CSP #2003 - Exoskeleton Assisted-Walking in Persons With SCI: Impact on Quality of Life
Phase: NA
Conditions: Spinal Cord Injury
Sponsor: VA Office of Research and Development

 
 
 
 
VA Cooperative Studies Program Protocol #2003 
 
Exoskeletal-Assisted Walking in Persons with SCI:  Impact on Quality of Life 
 
 
 
 
 
 
July 2021 
 
Version 7.2 
 
 
 
Study Chairperson:  Ann M. Spungen, Ed.D, JJPVAMC Bronx, NY  
Study Co-Chairperson:  William A. Bauman, MD, JJPVAMC Bronx, NY 
 
 
 
 
 
 
 
- P R I V I L E G E D   A N D   C O N F I D E N T I A L - 
Not to be Disseminated Beyond Official Use 
 
 
 

TABLE OF CONTENTS 
 
Glossary .................................................................................................................................i 
Executive Committee .............................................................................................................iii 
Executive Summary ...............................................................................................................vi 
I.  Introduction and Background ........................................................................................1 
     A.  Measurement of Quality of Life Outcomes in SCI .....................................................5 
     B.  Pilot Data .....................................................................................................................9 
     C.  Preliminary Data Employed for the Primary Outcome Variables ...............................11 
     D.  Supporting Data for the Major Secondary Outcome Variable ....................................13 
     E.  Secondary Outcomes ...................................................................................................14 
II.  Objectives .......................................................................................................................17 
     A.  Primary Objectives ......................................................................................................17 
     B.  Major Secondary Objective .........................................................................................17 
     C.  Secondary Objectives ..................................................................................................17 
     D.  Hypotheses ..................................................................................................................18  
III.  Experimental Design ....................................................................................................19 
     A.  Screening Phase ..........................................................................................................19 
     B.  Intervention Phase .......................................................................................................21 
     C.  Post Study Participation for the Control Group ..........................................................22 
     D.  Study Duration and Timeline ......................................................................................22 
IV.  Participant Recruitment ..............................................................................................27 
     A.  Recruitment and Screening .........................................................................................27 
     B.  Randomization System ................................................................................................27 
     C.  Population to be Studied .............................................................................................28 
V.  Intervention and Methods of Treatment .....................................................................28 
VI.  Methods of Follow-up...................................................................................................29 
VII.  Methods of Assuring Uniformity of Intervention ....................................................30 
VIII.  Determining Eligibility..............................................................................................30 

     A.  Inclusion/Eligibility Criteria .......................................................................................30 
     B.  Exclusion Criteria ........................................................................................................31 
     C.  Exoskeleton Component (“Training the Trainers”) ....................................................33 
     D.  ReWalk Fitting ............................................................................................................33 
     E.  EAW Basic Skills Test ................................................................................................34 
     F.  EAW Walking Skills Progression ...............................................................................35 
     G.  EAW Companion Training .........................................................................................36 
     H.  EAW Advanced Skills Test ........................................................................................38 
     I.  Weekly EAW Activity Log ..........................................................................................40 
IX.  Outcome Measurements ..............................................................................................40 
     A.  Primary Outcomes.......................................................................................................41 
     B.  Major Secondary Outcome ..........................................................................................41 
     C.  Secondary Outcomes ...................................................................................................41 
     D.  Additional Assessments ..............................................................................................42 
     E.  Quality Control (non-outcome) Measurements ...........................................................42 
     F.  Methods for Obtaining Outcome Measures Data ........................................................43 
     G.  Schedule of Observations and Laboratory Tests .........................................................44 
X.  Performance Measures and Study Management ........................................................44 
     A.  CSPCC ........................................................................................................................45 
     B.  Office of the Chair .......................................................................................................45 
XI.  Safety Monitoring .........................................................................................................46 
     A.  Study Group ................................................................................................................46 
     B.  Executive Committee ..................................................................................................47 
     C.  Data Monitoring Committee .......................................................................................47 
     D.  VA Central Institutional Review Board (CIRB) .........................................................47 
     E.  Definitions of Adverse Event (AE), Serious Adverse Event (SAE), and 
Unanticipated Adverse Device Effect (UADE) ..........................................................48 
     F.  Serious Adverse Event (SAE) Reporting ....................................................................49 
     G.  Adverse Event (AE) Reporting ...................................................................................49 
     H.  Participant Safety Stopping Rules...............................................................................50 

     I.  Site Participation Stopping Rules .................................................................................51 
     J.  Efficacy or Futility Criteria for Study Termination .....................................................51 
XII.  Quality Assurance Procedures...................................................................................52 
     A.  Summary of Monitoring and Auditing Plans ..............................................................52 
XIII.  Statistical Analysis Plan (SAP) .................................................................................53 
     A.  Introduction .................................................................................................................53 
     B.  Sample Size .................................................................................................................53 
     C.  Feasibility Phase ..........................................................................................................55 
     D.  Baseline Comparability ...............................................................................................56 
     E.  General Outcome Analysis Guidelines .......................................................................56 
     F.  Analysis of Primary and Major Secondary Outcome Measures ..................................56 
     G.  Secondary Analyses ....................................................................................................57 
     H.  Monitoring of Study by Study Group and Executive Committee ...............................58 
     I.  Study Monitoring by the Data Monitoring Committee ................................................62 
XIV.  Qualifications .............................................................................................................66 
     A.  Site Qualifications .......................................................................................................66 
     B.  Site Participation .........................................................................................................68 
     C.  Office of the Chair Qualifications ...............................................................................70 
XV.  Plans to Assure Security and Confidentiality of Study Data ..................................70 
XVI.  Data Management and Data Security Plans ...........................................................71 
XVII.  Plans for Dissemination of Study Results ..............................................................72 
    A.  Publication of Research Results ...................................................................................72 
    B.  Planned Publications ....................................................................................................73 
XVIII.  Human Subjects Protection Considerations ........................................................74 
     A.  Recruitment of Participants and Special Considerations ............................................74 
     B.  Inclusion of Women and Minorities in the Study .......................................................74 
     C.  Description of the Consenting Process........................................................................74 
     D.  Participant Compensation ...........................................................................................75 
     E.  Safety Considerations ..................................................................................................76 

     F.  Foreseeable Risks ........................................................................................................76 
     G.  Risk Management and Emergency Response .............................................................77 
     H.  Emergency Care Plan ..................................................................................................79 
     I.  Potential Benefits ..........................................................................................................79 
XIX.  Transition of Participants .........................................................................................80 
 
XX.   Impact of the SARS-CoV-2 (COVID-19) pandemic on screened participants ....81 
     A.  Background .................................................................................................................81 
     B.  Rationale......................................................................................................................82 
     C.  Methods .......................................................................................................................86 
     D.  Relevance ....................................................................................................................88 
     E.  Limitations ...................................................................................................................90 
XXI.  References ........................................................................................................................................90 
 

i 
CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
Glossary 
Acronym 
Meaning 
10mWT 
10 Meter Walk Test 
6minWT 
6 Minute Walk Test 
AD 
Autonomic Dysreflexia 
AE 
Adverse Event 
AIS 
American Spinal Injury International Standards Scale 
ASIA 
American Spinal Injury Association 
BE 
Bowel Evacuation 
BMD 
Bone Mineral Density 
BP 
Blood Pressure 
CBC 
Complete Blood Count 
CBOCs 
Community Based Outpatient Centers 
CIRB 
Central Institutional Review Board 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CSP 
Cooperative Studies Program 
CSPCC 
Cooperative Studies Program Coordinating Center 
CSPCRPCC Cooperative Studies Program Clinical Research Pharmacy Coordinating Center 
CSSEC 
Cooperative Studies Scientific Evaluation Committee 
DMC 
Data Monitoring Committee 
DVA 
Department of Veterans Affairs 
DXA 
Dual energy X-Absorptiometry 
EAW 
Exoskeletal-Assisted Walking 
FDA 
Food and Drug Administration 
FES 
Functional Electrical Stimulation 
FIM 
Functional Independence Measurement 
FPG 
Fasting Plasma Glucose 
FTE 
Full Time Equivalent 
FWA 
Federal Wide Assurance 
FY 
Fiscal Year 
GCP 
Good Clinical Practice 
H&PE 
Health and Physical Exam 
HDL-c 
High Density Lipoprotein cholesterol 
HIPAA 
Health Insurance Portability and Accountability Act 
HOMA-IR 
Homeostasis Model of Assessment-Insulin Resistance 
HR  
Heart Rate 
HRC 
Human Rights Committee 
HRQOL 
Health-Related Quality of Life 
ICH 
International Conference on Harmonization 
ISNCSCI 
International Standards for Neurological Classification of SCI 

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CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
ITTRS 
Interactive Touch Tone Randomization System 
JJPVAMC 
James J. Peters VA Medical Center 
LDL-c 
Low Density Lipoprotein cholesterol 
LOA 
Level of Assistance 
MCS 
Mental Component Summary 
MID 
Minimally Important Difference 
mL 
Milliliters 
NCMRR 
National Center for Medical Rehabilitation Research 
NIH 
National Institute of Health 
NINDS 
National Institute of Neurological Disorders and Stroke 
NODES 
Network of Dedicated Enrollment Sites 
ORO 
Office of Research Oversight 
pg 
Picograms 
PHI 
Protected Health Information 
PI 
Primary Investigator 
PMH 
Physical-Medical Health 
PPE 
Personal Protective Equipment 
PROMIS 
Patient Reported Outcomes Measurement Information System 
QC 
Quality Control 
QOL 
Quality of Life 
RPE 
Rating of Perceived Exertion 
RR&D 
Rehabilitation Research and Development 
SAE 
Serious Adverse Event 
SCI 
Spinal Cord Injury 
SCI/D 
Spinal Cord Injury/Disease 
SCI-FI 
Spinal Cord Injury Functional Index 
SD 
Standard Derivative 
SMART 
Site Monitoring Auditing and Resource Team 
SOC 
Standard of Care 
TC 
Total Cholesterol 
TG 
Triglycerides 
TNF 
Tumor Necrosis Factor 
TUG 
Timed-Up-and Go 
UADE 
Unanticipated Adverse Device Effect 
U/L 
Units per liter 
UTI 
Urinary Tract Infection 
US 
United States 
VHA 
Veterans Health Administration 
VINCI 
VA Informatics and Computing Infrastructure 
VR-36 
Veterans Rand 36 

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CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
CSP #2003 
Exoskeletal-Assisted Walking in Persons with SCI:  Impact on Quality of Life 
Executive Committee Members 
 
Ann M. Spungen, EdD, Chairperson                      James J Peters VA Medical Center 
(JJPVAMC), Bronx, NY 
Name           
Ann M. Spungen, EdD   
Title                 Associate Director, National Center of Excellence for the Medical Consequences 
of SCI 
Location         James J. Peters VA Medical Center 
 
 
130 West Kingsbridge Road, 7A-13 
Bronx, NY 10468 
Phone             718.584.9000, x5814 (office) 
 
914.954.3515 (cell) 
VA Email       ann.spungen@va.gov 
nonVA email  ann.spungen@gmail.com 
Altern. email  kenlys.fajardo@va.gov (Dr. Spungen’s Administrative Assistant) 
 
William A. Bauman, MD, Co-Chairperson            James J Peters VA Medical Center 
(JJPVAMC), Bronx, NY 
Name        
William A. Bauman, MD 
Title            
Director, National Center of Excellence for the Medical Consequences of SCI 
Location      
James J. Peters VA Medical Center 
 
 
130 West Kingsbridge Road, 7A-13 
Bronx, NY 10468 
Phone           718-584-9000, x5428 (office) 
 
914-329-4772 (cell) 
VA Email      william.bauman@va.gov 
nonVA email  wabauman@earthlink.net 
Altern. email   kenlys.fajardo@va.gov (Dr. Bauman’s Administrative Assistant) 
 
Karen M. Jones, MS, Study Biostatistician           Cooperative Studies Program 
Coordinating Center (CSPCC), Perry 
Point VAMC 
Perry Point, MD 
Name           
Karen Jones, MS 
Title           
Biostatistician, CSPCC 
Location      
Cooperative Studies Program Coordinating Center 
Department of Veterans Affairs Medical Center 
  
P.O. Box 1010 
  
Perry Point, MD 21902 

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CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
Phone            410-642-2411, x2/5297 (office) 
VA Email   
Karen.jones2@va.gov 
nonVA email   none 
Altern. email   none 
 
Sunil Sabharwal, MD, Site Investigator                 VA Boston Healthcare System 
West Roxbury, MA 
Name         
Sunil Sabharwal, MD      
Title          
Network SCI Director 
Location     
VA Boston Healthcare System 
 
1400 VFW Parkway, SCI-128 
 
West Roxbury, MA 02132 
Phone             857-203-6574 (office) 
VA Email        sunil.sabharwal2@va.gov 
nonVA email   none 
Altern. email   marilyn.kendall@va.gov (Dr. Sabharwal’s Administrative Assistant) 
 
Lance Goetz, MD, Site Investigator                        Hunter Holmes McGuire VA Medical 
Center Richmond, VA 
Name     
Lance Goetz, MD 
Title      
Staff Physician, Spinal Cord Injury and Disorders Service 
Location    
Hunter Holmes McGuire VA Medical Center 
 
1201 Broad Rock Blvd 
 
Richmond, VA 23249 
Phone           804-675-5455 (office) 
VA Email     lance.goetz@va.gov 
nonVA email  none 
Altern. email   none 
 
Kevin T. White, MD, Site Investigator                    James A. Haley Veterans Hospital 
Tampa, FL 
Name     
Kevin T. White, MD 
Title         
Chief, Spinal Cord Injury Service 
Location     
James A. Haley Veterans Hospital 
 
13000 Bruce B. Downs Blvd. 
 
Tampa, FL  33612 
Phone     
813-972-2000, x6400 (office) 
 
813-695-1575 (cell) 
VA Email     Kevin.White2@va.gov 
nonVA email  none 
Altern. email   Gail.Hartmaier@va.gov (Dr. White’s Administrative Assistant) 
 

v 
CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
Peter Gorman, MD, Chief, PM&R                         Baltimore VA Medical Center  
Baltimore, MD 
Name  
Peter Gorman, MD MS 
Title       
Attending Physician, PM&R Service 
Location     
VA Maryland Healthcare System 
 
10 North Greene Street 
 
Baltimore, MD 21201 
Phone          
410-448-6261 (office) 
VA Email      peter.gorman@va.gov 
nonVA email  PGORMAN@umm.edu 
Altern. email  LCasey@umm.edu (Dr. Gorman’s Administrative Assistant) 
 
Steven C. Kirshblum, MD, Medical Director        Kessler Institute for Rehabilitation (KIR) 
West Orange, NJ 
Name     
Steven C. Kirshblum, MD 
Title       
Medical Director and Director of SCI Services 
Location    
Kessler Institute for Rehabilitation 
 
1199 Pleasant Valley Way 
 
West Orange, NJ 07052 
Phone              973-731-3900 
VA Email        none 
nonVA email  SKirshblum@KESSLER-REHAB.com 
Altern. email  RBucci@KESSLER-REHAB.com (Dr. Kirshblum’s Administrative Assistant) 
 
Amanda Snodgrass, Clinical Research Pharmacist    Cooperative Studies Program Clinical 
Research Pharmacy Coordinating 
Center (CSPCRPCC), Albuquerque, 
NM   
Name    
Amanda Snodgrass, PharmD 
Title     
CSP, Adverse Event Specialist 
Location       VA Cooperative Studies Program, CSPCRPCC 
 
2401 Centre Ave 
 
Albuquerque, NM 87106 
Phone            505-248-3203 (office) 
 
505-206-8449 (cell) 
VA Email     Amanda.snodgrass@va.gov 
nonVA email   none    
Altern. email  none 
 
 
 
 

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CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
EXECUTIVE SUMMARY/ABSTRACT 
Background Veterans with spinal cord injury (SCI) have many adverse secondary medical and 
quality of life (QOL) changes as a result of immobilization.  Veterans with SCI who have 
completed rehabilitation after injury and are unable to ambulate receive a wheelchair as standard 
of care (SOC) for mobility.  Powered exoskeletons are a technology that has recently become 
available as an alternate form of mobility by providing an external framework for support and 
computer controlled motorized hip and knee joints to assist with overground ambulation.   
Research Questions (Objectives) Will Veterans with chronic SCI of ≥six months duration, who 
are medically stable and who use a wheelchair as SOC plus an exoskeletal-assisted walking (EAW) 
device in their home and community environments have clinically meaningful net improvements 
in mental health, bladder, bowel, and pain patient-reported outcomes compared with those who 
use only the SOC?   Additionally, will the use of an EAW device for four months in the homes 
and/or communities of the participants result in a reduction of total body fat mass?  
Study Design A two-group (Intervention and Control), randomized, clinical trial will be performed 
with a one-year feasibility component.  The Intervention group will receive SOC plus EAW.  The 
Control group will receive SOC only.  The study will require seven years in total to complete and 
includes fifteen VA SCI Services as study sites.  A feasibility phase will be employed using a 
staggered start by initially starting six sites, four sites starting one year later, and 5 other sites 
starting two years later.  These initial six sites will be used to assess the start-up activities [hiring, 
training, equipment procurement, Central Institutional Review Board (CIRB) paperwork, etc.], the 
rate of recruitment, and any other issues that may be of value for the successful completion of the 
study.  Lessons learned will be implemented for the remaining sites.    
Relevance to VA  In pilot studies conducted at the James J. Peters VA Medical Center, Bronx, 
NY, improvements in mental-emotional health, physical health and body composition were  
demonstrated by providing the participants the ability to walk for 4 to 6 hours per week over the 
course of three to five months.   As of July 2014, a Class 2 designation was established by the 
Food and Drug Administration (FDA) for “powered exoskeletons”.  To date, one device 
(ReWalk™) has received FDA Class 2 approval for institutional and home use and is currently 
available by prescription.  The Department of Veterans Affairs (DVA) is the largest single provider 
to persons with SCI in the USA, caring for about 26,000 of the 42,000 estimated Veterans with 
SCI.  The VA presently lacks the infrastructure to support Veterans with SCI to train to use this 
device in order to make this technology available for the home/community use.  A controlled 
research study would be anticipated to be the optimal manner to demonstrate the efficacy, amount 
of use and safety of a powered exoskeleton in the home and community environments; findings 
would be immediately transferable to clinical care. 
Number of Research Participants (Sample Size) One hundred-sixty participants (80/group) will be 
randomized.  Each of the 15 study sites will be expected to pre-screen ≥100 potential participants, 
screen ≥60 participants, to reach the target of 160 randomized over 15 sites. 

vii 
CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
Participating Sites Fifteen SCI Services will be selected on the basis of potential recruitment 
numbers (N=13,606 total Veterans with SCI in the sites’ catchment areas and N=7,022 followed 
annually at these sites) and geographic location, to permit an even distribution across the country.  
The fifteen sites include: Boston, Richmond, St. Louis, Tampa, Milwaukee, Minneapolis, Dallas, 
Houston, Palo Alto, Long Beach, Augusta, San Antonio, Bronx, Cleveland, and Albuquerque. Of 
these fifteen sites, five are VA Cooperative Studies Program (CSP) Network of Dedicated 
Enrollment Sites (NODES).  
Duration of Participant Intake (Study Duration) The CS #2003 study duration is projected to be a 
total of seven years:  The initial six sites will have a start-up year, followed by participant 
enrollment/data collection during years 1-4, and continued data collection/closeout during year 5, 
for a total of six years. The next four sites will begin the start-up year one year after the first six 
sites and follow the same enrollment, data collection and closeout schedule over the next five 
years. The next five sites will begin start-up one year after the four sites and follow the same 
enrollment, data collection and closeout schedule. All fifteen sites will be closed out after six years, 
and there is an additional year for the Coordinating Center and Chairperson’s Office to complete 
data analysis and manuscript writing, thus the study total time is seven years.  Participants in both 
groups will be asked to commit 33 weeks to this study.  Participants in the Control arm will be 
offered an additional 8 weeks to receive EAW training in the medical centers, without outcome 
data being collected. 
Treatment (follow-up)  The intervention being tested is four months of home and/or community 
use of a powered exoskeleton. 
Definition of Participant Samples (Study Population) One-hundred sixty male or female Veterans 
or military members with chronic SCI, ≥six months duration, ≥18 years of age, functional use of 
their hands, medically stable, and wheelchair users for indoor and outdoor mobility, will be eligible 
for screening.  All potential participants will be Veterans or military members with SCI. Study 
participants will generally be outpatients with the exception of those inpatients who meet the 
eligibility criteria, and who are approved by the Site Investigator (e.g., some inpatients may have 
been admitted for a wheelchair fitting or another non-medical reason).  Non-veterans with SCI will 
not be eligible. 
Treatment Arms All participants will receive four months of treatment, randomized into two arms:  
SOC plus EAW or SOC only.  
Endpoints  Primary outcome one will be the Mental Component Summary of the Veterans Rand-
36 (MCS/VR-36).  Primary outcome two will be the sum T-score of the SCI-QOL bladder 
management difficulties, bowel management difficulties and pain interference item banks.  The 
major secondary outcome will be total body fat mass. The two primary and the major secondary 
outcomes will be analyzed as the proportion of participants in each group who achieved a clinically 
meaningful change in score.  The endpoint will be success or failure for these outcomes. 

viii 
CSP #2003 
Exoskeletal Assisted Walking in Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
 
Protocol amendment due to COVID-19 pandemic:  In Fiscal Year 2020 (FY20), Quarter 2, the 
United States (US) experienced a coronavirus pandemic.  As a result, beginning in March of 2020, 
most of the country was placed on social distancing restrictions and/or quarantine. CSP #2003 was 
placed on a voluntary administrative hold on March 16, 2020.  During this pandemic, the Chair’s 
Office became aware of potential loss of services for our Veterans with SCI such as caregivers, 
medical appointments, wheelchair repair and others, and has proposed an amendment to CSP 
#2003.  This amendment is to conduct an SCI-specific survey to determine the effect of the 
pandemic on Veterans with SCI who have been previously screened for participation in this study.  
A follow-up survey and blood testing for the virus antibodies will also be conducted at least 1 
month after the initial survey. The administrative hold has been lifted for the COVID-19 survey 
and blood draw.

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
1 
I. INTRODUCTION AND BACKGROUND 
 
Veterans with spinal cord injury (SCI) have an overabundance of adverse secondary medical and 
quality of life (QOL) changes as a result of paralysis and immobilization.  Veterans with SCI who 
have completed rehabilitation after injury and are unable to ambulate receive a wheelchair as 
standard of care (SOC) for mobility.  Powered exoskeletons are a technology that has recently 
become available as an alternate form of mobility by providing an external framework for support 
and computer controlled motorized hip and knee joints to assist with overground 
ambulation.  These exoskeletal devices have been used primarily in a hospital setting, but have 
been approved for home/community use since 2014.  Identifying efficacy and safety of a powered 
exoskeleton to be used in the home or community environment for Veterans with SCI is an 
important issue. 
 
Physical, medical, and health-related quality of life changes following SCI:  SCI results in 
paralysis and near permanent loss of voluntary function below the level of lesion. Those with more 
severe neurological lesions lose the ability to perform the weight bearing activities of standing and 
walking.  Most become wheelchair users for indoor and outdoor mobility. The loss of the ability 
to walk is an obvious consequence of SCI. However, there are many less observable complications 
that result from loss of walking activity that serve to reduce quality of life (QOL), such as 
compromised bowel and bladder function, increased pain, extreme changes in body composition, 
and difficulty sleeping.  On a daily basis, coping with loss of bowel [1-3] and bladder [4, 5] 
function, chronic pain [6], and difficulty sleeping [7] takes a tremendous, and often unrecognized, 
toll on emotional and physical well-being. Chronic constipation [8] and difficulty with evacuation 
are time consuming, taking hours per week, requiring prescription of multiple types of stool 
softeners and laxatives, and often the use of enemas and/or digital stimulation to perform a bowel 
evacuation, all of which are over-shadowed by the ever-present anxiety of a potential bowel 
accident [1, 9].  Standing alone has not been demonstrated to be effective in decreasing time to 
first stool for a bowel evacuation [10].  Constant sitting often leads to chronic back pain and, in 
those with some sensation below their lesion, leg pain is also prevalent [11].  Uncontrolled muscle 
spasms, which are similar to leg cramps in those who are not paralyzed, also cause discomfort and 
pain and may be severe at times [12].  Sleep is unremittingly interrupted due to spasms, pain and 
other conditions directly related to paralysis [7, 13, 14].  Immobilization from SCI has severe 
consequences on body composition [15-18].  Within the first two years after SCI, persons with 
motor-complete lesions may be expected to gain as much as 10 kg of total body fat mass and to 
lose a similar amount of lean tissue mass (Spungen, et.al., manuscript under review). With these 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
2 
extreme changes in body composition and the forced reduction in levels of activity, there are 
associated carbohydrate and lipid metabolism abnormalities [19-21]. Impaired glucose tolerance 
or diabetes mellitus occurs in as many as 60% of the SCI population [21-24]. HDL-c levels below 
35 mg/dL (an independent risk factor for heart disease) are reported in 24 to 40% of persons with 
SCI [25, 26]. 
 
Ambulation efforts for persons with SCI:  Clinical therapeutic options available to assist persons 
with SCI to stand and walk have been, by and large, unsuccessful when extended to the home 
environment.  For people with motor-complete SCI who have good upper body strength, or those 
with motor-incomplete SCI, such as those who have some voluntary movement in the legs or can 
even weight bear to some degree, various types of gait orthoses have had limited success in 
allowing the individual to stand and walk [27-29].  The high energy cost of using gait orthoses, 
though, limits use to those with sufficient upper body strength to ambulate for short bouts, and 
extended walking does not occur with the use of gait orthoses [27, 30].  Locomotor training, with 
either manual assistance by two therapists or robotic assistance with a Lokomat to move the legs 
and feet in a walking motion over a treadmill while the patient is suspended in an overhead harness 
to off-load body weight, has demonstrated positive benefits on cardiovascular function, self-
esteem, and quality of life [31-35]. These body-weight supported treadmill training methods 
require significant staff commitment, equipment and space, and these approaches are not practical 
for home, work or community use; thus, these benefits are lost with the discontinuation of the gait 
training program.  Ambulation has also been accomplished with functional electrical stimulation 
(FES), but these FES systems have the challenge of controlling the joint movements appropriate 
for gait and because FES is an anaerobic form of exercise, the users invariably experience rapid 
muscle fatigue [36]. To reduce the challenge of controlling joint movement, hybrid systems have 
combined FES and a passive orthotic [37, 38], and have demonstrated improvements in energy 
expended while walking, but the challenge of rapid muscle fatigue still persists.  Several other 
types of hybrid systems, such as stored-energy hybrid systems which use FES to stimulate the 
muscle group for rotation of one joint and transfer energy to drive another joint, or controlled brake 
orthoses which use FES to power the movement but incorporate a computer controlled brake 
system to lock out the joint and control joint speeds during ambulation, have been or are being 
developed, but these approaches are still confined to the research setting [39-42].  As such, most 
of these devices for assisted FES walking have remained as concepts or prototypes and have not 
been commercialized, making viable options for walking outside the hospital or rehabilitation 
setting relatively limited.   

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
3 
Use of a wheelchair for mobility and daily activities remains the standard of care for Veterans who 
are unable to stand and walk as a result of paralysis due to SCI.  When a person becomes injured, 
initial rehabilitation is prescribed for usually no longer than four to six months, depending on the 
severity of the SCI.  Once discharged, there are very few rehabilitation programs or strategies for 
the home or as an outpatient that are being offered to Veterans with chronic SCI.  As such, our 
Veterans with chronic SCI remain wheelchair-bound and are part of a demographic that is one of 
the most sedentary known to man, with resultant numerous secondary medical consequences of 
longstanding, severe immobilization.   
 
Exoskeletal-assisted walking (EAW) in SCI:  Since 2011, a relatively new technology, that permits 
assisted standing and walking overground, has been available for people with immobilization due 
to paralysis from SCI. This robot-like exoskeletal technology uses a computerized, powered 
exoskeleton support frame, attached to the pelvis and legs, that allows a person with paralysis to 
stand and walk [43, 44].  Early in 2011, Dr. Ann M. Spungen and her team at the VA Rehabilitation 
Research & Development (RR&D) National Center of Excellence for the Medical Consequences 
of Spinal Cord Injury, James J. Peters VA Medical Center (JJPVAMC), Bronx, NY, began 
conducting pilot studies in the safety and efficacy of exoskeletal-assisted walking in persons with 
SCI.  They were the first Veterans Affairs (VA) investigators to acquire exoskeletal-assisted 
walking (EAW) technology to test the safety and efficacy and for use in persons with SCI [45-47].  
This powered exoskeleton (ReWalk™) [48] allows a person with paraplegia to stand  (Figure 1) 
and walk overground for extended periods of time (Figure 2).  
 
Figures 1 and 2.   Countertop reaching and walking in the exoskeleton 
 
Figure 1.   Examples of standing  
at a counter and at a petting zoo 
Photos with permission 
 
Figure  2. Walking outdoors  
at Riverside Park,  NYC 
Photo with permission 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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One distinct advantage of the powered exoskeleton over previous rehabilitation walking modalities 
is that it has the potential to be prescribed for use in the home and community. The exoskeletal 
technology has the potential to change the field of rehabilitation medicine by offering a modality 
that permits assisted walking not only in the rehabilitation setting, but also in the home and 
community environment.  This opens the possibility for continuous use and an option for 
increasing upright physical activity throughout life. To date, several DVA SCI Services have 
tentatively embarked on using this technology in the clinical institutional setting.  
  
The investigators at JJPVAMC have been studying the efficacy of using this device in persons 
with SCI on mobility and walking skills, quality of life, medical, and health-related outcomes.  
These investigators have demonstrated that people with SCI who are otherwise wheelchair-
dependent are able to tolerate performing EAW for four to six hours per week without difficulty, 
and they report improvements in QOL outcomes after approximately two to four months of 
exoskeletal training. Specific benefits have been documented in body composition [49], energy 
expenditure [50], bowel function, sleep, and pain reduction (See Preliminary data). The reported 
benefits from increased activity through upright mobility are not unexpected.  It has long been 
appreciated that increasing activity and exercise in a sedentary person has numerous health 
benefits.  It is relevant to note that, to date, the exoskeletal-assisted walking participants with SCI 
at the JJPVAMC have unanimously reported that being able to walk again has markedly changed 
their perceptions of their lives for the better, and this beneficial appraisal of participants is even 
with the use of this device being highly restricted to use in the institutional setting. It remains 
incredibly disheartening for these participants to complete the research program and no longer 
have a viable option for performing overground walking, but this would be a viable option if 
prescribed for home use.  The proposed VA Cooperative Study (CS #2003) would demonstrate 
the physical, mental, social, and emotional benefits of use of these robotic ambulatory devices in 
the home and community environments and, thus, have the potential to dramatically change the 
lives of our Veterans with SCI. 
   
Of note, the ReWalk is not the only exoskeleton commercially available [51, 52], or with the 
potential to be commercially available [53], but this specific device is currently the only one with 
Food and Drug Administration (FDA) approval as a Class 2 device for rehabilitation and home 
use [54].  Findings from the proposed study would be readily transferable to any future powered 
exoskeleton devices that may become available from development from VA, academic, or the 
private sectors. 
 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
5 
A. 
Measurement of Quality of Life Outcomes in SCI 
 
The Patient Reported Outcomes Measurement Information System (PROMIS) and the link to the 
SCI-QOL:  The National Institutes of Health (NIH) Roadmap for Medical Research in the 21st 
Century (now called the Common Fund) has supported major initiatives in biomedical research 
that no single institute could accomplish alone. One key Common Fund project was a multicenter 
cooperative group award to develop and validate a Patient-Reported Outcomes Measurement 
Information System (PROMIS U01 AR052177-02). PROMIS contributes to NIH re-engineering 
by building and validating common, accessible item banks to measure key symptoms and health 
concepts applicable to a range of chronic conditions. At the same time, the National Institute of 
Neurological Disorders and Stroke (NINDS) issued a request for proposals to construct a clinically 
relevant and useful health-related quality of life (HRQOL) measurement tool for major 
neurological diseases that affect the United States population. This measurement tool was 
developed to be consistent across the selected conditions to allow for cross-disease comparison, 
and yet flexible enough to capture condition-specific HRQOL issues. This contract was awarded 
to the same group that was developing PROMIS (Dr. David Cella and colleagues) and is called 
Neuro-QOL. The Neuro-QOL was a five year effort to construct a psychometrically-sound and 
clinically-relevant HRQOL measurement system for individuals with major neurological disorders 
[55].  Wherever possible, Neuro-QOL measures included relevant PROMIS items to allow for 
linking and cross-walking of scores between the two systems.  This is valuable because a multiple 
sclerosis investigator who uses a PROMIS measure could also derive a Neuro-QOL score and 
compare results in his/her study to other multiple sclerosis studies that have used Neuro-QOL [56].  
Early in the award period, a rigorous process was undertaken by investigators and outside experts 
to select 5 adult and 2 pediatric conditions (the budget would only allow this many) to represent 
the major issues and concerns faced by individuals with neurological disorders. After conducting 
interviews with 44 neurology professionals, an online survey with 89 members of the American 
Academy of Neurology and a day-long consensus meeting with an international panel of 
distinguished experts spanning the field of neurology, the following conditions were selected: 
stroke, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, epilepsy [adult and 
child], and muscular dystrophy.  Even though there was considerable interest throughout this 
process to include SCI among the selected adult conditions, in the end, it was not included [57].  
Nonetheless, it became clear that extending Neuro-QOL measurement development 
methodologies to SCI could significantly improve this field’s ability to assess important HRQOL 
outcomes and track clinical treatment changes.   In 2008, working closely with members of the 
Neuro-QOL team, Dr. David Tulsky was awarded funding from two agencies of the NIH:  NINDS 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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and the National Center for Medical Rehabilitation Research (NCMRR) to develop SCI-specific 
patient reported outcome measurement tools in physical-medical, emotional and social function 
(SCI-QOL) (NIH #5RO1HD054659). Additionally, the National Institute of Disability 
Rehabilitation Research (NIDRR) separately funded Drs. Tulsky and Alan Jette (from Boston 
University, Boston, MA) to develop a physical function index of HRQOL instruments for SCI 
(SCI-FI) (NIH #5RO1HD054659).  The goal and a major strength of the SCI-QOL and SCI-FI 
projects were to embed Neuro-QOL items (which include verbatim PROMIS items) at the core of 
the new targeted SCI-specific item banks.  The SCI-QOL utilized the PROMIS standards [58] for 
instrument development, incorporating both qualitative (i.e., focus groups, cognitive debriefing 
interviews) and quantitative (i.e., item response theory analyses and computerized adaptive 
testing) [59] methods to ensure that the final SCI-QOL was psychometrically sound while at the 
same time conceptually grounded to issues that are truly important to individuals with SCI [60, 
61].  The final SCI-QOL includes 22 item response theory calibrated item banks/scales across the 
domains of Physical-Medical Health, Physical Functioning (SCI-FI), Social Participation, and 
Emotional Health.  Notably, item banks that are based on PROMIS (e.g., Depression, Anxiety) or 
Neuro-QOL (e.g., Stigma, Ability to Participate in Social Roles and Activities) banks/items, the 
SCI-QOL scores have undergone a linear transformation back to the PROMIS or Neuro-QOL 
metric, respectively. In this way, SCI-QOL item banks are optimized for individuals with SCI (i.e., 
through selection and order of items administered) yet are directly comparable to individuals in 
the general population through this statistical transformation.  
The NIH/NIDRR funded initiatives have supported the creation of innovative health-related QOL 
measurement approaches, specific for individuals with SCI.  Two valid and useful SCI-specific, 
HRQOL measurement tools now enhance the efforts of clinicians and researchers who are 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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investigating interventions for improved function and quality of life in persons with SCI [59, 62-
68].  In 2011, Dr. Spungen received VA RR&D, Merit Review funding (#B7566-R) to add 
Veterans with SCI to the SCI-QOL database.  This VA Merit Review study is in its last year of 
data collection.  A graphic depiction of the PROMIS, Neuro-QOL and SCI-QOL is provided 
(Figure 3). 
 
Psychometric Properties of the SCI-QOL/SCI-FI:  Each of the final SCI-QOL/SCI-FI item banks 
is a unidimensional set of items (determined by confirmatory factor analysis) that have been 
calibrated with item response theory (IRT). The stability of the IRT calibrations provides 
preliminary evidence of the SCI-QOL’s validity [60]. Furthermore, all SCI-QOL banks 
demonstrate internal consistency (Cronbach’s alpha) and 2-week test-retest reliability. Finally, the 
SCI-FI (physical functioning) banks have demonstrated responsiveness to the naturally occurring 
change following SCI at both 6 month and 1 year time points.   
 
The PROMIS Sleep Disturbance outcome measure was validated and calibrated using classic 
validation techniques and IRT in more than 2,200 adults from an internet pooling sample and 
medical, psychiatric and sleep clinics [69, 70].  Moderate to high correlations were demonstrated 
between existing sleep scales and by statistically significant differences found between patients 
with known sleep disorders and those without any [69]. The PROMIS Sleep Disturbance outcome 
measurement was found to be sufficient because no unique questions that required SCI-specific 
content were thought to be needed [66]. The PROMIS Sleep disturbance outcome measure is a 
useful tool as is. 
 
A clinically significant difference of the patient-reported outcomes for the QOL measurement 
determined from any of the PROMIS, Neuro-QOL, SCI-QOL, or SCI-FI assessment tools has been 
undergoing evaluation.  In the interim, three prominent investigators in this field joined forces to 
determine a consensus of a clinically relevant change for any of these patient-reported outcome 
questionnaires [71].  These investigators support a ½ standard deviation (SD) as a conservative 
estimate for a clinically meaningful change.  A minimally important difference (MID) is expected 
to be below a ½ SD.  They report that, in lieu of a specifically tested effort to determine the MID 
in a specific population (such as SCI), use of the ½ SD is a strong and conservative approach [71]. 
 
In addition to a scientific rationale (please refer to the pilot data), there are ethical and financial 
considerations that support the justification for the VA to fund this initiative.  It has been long 
recognized that a sedentary lifestyle is deleterious for one’s health, self-esteem and well-being.  

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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The earliest survivors of an amputation had at least a wooden peg to assist them with ambulation.  
Fortunately, prosthetic limb technology has improved such that lower limb prostheses are 
sophisticated, computerized devices that permit an eligible amputee to walk, run, jump, climb 
stairs, swim, and perform almost all functions of ambulation and lifestyle activities that they were 
able to do prior to limb loss.  The problem of restoring ambulation to someone with paralysis from 
SCI has been far more challenging.  However, technology has finally advanced sufficiently to 
address the problem, and although not on par with the prosthetic limbs yet, exoskeletons offer an 
upright ambulatory solution for persons who are paralyzed and potentially other wheelchair users 
for mobility.  The exoskeletal-assisted walking technology represents a paradigm shift for Veterans 
with chronic SCI who only have had the option of the wheelchair for “ambulation” as standard 
care. This new paradigm for mobility and rehabilitation for our Veterans with chronic SCI has the 
obvious and distinct potential to improve their quality of life.  In the absence of a medical 
contraindication, rehabilitation clinicians would never consider the option of not prescribing a 
lower limb prosthetic to an eligible amputee. Should not a similar decision-making process be 
applied to our eligible Veterans with SCI?   
 
The DVA has 26 SCI Services that annually care for about approximately 26,000 of the estimated 
42,000 eligible Veterans with SCI (VA Fact Sheet, 2009).  What if only 1,000 of these Veterans 
with SCI are eligible and interested in being prescribed an exoskeleton for home/community use?  
The cost of purchasing 1,000 ReWalk exoskeletal units for Veterans with SCI would be about $78 
million dollars, not including the clinical staff needed for training and monitoring the use of this 
device.  However, if 10,000 Veterans with SCI wanted and were eligible for one of these devices, 
then including the support services, this would be approaching a billion dollar item for the DVA.  
Is it not prudent to study this device in the home/community environment to determine its safety 
and efficacy prior to being pressured to embark on this path by Veteran, public, or Congressional 
influence?  Further developments in exoskeletal technology and new products are inevitable.  Of 
note, however, the current state-of-the-art exoskeletal technology is not expected to change in the 
time-frame of this proposed study.  In addition, this study is uniquely designed as a template that 
would support any new exoskeletal developments.  It would benefit the VA to have a system in 
place for the assessment of this particular robotic device because the ReWalk is the first and only 
such device to date to receive FDA Class 2 approval for institutional and home/community use.  
Such an initiative could then provide the structure and generate the necessary experience to 
evaluate future exoskeletal technologies.  
 
Because the ReWalk exoskeleton is a radical and exciting departure from the traditional 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
9 
rehabilitation approaches, by permitting those with SCI to stand and walk overground, there has 
already been a fair amount of media and publicity on the exoskeletal-assisted walking technology.  
This technology is already highly visible in the public eye. The VA would be making a clear and 
unequivocal statement of its intent to improve the lives of Veterans with SCI by testing the efficacy 
of this device in the home and community environments. 
 
B. 
Pilot Data 
 
To date, 19 participants with SCI who were wheelchair users for indoor and outdoor mobility were 
consented and screened for eligibility.  Seven of the 19 participants were screening failures (two 
for low bone mineral density (BMD), one for medical issues, and four for scheduling conflicts) 
and 12 completed 15 or more EAW sessions.  Pre- and post-walking data were collected in all 12 
participants.  One of 12 participants was lost to follow-up for the QOL data after 15 sessions (the 
participant had been wait-listed for medical school and was suddenly accepted, necessitating 
abrupt withdrawal from the study); as such, walking data are reported on participants (Table 1).  
QOL data are reported on 11 participants (below in the section for the Primary Outcome 2).  The 
participant that was lost to follow-up for the QOL data was treated as study failure and was 
included as such for the power calculations.  Of the 12 participants who were trained in the 
exoskeletal device, compliance with attendance to the sessions was >90%.  If a session was missed, 
make-up sessions were easily scheduled, often at the request of the participant. The demographic 
data is reported in 12 participants with durations of injury ranging from 1 to 19 years (Table 1). 
The best walking tests achieved with the level of assistance (LOA) needed for this activity are also 
reported (Table 1.) 
 
 
 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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Heart rate (HR) and blood pressure (BP):  HR and BP responses were measured during each 
session in the resting seated position prior to standing and walking, immediately after walking 
while still standing and then again when seated, after the walking session.  The results at 18±5 and 
32±18 sessions are reported (Table 2).  The vital sign responses during sitting and post walking 
were in the expected ranges, demonstrating an increase in HR from seated to walking.  In the 
participants studied, there were no orthostatic hypotensive episodes with the postural changes from 
sitting to standing in the device.   
(s)
(m/s )
(m)
(m/s) (LOA)
1
34
173
66.7
Male
9
T4
B
39
0.256
90.2
0.251
Min
2
48
168
68
Male
4
T10
A
62
0.161
50.5
0.14
Min
3
44
183
77.1
Male
4.5
T4
A
20
0.58
209.0
0.581
MI
4
58
160
64.4
Female
1.5
C8/T8 A (NT)
24
0.417
139.0
0.386
MI 
5
61
175
72.6
Male
14
T11
A
23
0.435
137.4
0.382
MI 
6
24
185
74.8
Male
5
T5
A
56
0.179
60.2
0.167
Min
7
40
183
88.5
Male
1.5
T1
B
61
0.164
50.8
0.141
S
8
56
175
83.9
Male
3
T9
A
22
0.459
151.0
0.419
S
9
50
183
99.8
Male
11
T7
A
17
0.585
208.2
0.578
MI
10
37
170
65.8
Male
6
T2
A
22
0.459
150.0
0.417
Min
11
64
173
72.8
Male
3
T2
A
78
0.128
46.3
0.129
Mod
12
37
152
65.8
Female
19
C8
C (NT)
14
0.714
255.9
0.711
MI 
Table 1.
SID=subject identification number; y=years; cm=centimeters; kg=kilograms;
DOI=duration of injury; LOI=level of injury; AIS=American Spinal Injury International
Standards Scale; LOA=level of assistance; s=seconds; m=meters; and NT=non-traumatic
SCI. LOA was adapted from the FIM as one of the following: moderate assistance (Mod)
– participant performs 50% to 74% of the task and the trainer has both hands on the
participant or device at all times to provide occasional guidance or balance support;
minimal assistance (Min) – the user performs 75% or more of the task and the trainer has
one hand on the participant or device for infrequent guidance or balance support;
supervision (S) – the trainer is not touching the participant but is close enough to reach
in to provide support for balance or guidance as needed; and modified independence
(MI) – the trainer does not provide any assistance, and the participant is fully
independent while walking in device. Nineteen participants were consented for screening
eligibility. Seven participants (SID#'s 2, 3, 4, 8, 12, 13, and 17) were screening failures: two
for low BMD, one medical illness, and four for schedule conflicts.   
Table 1.  Characteristics of the Participants and Walk Test Results
Demographic Characteristics
Walk Tests (WT) and Levels of 
Assistance (LOA)
SID Age
(y)
Ht
(cm)
Wt
(kg) Gender DOI
(y)
LOI
AIS
10 m WT
6-min WT

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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Rating of perceived exertion (RPE):  RPE is a self-reported indicator of how hard the person 
perceives that they are performing an activity.  RPE correlates well with HR when a 0 is added to 
the rating value (for example, a RPE of 6 is equivalent to a HR of 60 bpm, a typical resting value; 
and a RPE of 20 is related to a maximal effort of a HR of 200 bpm [72, 73]. As the participants 
trained, more actual walking occurred during each session, yet their perception of exertion during 
walking was reduced (Table 2).   
 
C.  
Preliminary Data Employed for the Primary Outcome Variables 
 
Primary Outcome 1 (supporting data):  A commonly used measure of physical and mental patient-
reported health outcomes is the SF-36 [74].  The SF-36 has been reported in persons with SCI of 
less than 6 months post injury [75] and in those who were less than four years post injury [76].  In 
the Veterans Health Administration, the Veterans Rand 36 (VR-36) has been used to document 
health-related QOL outcomes in Veterans [77-79]. The SF-36 was administered to participants 
before (N=12) and after (N=11, one lost to follow-up) EAW training.  Using the MCS scores to 
calculate a mean difference and 95% CI for the upper and lower limits for the pre- and post- values, 
the average value for a net change demonstrated clinically significant improvement of 9.03 ± 
17.02, CI -2.4 to 20.5, p=0.1087 (Figure 4).  Four of 12 participants demonstrated a clinically 
relevant change of ≥4.0 on the MCS of the SF-36.  This proportion was used to calculate the 
power and sample size for the Primary Outcome 1 (MCS/VR-36) that is reported in the statistical 
section of the proposal.  [Note, the MCS SF-36 was used for the preliminary study, but the 
MCS/VR-36 will be used in this study as the Primary Outcome 1.] In support of the average 
improvement in the MCS scores, comparisons were made with those of other studies where the 
SF-36 was administered to persons with SCI within 6 months of injury [75] and then in another 
group who were less than four years since injury [76]. The MCS average scores for the pre- and 
RPE
Standing
Seated
Standing
Seated
Standing
Seated
Standing
(post EAW)
(pre EAW)
(post EAW) (pre EAW)
(post EAW) (pre EAW)
(post EAW)
1 to 10
14±2
79±13
102±22
127±12
130±14
72±8
73±10
11 to 25
12±3
80±9
112±22
123±15
122±20
73±13
68±20
26 to 40
10±3
75±11
113±17
122±19
123±17
68±9
70±8
> 40
8±2
79±13
114±25
128±13
127±17
72±9
72±2
Table 2. SBP=Systolic blood pressure; DBP=Diastolic blood pressure; mmHg=millimeters of mercury;  
EAW=exoskeletal-assisted walking
Table 2.  Group Average Heart Rate, Blood Pressure and Rating of Perceived Exertion 
Responses to Exoskeletal-Assisted Walking across Sessions
Sessions
Heart Rate (bpm)
SBP (mmHg)
DBP (mmHg)

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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post- ReWalk participants were compared to data from both studies. Lucke, et.al., who 
administered the SF-36 to persons with SCI of only 6 months duration [75] and Westgren et.al. 
who administered the SF-36 in those with SCI of <4 
years duration [76] (Figure 5).  Both of these studies 
reported MCS scores of 51.8 and 51.9 respectively; 
the MCS scores from these prior reports are 
consistent with the findings of our 11 participants at 
baseline (MCS of 52.3).  After EAW, the ReWalk 
participants increased to 61.5 (Figure 5).  
 
Primary Outcome 2 (supporting data):  Three item 
banks from the SCI-QOL Physical-Medical Health 
domain were used to assess pre- and post- changes 
after 40±15 sessions of exoskeletal-assisted walking 
in 11 participants (one of the 12 was lost to follow-
up for the QOL assessments).  These item banks consisted of patient-reported outcomes for bladder 
management difficulties, bowel 
management difficulties, and 
pain interference. The group 
means for the pre-and post-
values with the 95% CI are 
presented 
(Figure 
6).  
Participants reported significant 
improvement (indicated as a 
reduction in scores) in the 
bladder (Figure 6A) and bowel 
(Figure 6B) item banks.   Pain 
Interference also improved, but 
failed 
to 
reach 
statistical 
significance (Figure 6C).  In 
support of the SCI-QOL net pain improvements, analysis of the Physical Pain and Pain interference 
components from the SF-36 demonstrated significant net improvements from 50±24 to 76±12, 
p=0.0253.  Using a simple sum score of the three SCI-QOL item banks (bladder, bowel and pain) 
from the Physical-Medical Health (PMH) domain, the mean difference from pre- to post-EAW 
training was -27.1±34.3; 95% CI: -50.1 to -4.0, p=0.0257.  Five of the 12 participants 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
13 
demonstrated a clinically relevant improvement of at least 10% in the sum score of the three 
item banks. This proportion, 42% responders, was used to calculate the power and sample size 
for the Primary Outcome 2 (PMH/SCI-QOL) that is reported in the Statistical Analysis Plan 
(Section XIII) of the protocol. 
 
 
D. 
Supporting Data for the Major Secondary Outcome Variable 
 
 Body composition for fat and lean tissue mass was measured by the soft tissue components of a 
dual energy x-absorptiometry (DXA) scanner in the 12 participants of the pilot study.  Six of 12 
participants lost more than 1.0 kg of total body fat (-2.54±0.88 kg).  Two lost less than 1.0 kg and 
2 gained more than 3.0 kg of total body fat. One participant was lost to follow-up. The loss of ≥1.0 
kg of total body fat mass in one half of the participants is a remarkable finding because few efforts 
at an intervention (i.e. physical activity or dietary) have been successful in reducing fat mass in 
this population (Table 3). Six of 12 participants achieved a meaningful reduction in total body 
fat mass (≥1.0 kg loss). It is anticipated that during the four-month home use phase, 35% of 
the Intervention group will maintain a ≥1.0 kg fat loss from baseline. This proportion (35%) 
was used to calculate the power for the major secondary outcome. 

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E. 
Secondary Outcomes  
 
 The PROMIS Sleep Disturbance outcome 
measure was used to assess change in sleep 
disturbance.  Additional measurements of 
sleep and fatigue problems were assessed 
using the Epworth Sleepiness Scale [80] and 
the Fatigue Severity Scale [81, 82].  These 
tools are measures of daytime or wake-time 
sleepiness and tiredness.  Net improvements 
were noted in all three surveys, with 
statistically significant results in the PROMIS 
Sleep Disturbance outcome measure (Figure 
7).    
 
 
S's
Pre
(kg)
Post
(kg)
Diff
(kg)
 ≥1.0 kg 
loss
1
9.71
6.98
-2.73
yes
2
15.43
14.13
-1.30
yes
3
31.77
30.78
-0.99
no
4
24.22
21.77
-2.45
yes
5
25.84
25.06
-0.78
no
  6*
16.15
no
7
29.35
26.21
-3.14
yes
8
32.98
29.23
-3.74
yes
9
31.75
29.89
-1.87
yes
10
16.20
15.82
-0.38
no
11
21.29
24.76
3.47
no
12
34.88
38.50
3.62
no
6
Table 3.  Preliminary Data for Total Body Fat (kg)
(For the Major Secondary Outcome)
Responders 
 * Subject 6 was loss to follow-up, but was treated as a 
study failure in the preliminary data.

CSP #2003 
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Version 7.2 Protocol July 2021 
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Bowel function was also measured by two self-reported assessment tools (Bristol Stool Scale and 
Bowel Survey) before and after 20 to 30 sessions of ReWalk training.  The Bristol Stool Scale is 
an indicator of stool consistency.  Participants reported an overall softening of their stool with 
values, on average, reaching a “desirable” stool consistency after ReWalk training (Figure 8), and 
this finding was consistent with a reduction or discontinuation of the use of bowel medications.    
 
The Bowel Survey accounts for important items, such as daily time spent for a bowel evacuation 
(BE), frequency per week of BEs, monthly frequency of incontinent episodes, the amount of 
medication, mechanical, digit, and/or flushing extraction methods used to achieve a BE.  After 2 

CSP #2003 
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Version 7.2 Protocol July 2021 
16 
to 3 months of EAW at 4 to 6 hours per week, the group reported reduced time spent daily for a 
BE, increased BE frequency per week and reduction or discontinuation of the amount of BE 
medication and/or mechanical methods used (Table 4).   
 
Summary of Pilot Study:  The pilot EAW study using the ReWalk performed at the JJPVAMC 
trained 12 participants in the ReWalk exoskeleton for a combined total time of >1200 hours.  EAW 
of four to six hours per week was well-tolerated by the participants.  Time in the exoskeleton 
resulted in improved skill level.  One-half of the participants reported clinically significant 
improvements in bladder and bowel function and reduction in pain outcome measurements.   There 
were no study-related serious adverse events (SAEs).  Skin abrasions at the points of contact with 
the device occurred across 9 of the 12 participants; these were reported as “study-related adverse 
events.”  All skin abrasions were resolved with adjustments in padding and fit of the device to the 
participants.  One participant fell due to slipping on a wet floor, but was not injured.  These adverse 
events were consistent with those reported by others for exoskeletal-assisted walking [43, 44, 83]. 
 
Table 4.  Bowel Function Changes Pre and Post EAW Training 
  
Frequency of 
Bowel 
Evacuations 
(#/week) 
Time spent per 
Bowel Evacuation 
Day (minutes/day) 
Bowel 
Accidents     (# 
in past month) 
Laxative, Stool Softener, Enema, and/or 
Digital Stimulation Use 
S's 
Pre 
Post 
Pre 
Post 
Pre 
Post 
Change 
1 
1 to 2 
3 to 4 
60 to 180 
15 to 30 
1 to 2 
0 
Reduction in enema and digit stimulation 
2 
1 to 2 
3 to 4 
15 to 30 
15 to 30 
0 
0 
Discontinuation of laxative, reduction in 
enema and digit stimulation 
3 
2 to 3 
3 to 4 
60 to 180 
30 to 60 
5 to 6 
0 
Discontinuation of laxative and stool 
softener 
4 
1 to 2 
3 to 4 
60 to 180 
30 to 60 
≥ 7 
0 
Reduction in use of laxative, stool 
softener, enema, and digit stimulation 
5 
5 to 6 
5 to 6 
60 to 180 
30 to 60 
1 to 2 
0 
Discontinuation of laxative and 
supplemental fiber 
6 
3 to 4 
  
30 to 60 
  
3 to 4 
  
Lost to follow‐up 
7 
≥ 7 
5 to 6 
60 to 180 
30 to 60 
1 to 2 
0 
Reduction in use of laxative, stool 
softener, enema, and digit stimulation 
8 
3 to 4 
3 to 4 
15 to 30 
15 to 30 
3 to 4 
1 to 2 
Reduction in use of laxative, stool 
softener, enema, and digit stimulation 
9 
3 to 4 
≥7 
15 to 30 
15 to 30 
0 
0 
Reduction in use of laxative and stool 
softener 
10 
≥ 7 
5 to 6 
60 to 180 
60 to 180 
3 to 4 
3 to 4 
No change 
11 
3 to 4 
3 to 4 
30 to 60 
30 to 60 
0 
1 to 2 
Laxative and digital stimulation use 
increased, No change in enema use 
12 
≥ 7 
5 to 6 
5 to 15 
5 to 15 
0 
0 
No change 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
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II.  OBJECTIVES  
 
The short-term aims are to demonstrate in Veterans with SCI who are wheelchair users for indoor 
and outdoor mobility the efficacy for changes in QOL, improvements in body composition and the 
safety of home/community use of a powered exoskeleton for ambulation.  
   
The long-term aims are to share the knowledge gained from this research study with the 
Department of Veterans Affairs (DVA) Veterans Health Administration (VHA) Spinal Cord Injury 
Patient Care Centers’ clinical staff about the training procedures, education of and the development 
of guidelines for the clinical prescription of the exoskeletal-assisted walking device for 
home/community use in Veterans with SCI.  
 
The study sample size is powered from preliminary data for the two primary outcomes [Mental 
Component Summary (MCS) of the Veterans Rand-36 (VR-36) and Spinal Cord Injury Quality of 
Life (SCI-QOL) assessment tool] and the major secondary outcome (total body fat mass).  The 
secondary outcomes are exploratory and will not be used to power the study sample size. 
 
A. 
The Primary Objectives are to demonstrate that Veterans with chronic SCI of ≥six months 
duration who are medically stable and are wheelchair users for indoor and outdoor mobility as 
their standard of care (SOC) plus use of an exoskeletal-assisted walking device in their home and 
community environments will have clinically meaningful net improvements in the MCS/VR-36 
and in patient-reported outcomes for the SCI-QOL bladder, bowel, and pain item banks compared 
with those who use only SOC for home and community mobility.  The primary outcomes to be 
assessed will be the MCS value and the sum T-score of the SCI-QOL bladder management 
difficulties, bowel management difficulties and pain interference item banks.   
 
B. 
The Major Secondary Objective is to demonstrate that participants who use the 
exoskeleton in addition to SOC will have at least a 1.0 kg loss in total body fat mass by the end of 
the four-month Intervention phase. 
 
C. 
The Secondary Objectives are to demonstrate that participants who use the exoskeleton 
in addition to SOC will have greater net improvements than the participants who receive only SOC 
on the following outcomes: 
 
1. Global Impression of Change Scale (Participant- and Companion-rated). 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
18 
2. Disturbed sleep as measured by the T-score of the Patient Reported Outcomes 
Measurement Information System (PROMIS) Sleep Disturbance (short form). 
3. Self-reported methods and measures of bowel function for: 
a. frequency of bowel evacuation episodes, time per episode, number of self-reported 
“natural” bowel movements, the amount of bowel evacuation medications used 
(e.g., laxatives and/or stool softeners), frequency of enemas used, frequency of 
digital stimulation needed per week, stool consistency (by the Bristol Stool Scale), 
and  frequency of bowel incontinence/accident episodes; 
4. Sum T-score of the SCI Functional Index (SCI-FI) physical function short forms (basic 
mobility, self-care, fine motor, ambulation, wheelchair mobility, and assistive technology); 
5. Sum T-scores of the SCI-QOL Emotional domain (Separate T-scores for:  1) anxiety, 
depression, grief-loss, trauma, and stigma item banks, and 2) positive affect and well-being, 
self-evaluation, and resilience item banks) (short form); 
6. Sum T-score of the SCI-QOL Social Participation domain (ability to participate in social 
roles and activities, satisfaction with social roles and activities, and independence) (short 
form);  
7. Lipid Profile for high density lipoprotein cholesterol (HDL-c), low density lipoprotein 
cholesterol (LDL-c), triglycerides (TG), and total cholesterol (TC); 
8. Fasting plasma glucose (FPG) and insulin (FPI) levels for calculation of Homeostasis 
Model of Assessment-Insulin Resistance (HOMA-IR). 
 
D. 
Hypotheses 
 
Hypotheses are described for the Primary and Major Secondary Outcomes.  In Veterans with 
chronic SCI: 
 
1. Primary Hypotheses (a and b):   
a. 33% of the Intervention group compared with 10% of the Control group will 
demonstrate a clinically relevant change of ≥4.0 point improvement for the 
MCS/VR-36 for greater vitality and social functioning, and improved role-
emotional and mental health from baseline to the end of the Intervention phase. 
b. 42% of the Intervention group compared with 10% of the Control group will 
demonstrate a clinically significant change of 10% improvement from baseline to 
the end of the intervention phase on the sum T-score of the patient-reported 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
19 
outcomes from the combined SCI-QOL item banks for bladder management 
difficulties, bowel management difficulties and pain interference. 
 
2. Major Secondary Hypothesis:  It is anticipated that during the Training phase, at least 50% 
of the Intervention group will experience a total body fat mass loss of ≥1.0 kg from baseline 
to the end of the 25±5 sessions.  During the home/community use portion of the 
Intervention phase it is hypothesized that 35% of the total Intervention group will 
demonstrate at least maintenance of the ≥1.0 kg loss after four months of in-home use of 
the exoskeleton.  As such, 35% of the Intervention group will demonstrate a loss of ≥1.0kg 
of total body fat mass by the end of the Intervention phase relative to baseline values 
compared with 10% of the Control group. 
 
III. EXPERIMENTAL DESIGN 
 
Research Design:  A two-group (Intervention and Control), randomized, clinical trial will be 
performed with a one-year feasibility component.  The Intervention group will consist of SOC plus 
exoskeletal-assisted walking (EAW).  The Control group will consist of SOC only.  The study will 
have two phases: Screening and Intervention.  Fifteen VA SCI Services will participate as study 
sites.   The study will require seven years in total to complete.  A feasibility phase will be employed 
using a staggered start with six sites starting initially, four sites starting one year later, and five 
sites starting two years later.  These initial six sites will be used to assess the start-up activities 
(hiring, training, equipment procurement, CIRB paperwork, etc.), the rate of recruitment and any 
other issues that may be of value for the successful completion of the study.  Lessons learned will 
be implemented for the remaining sites.    
 
A. 
Screening Phase  
 
The Screening phase consists of pre-screening, consenting process, screening evaluations, baseline 
evaluations of the study outcomes, basic EAW training with a skills test, and randomization.  
During pre-screening, the potential participants will be first contacted by the Site Investigator, 
who is a SCI staff physician, through chart reviews, other physician referrals, pre-existing 
knowledge about their patients, access to contact information in a VA Informatics and Computing 
Infrastructure (VINCI) database, physician referrals at other VA hospitals, and/or through study 
flyers and study invitation letters.  Study flyers may also be given to potential participants in the 
SCI Clinic, posted in local area hospitals, or distributed at local and national SCI events. Study 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
20 
flyers may also be posted generally in areas where potential participants may see the information 
(i.e. local chapters of Veterans Organizations, SCI sporting events) and included in newsletters or 
journals with a focus on the SCI population. Each site is expected to prescreen at least 100 potential 
participants.  Pre-screened eligible and interested potential participants will be referred by the Site 
ReWalk Trainers and/or Site Coordinators for initiation of the consenting process and scheduling 
of the screening evaluations.  The screening evaluations will be performed only in consented 
participants by the Site Investigator, other Site Physician(s) and/or the site study team. These 
screening evaluations are for the inclusion/exclusion criteria for medical, physical and health-
related eligibility.  The screening evaluations include a history and physical examination (H&PE), 
a specific history of fragility fractures, unhealed traumatic fractures, swelling, bruising, redness, 
or other abnormalities of the lower extremities, International Standards for Neurological 
Classification of SCI (ISNCSCI) examination for neurological level and function [formerly called 
American Spinal Injury Association (ASIA) or American Spinal Injury International Standards 
Scale (AIS) examination], a BMD scan and a lateral foot x-ray of each calcaneus with potential 
for a clinical referral for a CT scan for further evaluation, if recommended.  Participants who pass 
the inclusion/exclusion criteria will then undergo a home evaluation and companion identification 
for continued eligibility.  The potential participant may have up to three companions who share in 
the EAW training with the participant.  All companions will be provided a separate consenting 
process and will either sign an informed consent form or assent over the phone to be enrolled.  
Baseline evaluations will be performed only in those participants who have passed all screening 
criteria to this point.  Once the baseline evaluations are completed, all participants will be fitted 
for the ReWalk and begin a five-session basic EAW training course.  In order to avoid a biased 
group selection, all participants will be trained for five sessions of EAW basic skills. The EAW 
basic skills training will be conducted at the VA hospitals at fifteen sites, in the Community Based 
Outpatient Centers (CBOCs) under the same Federal Wide Assurance (FWA) as the sites, or in the 
participant’s home/community. Only those who pass the EAW basic skills test (and all other 
screening criteria) will be eligible to be randomized to either the Intervention or Control group.  
Each site is expected to consent and screen at least 60 potential participants and randomize 4-24 
participants for an overall 160 randomized across 15 sites. 
 
Once randomized, the Intervention group will participate in 25±5 sessions of EAW Training and 
the Control group will participate in Orientation. The EAW training will be conducted at the VA 
hospitals at fifteen sites, in the CBOCs under the same FWA as the sites, or in the participant’s 
home/community. During Orientation (while the Intervention group is being trained on the 
ReWalk), the Control group will attend weekly meetings at the study site or be contacted by phone 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
21 
interview or secure messaging using My HealtheVet for review of their regular activities, which 
will serve as an “attention” balance to the Intervention group.  Participants in the Intervention 
group will be required to pass the EAW Advanced Skills Test at the end of the 25±5 sessions of 
EAW Training prior to taking the device home.  The companion is also required to pass part of 
this Advanced Skills Test.  Participants (and their companions) who fail the EAW Advanced Skills 
Test will not be able to take the ReWalk home and will be counted as study “failures”.  (Note: the 
PI and her team have observed that persons with SCI who are able to learn the basic standing and 
weight shift balance skills within five sessions, generally, also learn the advanced walking skills 
for home use within 20 to 30 sessions.  As such, in order to screen out those participants who are 
likely to fail the EAW Advanced Skills Test for home use, the five-session testing criteria will be 
used for all participants before randomization.)   
 
A study form listing the number of participants for Pre-screening, Screening evaluations, five-
session EAW training, and continuation (or not) to randomization will be recorded. The reasons 
for pre-screening and screening failures will be recorded. 
 
B. 
Intervention Phase  
 
After passing the EAW Advanced Skills Test at the end of the 25±5 sessions of EAW Training, 
the Intervention group will take the ReWalk home for four months. The Intervention group will 
continue to participate in wheelchair or other non-exoskeletal, non-wheelchair SOC activities as 
usual, but will also use the ReWalk in their home/community environment as per the specific 
recommendation by the study team during the home set-up.  The Control group will participate in 
four months of SOC only, defined as usual wheelchair use (or other non-exoskeletal, non-
wheelchair activities).  Both groups will be required to complete a weekly Usual Activity Log.  
Participants in the Intervention group will additionally have the number of steps taken recorded 
from the step counter that is built-in to the ReWalk device, and the location and time of the EAW 
activities in an EAW weekly log.  Site team members will contact participants in both groups on 
a weekly basis, either over the phone or through secure messaging using My HealtheVet to review 
the Usual and EAW Activity Logs and to identify problems or issues that may present. Participants 
in both groups will be encouraged to contact site team members with any questions pertaining to 
the study at any time. The Intervention and Control groups will receive the same pre- and post- 
outcome assessments and similar amounts of contact and attention from the study team during the 
Intervention phase.  Participants in both groups will return to the site for an Intervention phase 
assessment of the outcome tests at month 2 and again at the end of month 4 (primary outcome 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
22 
assessment time point).  Across all study sites, 160 participants are to be randomized.  Each site is 
expected to randomize between 4 and 24 participants.  Adverse events will be recorded in both 
groups.  
 
C. 
Post Study Participation for the Control Group  
 
In order to avoid potential participants not being interested in the study because of the 50% chance 
of not receiving the intervention, the Control group will be offered a two-month EAW training 
program after completion of the study protocol as an outpatient. Outcome data will not be collected 
during this outpatient, EAW post-study training for the Control group. The study site team will 
provide the EAW training to the former Control group participants during this phase and adverse 
events will be recorded during this post study component for the Control group.  After participation 
in the study, participants may be considered for home use prescription of the exoskeleton by the 
clinical SCI Service. 
 
D. 
Study Duration and Timeline  
 
CS #2003 is projected to be a seven-year study.  A staggered start approach will be employed with 
six sites starting during the first year of the study, four sites starting one year later, and five sites 
starting two years later.   The six sites will have a one-year start-up, four years of enrollment and 
an additional one year of data collection and study closeout. The four sites will follow the same 
plan, but starting one year later with three years of enrollment. The remaining five sites will start 
two years later and have two years of enrollment and one year of data collection and closeout. All 
15 sites will complete data collection and study closeout in the sixth year of the study.  An 
additional year for the Coordinating Center and Chair’s Office is planned for data analyses and 
write-up (seven years in total).  During the 6-week pre-start-up period, the Chair’s Office will 
begin staff hiring procedures by providing position description (PD) postings for the sites, and 
submit the protocol to the Central Institutional Review Board (CIRB) and local Research & 
Development (R&D) for review. The CSPCRPCC will submit the investigational device 
exemption (IDE) application to the FDA.   A year will be needed for study start-up activities for 
the sites CIRB and local R&D submissions, ordering of the equipment (ReWalks and iDXA 
scanners), site staff hiring, and the ReWalk and study protocol training.  During the enrollment 
years 1-4, participants will be prescreened, screened, and randomized.  Year five will be used for 
continuation of data collection; no new enrollment will occur in year six.  Data edits will be on-
going throughout the five years of data collection. Year six will be needed for general wrap-up and 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
23 
closeout at the study sites.  During Year 7, data analyses and manuscript writing will be performed.  
A detailed description may be found in the “Study Timeline” (Table 5).   
 
Participants in the Intervention group will require eight to nine months to complete the study. 
Participants in the Control group will require seven to nine months for study completion. The extra 
time is for the optional Control EAW in-hospital training sessions after the study is completed. 
This amount of time breaks out as follows.  Once consented, potential participants will need one 
week for the screening evaluations, one week for the baseline outcome evaluations, and two weeks 
for the device fitting and five-session basic skills training and skills test.  The Intervention group 
will go through a three-month Training phase, which includes the additional 25±5-sessions of 
supervised EAW training with their companion.  After randomization, the Control group will 
participate in a two-month Orientation phase. The Intervention phase will require four months for 
both groups.  The post evaluations will require one week. Those in the Control group will have the 
opportunity to participate in an additional two-month optional EAW outpatient training without 
data collection.  A detailed description may be found in the “Training and Testing Schedule” 
(Table 6).   
 
 
 

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
24 
 
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1 Q2 Q3 Q4 Q1
Q2
Q3
Q4
Administration start up
x
x
Chair's Office CIRB
x
x
CSPCRPCC IDE to FDA
x
x
Chair/Sites' PDs
x
x
Chair/Sites' R&D
x
x
Chair's funding received
x
x
Chair/Sites' staff hiring
x
x
x
Sites' CIRB
x
x
Equipment contracts
x
x
Equipment ships to sites
x
x
x
iDXA Site training
x
x
x
x
x
x
x
ReWalk onsite training
1
x
x
x
x
x
x
x
ReWalk training follow-
up2
x
x
x
x
x
x
x
x
x
Study meetings
x
x
x
x
x
x
Pre Screening
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Screening
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Randomization
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Data collection/edits
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Study close out
x
x
x
x
x
x
Data analyses/writing
x
x
x
x
x
x
Table 5.
Study Timeline
Funding notification (8/12/2015)
6-week Pre Start-up (no study costs)
Y1
Y2
Table 5 Legend. A total of 160 (80/group) participants will be enrolled and randomized across all 15 study sites.
CIRB=Central Institutional Review Board (VA); CSPCRPCC =Cooperative
Studies Program Clinical Research PharmacyCoordinating Center; IDE=Investigational Device Exemption; FDA=Food and Drug Administration; PD=Position descriptions for hiring staff;
R&D=Research and Development Committee (at Sites and Chair's Office);
iDXA=DXA scanner for bone mineral density and total body composition.
1ReWalk Site training is performed by
ReWalk Robotics, Inc. as onsite training.  2ReWalk Site trainig follow-up is performed by the CS #2003 National Coordinator as a follow-up training at the sites.
Start-up
Y6
Data Analyses and 
Manuscript 
Writing
FY22
Study analyses 
and write-up
Enrollment & Participant Data Collection
(160 Participants to be enrolled by end of Q4 Y4)
Enrollment Year 4 
(6 Sites)
Enrollment Year 3 
(4 Sites)
Enrollment Year 2 
(5 Sites)
Participant 
Carry-over and 
Study Close-out
(All 15 sites)
FY20
FY21
Y4
Y5
Study Closeout
Start-up Year 
(6 Sites)
Enrollment Year 
1 (6 Sites)
Start-up year
(4 Sites)
Y3
FY16
Enrollment Year 2 
(6 Sites)
Enrollment Year 1 
(4 Sites)
FY18
FY19
Enrollment Year 3
(6 Sites)
Enrollment Year 2
(4 Sites)
Start-up &
Enrollment Year 1
(5 Sites)
FY17

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
25 
 
Mo 5
Mo 6
Mo 7
Mo 8
Mo 9
17 to 20
21 to 24
25 to 28
29 to 32
33
SCREENING Evaluations
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x1
Exit survey
5 to 16
33 to 40
Consent Obtained
Screening Evaluations
Pre Evaluations (Baseline for both groups)
5 Session EAW Training
Randomization
Orientation/Training
Orientation/Training 
Phase Evaluations (Both 
Groups)
In-Home/Community
Post Intervention 
Phase Evaluations 
(Both Groups)
1 to 4
Intervention Group
(EAW Training)
Intervention Group
(Standard of Care plus Home EAW)
Home Evaluation
Bi-lateral foot x-ray
CT scan, if indicated
Phases:
Months:
Weeks:
Pre Screening
Table 6.  Testing and Training Schedules
Orientation/Training
Phase
Intervention
Phase
Control 
EAW
Mo 2 to 4
Mo 9 & 10
Screening
Phase
Month 1
(no Data)
Control Group
(Standard of Care Review)
Control Group
(Standard of Care)
Control Group;  No study data collection
(EAW In-hospital training, 3x/week for 2 months)
History & Physical Exam
ISNCSCI Exam 
BMD Scan 
Companion Evaluation
OUTCOME Assessments
iDXA Body Composition
VR-36
SCI-QOL
PROMIS Sleep Disturbance
Global Impression of Change Scale
SCI-FI
Bowel Function
Blood draw (Lipids/Glu/Ins)
QUALITY CONTROL Data
EAW Basic Skills Test 
Usual Activity Log 
1 x Weekly
1 x Weekly
Step Counter (Intervention group only)
1 x Weekly
EAW Mobility Tests (Intervention group only)
EAW Activity Log (Intervention group only)
Each Session
Each Session
1 x Weekly
EAW Advanced Skills Test
Home set-up
PRN Home Interim visits
x1

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
26 
 
 
 
Home and 
Companion 
Evaluations
OUTCOME 
Assessments
SOC
Standard of Care 
Review
EAW Training
EAW Advanced
Skills Test
Home set-up
Exit survey
Abbreviations
Only those participants and their companions who pass the EAW Advanced Skills Test will continue on to
home/community use. For these participants, a second home visit for set-up will be performed by a study team
member from the Site.
EAW = Exoskeletal-assisted walking; Intervention = Standard of care wheelchair use (i.e. usual lifestyle activities)
plus Exoskeletal-assisted walking; Control = Standard of care, wheelchair use (i.e. usual lifestyle activities);  ISNCSCI 
Exam = International Standards for Neurological Classifications for SCI (formerly, ASIA and AIS); BMD Scan =
bone mineral density scan; iDXA = Dual energy x-ray absorptiometry scan for fat and lean tissue masses; CT =
Computed tomography; SCI-QOL = Spinal Cord Injury Quality of Life patient-reported outcomes tool; PROMIS
Sleep Disturbance = Patient Reported Outcomes Measurement Information System component for Sleep
Disturbance; VR-36 = Veterans Rand-36; and SCI-FI = SCI Functional Index of patient-reported outcomes for
physical function.  
Outcome assessments will only be performed on those potential participants who have passed all screening criteria.
Screening failures and reasons will be recorded on study forms.
Intervention group attends the exoskeletal-assisted walking training for 25±5 sessions.
Home and companion evaluations will be performed on all participants who have passed the medical screening criteria
and will be performed prior to randomization to avoid unbalanced or biased groups.
Standard of care is defined as wheelchair use and usual lifestyle activities.
EAW Advanced Skills Test is a combined participant/user and companion test. NOTE: Participants and companions
must pass the EAW Advanced Skills Test to continue to home use; those who do not are treated as "study failures".
Participants complete an interview with a study team member to review usual lifestyle activities and Usual activity
weekly log.
Table 6.  Legend
Exit surveys may be completed with the Post Intervention Phase Evaluations for both groups or after the optional 
EAW in-hospital training for the control group

CSP #2003 
Exoskeletal Assisted Walking with Persons with SCI:  Impact on Quality of Life (PEPSCI) 
Version 7.2 Protocol July 2021 
27 
IV.  PARTICIPANT RECRUITMENT  
 
A. 
Recruitment and Screening  
 
The Site Investigator (a SCI staff physician) will be responsible for initially approaching each 
potential participant to be recruited and screened for eligibility. S/he will pre-screen from the 
medical records, referrals from other SCI physicians, known SCI patients for potential participants, 
access to contact information in a VINCI database (VA hubs and spokes and VAs geographically 
near participating local sites), and physician referrals at other VA hospitals. The Site Investigator 
may send study flyers and study invitation letters to potential participants. Additionally, the study 
flyers may be given to potential participants in the SCI Clinic, posted in local area hospitals and 
on local site FaceBook pages, or distributed at local and national SCI events. Study flyers may 
also be posted generally in areas where potential participants may see the information (i.e. local 
chapters of Veterans Organizations, SCI sporting events) and included in newsletters or journals 
with a focus on the SCI population. After the initial contact, by the Site Investigator, the Site 
Coordinator and/or Site ReWalk Trainers will participate and assist in the recruitment and 
consenting process.  If the individual provides informed consent to participate, s/he will be fully 
evaluated by the Site Investigator and other appropriate members of the site’s study team.    
Screening evaluations will be performed in all participants.  In order to assure that by completion 
of EAW training each participant is competent to use the exoskeleton in the home/community 
environment, a five-session basic EAW training with a Basic Skills Test will be conducted on all 
participants to determine the eligibility of the participant to be randomized.  Please note that the 
inclusion/exclusion criteria are also designed to exclude participants who have weak or absent arm, 
hand, and/or trunk stability and control, and thus wean out those who are not likely to achieve the 
necessary skills for home/community use. A pre-approved home evaluation and companion 
interview will be established and evaluated early in the screening process for all participants. Those 
who have provided written informed consent and have passed all Screening criteria including the 
EAW Basic Skills Test will be eligible to be randomized. One hundred-sixty participants (N=160) 
will be randomized and assigned to either the SOC plus EAW Intervention group (n=80) or the 
SOC Control group (n=80) across all 15 study sites.  Each site is expected to randomize between 
4 and 24 participants. Once a participant has been randomized, s/he may not be randomized again. 
 
B. 
Randomization System   
 
An Interactive Touch Tone Randomization System (ITTRS) will be used for randomization within 

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each site.  This system will be accessed through the Cooperative Studies Program Coordinating 
Center at the Perry Point VA Medical Center, Perry Point, MD. 
 
C. 
Population to be Studied   
 
One hundred-sixty male or female Veteran or active duty military personnel with chronic SCI, of 
≥six months duration, who are ≥18 years of age, and who are medically stable and wheelchair 
users for indoor and outdoor mobility, will be eligible for screening to be enrolled in the study.  
All potential participants will be Veterans or active duty military personnel with SCI who are 
affiliated with or transferred to one of the fifteen VA SCI Services that will be participating in this 
study. Study participants will generally be outpatients with the exception of those inpatients who 
meet the eligibility criteria and are approved by the Site Investigator (e.g., some inpatients may 
have been admitted for a wheelchair fitting or another non-medical reason).  Non-veterans, other 
than active duty military personnel getting treatment at the VA, will not be eligible to participate. 
Eighty participants will receive SOC plus EAW (Intervention group) and 80 will receive SOC 
(Control group).  It is expected that no more than 15% of the participants will withdraw early 
(dropout rate) and this attrition rate is expected to be evenly distributed between the two groups 
(12 withdrawals/group).  One hundred-thirty-six participants are expected to complete the study 
(68/group).   
 
V.  INTERVENTION AND METHODS OF TREATMENT 
 
Standard of care (SOC) is defined as wheelchair use for indoor and outdoor mobility and any other 
non-wheelchair activities (such as, standing frame use, swimming, arm bikes for cycling, etc.) that 
the participant may engage in during their usual lifestyle activities.  The Intervention group 
receives SOC activities plus EAW training (25±5 sessions) to develop a skill set to use the 
exoskeleton, accompanied by their companion, during a four-month trial with the exoskeleton in 
the participant’s home/community environment.  The Control group will receive SOC alone. 
Accurate recording of SOC and EAW activities is an important component of this study.  Two 
activity logs will be obtained: 1) Usual Activity Log and 2) EAW Activity Log.  The Usual Activity 
Log is designed to capture usual lifestyle physical and recreational activities (non-EAW) that the 
Veteran or member of the military with SCI participates in weekly.  Both groups will be instructed 
to record any type and amount of time of physical or recreational wheelchair or non-wheelchair 
activity (i.e., standing frame use, swimming, etc.) that is being performed during the course of the 
two-three month Orientation/Training and four-month Intervention phase of the study.  EAW and 

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Usual Activity Logs with check-off categorical grouping answers for the type and duration of the 
activity will be provided to reduce participant burden and to provide standardized answers for 
analysis. The EAW Activity Log will be used by the Intervention group only to record weekly use 
for location and time spent in the ReWalk device during the training (hospital halls, SCI service, 
grounds, CBOCs, home/community etc.) and home/community (e.g., sidewalks, local mall, in 
home, parks, etc.)  phases of the study. The number of steps taken in the ReWalk during training 
and home use will be recorded on a weekly basis from the built-in step counter. Detailed 
descriptions of the Intervention and Control schedules of testing are provided (Table 6). 
Information from the activity logs may be given to the Coordinator over the phone, in-person, or 
through secure messaging, using My HealtheVet. 
 
VI.  METHODS OF FOLLOW UP   
 
The Orientation/Training phase is performed in the hospital or in the participant’s 
home/community. Participants in the Intervention group will be required to meet with the study 
team for 3 to 5 sessions per week for 20 to 30 sessions.  Participants who miss sessions will be 
contacted by the Site’s Study Coordinator or ReWalk Trainers for rescheduling.  During the 
Intervention phase, the participants will be using the exoskeleton in their home/community.  
During this phase, follow-up contact by the study team members with the participants on a weekly 
basis will be critical for compliance and troubleshooting of any problems.  This contact will be 
necessary to assist the participants with compliance of completion of the Usual Activity Log and 
the EAW Activity Log and identification of adverse events in the Intervention group. Contact will 
be made in person, over the phone, or through secure messaging, using My HealtheVet. 
 
During the Orientation/Training phase, the Control group will make weekly outpatient visits and/or 
receive contact from members of the site’s study team on a weekly basis.  During the Intervention 
phase, follow-up contact by the study team members with the participants in the Control group 
will be at a minimum of one time weekly.  This contact will be critical for compliance of 
completion of the Usual Activity Log and identification of adverse events in the Control group.  
Site team members will be instructed in the weekly and monthly participant contact procedures for 
both groups to collect data, encourage compliance, and identify issues. Contact will be made in 
person, over the phone, or through secure messaging, using My HealtheVet. 
 
Primary and Secondary outcome assessments will be completed at the SCI Centers at the end of 
month 2 and month 4 of the Intervention phase in both groups. 

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VII.  METHODS OF ASSURING UNIFORMITY OF INTERVENTION  
 
Uniformity of the intervention within and across the sites is critical.  Standardization of staff 
training procedures has been identified for two main areas: 1) EAW components for the home 
evaluation, companion interview, ReWalk fitting, EAW Basic Skills Test, EAW walking skill 
progression, EAW walking test evaluations, EAW Advanced Skills Test, and EAW Activity Log; 
and 2) administration of the outcome assessments for the VR-36, SCI-QOL, Global Impression of 
Change Scale, PROMIS Sleep Disturbance, Bowel function, and SCI-FI.  Onsite training of 
procedures will be conducted at each site in order to standardize EAW training techniques across 
the sites.  The ReWalk Trainers will be required to demonstrate knowledge and capability to 
perform the required procedures related to the EAW training and assessments. The Study 
Coordinator at each site will be responsible for the QOL outcome assessments.  This strengthens 
the study because the staff persons providing the intervention are not the ones performing the 
outcome assessments. 
 
VIII.  DETERMINING ELIGIBILITY  
 
The determination of eligibility for this study has several levels.  First, the Site Physician will pre-
screen potential participants from the medical records and knowledge of the person to include 
those with traumatic or non-traumatic, complete or incomplete SCI duration ≥6 months who are 
≥18 years old and are wheelchair-dependent for indoor and outdoor mobility.   
 
Second are the Screening evaluations; those potential participants who pass pre-screening and are 
interested to be consented will begin the consenting process with the Site Physician and site study 
team.  Those who complete the consenting process will undergo a series of screening evaluations 
that include:  a BMD scan, fracture history, lateral foot x-rays of each calcaneus, history and 
physical examination and ISNCSCI assessment to determine medical wellness, anthropometric 
compatibility with the device, level and completeness of injury, hand function, ability to have a 
companion, and a home evaluation for suitability.  Female participants will also receive pregnancy 
testing.  The specific inclusion and exclusion criteria are itemized below. 
 
A. 
Inclusion/Eligibility Criteria   
Veteran/Active Duty Participants: 
1. Veterans or active duty military personnel who are at least 18 years of age; 
2. Traumatic or non-traumatic SCI ≥6 months duration of SCI; 

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3. Wheelchair-user for indoor and outdoor mobility; 
4. Anthropometric compatibility with the device:  
a. Weight <220 lb. (100 kg), 
b. Thigh length between 14 and 19 in (36 and 48 cm), 
c. Shank length between 17 and 22 in (43 and 55 cm);  
5. Able to hold the crutches in hands without modifications;  
6. Able to have a companion who can attend approximately one-third of the training sessions 
who will assist them at home and in the community; and  
7. Able to provide informed consent.   
 
Companion Participants: 
1.  Male/female greater than or equal to 18 years of age; 
2.  Demonstrates understanding of the time commitment to be a companion; 
3.  The companion and the user are willing to receive training on how to assist the user with 
learning to use the device; 
4.  The companion agrees to ensure that the exoskeleton is used with the crutches at all times; 
5.  Site Physician and study team members must deem the companion physically able to assist 
the participant with tasks outlined in the exoskeleton skills inventory (i.e. the companion 
is able-bodied and is physically able to bend, stoop, squat, kneel, etc.) 
 
B. 
Exclusion criteria  
Veteran/Active Duty Participants: 
1. Diagnosis of neurological injury other than SCI;  
2. Progressive condition that would be expected to result in changing neurological status; 
3. Severe concurrent medical disease, illness or condition judged to be contraindicated by the 
Site Physician; 
4. Unhealed or unstable traumatic or high impact lower extremity fracture (definition below) 
of any duration that is in the clinical judgement of the study physician to be exclusionary 
for standing and walking; 
5. Knee BMD < 0.60 gm/cm2; 
6. Total hip BMD T-scores < -3.5;  
7. Fragility, minimal trauma or low impact fracture of the lower extremity since spinal cord 
injury (definition below); 
8. Untreatable severe spasticity judged to be contraindicated by the Site Physician;  
9. Flexion contracture > 15º at the hip and/or > 10º at the knee;  

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10. Limitations in ankle range of motion that cannot be adapted with an orthotic device (plantar 
flexion > 00); 
11. Untreated or uncontrolled hypertension (systolic blood pressure >140 mmHg; diastolic 
blood pressure >90 mmHg);  
12. Unresolved orthostatic hypotension (systolic blood pressure <90 mmHg; diastolic blood 
pressure <60 mmHg) as judged to be contraindicated by the Site Physician;  
13. Current pressure ulcer of the arms, trunk, pelvic area, or lower extremities; 
14. Psychopathology documentation in the medical record or history that may conflict with 
study objectives; and/or  
15. Pregnancy or women who plan to become pregnant during the study period. 
 
Definition of a traumatic or high impact fracture:  Fracture from a forceful event, such as seen in 
any or all of the following, but not limited to these circumstances: 
 Fracture from a motor vehicle accident 
 Fracture from a fall from a height greater than adult height standing (i.e. down steps or 
stairs) 
 Fracture from a heavy object falling on any lower extremity body part 
 
Definition of a fragility, minimal trauma, or low impact fracture in the nonSCI population by the 
National Osteoporosis Foundation (NOF) is:   Any fall from a standing height or less, that results 
in a fracture.”  Normal bones should be able to sustain a fall from this height, without a fracture, 
unless there is some underlying cause to suspect a bone disorder, such as osteoporosis or 
osteopenia that weakens bone structure.  In SCI, a fragility fracture may include any, or all, but 
are not limited to the following conditions and/or circumstances: 
 Fracture that occurred without the person having knowledge of the occurrence or cause 
 Fracture that resulted from a fall from a wheelchair, bed, toilet, etc. 
 Fracture that occurred while performing stretching 
 Fracture that resulted from, or during, a transfer 
 Fracture from bumping or banging the lower extremity 
 Fracture from dropping the foot to the ground or wheelchair footplate 
 Fracture from a light object falling on any lower extremity body part 
 Fracture from carrying something or someone in their lap 
 
And thirdly, potential participants who pass the Screening criteria (i.e., the inclusion and exclusion 
criteria) will be eligible for the five-session EAW basic training.  The final part in the eligibility 

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process is the EAW Basic Skills Test after the five-session initial training; those potential 
participants who pass the EAW Basic Skills Test are then eligible to be randomized. 
 
C. 
Exoskeleton Component (“Training the Trainers”)  
 
Basic and Advanced ReWalk training courses will be provided by ReWalk Robotics, Inc. at each 
of the sites for the designated ReWalk Trainers.  Trainers will be taught how the device functions 
to accomplish walking.  Initially, the Trainers will practice to use the exoskeleton with another 
able-bodied member of the research team. The Trainers will practice fitting the device and teaching 
the able-bodied person how the device functions and how to use the computer settings.  Once the 
Trainers are competent with the device in an able-bodied person, they will be able to fit the device 
and train the enrolled Veterans with SCI in the exoskeleton.   Trainers will demonstrate an 
understanding of the system components and be able to teach the participants and their walking 
companions the system components. Trainers will demonstrate understanding of how the 
communicator functions and what the icons represent. Trainers will know where the different wire 
connections should be placed and understand the different error codes if a connection were to 
become loose, or if the battery power is low. They will be required to identify any defect or damage 
to any system components to ensure continued safe use. They will demonstrate knowledge of the 
strapping system and locations of required strapping. They will need to have working knowledge 
of all the screw locations to be able to make adjustments in the limb lengths. Trainers will need to 
have a working knowledge of the exoskeleton software and what each component does and how 
changing the values will change the walking parameters. The Trainers will need to be able to 
follow the standard operating procedures (SOP) manual in the event that there is a defective 
system.  
 
D. 
ReWalk Fitting  
 
The goals of the fitting are to properly measure the hip and lower limb segments of the participant 
and to adjust the exoskeleton to those measurements. The proper fit to the exoskeleton consists of: 
pelvic width, determined according to the width of the user’s waist; thigh length, by measuring 
from the most prominent point of the greater trochanter to the joint line of the knee; and shank 
length, determined by measuring the knee joint line center to the bottom of the foot.  Each Trainer 
will be required to observe areas of contact points with the device as these may be prone to skin 
breakdown. Additional padding, as applicable will be added in appropriate locations in order to 
avoid any skin breakdown. If skin breakdown occurs, Trainers and/or the Site Physician will need 

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to determine if training should be discontinued, or if adjustments to the padding can be put in place 
to avoid farther breakdown and allow the wound to heal with continued training.  Skin breakdowns 
are to be reported as adverse events (AEs), unless otherwise indicated as an SAE according to the 
SAE criteria. 
 
E. 
EAW Basic Skills Test  
 
Initially, the participants will be required to learn to transfer in and out of the device, and how to 
don and doff the device. They will be provided an explanation of how the system works and what 
to expect when using the exoskeleton for ambulation.  Videos may be used to assist with the verbal 
explanations.  Each participant will be required to demonstrate the ability to perform a set of basic 
skills at the level of 4 (Minimal Assist) according to the following Functional Independence 
Measurement (FIM) scale rating: 
FIM Scale for level of assistance (LOA) during EAW 
7 Complete Independence (CI) (timely, safely, no assistive device used) (Note, while CI is a 
part of the FIM scale, it is not applicable for this study as all participants will require the use 
of the exoskeleton, thus negating the ability of complete independence.); 
6 Modified Independence (MI) (extra time, patient requires an assistive device, no 
assistance); 
5 Supervision (S) (cuing, coaxing, prompting); 
4 Minimal Assist (Min) (performs 75% or more of task); 
3 Moderate Assist (Mod) (performs 50%-74% of task); 
2 Maximal Assist (Max) (performs 25% to 49% of task); 
1 Total Assist (TA) (performs less than 25% of task); or 
0 Activity does not occur. 
 
The EAW Basic Skills (with the Trainer using the ReWalk mode selector wrist band), assessed 
after five sessions, are as follows: 
1. Standing up; 
2. Sitting down; 
3. Two-handed balance for 30 seconds; 
4. One-handed balance with the left arm, maintaining balance for 30 seconds; 
5. One-handed balance with the right arm, maintaining balance for 30 seconds; 

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6. Perform a weight shift where crutch support is needed behind the participant, followed by 
a weight shift where crutch support is needed to either side, followed by a weight shift 
where crutch support is needed in front of the participant; 
7. Shift their center of mass so that their weight is on the right leg; 
8. Shift their center of mass so that their weight is on the left leg;  
9. Able to adjust their weight so that it is evenly distributed between both feet; and 
10. Able to take two consecutive steps on each leg. 
These skills are needed for progression to walking and are expected to be achieved by session five 
or the participant will not be permitted to continue with further training.  In our experience, most 
participants learn these skills in one or two sessions, but those who took longer than five sessions 
were likely not to achieve the needed skill set for the recommendation for home/community use 
of the exoskeleton by 20 to 30 sessions.  Once the participant is able to perform the one-handed 
static balance for a minimum of 30 seconds, the standing up and sitting down tasks with a FIM 
score of 5 (supervision), they will be taught to use the mode selector wrist band and asked to wear 
it throughout the remaining training sessions.  Participants who are screening failures due to an 
inability to pass the five-session Basic Skills Test may be re-screened at a future time, provided 
no new potentially eligible candidates are available.  However, once a participant is randomized, 
they may not be re-randomized at a later date. 
 
  
F. 
EAW Walking Skill Progression  
 
Each training session will have predetermined goals that will be communicated to the participant. 
Initial goals will be to coordinate crutch timing with the end of swing phase, followed by practicing 
appropriate weight shifting for walking. Once these basic concepts are learned and the participant 
is stable when balancing with one crutch, then the use of the mode selector will be incorporated. 
As a participant progresses, system parameters should be adjusted according to the SOP manual 
for walking progression in order to obtain faster walking speeds.  
 
The initial computer settings will be the same for all participants as follows: 
1. Normal walking mode;  
2. Hip flexion of 18 degrees; 
3. Knee flexion of 39 degrees; 
4. Step time of 1200 ms; 
5. Delay between steps of 300 ms; 
6. Tilt angle of 9 degrees; 

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7. Walking resistance of 7; and 
8. Standing resistance of 10. 
Settings are expected to change as the participant becomes more comfortable with using the 
exoskeleton.  Hip flexion should be changed by 1 or 2 degrees in order to increase the step length 
as a participant can perform longer weight shifts. Knee flexion should only be adjusted if the foot 
catches during terminal stance and the initiation of the swing phase of the gait. The step time 
should be decreased by 100-200 ms increments as the participant becomes more comfortable with 
the frequency of weight shifting. Delay between steps should be lowered by 50-100 ms as 
participants become better with weight shifting from one foot to the other during EAW. The tilt 
angle should remain within a range of 7-10 degrees but could be decreased or increased slightly 
depending on the participant’s stability during standing. Walking resistance should be increased 
by 1 if the system stops too easily, or the participant has more tone in the legs. Walking resistance 
should be decreased when walking on smoother surfaces such as tile, or if the participant has 
difficulty stopping the unit on command or when desired. Standing resistance should remain the 
same. 
 
G. 
EAW Companion Training   
 
The FDA has designated this class of device to be used in conjunction with a trained walking 
companion.  The study calls for the use of a “walking companion”, not a caregiver per se.  The 
companion can be anyone who has met the companion criteria (below) and has undergone formal 
training with the participant on the use of the exoskeleton.  Companions may be a family member, 
friend, neighbor, volunteer, or other such individual.  Therefore, the companions are not likely to 
be the typical caregiver.  That being appreciated, if a “caregiver” is available, eligible and 
agreeable, they may be an EAW companion.  
 
Each participant will be required to have an EAW companion that will accompany them when the 
participant is using the device. There may be multiple people trained to be the EAW companion.  
An EAW companion will always need to be in close proximity to the participant when the system 
is in use while in the home or community environments.  The companion’s job is to be there to 
assist the participant with tasks such as navigating doors, bring them a chair, picking up items 
needed from the floor, countertops, furniture, tabletops, etc., provide close guard or contact assist 
when necessary, moving the device for donning or after donning, and to assist the participant with 
device checking, battery charging and storage.  If a participant does not have a suitable companion, 
then they will not be eligible to participate in the study and are considered to be a screening failure.  

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Training of more than one companion is strongly encouraged. The potential participant may have 
up to three companions who share in the EAW training with the participant. All companions will 
be provided a separate consenting process and will either sign an informed consent form and 
HIPAA authorization or assent over the phone to be enrolled.   If a companion withdraws during 
the Intervention Phase and no other companion was trained or available, the participant must 
complete additional companion(s) training.  The new companion must pass the EAW Advanced 
Skills Test with the participant to be given clearance to return to the home/community use 
environment with the exoskeleton. 
 
The companion screening criteria are meant to be general guidelines, but it is ultimately in the 
clinical judgment of the Site Physician to permit an acceptable companion. 
 
Companion Criteria: 
1. 
Male or female, age ≥18 years; 
2. 
Demonstrates understanding of the time commitment to be a companion (to be available 
for approximately one-third of the training sessions, and walking at home or in the 
community with the participant); 
3. 
The companion and the user are willing to receive training on how to assist the user with 
donning/doffing the device, use of the controller, and performing the standing, sitting, 
walking, and stopping skills while in the device; 
4. 
The companion and the user are able to understand how to operate, charge, and maintain 
the device; 
5. 
Demonstrate proper care and storage of device; knowledge of the major components of 
device (battery, waistpack, computer, right and left leg connection checks in computer 
waistpack); 
6. 
Demonstrate understanding that the companion plus the user are examined as one team for 
the exoskeleton skills assessments; 
7. 
The companion provides close supervision to minimal physical assistance to the participant 
when s/he is in the exoskeleton and provides assistance with tasks that may be difficult for 
the participant to perform while in the exoskeleton (i.e. opening manual doors and holding 
elevator doors); 
8. 
The companion remains alert and on the lookout for potentially dangerous obstacles.  If the 
companion sees a situation which could be dangerous, s/he should feel comfortable 
expressing their concerns to the user in the exoskeleton; 

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9. 
The companion ensures that the exoskeleton is used with the crutches at all times and in 
the manner in which both were taught; 
10. In the event of equipment malfunction, the companion will be able to assist the participant 
down to a flat surface and be able to direct an additional individual in assisting them, if 
necessary, for a low impact descent to the floor;  
11. In case of a medical emergency, the companion will be able to get help for the participant 
including activating an emergency response and be able to direct an additional individual 
in assisting them, if necessary; and 
12. The Site Physician and study team members must deem the companion physically able to 
assist the participant with tasks outlined in the exoskeleton skills inventory (i.e. the 
companion is able-bodied and is physically able to bend, stoop, squat, kneel, etc.).  
 
During the weekly contact with the participant, the study staff will inquire about the frequency of 
walking and the availability of the companion.  If the companion has not been able to walk with 
the participant in a past week, the study staff will try to resolve the problems.  Additional 
companions will be suggested.  Availability of the EAW companion(s) is an important 
consideration and a close eye on this process will be necessary.  Since these exoskeletal devices 
are going to require walking companions as per the FDA, it will be important to know the 
feasibility of our Veterans and military members with SCI to have viable walking companions for 
use of an exoskeleton in the home/community environment. The number of eligible companions 
and the actual amount of walking time that the companions are available for the participants during 
the home-use phase can be determined in the Feasibility component of the study.  If the companion 
requirement proves to be an obstacle during the feasibility, it can be addressed with each case and 
solutions can be made available for all study participants. If a companion is lost or withdraws from 
the study, then the participant will be obligated to re-train another companion, or the participant 
will be terminated from the study, an outcome that will be strenuously avoided. Of note, as a 
consequence of this clinical trial, it will also be determined if identifying a companion is a major 
obstacle to the use of the exoskeleton in our Veteran or military member population with SCI 
because, as previously stated, these devices cannot be prescribed for home use without a 
companion in attendance when this device is being used. 
 
H. 
EAW Advanced Skills Test  
 
The EAW Advanced Skills are in addition to the EAW Basic Skills.  The EAW Advanced Skills 
Test will be passed by the participant and their companion(s) prior to being sent home with an 

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exoskeleton and as soon during the training course as the ReWalk Trainers and the participants 
(with their companions) feel they can achieve the skills (at a minimum of 20 sessions).  However, 
if by 30 sessions the participants are unable to achieve these skills, they will not be sent home with 
the device and will be treated as a study “failure”.   Participants (with their companions) will need 
to demonstrate the following skills according to the SOP manual: 
 
 Transfer into and out of the 
exoskeleton; 
 Don and doff the device with all the 
straps and any additional padding 
provided by the Trainer in the 
correct places; 
 Standing balance using both 
crutches for a minimum of one 
minute, showing good vertical 
position; 
 Standing balance with one arm for 
30 seconds with the ability to reach 
for the remote wrist band 
communicator; 
 Perform sit-to-stand and stand-to-sit; 
 Demonstrate full understanding of 
the sit, stand, walk, and manual 
mode functions of the remote 
communicator; 
 Perform a 10 meter walk test 
without any stops 5 times at a speed 
greater than 0.40 m/s (10m EAW in 
≤25 seconds); 
 EAW ≥110 meters in a 6-minute 
walk test; 
 EAW 10m on asphalt in ≤25 
seconds; 
 EAW timed-up-and-go (TUG) in 
≤90 seconds; 
 EAW ≥20m over surfaces such as 
tile, carpet, grass, and concrete in 
≤60 seconds; 
 EAW up and down a ramp that 
meets or exceeds Americans with 
Disabilities Act (ADA) 
specifications; 
 EAW while talking and answering 
questions; 
 EAW in a noisy environment; 
 Reach for and remove an object 
from an overhead cabinet to a 
countertop level; 
 Turn 180 degree while EAW; 
 EAW through a door threshold; 
 EAW to a wall, turn and lean (“wall 
rest”); 
 Explain purpose of the “graceful 
collapse” function in case it of 
emergency; 
 Demonstrate with companion the 
graceful collapse function; 
 Demonstrate ability to check skin 
integrity; 
 Demonstrate knowledge equipment 
components; and 
 Able to charge the system at the end 
of the day 

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I. 
Weekly EAW Activity Log 
 
ReWalk Trainers will be required to follow-up with each participant on a weekly basis. There will 
be a standard list of questions as per the SOP manual to ask in order to ensure the system is fully 
functional.  If there have been any adverse events, or if the participant has any questions, s/he will 
be informed to contact a member of the site’s study team. The participant will be required to 
complete a weekly EAW Activity Log of the location of where the device was used and for how 
long.   
 
Intervention Group:  Training for the Intervention group will consist of 25±5 sessions of EAW 
training followed by an EAW Advanced Skills Test that will determine the eligibility of the 
participant to take the device home. Training will take place at the VA hospitals, in the CBOCs 
under the same FWA as the sites, or in the participant’s home/community. Participants in the 
Intervention arm will take the device home to use.  During the training and home/community use 
components of the study, the built-in step counter on the device will record the weekly total number 
of steps taken.  The EAW Activity Log will be completed by each participant on a weekly basis to 
record the location, duration and frequency of device use. The Trainers will follow up weekly with 
the participants for completion of this task. 
 
Control Group:  In order to provide a similar level of attention to the Control group during the 
Orientation/Training phase, the Control group will receive interviews to identify types of physical 
activities in which they usually participate.  Control participants will be instructed to complete the 
Usual Activity Log on a weekly basis during the Orientation/Training course and during the four-
month Intervention phase. Weekly contact by the study team will be provided to the Control group 
during the Orientation and Intervention phases, in person, over the phone, or through secure 
messaging using My HealtheVet. 
 
IX.  OUTCOME MEASURMENTS 
 
The frequency and specific time points of each of the outcome measurements can be found in the 
“Training and Testing Schedules” (Table 6).   
 
The two primary, major secondary and secondary outcomes are measured at baseline, post 
Orientation/Training phase, post 2-month Intervention phase, and post 4-month Intervention 
phase.  The main comparison for the two primary and major secondary outcomes is the change in 

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the outcome measures from baseline to post 4-month Intervention phase. 
 
A. 
Primary Outcomes 
 
1. Mental Health Component Summary (MCS) of the Veterans Rand-36 (VR-36) for Vitality, 
Social Functioning, Role-Emotional, and Mental Health. 
2. The sum T-score for the SCI-QOL Physical Medical Health domain (three item banks of 
Bladder Management Difficulties, Bowel Management Difficulties, and Pain Interference).   
 
B. 
Major Secondary Outcome 
 
1. Total body fat mass (by DXA scan) (results will be blinded) 
C. 
Secondary Outcomes 
 
1. Global Impression of Change Scale (Participant- and Companion-rated); 
2. PROMIS Sleep Disturbance T score; 
3. Assessment of bowel function for: 
a. Bowel evacuation (BE) time per episode in the past week,  
b. Frequency of BE episodes, 
c. Number of self-reported “natural” bowel movements in the past week, 
d. Frequency of digit stimulation in the past week,  
e. Stool consistency by the Bristol Stool Scale in the past week, and  
f. Frequency of enema use and amount of laxatives and/or stool softener used in the 
past month, and 
g. Frequency of bowel incontinence/accidents in the past month; 
4. SCI-QOL Physical-Medical Health for bladder complications (scale) and pain behavior 
(scale); 
5. SCI-QOL Emotional Health for positive affect and well-being, depression, anxiety, stigma, 
resilience, grief-loss, self-evaluation, and trauma; 
6. SCI-QOL Social Participation for ability to participate in social roles and activities, 
satisfaction with social roles and activities, and independence; 
7. SCI Functional Index (SCI-FI) for Physical Function for basic mobility, ambulation, fine 
motor, self-care, wheelchair mobility, and assistive technologies; 
8. Abdominal fat mass by DXA scan (this is acquired as part of the total body scan); 

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9. Lipid profile analysis for HDL-c, LDL-C, TG, and TC will be shipped to the Chair’s Office 
for batch analysis by the JJPVAMC laboratory (results will be blinded); and 
10. FPG and FPI for HOMA-IR calculation.  FPG and FPI will be shipped to the Chair’s Office 
for batch analysis by their Core research laboratory.  
 
D. 
Additional Assessments 
 
1. EAW Basic Skills Test will be performed: 
a. During the five-session basic EAW Training (both groups), 
b. Post Training phase (Intervention group only), and 
c. Post 4-month Intervention phase (Intervention group only); 
2. EAW Advanced Skills Test performed: 
a. Post Training phase (Intervention group only) and 
b. Post 4-month Intervention Phase (Intervention group only). 
 
E. 
Quality Control (non-outcome) Measurements 
 
1. Weekly SOC activities (Usual Activity Log) will be recorded for wheelchair activities and 
other, non-wheelchair activities (e.g., standing frame, swimming, or other non-wheelchair 
activities). This is measured weekly in both groups.   
2. In the Intervention group only; 
a. Weekly EAW Activity Log in the Intervention group only, 
b. Weekly number of steps taken recorded on the step counter, and 
c. Walk tests and mobility assessments are recorded during each session once the 
participant is able to perform them and for the duration of the Training phase for 
the: 
i. 10 meter walk test for time (10mWT), 
ii. 6 minute walk test for distance (6minWT), and 
iii. Timed-up-and go (TUG).  
d. Walk tests and mobility assessments are recorded at months 2 and 4 during the 
Intervention phase as an outpatient visit. 
3. Exit survey: participants and companions will be asked questions about their satisfaction 
with the study overall, and specifically about the device and training. 
a. Previously randomized participants and their companions will be called to complete 
the “Exit Survey”. 

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F. 
Methods for Obtaining Outcome Measures Data 
 
The Site ReWalk Trainers and Assistant ReWalk Trainers will perform the mobility skills and 
walking tests and be responsible for recording the EAW data.  Exoskeletal-assisted mobility 
walking test assessments are measured in distance and/or time.  Other mobility skills such as 
arresting gait on command, maneuvering to a wall rest, navigating doors, etc., will be scored one 
session per week as “able” or “unable” to perform the task; in addition, the level of assistance 
needed to complete the task will be recorded with each assessment.  
 
The Site Coordinator will be responsible for administering the QOL outcome assessments (VR-
36, SCI-QOL, Global Impression of Change Scale (Participant- and Companion-rated), PROMIS 
Sleep Disturbance, SCI-FI, and bowel function surveys) through in-person or phone interviews.  
The Site Coordinators will record all answers on the fixed forms. The site Trainers may assist as 
back-up QOL assessors only if necessary. In order to have continuity of assessment, the Site 
Coordinators will administer the surveys at all of the time points. Each SCI-QOL, PROMIS Sleep 
Disturbance and SCI-FI survey is reported as a T-score (mean=50, SD=10).  The VR-36 is in a 
fixed form and administered sequentially.    
 
The Site Coordinator will be responsible for administering the Global Impression of Change Scale.  
This scale is a self-assessment completed by the participant (and separately by the companion) 
with questions about feeling better from “No change (or condition has become worse); Almost the 
same (hardly any change at all);  A little better (slightly noticeable, but has not made any real 
difference);  Somewhat better (the improvement is small, slightly noticeable difference);  
Moderately better (the improvement is a noticeable change); Significantly better (a definite 
improvement, a real and worthwhile difference) to Extremely better (a comprehensive 
improvement that has made all the difference)”.  Each question is scored from 1 to 7, with 1 being 
no change or worse and 7 being the best change in improvement.   The change reported on 
participant’s self-assessment on the global scale will be examined with the change reported on the 
SCI-QOL for correlation.  The companion’s impression of the participant’s global change will be 
used as a proxy validation of the participant’s self-assessment.  Analysis of the mean change scores 
for both tools would help to confirm the clinical relevance of the hypothesized 10% improvement 
from baseline in the SCI-QOL as a clinically relevant improvement. 
 
The Site Coordinator will be responsible for administering the bowel function surveys and will 
explain to each participant to select the response that best represents what is asked by the 

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question.  These set of questions ask about the participants views about their bowel function. The 
Site Coordinator will ensure that each participant answers every question, by marking the answer 
as indicated.  If the participant is unsure about how to answer a question they will be instructed to 
provide the best answer they can.  The Site Investigator will be responsible for the history and 
physical examination and administering the International Standards for Neurological 
Classification of SCI (ISNCSCI) Examinations for level and completeness of SCI.   A radiology 
technician or designated DXA technician at each site will perform the DXA scans.  The cost of 
this service has been added to the budget. 
 
G. 
Schedule of Observations and Laboratory Tests 
 
A detailed description of the schedule of tests is provided (Table 6).  Five DXA Scans will be 
performed over the course of the study, one for screening BMD and four for total body fat mass 
(includes abdominal fat mass) measurements.  Four fasting blood draws (15 ml each time) will be 
performed over the course of the study for the lipid profile and FPG and FPI. Bilateral calcaneus 
x-rays will be obtained during screening.  Other data collection will be in the form of Case report 
forms (CRFs), sequential fixed forms, and Microsoft Access database or potentially other 
electronic databases behind the VA firewall. Data collection may also take place through secure 
messaging using My HealtheVet. 
 
X.  PERFORMANCE MEASURES AND STUDY MANAGEMENT 
The primary performance measure for the sites is enrollment. Performance measures will be 
established early in the start-up year by review of the prescreening and screening forms. Sites that 
do not meet the goals of 100 participants prescreened and 60 participants screened will be notified 
for consideration of probation. Across all study sites, 160 participants are to be randomized.  Each 
site is expected to randomize between 4 and 24 participants.   
 
The overall management plan is for the sites’ study team (Site Investigator, Site ReWalk Trainer, 
Site Assistant ReWalk Trainers, and Site Coordinator) at the participating medical centers to 
conduct the daily activities of the study.  The Chair’s Office and the CSPCC at the Perry Point, 
MD VAMC will provide leadership and guidance to the local sites as specifically described below. 
 
 
 

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A. 
CSPCC 
 
The Perry Point Cooperative Studies Program Coordinating Center (CSPCC), located in Perry 
Point, Maryland, will provide administrative, data processing and statistical support for the study.  
Data forms will be submitted by the local site study team members to the CSPCC for processing. 
The CSPCC will edit the data and create the study database.  CSPCC staff will provide guidance 
on completion of forms.  All reports during the ongoing phases of the study and the final statistical 
analyses will be the responsibility of the CSPCC.  CSPCC staff will also monitor study progress 
to ensure that the study is proceeding as scheduled.  A CSPCC study team dedicated to this study 
will be established.  This team will be headed by the study biostatistician and will include a CSPCC 
project manager, a statistical programmer, a database programmer and two computer assistants. 
 
B. 
Office of the Chair  
 
Ann M. Spungen, EdD, study Chair and William A. Bauman, MD, Co-Chair will provide 
leadership for the study.  The Chair’s Office is located at the James J. Peters VAMC, Bronx, New 
York.  In order to facilitate organizing and coordinating this ten-site multi-center study, the Chairs 
have elected not to include the Bronx VA as a study site.  The Chair’s Office personnel will be in 
routine contact with the participating sites to ensure that the study is performed in accordance with 
the protocol and that each local site team is able to meet the enrollment goals and follow-up 
activities on schedule.  The Chair and Co-Chair will preside over all meetings and will represent 
the study, along with the study biostatistician at any meetings of outside review committees. The 
Chair’s Office will be funded with a full-time National Study Coordinator (1.0 FTE), a Co-
National Coordinator (1.0 FTE), a Staff Assistant (1.0 FTE) and a part-time iDXA Analysis 
Technician.  Dr. Spungen will be responsible for all study executive decisions. She will serve as 
the Chair of the CS #2003 Executive Committee.  Dr. Bauman, Co-Chair, will provide medical 
advice and direction for the National Coordinators and administrative staff as needed.  Dr. Spungen 
will be a resource for protocol details and compliance issues.  She will serve as a liaison with other 
study personnel for the Chair’s Office. Dr. Spungen is a member of both the Executive and 
Planning Committees.   
 
Overall, the National Study Coordinators are responsible for maintaining enthusiasm, quality 
standards across the sites, discussing problems, problem solving, and identifying any 
procedural/definitional modifications that might be required.  The CS #2003 National Study 
Coordinators will be responsible for overseeing all study activities in the Chair’s Office on a day-

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to-day operational basis. In addition to the specific job responsibilities outlined in the “Description 
of Responsibilities” section of this submission, the National Coordinator and Co-National 
Coordinator will:  
 
1) Assist the Chairpersons in coordinating and administering all aspects of the study; 
2) Assist the Chairpersons in monitoring the progress of the study; 
3) Maintain close contact with the participating Site Investigators, Site ReWalk Trainers, and 
Site Coordinators to assist them in any procedural details of the study;  
4) Maintain close contact with the study’s supervisory committees; and  
5) Work collaboratively with the Perry Point CSP Coordinating Center team to organize and 
plan periodic meetings of participating Site Investigators and other study team members 
for the purposes of reporting progress of the study.  
 
XI.  SAFETY MONITORING  
 
Timely and complete reporting of safety information assists study management in identifying any 
untoward medical occurrence, thereby allowing: a) protection of safety of study participants, b) a 
greater understanding of the overall safety profile of the study treatments and therapeutic 
modalities, c) improvements in study design or procedures, and d) compliance with regulatory 
requirements. The Site Investigator will be responsible for reviewing the accuracy and 
completeness of all reported events, compliance with VA CIRB policies for reporting adverse 
events (AE), serious adverse events (SAE), Unanticipated Adverse Device Effects (UADE), and 
closely monitoring research participants at each study visit for any new SAEs. 
 
A number of groups will be charged with monitoring the study. These groups include the Study 
Group, the Executive Committee, the Data Monitoring Committee (DMC), , the VA Central 
Institutional Review Board (CIRB), the CSPCC Human Rights Committee and the Cooperative 
Studies Scientific Evaluation Committee (CSSEC).  In addition, the CSP Site Monitoring Auditing 
and Resource Team (SMART) will routinely visit the participating centers.  This monitoring will 
not preclude the yearly monitoring that the local R&D Committee and CIRB must also perform.    
 
A. 
The Study Group consists of all participating Site Investigators, Site ReWalk Trainers and 
Site Coordinators, as well as staff from the Chair’s Office, CSPCC, and CSPCRPCC.  It meets 
prior to the start of participant intake and annually to discuss the plans/progress of the study, as 

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well as to identify any problems encountered during the conduct of the trial.  No outcome data are 
presented to this group. 
 
B. 
The Executive Committee is the management and decision-making body for the 
operational aspects of the study.  Chaired by Dr. Spungen, the committee consists of the Chair and 
Co-Chair, the study biostatistician, the Adverse Event Specialist, a minimum of three Site 
Investigators, and outside consultants, if necessary.  This committee monitors the performance of 
participating medical centers and quality of data collected.  The Executive Committee formulates 
plans for publications and oversees the publication and presentation of all data from the study.  
Permission from this committee must be granted before any study data may be used for 
presentation or publication.  This committee typically meets on the same schedule as the Study 
Group.  This group also does not receive outcome data during the course of the study.  
 
C. 
The Data Monitoring Committee (DMC) is a group of outside experts in the area of spinal 
cord injury, clinical trials and biostatistics that reviews the progress of the study and monitors 
participant enrollment, outcomes, adverse events, and other issues related to patient safety. The 
DMC makes recommendations to the Director of the Cooperative Studies Program (CSP) as to 
whether the study should continue, or be modified or stopped.  The DMC can consider patient 
safety or other circumstances as grounds for early termination, including either compelling internal 
or external evidence of treatment differences or lack of feasibility of addressing the study 
hypotheses (e.g., poor patient intake, poor adherence to the protocol).  The DMC will meet 
annually to review data reports prepared at the Perry Point CSPCC.  At the six-month interval 
between the annual meetings, the DMC will receive another data report for review without a 
meeting.  Any member of the DMC can ask for a meeting of the group if s/he feels that it is 
necessary, based upon the data. 
 
D. 
The VA Central IRB (CIRB) will be the study’s primary IRB and the IRB of record for 
the study.  It will be responsible for the initial and continuing IRB reviews of the study.  The CIRB 
must review and approve amendments (changes to inclusion/exclusion criteria, protocols, 
informed consents, etc), deviations, and review reports about adverse events and problems, 
complaints, terminations, etc..    The CIRB approves the original informed consent template and 
any requested changes to the informed consent forms.  The CSPCC Human Rights Committee 
(HRC) may be asked to convene if there is any serious adverse event requiring its attention. 
 

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E. 
Definitions of Adverse Event (AE), Serious Adverse Event (SAE), and Unanticipated 
Adverse Device Effect (UADE)   
 
An Adverse Event (AE) is defined by the International Conference on Harmonization (ICH) for 
Clinical Safety Data Management (ICH-E2A) as “any untoward medical occurrence in a clinical 
investigation participant that is subjected to one of the study treatments that does not necessarily 
have to have a causal relationship with the treatments. An AE, therefore, can be any unfavorable 
or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the study interventions.”  In this study, all AEs will be collected by the Sponsor.  
The reporting period for AEs begins when the participant signs the informed consent form and 
continues until the participant’s completion or early termination of participation or the end of the 
study.    
 
A Serious Adverse Event (SAE) is defined by the ICH for Clinical Safety Data Management and 
CSP Global SOP 3.6.2, as any untoward medical occurrence that: results in death, is life 
threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant disability or incapacity, a congenital anomaly/birth defect, or any other 
condition that, based upon medical judgment, may jeopardize the subject and require medical, 
surgical, behavioral, social or other intervention to prevent such an outcome.  Participants will be 
monitored for SAEs at each study visit. All SAEs will be reported on an SAE Form, regardless of 
relationship to the intervention. Active monitoring for SAEs begins at the time the Informed 
Consent Form is signed and continues until the earlier of the 30 days after the participant’s 
completion or early termination of study participation or the end of the study. All SAEs require 
prompt reporting to the CSP Clinical Research Pharmacy Coordinating Center (CSPCRPCC) 
within 72 hours of the Site Investigator becoming aware of the event.  All unresolved SAEs must 
be followed up at least every 30 days until resolved or when no further change is expected (i.e. 
event is ongoing recovering/resolving or not recovered/not resolved. No changes to the event will 
occur in the future.) All SAEs are followed until no changes are expected or the study is 
discontinued.   
 
An unanticipated adverse device effect (UADE) is defined in 21 CFR 812.3(s) as any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or associated 
with, a device, if that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application (including a supplementary plan or 

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application), or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects 
 
Starting with each site, at the local level, the site study team members will be responsible for 
recording adverse and serious adverse events, as well as unanticipated adverse device effects and 
submitting them to the appropriate authorities in the time frames listed below.   
 
F. 
Serious Adverse Event (SAE) Reporting   
 
Any Serious Adverse Event (SAE) is reported on both the SAE and AE case report forms.  The 
Site Investigator will be responsible for reporting a SAE, ascertaining the participant’s study 
identification number, date of event, and will determine if the SAE is related, possibly related or 
not related to the protocol.  A description of any outcome or response to the SAE will also be 
included in this report.  As more information about a SAE becomes available, updates to this initial 
report must be made on the SAE Follow-Up form.  It is the responsibility of each Site Investigator 
to report SAEs from their site to the CIRB within the timelines they require.  SAE data are 
tabulated by the CSPCC at Perry Point, MD and the CSPCRPCC at Albuquerque, NM, and 
summarized and in the report to the DMC.  ReWalk Robotics, Inc. will be provided a summary of 
SAEs annually.   
 
G. 
Adverse Event (AE) and Unanticipated Adverse Device Effect (UADE) Reporting  
 
Any mild (awareness of symptom, but easily tolerated), moderate (discomfort enough to cause 
interference with usual activity) or severe (incapacitating with inability to work or do usual 
activity) AE must be reported on the AE case report form.  Any AE which also meets the criteria 
for a SAE must also be reported on the SAE form.  It is the responsibility of each Site Investigator 
to report AEs from their site annually to the CIRB.  Participants will be monitored at a minimum 
of one time per week for AEs and recorded on the appropriate form should any occur.  AE data 
are tabulated by the CSPCC at Perry Point, MD and the CSPCRPCC at Albuquerque, NM and 
summarized in the report to the DMC. 
 
UADEs must be reported by the clinical investigator to the sponsor and the CIRB, Investigators are 
required to submit a report of a UADE to the sponsor and the reviewing IRB as soon as possible, but 
in no event later than 10 working days to the sponsor and no later than 5 days to the CIRB after the 
investigator first learns of the event.  This reporting will be to the CSP Clinical Research Pharmacy 

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Coordinating Center on an AE or SAE form, as appropriate, and to the CIRB on the relevant IRB 
form.  The reporting period for UADEs begins when the participant signs the informed consent form 
and continues until the participant’s completion or early termination of participation or the end of the 
study 
 
As part of the orientation and training for each participant on the device, the expected occurrence 
of routine AEs will be described to the participants, including that they may experience skin 
abrasions, and hand, shoulder or any other joint discomfort. During the five-session Basic Training 
and in the Screening Phase and the Orientation/Training Phase, participants will be asked during 
each session if they are experiencing any discomfort or pain.  Hand or shoulder discomfort, if they 
occur, are expected to occur early on in training when the participant is learning to use the device.  
Participants who report any pain or other medical problem will be referred to the Site physician. 
The Site physician will be responsible for taking the appropriate course of action for the AE or 
SAE. The study staff will be responsible for recording the occurrence of AEs or SAEs 
appropriately, as they occur. Additionally, the SMART unit will be charged with monitoring the 
informed consent documentations, source documents, AE and SAE forms, as well as assessing if 
the Site study team is carrying out the study correctly.   
 
The Site Investigator will be responsible for monitoring these events on a regular basis at his/her 
site.  The immediate and ongoing safety review of study data to monitor for evidence of adverse 
events will be conducted by the Cooperative Studies Program Clinical Research Pharmacy 
Coordinating Center (CSPCRPCC) in Albuquerque, NM. The Data Monitoring Committee (DMC) 
will review AEs and SAEs on a regular basis. 
 
H. 
Participant Safety Stopping Rules  
 
The Site Physician will make the decision for participants who have a safety or medical concern 
such as: skin breakdown, edema, joint discomfort, muscle soreness, extreme fatigue, or any other 
medical condition as to whether they are to be continued as is, continued with modifications to the 
equipment, temporarily discontinued, or withdrawn from the study.  Re-entry to the Training or 
Intervention phases of the study will be based on the Site Physician’s medical clearance and the 
participant’s safety to begin again. 
 
 
 

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I. 
Site Participation Stopping Rules  
 
Each site must enroll at least 8 participants in the first year of enrollment.  Sites that do not meet 
this enrollment goal will be considered for probation.  Rapid improvement is expected to avoid 
termination from the study.  Sites that continue to fail to meet their recruitment goals will be 
discontinued and replaced with another site, if time permits during the study. The Chair’s Office 
and the CSPCC will work with any site that is below recruitment goals to assist in overcoming 
obstacles which may have contributed to their falling behind, thus allowing them the opportunity 
to catch up.  If this is not feasible, then resources will be shifted to either allow the other sites to 
recruit more participants, or phase out one site and start another.  
 
Pre-screening and screening logs will be closely monitored by CSPCC and the Chair’s Office.  
Study sites that have not met their recruitment goals will be closely reviewed for reasons why.  An 
indicator for unmet enrollment, which can be assessed early in the start of the study, is lack of 
prescreened and screened potential candidates. Sites will be expected to prescreen 100 and screen 
60 potential participants over the years of study enrollment.  Viewing the sites’ prescreening and 
screening histories early can help to identify sites that are not performing as expected.  The 
feasibility component will be used to formally assess the enrollment rates for the first six sites. 
 
J. 
Efficacy or Futility Criteria for Study Termination   
 
The DMC will be responsible for review of the SAEs and AEs for each site and across the study 
as a whole.  The DMC will make all decisions for stopping the study based on safety concerns, 
should any present.  Early analyses before the study is completed may result in stopping of the 
study.  For example, if it is statistically demonstrated that the results for either efficacy or futility 
to date could not be changed with further enrollment, the study may be stopped.  When repeated 
significance tests are performed on accumulating data as part of a routine monitoring function, the 
overall type-I error rate is inflated and the probability of a false positive finding is also increased.  
A number of methods have been developed to provide guidance on study termination rules based 
on multiple looks at the primary outcome measures for the review committees while keeping the 
overall type-I error rate maintained at 5%.  For this study, the O’Brien-Fleming method for alpha 
spending and rejection/acceptance boundaries will be suggested for Type-I error rate control (see 
Statistical Analysis Plan (SAP – Section XIII) for further details) but the DMC will make the final 
decision on the type of stopping rule that will be used for the study. 
 

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XII.  QUALITY ASSURANCE PROCEDURES    
 
Centralized and on-site reviews and monitoring of clinical site practices will be conducted at 
several levels.  The National Coordinator will visit each site two times per year during the 
enrollment years to monitor the EAW Training, patient safety, and compliance with the study 
protocol.  The Co-National Coordinator will visit each site one time annually during the enrollment 
years to monitor standardization of the QOL assessments and protocol compliance.  Participant’s 
medical records will be made available to the CSP Site visitors as a requirement for participation 
in this study. 
 
This trial will be conducted in compliance with Good Clinical Practice (GCP) regulations. The 
intent of these regulations is to safeguard participants’ welfare and assure the validity of data 
resulting from the clinical research. The VA Cooperative Studies Program will assist local site 
Investigators in complying with GCP requirements through its Site Monitoring, Auditing and 
Resource Team (SMART) based in Albuquerque, NM. SMART serves as the Quality Assurance 
arm of CSP for GCP compliance.  SMART will provide training, manuals and materials to assist 
study personnel in organizing study files and will be available throughout the trial to advise and 
assist Site Investigators regarding GCP issues. 
 
A. 
Summary of Monitoring and Auditing Plans 
 
1. Monitoring Visits 
 One routine monitoring visit per site 
 Additional monitoring visits may be conducted as deemed necessary by study leadership 
or SMART. 
2. Audits 
 
 Routine audits – independent site visits to one or more sites per year as determined by 
SMART. 
 For-Cause audits –independent audit of a site as requested by study leadership or CSP 
Central Office. 
 Audits may be scheduled or unannounced. 
 
 

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XIII.  STATISTICAL ANALYSIS PLAN (SAP) 
 
A. 
Introduction 
 
There are two primary outcome measures in this study:  the first is the score on the Mental 
Component Summary of the Veterans Rand-36 (MCS/VR-36) and the second is the sum T-score 
for the SCI-QOL Physical Medical Health domain (three item banks for bladder management 
difficulties, bowel management difficulties and pain interference).  The primary study hypotheses 
are:  1) 33% of the intervention group (EAW+SOC)  compared with 10% of the control group 
(SOC) will demonstrate a clinically relevant change (improvement) of ≥ 4.0 points in the 
MCS/VR-36, for greater vitality and social functioning, and improved role-emotional and mental 
health, from baseline to the end of the intervention phase, and 2) 42% of the intervention group 
compared with 10% of the control group will demonstrate a clinically significant improvement 
from baseline of ≥ 10% in the sum T score, indicating improvement in patient reported outcomes 
for SCI-QOL bladder management, bowel management and pain interference. 
 
A major secondary objective of the study is to demonstrate that participants who use the 
exoskeleton in addition to SOC (EAW+SOC) will have at least a 1.0 kg loss in total body fat mass 
by the end of the four-month intervention compared to those who receive SOC only.  Other 
secondary objectives are to demonstrate that participants in the EAW+SOC group will have greater 
net improvements than participants in the SOC only group in the following outcomes:  1) Global 
Impression of Change (participant- and companion-rated), 2) disturbed sleep as measured by the 
T-score of the Patient Reported Outcomes Measurement Information System (PROMIS) Sleep 
Disturbance, 3) self-reported methods and measures of bowel function,  4) sum T scores of the 
SCI Functional Index (SCI-FI) physical function short forms, 5) sum T scores of the SCI-QOL 
Emotional domain, 6) sum T scores of the SCI-QOL Social Participation domain, 7) lipid profile 
for high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), 
triglycerides (TG), and total cholesterol (TC), and 8) fasting plasma glucose (FPG) and insulin 
(FPI) levels for calculation of Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). 
 
B. 
Sample Size 
 
Using preliminary data generated from the Exoskeletal-assisted Walking Program at the James J. 
Peters VA Medical Center, three separate power calculations were performed, one for each of the 
primary outcome measures, the MCS/VR-36 and the sum t-score of the SCI-QOL bladder, bowel 
and pain item banks, and one for the major secondary measure, total body fat mass.  The sample 

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size estimates are based on the preliminary data from these three outcome measures as a proportion 
of participants who achieved a clinically significant change score (MCS/VR-36 and Total Body 
Fat Mass) or a clinically significant percent change (SCI-QOL PMH).   
 
Sample size/power calculation for the Primary Outcome (1) MCS/VR-36:   A minimally important 
difference for the MCS/VR-36 is 4.0.  It is hypothesized that 33% of the Intervention group and 
10% of the Control group will achieve a 4.0 or greater change on the MCS/VR-36 (Table 7). 
 
Sample size/power calculation for the Primary Outcome (2) SCI-QOL for Bladder, Bowel and 
Pain:  An improvement of 10% in the sum T-score of the patient-reported outcomes from the 
combined SCI-QOL item banks for bladder management difficulties, bowel management 
difficulties and pain interference is clinically significant.  As such, it is hypothesized that 42% of 
the Intervention group compared with 10% of the Control group will demonstrate a clinically 
significant change of 10% improvement from baseline to the end of the intervention phase on the 
sum T-score in the combined SCI-QOL item banks for bladder management difficulties, bowel 
management difficulties and pain interference.  (Table 7). 
 
Sample size/power calculation for the Major Secondary Outcome for Total Body Fat Mass:  
Patients with a new SCI can be expected to gain an average of 6.0±8.9 kg of fat mass in the first 14 
months after injury (manuscript in preparation from our Center).  This gain in fat mass appears to 
continue throughout the duration of their life after SCI.  As demonstrated in the preliminary data, 
an intervention that supports a 1.0 kg (2.2 lb.) loss of fat mass is a substantial amount of fat mass 
to lose in three months for a person with SCI.  Very few interventions have demonstrated changes 
in body composition of this magnitude in the SCI population.  It is expected that 35% of the 
Intervention group compared with 10% of the Control group will maintain total body fat mass loss 
during the home/community use phase of the intervention. 
 
Assuming the proportion in the control group achieving a clinically meaningful change to be 10% 
(or 0.100) for all three outcome measures, and estimating the attrition rate at 15%, the sample sizes 
range from a low of 71 per group (95% power) for the SCI-QOL PMH outcome to a high of 79 
per group (80% power) for the MCS/VR-36 group.  As a note about Table 7, to adjust for multiple 
outcome measures, a significance level of 0.025 was used in the sample size calculations for the 
co-primaries (MCS/VR-36 and SCI-QOL) and also for the major secondary outcome measure 
(Total Body Fat Mass).  Based on the sample size and power calculations in Table 7, the study will 
enroll a total sample size of 160 participants, 80 per group. 
 
 
 
 
 

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Table 7:  Sample Size/Power Calculations 
Two group continuity corrected χ2 test of 
equal proportions (odds ratio = 1) (equal n’s) 
MCS/VR-36 
SCI-QOL 
(PMH) 
Total Body 
Fat Mass 
Test significance level, α 
0.025 
0.025 
0.025 
1 or 2 sided test? 
2 
2 
2 
Control proportion, π1 
0.100 
0.100 
0.100 
Intervention proportion, π2 
0.333 
0.420 
0.350 
Odds ratio, ψ = π2 (1 - π1) / [π1 (1 - π2)] 
4.493 
6.517 
4.846 
Power (%) 
80 
95 
85 
n per group 
67 
60 
66 
n per group with 15% attrition 
79 
71 
78 
 
C. 
Feasibility Phase 
 
In order to confirm the hypothesized control proportion for the two primary and major secondary 
outcomes, to determine the feasibility of recruiting participants at each site, and to assess other 
operational aspects of the study, a feasibility phase has been built into this study. The planned 
duration of the feasibility phase of the study is one year. Six out of fifteen planned sites (including 
three sites that are designated CSP NODES) will be brought up in the first year.  
 
During the feasibility phase, several site start-up activities and operational aspects of the study will 
be examined. These activities will include the hiring of site personnel (including classification of 
position descriptions, position announcements and recruitment), the processes for procuring and 
distributing the ReWalk and iDXA devices to the sites, the methods by which site staff are trained 
on the use of the devices and on data collection and management activities, the number of sessions 
needed for participants in the intervention group to pass the Advanced Skills Test, the practicality 
of Veterans or members of the military with SCI to find motivated and eligible walking 
companions, and attrition (drop-out) rates. The lessons learned during this phase will be 
implemented during activation of the remaining participating sites. 
 
Recruitment rates at the six active sites will be closely monitored during this phase.  The initial six 
sites are expected to enroll a total of 48 participants by the end of the first year.  The actual 
recruitment experience of the six sites in the first year will be used to revise the projected 
recruitment rate for the remainder of the study and may lead to a lengthening or shortening of the 
total recruitment period, as appropriate. 
 
Besides the verification of the assumed recruitment rate and other site start-up activities, the 
feasibility phase also provides an opportunity to assess the assumed success rates in the control 
(SOC) group. As stated above in section II, we have hypothesized that 10% (0.100) of the control 

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group will have a clinically meaningful change in the outcome measures for sample size/power 
calculations.  Ten percent is thought to be a conservative estimate as there is no reason to expect 
the control group to have clinically meaningful changes in quality of life measures or in total body 
fat mass while continuing to receive SOC for their spinal cord injury.  However, as a means of 
verifying the control proportion of 10% (or 0.100), the proportion of participants considered 
successful in the control group for all three outcomes and 95% confidence intervals for the 
proportions will be reviewed upon the completion of the feasibility phase.  Based on the extensive 
experience with this population it is highly unlikely that the assumed success rates in the control 
group (SOC) will be any higher than the assumed 10%.   
 
At the completion of the feasibility phase, the study will be moved to a continuation phase where 
the remaining sites (9 remaining sites) will be activated and the remaining participants will be 
recruited.   
 
D. 
Baseline Comparability 
 
Baseline comparability between the treatment groups will be evaluated with respect to such 
variables as demographics (e.g., age, gender, and race) and baseline values of outcome measures 
(MCS/VR-36, SCI-QOL, total body fat mass, etc.).  Chi-square and analysis of variance 
techniques, as appropriate, will be used to determine any differences in distribution of the variables 
across the treatment groups.  Any variable that appears to be different between the groups (p<0.10) 
will be considered as a potential covariate in statistical analyses.   
 
E. 
General Outcome Analysis Guidelines 
 
All statistical tests will be 2-sided.  The two primary and major secondary outcome measures will 
be tested at a 0.025 level of significance.  Because of the large number of secondary outcomes to 
be analyzed, all other secondary outcomes will be tested at a significance level of 0.01 to maintain 
control over Type I error.  SAS 9.4 will be used to conduct all the statistical analyses. A variety of 
analytic methods will be used for the primary endpoints, secondary endpoints and other analyses.   
 
F. 
Analysis of Primary and Major Secondary Outcome Measures 
 
The primary analysis will be based on an intent-to-treat (ITT) model.  All participants who are 
randomized will be included for both groups, whether they are study completers (participants who 
complete the study through the four-month intervention phase) or early terminators (drop-outs).  
In order to test the hypotheses for the primary and major secondary outcome measures, each 
randomized participant will be deemed a success or failure at attaining:  1) ≥ 4.0 point 
improvement in the MCS of the VR-36, 2) ≥ 10% improvement in the SCI-QOL bladder 
management difficulties, bowel management difficulties and pain interference sum T score, and 

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3) ≥ 1 kg. total body fat mass loss.  For each of the outcomes, the proportion of participants 
successful at achieving a clinically significant improvement will be compared between the two 
groups (Intervention vs. Control) using a chi-square analysis.  These will constitute the primary 
and major secondary efficacy analyses. Participants who drop out will be treated as failures.  As 
such, by design, there will be no missing data: participants either meet the outcome criteria 
(successes), do not meet these criteria (failures) or they drop out (also failures).     
 
G. 
Secondary Analyses 
 
In addition to the primary analysis, several secondary analyses will be performed and are described 
below. 
 
1. Analyses will be performed that include only those participants who complete the study 
(excluding drop-outs):   
 
a) Chi-square analyses of the primary and major secondary outcome measures 
(proportion of successes) will be repeated for only those participants who complete 
the 4-month intervention phase. 
 
b) Analyses of the MCS/VR-36, SCI-QOL, total body fat mass loss, Global 
Impression of Change and other secondary outcome measures will include 
comparisons of the mean difference scores (change from baseline to the end of the 
intervention phase) of these outcome variables using t-tests. 
 
2. Interim time points of data collection for all outcome variables have been incorporated into 
the study design. These time points are: baseline, after training/orientation phase, two 
months into the intervention phase, and then again after four months of the intervention 
phase (primary and major secondary outcomes main time point).  Secondary analyses of 
the MCS/VR-36, SCI-QOL, total body fat mass loss, Global Impression of Change and 
other secondary outcome measures will include comparisons of the mean difference scores 
(change from baseline to the end of each time point) of these outcome variables using t-
tests.  Other secondary analyses of outcome measures will be performed that use the all 
data available.  For these continuous variables, repeated measures analysis of covariance 
will be used to analyze them, with baseline scores, plus any variables determined from the 
baseline comparisons, being used as covariates in the analyses. SAS MIXED and 
GENMOD procedures, which allow for the use of incomplete data sets, will be used if it 
can be safely assumed that missing data are missing at random.  If this assumption is not 
valid, a multiple imputation strategy of the missing responses will be implemented which 
does not rely on the assumption that missing data occur at random.  This will allow an 
intent-to-treat approach for the statistical analyses, where complete cases are not required.   
 

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3. An analysis to determine the characterization of the drop-outs will be performed by using 
descriptive and correlation statistics.  The reasons for drop-out and the number of 
sessions/time points completed will be described.  A correlation analysis will be performed 
with the reasons for drop-out and the demographic variables and other potential variables 
to identify characteristics of persons who drop out of the study. 
 
H. 
Monitoring of Study by Study Group and Executive Committee 
 
The Study Group (all of the Site Investigators) and Executive Committee will meet 6 to 9 months 
after patient recruitment begins and at annual intervals thereafter until the end of the study.  Three 
weeks prior to these meetings and at 6-month intervals between the meetings, these groups will be 
provided a report that will allow them to assess study progress.  Since both groups are composed 
of study participants, no outcome data will be provided in these reports.  The information provided 
will include data on: 
1. Screening, enrollment and retention 
2. Patient background characteristics at entry 
3. Data quality and protocol adherence. 
 
1.  Screening, Enrollment and Retention 
 
During the pre-screening phase of the study, potential participants will be first contacted by the 
Site Investigator through chart reviews, other physician referrals, pre-existing knowledge about 
their patients, access to contact information in a VINCI database, physician referrals at other VA 
hospitals, and/or through study flyers and invitation letters.  Study flyers may also be given to 
potential participants in the SCI Clinics, posted in local area hospitals, or distributed at local and 
national SCI events. Study flyers may also be posted generally in areas where potential participants 
may see the information (i.e. local chapters of Veterans Organizations, SCI sporting events) and 
included in newsletters or journals with a focus on the SCI population. Eligible and interested 
potential participants will be contacted by the Site ReWalk Trainers and/or Site Study Coordinators 
for initiation of the consenting process and the screening and baseline evaluations. Any participant 
who consents to the study and passes all screening and baseline evaluations is eligible to be 
randomized into the study. 
 
The progress of patient accrual will be presented to the monitoring groups in two formats.  Table 
8 gives the first format, which presents, by site and month, the actual number of patients entered 
into the study. This table will indicate if recruitment is improving or worsening over time at the 
various sites.   
 
 
 
 

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Table 8.  CS #2003 Number of Participants Entered Each Month by Site 
Month 
Site 1 
Site2 
… 
Site 15 
Total 
September 2016 
 
 
 
 
 
October 2016 
 
 
 
 
 
November 2016 
 
 
 
 
 
September 2016 
 
 
 
 
 
. 
 
 
 
 
 
. 
 
 
 
 
 
. 
 
 
 
 
 
Total 
 
 
 
 
 
 
Intake data will also be plotted over time for the total number of participants recruited, as in Figure 
9.  An expected intake line is given for comparison purposes, assuming a staggered start of sites:  
6 sites expected to enroll 48 participants in the first year of recruitment, 10 sites projected to enroll 
80 participants during the second year of recruitment and 15 sites enrolling 32 participants during 
the third and fourth years of recruitment, for a total of 160 participants randomized. 
 
 
 
The number of participants screened and the number of those that randomize in the study will be 
presented in Table 9.  The reasons for the exclusion of screened participants will be presented in 
Table 10. 
0
20
40
60
80
100
120
140
160
0
3
6
9
12 15 18 21 24 27 30 33 36 39 42 45 48
# of Participants
Months
Figure 9.  CS #2003 Observed vs. Expected Recruitment 
Expected
Observed

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Table 9.  CS #2003 Cumulative Screening Summary:  All Participants by Site 
 
Site 
Screened 
Excluded 
Randomized 
% Excluded 
1 
 
 
 
 
2 
 
 
 
 
3 
 
 
 
 
. 
 
 
 
 
. 
 
 
 
 
15 
 
 
 
 
Total 
 
 
 
 
 
Table 10.  CS #2003 Summary of Ineligibility: Primary Reason for Exclusion, All Sites 
 
Primary Reason for Exclusion 
# 
Screened 
# 
Excluded 
% of Screened 
Less than 18 years of age 
 
 
 
Duration of SCI less than 6 months 
 
 
 
. 
 
 
 
. 
 
 
 
. 
 
 
 
No companion to assist at home 
 
 
 
Inability to provide informed consent 
 
 
 
Diagnosis of neurological injury 
other than SCI 
 
 
 
Progressive condition likely to result 
in changing neurological status 
 
 
 
. 
 
 
 
. 
 
 
 
. 
 
 
 
Psychopathology documentation that 
may conflict with study objectives 
 
 
 
Pregnancy or women planning to 
become pregnant during study 
 
 
 
Total 
 
 
 

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2.  Background Characteristics at Entry 
 
Background characteristics of study participants are collected on the Screening/Baseline and 
History & Physical Forms.  Tables summarizing the important background characteristics by site 
will be prepared and submitted to the Study Group so they will have an idea of the population 
being studied and comparisons of enrollment among the sites can be made.  This information will 
be presented as means and medians for continuous variables and as frequency tables for discrete 
variables.  Table 11 shows how the continuous variable age will be presented.  Other variables that 
will routinely be presented will include gender, race, education and smoking history.  Analysis of 
variance and chi-square techniques will be used to identify any statistically significant differences 
that may exist among the sites. 
 
Table 11.  CS #2003 Age Statistics by Site 
 
 
Site 
 
N 
 
Mean (Years) 
Standard 
Deviation 
 
Median 
1 
2 
. 
. 
. 
15 
 
 
 
 
Total 
 
 
 
 
 
3.  Data Quality and Protocol Adherence 
 
The final type of information that will be given to the Site Investigators is data that will allow them 
to assess the quality of the data being submitted as well as how well the sites are adhering to the 
protocol.  These data will be given by site, so sites performing substantially below average can be 
identified and remedial action taken to improve their performance. 
 
One piece of information that will be routinely provided is the number of forms that are missing 
according to the participant’s testing and training schedule.  Table 12 indicates how this 
information will be displayed. 
 
In addition to the tables for the reports, the computer auditing system produces Quality Control 
(QC) reports that indicate the number of errors that were found on the individual forms.  QC reports 
that are overly large will identify those sites requiring additional training on forms completion.  A 

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monthly report summarizing data submission and problem identification for each site will be sent 
to the Study Chairperson so that she can monitor how the participating sites are doing. 
 
Table 12.  CS #2003 Number of Missing Forms by Site 
 
# of Participants 
Site 
Total 
1 
2 
… 
15 
Form 01 
N 
 
 
 
 
 
% 
 
 
 
 
 
Form 02 
N 
 
 
 
 
 
% 
 
 
 
 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
. 
 
 
 
 
 
 
Form X 
N 
 
 
 
 
 
% 
 
 
 
 
 
 
I. 
Study Monitoring by the Data Monitoring Committee (DMC) 
 
An independent oversight committee called the Data Monitoring Committee (DMC) will monitor 
study progress.  This committee meets on the same basic schedule as the Study Group and 
Executive Committee, i.e., they will meet at 6 to 9 months after the start of patient recruitment and 
yearly thereafter.  This committee does not usually meet during the last six months of a study.  
They will also meet once prior to the study startup to acquaint themselves with the study and to 
establish their procedures for reviewing and monitoring the study. 
 
The major responsibility for the DMC members when they meet is to make a recommendation to 
the Director of the Cooperative Studies Program as to whether or not the study should continue.  
The study could be recommended for termination due to poor recruitment, treatment differences 
so large that it is possible to reach a final decision or treatment differences so small that 
continuation would be irresponsible.  The DMC also reviews the participating sites’ performance 
and makes recommendations concerning them.   Data collected during the feasibility phase of the 
study, including site performance, verification of success rates in the control group and other 
operational measures, will be presented to the committee for its review and recommendations.   
Their final responsibility is to review all proposed protocol changes and sub-protocols and to make 
recommendations about their acceptability. 
 
For the DMC to carry out its responsibilities, the CSPCC Study Team will provide the committee 
with a report approximately three weeks prior to their meetings.  The report will consist of the 
tables described previously for the Study Group and Executive Committee reports as well as those 

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presenting baseline participant characteristics and outcome measures by treatment group.  
Differences between treatment groups on participant characteristics may indicate a need to use any 
significantly different characteristics as covariates for the outcome measures.  Formal testing of 
the differences between treatment groups will be done at the study’s conclusion.  Analyses of 
variance techniques will be used to test characteristics that are continuous in nature, while chi-
square techniques will be used for the discrete variable characteristics.  The analyses of the primary 
and major secondary outcome measures are described above in section F.  The results of these 
analyses will be provided in table format and will include the p-value from the chi-square analysis.  
Table 13 indicates how the MCS/VR-36 outcome measure will be displayed.  Analyses of the SCI-
QOL Physical Medical Health domain (three item banks for bladder management difficulties, 
bowel management difficulties and pain interference) and total body fat mass outcome measures 
will be presented in a similar fashion. 
 
Table 13.  CS #2003 Primary Outcome Measure: Mental Component Summary (MCS) of 
the VR-36 
 
≥ 4-point improvement 
in MCS/VR-36 from 
baseline to end of 4-
month intervention 
SOC   
EAW + SOC   
Total  
p-value 
n 
% 
n 
% 
n 
% 
Success 
 
 
 
 
 
 
 
Failure 
 
 
 
 
 
 
Total 
 
 
 
 
 
 
 
Secondary outcome measures and analyses (as outlined in section G above) will also be provided 
in tabular format. These tables will present statistics for the outcome variables at all the time points 
at which the outcome measures are assessed:  baseline, after the training/orientation Phase, two 
months into the 4-month intervention phase, and then again at the end of the intervention phase.  
Again using the MCS/VR-36 as an example, Table 14 indicates how these data may be presented.  
The p-values from the comparison of the difference scores (difference from baseline to the end of 
each time point) and from the mixed models analyses, as appropriate, will also be presented in 
these tables.  
 
Table 14.  CS #2003:  VR-36 Mental Component Summary (MCS) Scores 
 
Time Point 
SOC 
EAW + SOC 
N 
Mean 
Std. Dev. 
Median 
N 
Mean 
Std. Dev. 
Median 
Baseline 
 
 
 
 
 
 
 
 
Post-Training/Orientation 
 
 
 
 
 
 
 
 
Two Months into Intervention Phase 
 
 
 
 
 
 
 
 
Post-Intervention Phase 
 
 
 
 
 
 
 
 

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For the DMC to make its recommendation for continuation of the study, it will be necessary for 
them to see the analysis of the primary and major secondary outcome measures every time they 
are provided a report of study progress and it is possible to calculate these measures.  Periodic 
monitoring of interim results can significantly affect the probability of making an incorrect 
decision (Type-I error rate). One interim look at the primary outcome measures (in addition to the 
final “look” at study’s end) will be proposed to the DMC for making the recommendation about 
whether or not to continue the trial or to stop for early efficacy.  It is proposed that the one look 
occur when 80 (50%) patients have completed participation in the study. The O’Brien-Fleming 
method for alpha spending and rejection/acceptance boundaries will be suggested for Type-I error 
rate control.  The O’Brien-Fleming boundaries for rejection (α) and acceptance (β) as well as the 
Type-I error rates for the two looks are given in Tables 15 and 16 for the MCS/VR-36 and SCI-
QOL/PMH outcomes, respectively.  The boundaries are presented graphically in Figures 10 and 
11 for the two primary outcome measures. 
 
 
Table 15.  CS #2003:  Two-sided O’Brien-Fleming Boundaries for Rejection (α) and 
Acceptance (β) – MCS/VR-36 
Interim 
Look 
(Stage) 
No. of 
Randomized 
Participants 
Std. z (Rejection) 
Std. z (Acceptance) 
Type-I 
error 
Lower 
Upper 
Lower 
Upper 
1 
80 
-3.12376 
3.12376 
-0.88945 
0.88945 
0.00089 
2 
160 
-2.20883 
2.20883 
-2.20883 
2.20883 
0.01250 
 
 
Figure 10.  CS #2003 Combined Boundary Plot for MCS/VR-36 
 
 

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Table 16.  CS #2003:  Two-sided O’Brien-Fleming Boundaries for Rejection (α) and 
Acceptance (β) – SCI-QOL Physical Medical Health (PMH) domain 
 
Interim 
Look 
(Stage) 
No. of 
Randomized 
Participants 
Std. z (Rejection) 
Std. z (Acceptance) 
Type-I 
error 
Lower 
Upper 
Lower 
Upper 
1 
80 
-3.16956 
3.16956 
-0.40071 
0.40071 
0.00076 
2 
160 
-2.24122 
2.24122 
-2.24122 
2.24122 
0.01250 
 
Figure 11.  CS #2003 Combined Boundary Plot for SCI-QOL Physical Medical Health 
(PMH) Domain 
 
 
As with any clinical trial, the safety of the participants will be of utmost concern.  Safety will be 
monitored closely and data will be collected on adverse events (AEs) and serious adverse events 
(SAEs) throughout the course of the study. All AEs and SAEs will be systematically recorded on 
case report forms and coded by the CSP Clinical Research Pharmacy Coordinating Center 
(CSPCRPCC) at Albuquerque using the MedDRA system.  The MedDRA system employs 
standard terminology to present adverse events and to organize them by body system.  The 
incidence of adverse events will be summarized for each treatment group and overall by body 
system and MedDRA preferred term. The incidence differences between the control and 
intervention groups for each event will be tested using the Pearson chi-square test or Fisher’s Exact 
test.  Table 17 illustrates how AE data may be presented for this study. 
 
 
 

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Table 17.  CS #2003 Cumulative Incidence of Adverse Events by Body System and 
MedDRA Term  
 
Body System and Preferred Term 
SOC 
 (n = ?) 
EAW + SOC  
(n = ?) 
All Participants  
(N = ?) 
p-value 
n (%) 
n (%) 
n (%)   
All Adverse Events 
 
 
 
 
Subjects with at least one Adverse Event 
 
 
 
 
 
 
 
 
 
Body System 1 
 
 
 
 
     Event 1 
 
 
 
 
     Event 2 
 
 
 
 
     Event 3 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
Body System 2 
 
 
 
 
     Event 7 
 
 
 
 
     Event 8 
 
 
 
 
     Event 9 
 
 
 
 
     Event 10 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
Body System N 
 
 
 
 
     Event 14 
 
 
 
 
     Event 15 
 
 
 
 
     Event 16 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
          . 
 
 
 
 
     Event N 
 
 
 
 
 
It is the responsibility of the CSPCC Study Team to provide the DMC with whatever information 
they feel they need to successfully monitor the study.  Thus, additional tables will be added as 
required.  In addition to the reports for the yearly meetings, the DMC will also be provided with 
reports between meetings at 6-month intervals. 
 
XIV.  QUALIFICATIONS 
 
A. 
Site Qualifications 
 
 The Site Investigator is required to be a SCI staff physician.  S/he will be responsible for the initial 

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contact with any potential participants.  Once a potential participant expresses verbal interest, 
additional study team members may continue the informed consent and eligibility screening 
process.  The Site Investigator will perform the History and Physical (H&PE) and INSCSCI 
examinations.  If there is skin breakdown or an abrasion due to contact friction with the 
exoskeleton, the Site Investigator/Physician works with the Trainers and participant to determine 
if the participant needs to take time off to allow it to heal or if the addition of padding or equipment 
adjustments is sufficient to prevent further breakdown and the participant may continue in the 
training sessions.  Additional, co-Investigators who are physicians are welcome to help defray 
some of the workload from the Site Investigator; however, the Site Investigator will ultimately be 
responsible for overseeing all conduct related to the CS #2003 at their site.  Co-Investigators from 
other disciplines are also welcome to be part of this study.  Each site will need to provide a clear 
description of additional co-Investigator roles in the study.   
 
The proposed study will require fifteen sites.  Each site will have four full time staff who would 
be solely dedicated to the conduct of the study (1 ReWalk Trainer, 2 Assistant ReWalk Trainers 
and 1 Study Coordinator).  Two staff persons are needed during the initial EAW Training phase 
for each of the participants.  The ReWalk Trainer will have a clinically relevant professional 
background such as a biomedical, electrical or mechanical engineer, physical therapist, exercise 
physiologist, occupational therapist, nurse, athletic trainer, or equivalent. The ReWalk Trainer will 
be responsible for the screening of participants, scheduling, fitting and training of the exoskeleton, 
and mobility measurement aspects of the protocol.  The ReWalk Trainer and Assistant ReWalk 
Trainers will be responsible for the administrative paperwork, assist with eligibility screening, 
assist with the informed consent process, scheduling of participants, the home evaluation when 
needed, the EAW training, weekly and monthly participant contact during the orientation and 
home use phases of the study, ensuring the Usual Activity log and EAW Activity Log are 
completed, reporting adverse events, and all other aspects of the study protocol.  The Assistant 
ReWalk Trainers will assist the trainer in all EAW aspects of the study.  All of the Trainers must 
be capable of assisting with the EAW training and as such, are expected to be healthy and free of 
back or other medical problems that would be contraindicated for lifting and carrying 60 pounds 
across a room. The Trainers must be able to lift the exoskeleton from one chair to another, or to 
place one in or take it out of the trunk of a car or van.  
 
CS #2003 study will also support a Site Coordinator.  The Site Coordinator will be responsible for 
the administration of the QOL outcome surveys, local Research & Development and CIRB 
application paperwork and assisting with scheduling and data entry.  The study Coordinators may 

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be physical therapists, PT assistants, exercise physiologists, nurses, nurse assistants, research 
health science specialists or technicians, or other comparable disciplines that have experience with 
research methods and procedures and experience and knowledge about persons with SCI.  
Approved and classified PDs will be provided to the sites for recruitment of study personnel if 
requested. 
 
Each Site will need the following: 
1. Access to a bone mineral densitometer or space for the ones to be provided by CS #2003; 
2. Secure space for storage of the ReWalk units; 
3. Space for overnight battery charging of the ReWalk units; 
4. Space for training participants to walk in the units (e.g., hallways, sidewalks, etc.); 
5. Space for desk or office for study personnel (x4); 
6. Access to the VA car pool; 
7. Secure space for study files; 
8. Dedicated study VA computer;  
9. Evidence of medical center support; and 
10. Access to a fax machine. 
 
B. 
Site Participation   
 
An invitation letter and brief description of the CS #2003 was sent to each of the SCI Service 
Chiefs to establish level of interest and available resources.  Eighteen potential study sites 
responded with interest in participating in this study.  Fifteen sites have been selected as the 
primary sites (Table 19).  Criteria for site selection included:  interest in being part of the study, 
the number of SCI patients seen in the catchment area, the number who use the site for outpatient 
visits, CSP NODE status, geographic location, availability of a bone mineral density (BMD) 
scanner for the BMD criteria, hospital space for the ReWalk training, secure storage of the devices, 
study files, and availability of staff desk and computer space.  Additionally, in an effort to place 
sites at VAMCs in the geographic sections of the whole US, geographic location was used as a 
selection factor.  Having more than 400 SCI patients seen annually in the outpatient clinic and 
being a Node were the two highest priority selection criteria, followed by geographic location.   

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Table 19.  CSP #2003 Study Sites 
VA Medical Center 
and NODE Site 
Site Investigator 
Email 
Type of Scanner 
iDXA Status 
# SCI 
Veterans 
in 
catchment 
# SCI 
Veteran 
outpatient 
visits/y 
1 
Boston 
Sunil Sabharwal, MD 
sunil.sabharwal@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
1200 
500 
2 
Richmond 
Lance L. Goetz, MD  
lance.goetz@va.gov 
DXA (SCI Service) 
iDXA needed 
1400 
501 
3 
Tampa 
Kevin T. White, MD 
kevin.white2@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
1200 
820 
4 
Houston (Node) 
Sally Ann Holmes, MD 
SallyA.Holmes@va.gov 
iDXA (Medical 
Center) 
upgrade only 
610 
400 
5 
Palo Alto (Node) 
Doug Ota, MD 
Doug.Ota@va.gov 
iDXA (SCI Serevice) 
upgrade only 
1028 
400 
6 
Long Beach 
(Node) 
Alice Jennifer Hon, MD 
alice.hon3@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
773 
275 
7 
Minneapolis 
(Node) 
Byron Eddy, MD 
Byron.Eddy@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
700 
175 
8 
Dallas (Node) 
Bridget R. Bennett, MD 
Bridget.Bennett@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
900 
700 
9 
Milwaukee 
Denis F. Castillo, MD 
Denis.Castillo@va.gov 
Hologic (Medical 
Center) 
iDXA needed 
433 
394 
10 
St. Louis 
Katherine C. Stenson, MD 
Katherine.Stenson@va.gov 
iDXA (Medical 
Center) 
upgrade only 
433 
394 
11 
Augusta 
Michael Priebe, MD 
Michael.Priebe@va.gov 
iDXA (Medical 
Center) 
iDXA needed 
1200 
900 
12 
San Antonio 
Michelle Trbovich, MD 
Michelle.Trbovich@va.gov 
GE Lunar (Medical 
Center) 
iDXA needed 
451 
240 
13 
Bronx 
Stephen Kornfeld, DO 
Stephen.Kornfeld@va.gov 
iDXA (SCI Serevice) 
iDXA needed 
711 
333 
14 
Albuquerque 
Nancy Cutter, MD 
Nancy.Cutter@va.gov 
iDXA (Medical 
Center) 
iDXA needed 
500 
400 
15 
Cleveland 
Mary Kristi Henzel, MD, 
PhD 
Mary.henzel@va.gov 
iDXA (Medical 
Center) 
iDXA needed 
1200 
400 
Sub Total 
13,606 
7,022 

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C. 
Office of the Chair Qualifications 
 
CS #2003 has two study principal proponents, Dr. Ann M. Spungen (Chair) and Dr. William A. 
Bauman (Co-Chair).  The Chair’s Office is requesting two National Coordinators and a Staff 
Assistant.  The two National Coordinators will perform separate and distinct functions to ensure 
successful completion of the clinical trial.  One FTE would be for a biomedical engineer at the 
GS-13 level, and s/he will have significant experience and be an expert in conducting ReWalk 
fitting, training and troubleshooting; this person would oversee all training and standardization 
with the exoskeletal device. The Co-National Coordinator (1.0 FTE) would be at the GS-12 level, 
and s/he must have significant experience in performing and teaching the administration of the 
SCI-QOL and other participant-reported measures of quality of life. This person would oversee 
the standardization across sites for all of the QOL assessment tools proposed to be administered 
and ensure that the Site Coordinators are trained in the administration of these assessment tools.  
The Staff Assistant (GS-9, 1.0 FTE) will assist the Chair’s Office with administrative paperwork, 
travel paperwork, and scheduling of site training.  Complete descriptions of the Chair’s Office 
staff responsibilities may be found in the position descriptions in the Budget Justification section.   
 
XV.  PLANS TO ASSURE SECURITY AND CONFIDENTIALITY OF STUDY DATA 
 
Each participant will be assigned a participant number and unique alpha code for the case report 
forms and source documents.  A code key (screening log) will be maintained at each investigational 
site. The participant number will be assigned as they are consented in the study. The site number 
along with their participant number will uniquely identify that person; however, it will not contain 
any personal identifiable information.  
 
Data collection which contains any protected health information (PHI) such as informed consent 
forms, Health Insurance Portability and Accountability Act (HIPAA) forms, and contact 
information will be stored within each individual site and will remain either in locked cabinets or 
electronically behind the VA firewall in a password-protected file. Only approved study personnel 
will be permitted access to view study related folders.  In addition, access to the study folders 
stored on the VA network will be restricted to personnel listed on this study. This will further limit 
access to files stored on the VA network that contain PHI and outcome data related to this study.  
 
SharePoint will be utilized within this study as it has been considered an approved collaboration 
environment and access to the SharePoint site can be restricted by the study team as needed. 

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SharePoint will be utilized as an intranet portal to maintain documents, manage files and other 
collaborative efforts securely. All data will be sent to the Coordinating Center at Perry Point using 
DataFax which is a system to send case report forms using a fax machine to Perry Point which will 
maintain the data repository for all sites. To ensure that all questions are answered on the QOL 
outcome assessments (VR-36, SCI-QOL, Global Impression of Change Scale (Participant- and 
Companion-rated), PROMIS Sleep Disturbance, SCI-FI, and bowel function surveys), the site’s 
study staff will conduct in-person or telephone interviews.  Testing and survey procedures will be 
conducted in private rooms and training will be performed in rooms and hallways of the VA SCI 
Services, on the medical center grounds when weather conditions permit, at Community Based 
Outpatient Centers (CBOCs) under the same FWA number as the VA facility conducting the 
research, and/or in the participant’s home or community. 
 
XVI.  DATA MANAGEMENT AND DATA SECURITY PLANS 
 
Most data collection will be non-sensitive data that will be coded using a subject number that will 
link the data to a specific subject. Data collection may also take place through secure messaging 
using My HealtheVet. The code to the subject number will be stored in a separate secure location 
within the VA Network at each site.  Access to sensitive data will be restricted to authorized users; 
access will be related to VA-approved research, data users and custodians.   VA and non-VA staff 
will be aware that they must immediately report theft or loss of VA sensitive data or media 
containing VA sensitive data to the site VA Information Security Officer (ISO).  Electronic VA 
sensitive data will be collected, used and stored on VA computers on the VA network (behind the 
VA firewall), on restricted access drives, and in password protected files.  Hard copies of VA 
sensitive data will be collected and used, and stored in locked cabinets in locked rooms. Any code 
linking identities to data will be stored separately from the data, electronically behind the VA 
firewall or hard copy in a locked cabinet in a locked room. Special access will be granted to study-
related data to the sponsor and regulatory boards upon request. This will include representatives 
of the Food and Drug Administration (FDA), the Central Institutional Review Board (CIRB), 
Office of Research Oversight (ORO), and compliance officers, etc. Written documentation of any 
review of study related files will be required. This documentation will be stored with the study 
related paperwork. All subjects that are enrolled in the CS #2003 study will be informed of any 
potential review by these regulating bodies during the consent process. 
 
Training for data collection and management will be conducted for all sites prior to initiating the 
study in order to ensure that the data is collected in the same manner and all study staff understand 

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the source documents and case report forms.  Data from the sites will be sent to the Coordinating 
Center, Perry Point, MD. All hard copies of case report forms collected will be stored within locked 
cabinets at the sites.  Electronic data will be stored on servers protected by the VA firewall. This 
study will utilize SharePoint as a method of maintaining documents and collaborating across the 
other VA sites. Restricted and selective access can be granted administratively to the SharePoint 
environment in order to prevent unauthorized access.  
 
QOL outcome assessments (VR-36, SCI-QOL, Global Impression of Change Scale (Participant- 
and Companion-rated), PROMIS Sleep Disturbance, SCI-FI, and bowel function surveys) will be 
completed by each participant during an in-person or phone interview by a member of the study 
site staff.   The interviewer will record the answers, making sure that all questions are answered.  
This data will be sent to the CSPCC via a Datafax system.  
 
XVII.  PLANS FOR DISSEMINATION OF STUDY RESULTS 
 
A. 
Publication of Research Results  
 
It is the policy of the Cooperative Studies Program not to reveal outcome data to Site Investigators 
until the data collection period of the study is complete.  This policy is meant to prevent possible 
biases that might affect data collection.  Members of the DMC will be reviewing outcome results 
to ensure that the study will be terminated early if a treatment is identified as prohibitively 
dangerous or if a definitive answer is reached prior to the scheduled study termination date. 
 
All presentations and publications resulting from this study will follow CSP policy as specified by 
the CSP guidelines.  The presentation or publication of any or all data collected by Site 
Investigators on patients entered into a Department of Veterans Affairs Cooperative Study is under 
the direct control of the study’s Executive Committee.  No individual Site Investigator has the 
right to use the study’s data to perform analyses or interpretations, or to make public presentations 
or seek publication of any or all of the data without specific approval of the Executive Committee. 
 
The Executive Committee has the authority to establish any number of publication committees, 
which usually will comprise of subgroups of Site Investigators and some members of the Executive 
Committee, for the purpose of producing manuscripts for presentation and publication.  Any 
presentation or publication related to this study should be circulated to the Executive Committee 
for review, comments and suggestions at least four weeks prior to submission of the manuscript to 

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the presenting or publishing body. 
 
All publications must give proper recognition to the funding source and should list all study 
participating site personnel (not necessarily as authors of the manuscript).  If an investigator’s 
major salary support and/or commitment is from the VA, it is obligatory that the investigator lists 
the VA as his/her primary institutional affiliation.  Submission of manuscripts or abstracts must 
follow the usual VA policy; ideally, a subtitle states, “A Department of Veterans Affairs 
Cooperative Study.”  The CSP also requires that every manuscript be reviewed and approved by 
the CSPCC Director prior to submission as a final quality control step.  Mechanisms for appeal by 
an investigator will follow procedures defined by the VA Office of Research and Development.   
Participation in a Department of Veterans Affairs Cooperative Studies Program clinical trial is 
voluntary.  Any investigator who cannot accept these operational guidelines regarding publication 
policy should not volunteer to participate in the study. 
 
B. 
Planned Publications  
 
The Executive Committee, led by the study Chair, Dr. Spungen, on behalf of the study group, will 
prepare the primary outcome manuscript and investigators with special interest will prepare the 
secondary outcome manuscripts in each of these areas, as to be determined by the Executive 
Committee.  The Executive Committee will consider additional ideas for sub-study manuscripts 
from members participating in the study. Sub-study activities (within the scope of this original 
protocol) may be authorized by the Executive Committee to address other important research 
questions raised. 
 
Primary publication:  Upon completion of the study, a manuscript will be prepared that focuses on 
the primary outcome, i.e. the proportion of subjects demonstrating a clinically significant change 
in MCS/VR-36 and the patient-reported outcomes for SCI-QOL bladder management difficulties, 
bowel management difficulties and pain interference, as compared between the Intervention and 
Control groups.  This proportion of participants who achieved the major secondary outcome for 
total body fat mass changes will also be reported in the primary manuscript.  Any adverse events 
will be reported as well. 
 
Other publications:  Upon completion of the study and the acceptance of the primary manuscript 
for publication, the secondary outcomes will be analyzed for the PROMIS sleep disturbance, bowel 
function survey, the remaining items in the SCI-QOL that were not included in the primary 

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outcomes, the physical function domains from the SCI-FI, and lipid profile  results.  The amount 
of time spent in the device and location of use will be reported in conjunction with any of the above 
manuscripts.   
 
XVIII.  HUMAN SUBJECTS PROTECTION CONSIDERATIONS 
 
A. 
Recruitment of Participants and Special Considerations   
 
The targeted study population to be studied is Veterans or military members with SCI (>6 months) 
who are non-ambulatory and a primary wheelchair user for mobility.  The Site Investigator is 
required to be a SCI staff physician.  S/he will be responsible for the initial contact with any 
potential participants.  Once a potential participant expresses interest and gives verbal permission 
to learn more, additional study team members will assist the Site Investigator with the informed 
consent and eligibility screening process.  There are no race, ethnicity or gender limitations for 
enrollment.  The age range is limited to who are at least 18 years of age.  There is no upper age 
limit because if someone passes all the inclusion and exclusion criteria, being of an older age, but 
in good health should not be exclusionary in of itself. Special classes of subjects such as pregnant 
women, prisoners, institutionalized individuals, or other populations that may be considered 
vulnerable will be excluded from this study with the exception of economically and educationally 
disadvantaged persons. There are Veterans and military members who are economically, 
educationally or socially disadvantaged individuals and they will be given the opportunity to 
participate in this research project. These disadvantaged persons will be given the same treatment 
as individuals who are not considered to be vulnerable.   
 
B. 
Inclusion of Women and Minorities in Study 
 
Consistent with the Belmont Report, “Ethical Principles and Guidelines for the Protection of 
Human Subjects,” and Congressional legislation, eligible women and minorities will be included 
in this study.   
 
C. 
Description of the Consenting Process 
 
Consent will be obtained prior to study enrollment by the Site Investigators or a member of the 
study research team. Study team members will be trained to obtain consent.  They will be 
responsible for explaining the proposed clinical trial and answering questions before obtaining 

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informed consent.  The consent will be explained in its entirety by the study team. The terms of 
the consent form will be explained prior to obtaining the individual’s signature.  Individuals will 
be given the opportunity to take the consent home for review with family members (if they so 
choose), to think about it overnight, and to ask questions prior to signing the consent form.  
Participants will be asked to explain back to the study team member what they believe the study 
entails, thus giving the opportunity for the study team member to correct any misunderstandings 
or add further detail.  Potential participants will be informed of their right to ask questions at any 
time during the trial and/or to withdraw at any time.  The potential participants will be informed 
that choosing to not participate or to withdraw will not infringe on any of their regular VA benefits 
or medical care.  
 
The timing of the consent process will take place prior to any screening assessments.  The location 
of the consent process will primarily be in the site’s area where the research will be conducted, but 
is not limited to these areas.  Additional locations where the consent process could take place 
include a physician’s office, the investigator’s offices, and/or designated rooms where privacy can 
be maintained (to include Community Based Outpatient Centers (CBOCs) under the same FWA 
number as the VA facility conducting the research). Additional locations could include the 
participant’s home or community space where privacy can be maintained. 
 
During the consent process, the participant’s privacy will be maintained by using a private room.  
Participants who wish to have a family member or a friend in attendance during the consent process 
may do so.  Ample time for decision making will be provided and the potential participant will be 
allowed and encouraged to discuss the proposed clinical trial with anyone before making a 
decision.  
 
There will not be a plan for the consent of the individual’s Legally Authorized Representative 
because an inability to sign consent is exclusionary to this clinical trial. 
 
*Consenting of the companions may be obtained at the time the participant consents or during the 
Screening Phase for the enrolled participants. Consenting of the companions may take place in 
person or assent may be obtained over the phone. 
 
D. 
Participant Compensation 
 
A potential barrier to recruitment is the travel and time commitment for persons with SCI to enroll 

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in this study.  A small stipend of $30 per visit to the SCI Centers has been included in the budget 
to help defray some of the expense and inconvenience of travel for participants in this study. 
During Screening, stipends will be given for up to 3 visits for screening/baseline evaluations (max. 
$90) and up to 5 days for EAW basic training (max. $150).  At JJPVAMC, during the pilot study, 
it was found that participants were highly motivated to attend the 3 times weekly exoskeletal-
assisted walking sessions and compliance was greater than 90%.  Reimbursement for 
transportation and lodging may be made available to participants and companions who live more 
than 45 miles away from the SCI Centers. The amount will vary based on distance and will be 
arranged in advance with the study team.  
 
E. 
Safety Considerations 
 
Trainers will be able to identify symptoms and signs of autonomic dysreflexia (AD), such as rapid 
increase in blood pressure, flushing in the face, sweating above the level of injury; or symptoms 
of orthostatic hypotension, such as paling of the face and participant reporting lightheadedness. 
Study Trainers will have a policy in place at their facility in order to address these types of 
emergencies.  These policies should include a place where the participant can be brought to a 
sitting position or safely laid down on the floor. Once they are in a safe position, the cause of the 
problem can be assessed, and appropriate steps can be taken.  If there is an “error” in the ReWalk 
device, the Trainers will assist the participant to a sitting position using the graceful collapse 
feature. It will be strongly recommended that participants receiving anticoagulation therapy wear 
a helmet during use of the exoskeleton. 
 
F. 
Foreseeable Risks 
 
The potential risks associated with having a person with SCI dynamically load in an upright 
position and walk overground with a powered exoskeleton include: hypotension, low-impact 
fracture, falls resulting in bone fracture, muscle soreness or tear, joint damage, or other 
musculoskeletal injury, skin breakdown, and/or AD.  
 
To date the investigative staff at the JJPVAMC has trained 12 participants to use the ReWalk 
system.  In these initial 12 participants, there were no study related SAEs.  One participant fell as 
a result of undetected water on the floor, but was not injured from the fall. There were minor skin 
abrasions (reported as study-related adverse events), which were resolved with additional padding 
and alterations in the fitting of the device.  The group who initially studied the ReWalk at Moss 

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Rehabilitation Hospital, Philadelphia, PA reported their adverse events [43].  Esquenazi et. al., 
reported the following adverse reactions during his phase 1 clinical trial performed at Moss 
Rehabilitation Hospital, Philadelphia, PA: “(1) skin abrasions in areas of contact with the device, 
(2) lightheadedness, and (3) edema of the lower limbs [43, 83]. They were all managed by the 
appropriate use of (1) foam and padding, (2) caffeinated beverage intake and adjustment of blood 
pressure medication, (3) elastic stockings and rest, respectively. There were no detrimental 
changes in vital signs or complaints of lightheadedness with prolonged standing.” Additional 
hazards to walking overground using a robotic exoskeleton include the risk of equipment 
malfunction, battery dying, or any unknown or unpredictable problem.  
 
There are also some risks associated with the measurements obtained by the dual x-ray 
absorptiometry (DXA) scanner and the bilateral calcaneus x-rays.  These medical diagnostic 
devices emit small amounts of radiation, approximately 8µSv (DXA) and 2µSv (bilateral x-rays).  
This amount of radiation is similar to normal background radiation amounts from radon, food, 
water, and cosmic radiation.   There are risks associated with phlebotomy which include pain, 
swelling, bruising or skin irritation at the site of the venous puncture and rarely, syncope in persons 
who are susceptible to a vasovagal response. There are risks associated with anticoagulation 
therapy if a participant were to fall and hit their head. It will be strongly recommended that 
participants receiving anticoagulation therapy wear a helmet during use of the exoskeleton. 
 
G. 
Risk Management and Emergency Response 
 
All potential participants will be examined and their medical charts will be reviewed by the study 
team physician (who is also a member of the study site’s medical center staff) before being cleared 
for participation.  Study personnel will be in attendance at all times while a participant is using the 
exoskeleton and while all testing is being performed. Blood pressure and heart rate will be 
monitored before, during, and after the training sessions, primarily to identify changes in blood 
pressure.  The study staff will query the participants throughout each session for early signs or 
symptoms of hypotension such as feeling light headed or queasiness.  During the sessions, persons 
with a fall in blood pressure from their pre-session seated BP of >20/10 mmHg will be seated or 
brought to a supine position.  The staff involved with this study will be trained to look for signs 
and symptoms of AD.  Most persons with SCI are also knowledgeable about AD, but all 
participants will also be made aware of these signs and symptoms of AD.  The legs where the 
straps are fastened will be examined for skin breakdown during (as needed) and after training 
sessions to ensure that there are no areas that may be abrading. If evidence of skin redness, 

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irritation or breakdown exists, alternate placements for straps and/or padding will be used to 
protect the area. Participants who have continued breakdown will be temporarily discontinued. 
Participants will be checked after each session for signs of edema.  If edema is present, participants 
will be instructed to elevate their feet, use compression socks for the next session, and/or reduce 
the upright time or training frequency. If edema persists more than one day, the participant will be 
referred to the Site Physician.  Training sessions will be discontinued if need be. 
 
The ReWalk powered exoskeleton has safeguards built within the device to prevent or minimize 
injury to the user. The system can detect if there is a mechanical or electrical problem and 
automatically causes the device to remain in the standing position, preventing the user to walk in 
the system. The only movement the device will be able to do is sit down so that the user can be 
removed from the system safely.  If there is a mechanical error while in the sitting position, the 
device will not allow the user to stand in the system, and there will be a sound alerting the person 
that there is a problem. If there is a sudden loss of power while standing or walking, there is a 
safety mechanism that will stiffen the joints of the exoskeleton passively and cause the joints to 
rotate slowly so that the person can have a “graceful” collapse to the floor without causing them 
harm.  The “graceful” collapse function allows time for a protective response with the arms to 
reach for the ground.  The ReWalk exoskeleton is instrumented with two power sources; one main 
battery which has power for up to 4 hours of continuous walking and an additional back up battery 
which has power for up to an additional 30 min of walking.  The participant, companion and study 
team members will be instructed to ensure that the power source of the system is fully charged 
prior to any use of the ReWalk. 
 
To prevent tripping over obstacles, the areas used for the sit-to-stand, stand-to-sit, walking, and 
stepping will be checked before and during each session to be free of any obstacles and water on 
the floor.  There are risks associated with anticoagulation therapy if a participant were to fall and 
hit their head. It will be strongly recommended that participants receiving anticoagulation therapy 
wear a helmet during use of the exoskeleton. To prevent a potential fall, participants will not be 
progressed to walking until they have mastered the basic skills set.  Additionally, all participants 
will be spotted by at least one study team member (and/or their companion once trained) while 
using the ReWalk and never left unattended.  
 
Additional efforts to minimize the risk of fracture will be done by excluding those veterans with 
BMD in the extremely low range.  Measurement of the BMD is part of the screening and eligibility 
criteria for participation in this study.  Those potential participants who have low bone mass will 

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be excluded from the study (please see inclusion/exclusion criteria for details).  There is risk 
associated with radiation exposure.  The BMD assessment has a small amount of radiation 
exposure from the DXA scan. Measurements of two areas for BMD (hips and knees) will be 
performed one time for screening. The total body scan will be performed at baseline and will be 
repeated three additional times during the study.  The following is a list of radiation exposure 
associated with each scan area obtained in this study. 
 
Scan Type 
 
Entrance Dose  
Effective Dose 
Scan Time 
Hips 
 
 
329 μGy 
 
12.3 μSv 
 
212 sec 
Knee  
 
34 μGy 
 
unavailable 
 
54 sec 
Total Body 
 
6 μGy  
 
8.62 μSv 
 
739 sec 
Foot x-ray 
 
unavailable 
 
2.0 μSv 
 
<1 sec 
 
Values of radiation absorption (i.e. Effective Dose) for knee scans do not exist at this time. 
However, considering both the amount of radiation emitted and the scan time is lower than that of 
the other scans, the absorbed amount should also be lower than that of the hips (GE Medical 
Systems, Madison WI). The estimated sum quantity of radiation exposure from all of these DXA 
measurements combined is <35 μSv of absorbed radiation.  This measurement is minimal even 
when compared to a routine chest x-ray which has an approximate dose of 60 μSv.  In addition, 
the average person in New York City receives approximately 3000 μSv/year. Therefore, these tests 
would need to be repeated 85 times to receive an equivalent dose. 
 
H. 
Emergency Care Plan 
 
This study will be conducted in the VA hospitals at fifteen sites, in the CBOCs under the same 
FWA as the sites, or in the participant’s home/community.  During site visits and when training is 
conducted in the VA hospitals, the VA Hospital’s emergency department would be called in the 
event of a medical emergency.  If a participant is injured as a result of this study, the hospital site 
will be responsible for their medical care and the costs of this care.  If a participant is seriously 
injured in their home or community environment during training or when using the device in their 
home, the study team and the participant (or their companion) will be instructed to call 911. 
 
I. 
Potential Benefits 
 
The information gained from this study may be scientifically useful to the field of SCI medicine.  

CSP #2003 
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The individual may experience improvements in QOL, but this is not guaranteed.  An additional 
benefit of this study is to share the knowledge gained with the SCI Clinical Services in the VA 
system. 
 
The participant will have both the participant version of the Informed Consent and HIPAA forms 
to sign. The Companion will have the option to sign the companion version of the Informed 
Consent and HIPAA authorization or provide assent over the phone.  Only demographic 
information and AE / SAE information will be collected on the companions.  A sample version of 
these five documents may be viewed in the Human Rights section. 
 
XIX.  TRANSITION OF PARTICIPANTS 
 
The long-term aim of this study is to acquire information and share the new found knowledge and 
insights with the clinical SCI Services.  This information will assist the SCI Services to gain the 
necessary skills to develop and provide exoskeletal-assisted walking programs in-house with the 
anticipation of providing home prescription to interested and eligible Veterans and military 
members with SCI. It should be noted that before clinical staff can train patients at their facilities 
in the use of the exoskeleton, they will receive specific instruction/training in the use of the device.   
 
In addition to having a truly immediate translation to clinical care, our study will actually make 
possible the clinical use of the exoskeleton by training local professional staff to become 
sufficiently skilled in the training of Veterans and military members with SCI who wish to use this 
technology for upright ambulation.  In summary, clinical staff at the study sites will have the 
opportunity to directly participate in exoskeletal training, which will provide hands-on experience 
that will be readily transferrable to clinical care.  This study will provide important clinical 
information, such as who are the best candidates for home use of an exoskeleton, the average 
number of sessions needed to pass the advanced skills test, the level and completeness of SCI that 
is related to successful use of the device, how often and in what locations the exoskeletons should 
be used, and any unexpected adverse events or serious adverse events, if they should occur, 
associated with home use. The prosthetics and orthotics departments will gain the opportunity to 
learn about the system and how to fabricate additional padding, if needed, for participants in 
addition to setting up contracting for purchasing these types of devices. There are other 
exoskeletons which will become available. The experience that the facilities gain from 
participation in this study will be a basis to identify the important features these new systems may 
offer to improve clinical care provided to veterans with SCI. Perhaps most importantly for the 

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clinical services, is the question of there being unexpected adverse events or serious adverse events 
associated with home use as well as how much is this device actually being used in the 
home/community environment.   
 
XX.    IMPACT OF THE SARS-COV-2 (COVID-19) PANDEMIC ON VETERANS WITH 
SPINAL CORD INJURY  
 
This section has been added to the protocol to identify the impact of the COVID-19 pandemic on 
the screened participants from CS #2003. The questions to be asked are unrelated to the original 
research design and outcomes of CS #2003. A baseline questionnaire will be completed with 
screened participants as well as a follow-up questionnaire and a blood draw. These additions are 
at no additional cost to the study. All costs will remain budget neutral within each site. Although 
a budget for each site will be provided, it is understood that each site will cover these costs within 
the approved budget for their site. 
 
A. Background 
 
In the United States (US), the first case of the 2019 novel coronavirus disease (COVID-19), caused 
by the severe acute respiratory syndrome SARS-CoV-2 virus, was reported on January 19, 2020 
(Holshue, et.al., NEJM March 2020). As of May 
26, 2020, the US had 1,697,361 confirmed cases 
with 99,462 deaths and in the Veteran’s Affairs 
Health system, there had been 13,327 positive cases 
and over 1,133 deaths. The numbers of positive 
cases and deaths in the cities where the VA CS 
#2003 study sites are located is provided (Table 
20).   
 
There is limited information available on how 
Veterans with SCI have been affected by COVID-
19.  The most severe and direct negative impact for 
Veterans with SCI would be to contract COVID-
19. Indirect negative impacts may also stem from 
the loss of caregiver or home attendant services, 
difficulty accessing routine healthcare, maintaining 

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wheelchairs, assistive and/or adaptive equipment, and other inconvenient and potentially harmful 
disruption of services that may be occurring. Positive indirect benefits may also be occurring, such 
as increased access to internet-based activities. 
 
B. Rationale  
 
Veterans with SCI are often immunosuppressed and have chronic health conditions (e.g. 
cardiovascular disease, respiratory compromise, metabolic disease including diabetes mellitus) 
that place them at a potentially higher risk of complications and more severe symptoms should 
they contract COVID-19. Additionally, individuals with SCI may be debilitated from poor 
nutrition, experience chronic pressure injuries with or without osteomyelitis, have concurrent 
respiratory infections, and experience frequent urinary tract infections (UTI). Of note, individuals 
with higher cord lesions who have difficulty clearing secretions from their lungs because of an 
impaired or absent cough due to respiratory muscle weakness from paralysis are at a higher risk of 
developing pneumonia and its complications. The signs and symptoms of COVID-19 may be 
different in individuals with SCI than the general population. For example, the high fevers 
characteristic of COVID-19 in the general population may not be observed in persons with 
tetraplegia, who experience lower core body temperatures, thereby requiring a different definition 
of fever for symptom surveillance and clinical diagnosis. Also, the common feeling reported of 
chest pressure may be absent in those who are insensate in this area. Persons with respiratory 
compromise, may experience shortness of breath earlier in the course and decline more rapidly, an 
indication for earlier admission and closer surveillance. 
 
In the Veterans Health Administration (VHA) and the Spinal Cord Injury and Disease (SCI/D) 
National Registry, there are 17,806 Veterans with SCI.  It is not known how many Veterans with 
SCI are, or will be, directly infected by this virus, nor the severity of their symptoms and survival 
rates.  However, it is anticipated that, due to their high risk of immunodeficiency and other co-
morbidities, the occurrence may be higher, with the potential for more severe symptoms and 
greater mortality than in the general population.   
 
Additionally, of great concern, is the anecdotal report of loss of services, including routine medical 
care for non-COVID-related conditions (i.e. pressure injuries, urinary tract infections, etc.), loss 
or interruption of caregiver services, and wheelchair or assistive devices repair options, that has 
been an unfortunate consequence of the pandemic. Mr. James Weisman, President and CEO of 
United Spinal Association, Inc. (a membership of 58,000 nationwide which includes about 1500 

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Veterans with SCI) stated on March 30, 2020: “Homecare workers, always in short supply, are 
staying home watching their kids, self-isolating because of potential exposure--or exposure, and 
traveling via public transportation to patients and potentially exposing them. More than ever, it 
has become obvious that adequate homecare services are a fundamental necessity of the SCI 
community in order to stay out of nursing homes and hospitals…. And many are replacing 
caregivers with family members out of fear they will become infected from the caregiver”.     
 
The VA Cooperative Study Program’s CS #2003 is able to use the existing study staff to 
conduct a baseline survey/medical chart review, a follow-up survey and a blood draw.  The 
survey would be used to determine the participant-reported direct medical effects of 
COVID-19 (with the use of the medical record when and if information is available) and the 
indirect psychosocial and environmental impacts of 
COVID-19 on Veterans with SCI who have been screen-
consented for CS #2003.  This knowledge would provide 
a “snapshot” of what is occurring across the nation in 
Veterans with SCI and will enable us to plan to meet the 
immediate needs of the Veteran SCI community as the 
course of the pandemic becomes known across the US. This 
information will be important to the VHA and the SCI/D 
National Service to be able to better prepare for future 
pandemics and other natural disasters. Immediate benefit 
may be the identification of Veterans with SCI who are in 
urgent need of services. This information would be relayed 
back to the medical center providers. As of the date of the 
administrative hold for CS #2003 on March 16, 2020, more 
than 400 Veterans with SCI had been screened for 
participation across 15 VA sites.  A list of the number 
screened by site is provided (Table 21). 
 
The infrastructure for VA CS #2003 is in place with funding on stations through September 30, 
2020 and a full budget (4 staff per site at 14 sites) is requested for fiscal year (FY) 21 (Houston 
was withdrawn as a site in 2018, but those screened participants can be contacted by the San 
Antonio site staff). VA CS #2003 was put on a voluntary administrative hold on March 16, 2020.  
CS #2003 study staff will be trained to conduct the surveys and medical chart reviews while other 
clinical research is on hold and to continue to conduct the surveys once the administrative hold has 

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been lifted. The administrative hold has been lifted for the COVID-19 survey and blood draw. 
 
The initial phone or in-person survey serves to capture COVID-19 information from the Veterans 
with SCI themselves that may not be in the medical record.  This survey includes SCI-specific 
questions related to demographics, neurological characteristics and any loss of services during the 
pandemic.  For example, information will be recorded such as the amount of assistance provided 
before the pandemic, the loss or reduction in home care services since the pandemic, other 
potentially negative consequences, and potential positive consequences such as offering of and 
inclusion in more internet-based social activities or telehealth medical services.  The phone survey 
will be the primary method of collecting the information, with the option to complete the survey 
in person. 
 
A medical chart review will be used for retrieving medical history and COVID-19 medical 
information when applicable (some Veterans with SCI may not be treated at their VA hospital, but 
rather at a local non-VA hospital, in which case this medical information may not be available to 
the study staff).  The chart review will consist of information from the Spinal Cord Injury and 
Disease (SCI/D) National Office for COVID-19, using the “Coronavirus Disease 2019 SCI Screen 
(COVID-19 SCI Screen)” and other COVID-19-related medical records, if applicable. The 
medical records of Veterans with SCI may contain the COVID-19 SCI Screen information and 
will be recorded on the survey.  Any additional medical information will be recorded as 
appropriate.   
 
A follow-up “in-person” visit to update information from the initial survey and to collect blood 
samples for virus testing, anti-viral antibody, and other immune analyses relevant to the COVID-
19 disease will be planned at least one month after the initial survey. The antibody, cytokine, and 
other immunological analyses at a future date when our country has recovered from this current 
pandemic will be critical for determining the number of Veterans with SCI who were infected with 
the virus, the relationship with the signs and symptoms of infection, if any, and the rate of survival 
in this population sample. There will also be an option to complete the follow-up survey over the 
phone for participants who do not wish to travel to the local VAs. An option to complete the blood 
draw in the home will be available through the services of a VA contracted phlebotomist vendor, 
ExamOne. 
 
The initial survey and follow-up survey, medical chart review, and blood draw are intended to 
capture the following information: 

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Questions related to the direct impact of COVID-19 on Veterans with SCI will be collected by 
phone interview using Doximity.  Doximity allows for a registered physician (or delegate) to log 
in and set a phone number, such as each local VA Medical Center who would be represented in 
this study.  The person receiving the call sees the VA Medical Center as the caller ID. Participants 
will also have the option to complete the initial survey by in-person interview. 
 
In Veterans with SCI, the following information will be collected (but not limited to): 
a) The number who are/were diagnosed with COVID-19, determined from the medical 
records and/or interviews; 
b) The number who presented with symptoms, determined from the medical records and/or 
interviews; 
c) The type, duration and severity of symptoms, determined from the medical records and/or 
interviews;  
d) The number who have anti-SARS-CoV-2 antibodies, with testing to be performed at least 
one month after initial interview (or whenever is deemed safe for an in-person visit to the 
medical centers); and 
e) The number and characteristics of those who survived. 
 
Questions related to the indirect impact of COVID-19 pandemic on Veterans with SCI who rely 
on caregiver assistance and other services that may have been interrupted during the COVID-19 
outbreak will be determined via interview. 
 
The following information will be collected (but not limited to): 
a) The number who report any caregiver assistance; 
b) The relationship to the person(s) who provides the assistance (family, friend, aide, 
healthcare worker, etc.); 
c) The number whose caregivers live with them; 
d) The number whose caregivers travel to their homes; 
e) Adverse health consequences that resulted from reduced or lack of caregiver assistance 
a. Any clinically relevant/significant health event during the study period, such as: 
pressure injury, UTI, fracture, or other, 
b. Lack of access to in-person medical services when requested or needed (in other 
words-is the overwhelmed healthcare system also affecting their more general 
access to care?). 
b) Other adverse consequences of the COVID-19 pandemic on persons with SCI, such as: 

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a. Wheelchair maintenance/repair interruption, 
b. Prescription renewal interruption, 
c. Social isolation (lack of interactions with others), 
d. Became unemployed, or 
e. Other 
 
Questions related to the potential positive consequences of the COVID-19 pandemic would also 
be explored for: 
a) Participation in virtual support groups (i.e. chat groups, other) 
b) Participation in virtual exercise/physical therapy programs 
c) Participation in virtual recreation therapy programs, or 
d) Other. 
 
Most of the survey questions have been developed with fixed-format answers, with as few open-
ended questions as possible.   
 
C. Methods 
 
Participants: Veterans with SCI who were initially screened for CS #2003 will be contacted to 
determine willingness to be consented for participation in the survey and medical chart review and 
to be consented for the follow-up survey and blood draw at least one month from the initial survey. 
 
The goal is to interview as near to 100% of the 400 plus Veterans with SCI as possible.  We believe 
it is possible to recruit as many as 90% (approximately n=381), but to be conservative, we are 
expecting 80% (approximately n=338).  Eighty percent (80%) is realistic because the sites’ staff 
already know these Veterans with SCI, many of whom would be motivated to know if they have 
anti-SARS-CoV-2 antibody, will have missed their annual physicals during the pandemic, and will 
already be scheduled, or in the process of scheduling, to visit their VAMC. (In these cases, the CS 
#2003 staff would coordinate with the SCI/D service whenever possible to schedule both visits at 
the same time.) 
 
Baseline/Initial Survey:  Two survey forms will be used to collect the medical chart information 
and the responses from the participant.  The medical chart review contains SCI-specific questions 
to record SCI characteristics of the participants.  The survey will also record the loss or reduction 
in home care services and other potentially negative or positive consequences.   

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Follow-up Visit:  After the COVID-19 national crisis has subsided, a follow-up visit (at least one 
month after the initial survey) will be scheduled at the VA Medical Centers for any of the Veterans 
with SCI who participated in the initial survey.  During this follow-up visit, the participant will 
have the option to complete a blood draw and follow-up survey. Additionally, any of the over 400 
Veterans with SCI who present to the VA Medical Centers who had not received the initial contact 
and interview would also be eligible to be interviewed in-person and for the blood draw. If 
participants complete the follow-up survey, they will receive a stipend of $50. No additional 
funding is being requested from CSP for this stipend. All costs will remain budget neutral within 
each site. 
 
Blood collection:  A single blood draw for a total of 20.0 mL of blood for the following will be 
performed: 
1. To be analyzed at each site’s local VA laboratory: 
a. One red top tube (6.0 mL) for c-reactive protein (CRP), spun down for serum and 
separated into 4.0 mL for the local lab and 2.0 mL to be frozen and shipped to the 
Chair’s Office for antibody testing. 
b. One purple top tube (6.0 mL) for complete blood count with differential (CBC 
w/Diff) as whole blood (not spun down) for the local lab. 
c. Note:  Each site will need a laboratory agreement to pay for the costs of the CBC 
w/Diff and CRP tests.  
2. To be shipped to the Chair’s Office for analyses: 
a. From the red top tube above, 2.0 mL, frozen serum for antibody testing 
b. One green top tube (5.0 mL) spun down for plasma and frozen for cytokine testing 
c. One PAX gene tube (3.0 mL) frozen as whole blood for transcriptional analysis 
 
If participants complete the blood draw, they will receive a stipend of $50. No additional funding 
is being requested for this stipend. All costs will remain budget neutral within each site. 
 
There will be an option to complete the blood draw at the participant’s home through services 
provided by a VA contracted phlebotomist vendor. The vendor, ExamOne, will only provide the 
blood collection service. They will not be engaged in research activities. All questions about the 
study (other than blood collection visit schedules and blood draw procedures) will be directed to 
the local site team and/or the Chair’s Office. ExamOne will spin down the samples, as appropriate, 
and deliver them to the local site personnel for freezing or local site lab analysis. 
 

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All blood samples will be labeled with the study ID, date and a coded participant ID number.  The 
serum and plasma of each spun down tube and the PAX gene tube with whole blood will be stored 
in a freezer for shipment to the James J Peters VA Medical Center, Bronx, NY (Chair’s Office). 
The cytokine testing will include:  Interleukin-1 (normal range 0-5 pg/ml);  Interleukin-6 (normal 
range 5-15 pg/ml); Interferon-alpha (normal range 0 to 35 U/L), Interferon-gamma (normal range 
<8.1 pg/mL), tumor necrosis factor (TNF)-alpha (normal range ≤ 2.8 pg/mL, and TNF-gamma 
(normal range <10 pg/ml). 
 
The optimum methodology to perform the antibody analyses will be determined in consultation 
with the VHA Infectious Disease Service and the Clinical Laboratory at the time of sample 
analysis. In the future, biological values and other clinical data will may be compared to other 
populations, including Veterans without SCI or non-Veterans with SCI. 
 
Timeline:  It is estimated the study staff can complete the initial surveys on screened participants 
by the end of September 2021. Once the medical centers have re-opened to outpatient visits, the 
in-person or phone visits for the follow-up surveys and in-person visits for blood draws can be 
completed by the end of FY21, which is within the timeframe of the completion of CS #2003.  An 
estimated timeline is provided (Table 22). 
 
D. Relevance   
 
This information will be used to inform the VHA of the medical, sociological and/or quality of life 
impacts from the COVID-19 pandemic on Veterans with SCI who were screened for CS #2003.  
Specifically, for the medical impact, we will learn about the number in this sample who were 

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infected, their symptoms (if any) and severity, any associated illnesses, immunological responses, 
and the number of individuals who recovered and survived.   The sociological and quality of life 
impact of this virus will also be reported, including the interruption of vital services such as 
caregivers, medical appointments, wheelchair repair, levels of anxiety, and other aspects.   We will 
also learn about any positive occurrences that may be reported such as usage of telemedicine, and 
more access to online social groups or web-based activities. Important benefits from this project 
will be to improve preparedness for future local and/or national disasters in order to protect 
Veterans living with SCI from untoward exposure and/or loss of services. 
 
Notes for consideration: 
 
 On the follow-up visit, if the participant has a positive test for anti-SARS-CoV-2 antibodies, 
we will know that they had the COVID-19 infection at some time in the past (and even could 
have been asymptomatic); these individuals would be categorized as persons who have 
survived.  If they test negative for anti-SARS-CoV-2 antibodies, then we will know they had 
not been infected as of the date of the test. 
 Some of the Veterans with SCI who participate in the baseline/initial survey will have already 
been diagnosed with viral infection and/or COVID-19 (many of our institutions already have 
some Veterans with SCI who have tested positive for the virus).  Some Veterans with SCI are 
being treated for COVID-19 based on severe symptoms and may not have been tested for viral 
infection by lab diagnostics until after they have been treated. Other individuals with less 
severe symptoms, that did not require hospitalization, may not have been tested for COVID-
19 using lab tests.  In these cases, the antibody testing will reveal how many people with SCI 
in our study sample had the virus.  
 If a Veteran with SCI who was screened for our study has died during this time, the information 
about the death may be in the medical record at that Veteran’s VA medical center and we will 
be able to capture it from chart review.  However, it is recognized that information about those 
who did not survive will be the most difficult to get for many reasons: lack of documentation 
in the medical record, lack of definitive information about the cause of death, lack of a COVID-
19 diagnosis, etc. 
 If a Veteran with SCI who participates in the baseline/initial survey dies at some time 
afterwards, then upon follow-up, we may learn about the death and be able to acquire some of 
this information from medical records.   
 

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o The additional workload to conduct the survey and in-person visit with the blood 
draw will be able to be continued without interruption to the usual tasks and duties 
that are required for CS #2003. 
 
E. Limitations   
 
The screened participants for CS #2003 would have met the inclusion criteria for CS #2003.  As 
such, the Veterans with SCI in this survey sample would have tended to be those with more 
function and, as a result, will be a biased sample.  The generalizability for the results would 
therefore be limited to the demography of this sample. 
 
If some, or all, of the Sites’ VA medical centers have not re-opened by next year, the study staff 
could still complete the follow-up survey and chart reviews from telework.  The survey is of value 
even without the blood draw since identification of adverse and/or positive aspects of the pandemic 
would be informative for future preparedness for Veterans with SCI. 
 
Considerations for how the blood draws can safely take place will be discussed at that time and 
may include solutions such as staff in full Personal Protective Equipment (PPE) going to the 
Veterans home to take the blood sample. 
 
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