Academy of Sciences, USA. 1995;92(25):11834-8. 
21. 
Rutherford LC, et al. Brain-derived neurotrophic factor mediates he activity-dependent regulation of 
inhibition in neocortical cultures. The Journal of Neuroscience. 1997;17(12):4527-35. 
22. 
Demerens C, et al. Induction of myelination in the central nervous system by electrical activity. 
Proceedings of the National Academy of Sciences, USA. 1996;93(18):9887-92. 
23. 
Barres BA, et al. Multiple extracellular signals are required for long-term oligodendrocyte survival. 
Development. 1993;118(1):283-95. 
24. 
Lubetzki C, Stankoff B. Role of axonal signals in myelination of the central nervous system. Pathologie-
biologie. 2000;48(1):63-9. 
25. 
Coman I, Barbin G, Charles P, Zalc B, Lubetzki C. Axonal signals in central nervous system myelination, 
demyelination and remyelination. Journal of the Neurological Sciences. 2005;233(1-2):67-71. 
26. 
Gage FH. Stem cells of the central nervous system. Current Opinion in Neurobiology. 1998;8(5):671-6. 
27. 
Kempermann G, Gage FH. New nerve cells for the adult brain. Scientific American. 1999;280(5):48-53. 
28. 
Barres BA, Raff MC. Proliferation of oligodendrocyte precursor cells depends on electrical activity in 
axons. Nature. 1993;361(6409):258-60) 
29. 
McDonald, J.W., Repairing the damaged spinal cord. Sci Am, 1999. 281(3): p. 64-73. 
30. 
Belegu, V., et al., Restoring function after spinal cord injury: promoting spontaneous regeneration with 
stem cells and activity-based therapies.NeurosurgClin N Am, 2007. 18(1): p. 143-68, xi. 
31. 
McDonald, J.W., Repairing the damaged spinal cord: from stem cells to activity-based restoration 
therapies.ClinNeurosurg, 2004. 51: p. 207-27. 
32. 
Lavrov I, Gerasimenko YP, Ichiyama RM, Courtine G, Zhong H, Roy RR, Edgerton VR. Plasticity of 
spinal cord reflexes after a complete transection in adult rats: relationship to stepping ability. J 
Neurophysiol. 2006;96(4): 1699–1710. 
33. 
Huang H, He J, Herman R, Carhart MR. Modulation effects of epidural spinal cord stimulation on muscle 
activities during walking. IEEE Trans Neural SystRehabil Eng. 2006;14(1):14–23. 
34. 
Cai LL, Courtine G, Fong AJ, Burdick JW, Roy RR, Edgerton VR. Plasticity of functional connectivity in 
the adult spinal cord. Philos Trans R SocLond B Biol Sci. 2006;361(1473):1635–46. 
35. 
Simpson RK Jr, Robertson CS, Goodman JC. Segmental recovery of amino acid neurotransmitters during 
posterior epidural stimulation after spinal cord injury. J Am Paraplegia Soc. 1993;16(1):34–41. 
36. 
Hosobuchi Y. Electrical stimulation of the cervical spinal cord increases cerebral blood flow in humans. 
Appl Neurophysiol.1985;48(1–6):372–76. 
37. 
Visocchi M. Spinal cord stimulation and cerebral haemodynamics. ActaNeurochir Suppl. 2006;99:111–
16. 
38. 
Al-Majed AA, Brushart TM, Gordon T. Electrical stimulation accelerates and increases expression of 
BDNF and trkB mRNA in regenerating rat femoral motoneurons. Eur J Neurosci. 2000;12(12):4381–90. 
39. 
Al-Majed AA, Tam SL, Gordon T. Electrical stimulation accelerates and enhances expression of 
regenerationassociated genes in regenerating rat femoral motoneurons.Cell MolNeurobiol. 
2004;24(3):379–402. 
40. 
Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed 
and accuracy of motor axonal regeneration. J Neurosci. 2000; 20(7):2602–8. 

Protocol No. 
ERMS # 08284002 and #09181006, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
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41. 
Balkowiec A, Katz DM. Activity-dependent release of endogenous brain-derived neurotrophic factor 
from primary sensory neurons detected by ELISA in situ. J Neurosci. 2000;20(19):7417–23. 
42. 
McDonald, J.W., et al., A Cohort Study of Activity-Based Restorative Therapy (RT):  Physical and 
Functional Recovery in Chronic Spinal Cord Injury [abstract], in American Neurological Association 
Annual Meeting 2005: San Diego, CA. 
43. 
McDonald, J.W. and C. Sadowsky, Spinal-cord injury. Lancet, 2002. 359(9304): p. 417-25. 
44. 
Hsieh, J.T., et al., Spasticity outcome measures in spinal cord injury: psychometric properties and clinical 
utility. Spinal Cord, 2007. 
45. 
Marino, R.J., J.A. Shea, and M.G. Stineman, The Capabilities of Upper Extremity instrument: reliability 
and validity of a measure of functional limitation in tetraplegia. Arch Phys Med Rehabil, 1998. 79(12): p. 
1512-21. 
46. 
Jebsen, R.H., et al., An objective and standardized test of hand function. Arch Phys Med Rehabil, 1969. 
50(6): p. 311-9. 
47. 
Mathiowetz, V., et al., Adult norms for the Box and Block Test of manual dexterity.Am J OccupTher, 
1985. 39(6): p. 386-91. 
48. 
Ware, L.J., et al., Evaluation of the Revised Faces Pain Scale, Verbal Descriptor Scale, Numeric Rating 
Scale, and Iowa Pain Thermometer in older minority adults. Pain ManagNurs, 2006. 7(3): p. 117-25. 
49. 
Savic, G., et al., Inter-rater reliability of motor and sensory examinations performed according to 
American Spinal Injury Association standards. Spinal Cord, 2007. 45(6): p. 444-51. 
50. 
Hjeltnes N, Aksnes AK, Birkeland KI, Johansen J, Lannem A, Wallberg-Henriksson H. Improved body 
composition after 8 wk of electrically stimulated leg cycling in tetraplegic patients. Am J Physiol 1997; 
273(3 Pt 2):R1072-R1079. 
51. 
Bhambhani Y, Tuchak C, Burnham R, Jeon J, Maikala R. Quadriceps muscle deoxygenation during 
functional electrical stimulation in adults with spinal cord injury. Spinal Cord 2000; 38(10):630-638). 
52. 
Raymond J, Davis GM, Climstein M, Sutton JR. Cardiorespiratory responses to arm cranking and 
electrical stimulation leg cycling in people with paraplegia. Med Sci Sports Exercise 1999; 31(6):822-
828. 
53. 
Hooker SP, Scremin AM, Mutton DL, Kunkel CF, Cagle G. Peak and submaximal physiologic responses 
following electrical stimulation leg cycle ergometer training. J Rehabil Res Dev 1995; 32(4):361-366. 
54. 
Hooker SP, Figoni SF, Rodgers MM, Glaser RM, Mathews T, Suryaprasad AG et al. Physiologic effects 
of electrical stimulation leg cycle exercise training in spinal cord injured persons. Arch Phys Med Rehabil 
1992; 73(5):470-476. 
55. 
Hooker SP, Figoni SF, Glaser RM, Rodgers MM, Ezenwa BN, Faghri PD. Physiologic responses to 
prolonged electrically stimulated leg-cycle exercise in the spinal cord injured. Arch Phys Med Rehabil 
1990; 71(11):863-869). 
56. 
Mutton DL, Scremin AM, Barstow TJ, Scott MD, Kunkel CF, Cagle TG. Physiologic responses during 
functional electrical stimulation leg cycling and hybrid exercise in spinal cord injured subjects. Arch Phys 
Med Rehabil 1997; 78(7):712-718. 
57. 
Lyle RC. A performance test for assessment of upper limb function in physical rehabilitation treatment 
and research.Int. J Rehabil Res. 1981;4:483-492. 
 

Protocol No. 
ERMS # 08284002, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
Appendix: 
Study Related Documents 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
32/33 
XXI. 
Appendix: Study Related Documents 
a. Recruitment forms: 
Subject Recruitment Flyer:File is “14481 Subject Recruitment Flyer 2010-09-07.docx” 
ICSCI Newsletter language:File is “14481 Newsletter language 2010-09-07.docx” 
KKI Facebook page language: File is “14481 KKI Facebook language 2001-03-24.docx” 
KKI On-Hold phone message: File is “14481 KKI On-Hold Message 2011-03-23.docx” 
KKI Press Release: File is “ICSCI DoD Research Release 2011-June.docx” 
 
Waiver of privacy authorization from the IRB on Record: File is “14481 HIPAA Form4 2010-09-07.docx” 
Medical Chart Review Form:File is “14481 Medical Chart Review Form 2010-09-07.docx” 
Phone Screening Form:File is “14481 Phone Screening Form 2010-09-07.docx” 
Inc/Exclusion Criteria Index Card: File is “14481 Index Card 2010-09-03.docx” 
Inc/Exclusion Wall Index: File is “14481 Wall Listing 2010-09-03.docx” 
Cover letter: File is “14481 Inclusion-Exclusion guide 2010-09-07.docx” 
b. Informed Consent forms: 
File is “14481 Consent Form 2011-06-10.docx” 
 
c. Case Report Forms: 
File is “14481 Case Report Form 2011-03-24.docx” 
File is “14481 Test 0 Screening Form 2008-09-15.doc” 
File is “14481 Test 1 Subluxation 2009-05-01.doc” 
File is “14481 Test 2 Modified Ashworth 2009-05-01.doc” 
File is “14481 Test 3 CUE 2009-05-01.doc” 
File is “14481 Test 4 Jebsen-Taylor 2009-05-01.doc” 
File is “14481 Test 5 Box & Blocks 2009-05-01.doc” 
File is “14481 Test 6 ROM 2009-05-01.doc” 
File is “14481 Test 7 NRS 2009-05-01.doc” 
File is “14481 Test 8 ASIA 2009-05-01.doc” 
File is “14481 Test 9 Meds 2009-05-01.doc” 
File is “14481 Test 10 Functional Reach 2009-05-01.doc” 
File is “14481 Test 11 PFTs 2009-05-01.doc” 
File is “14481 Test 12 ARAT 2010-01-15.doc” 
File is “14481 Test 13 FES Eval 2010-02-18.doc” 
File is “14481 Payment Form 2010-08-16.docx” 
 
d. Serious Adverse Event report forms: 
Any adverse event is reported to the IRB of record electronically as a Further Study Action(FSA), using the 
local IRB of Record website (https://e-irb.jhmi.edu). 
The report will be printed and forwarded to the ORP HRPO as described in section 0. of this protocol.A 
template of the IRB Problem/Event Report Form is provided. 
File is “IRB Problem Event Report Form Template.pdf” 
 

Protocol No. 
ERMS # 08284002, Local IRB:NA_00014481. 
Principal Investigator: Dr. Cristina Sadowsky, M.D. 
Appendix: 
Medical Device Related Documents 
 
Version/Date: 11.0, 16-Sept-2013 
NOV 2006 
33/33 
XXII. Appendix: Medical Device Related Documents 
 
The device is FDA cleared under section 510(k).  The device, RT300-SLSA, clearance number is K072398. 
File is “K072398.pdf”