The Effects of Incorporated Exoskeletal-Assisted Walking in Spinal Cord Injury (SCI) Acute Inpatient Rehabilitation
Phase: NA
Conditions: Spinal Cord Injuries, Inpatient
Sponsor: Icahn School of Medicine at Mount Sinai

The Effects of Incorporated Exoskeletal-Assisted Walking in SCI Acute Inpatient Rehabilitation
PI: Ann M. Spungen EdD
NCT04221373
Document Date: April 24, 2023

The Effects of Incorporated Exoskeletal-Assisted Walking in SCI Acute Inpatient Rehabilitation
Version 0.035
Protocol : STUDY-19-00614
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NIH-FDA Clinical Trial Protocol Template – v1.0 2017-04-07
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The Effects of Incorporated Exoskeletal-Assisted 
Walking in SCI Acute Inpatient Rehabilitation
Unique Protocol Identification Number: 
National Clinical Trial (NCT) Identified Number: NCT04221373
Principal Investigator: Ann M. Spungen
IND/IDE Sponsor: N/A, the device has got FDA approval.
Funded by: New York State Department Of Health
Draft Number: 0.035
21 May 2021
Summary of Changes from Previous Version:
Affected 
Section(s)
Summary of Revisions Made
Rationale
Table of Contents
 Table of Contents - Please right-click and choose 'Update Field'.
Effective Date: 4/24/2023
End Date:4/23/2024

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STATEMENT OF COMPLIANCE
Provide a statement that the trial will be conducted in compliance with the protocol, International 
Council on Harmonisation Good Clinical Practice (ICH GCP) and applicable state, local and federal 
regulatory requirements. Each engaged institution must have a current Federal-Wide Assurance (FWA) 
issued by the Office for Human Research Protections (OHRP) and must provide this protocol and the 
associated informed consent documents and recruitment materials for review and approval by an 
appropriate Institutional Review Board (IRB) or Ethics Committee (EC) registered with OHRP. Any 
amendments to the protocol or consent materials must also be approved before implementation. Select 
one of the two statements below. If the study is an intramural NIH study, use the second statement 
below:
1.
The trial will be carried out in accordance with International Council on Harmonisation Good
Clinical Practice (ICH GCP) and the following:
o
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training.
OR
2.
The trial will be conducted in accordance with International Council on Harmonisation Good
Clinical Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and
the [specify NIH Institute or Center (IC) [ Terms and Conditions of Award. The Principal
Investigator will assure that no deviation from, or changes to the protocol will take place
without prior agreement from the funding agency and documented approval from the
Institutional Review Board (IRB), and the Investigational New Drug (IND) or Investigational
Device Exemption (IDE) sponsor, if applicable, except where necessary to eliminate an
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study
have completed Human Subjects Protection and ICH GCP Training.
For either option above, the following paragraph would be included:
The protocol, informed consent form(s), recruitment materials, and all participant materials will
be submitted to the IRB for review and approval. Approval of both the protocol and the consent
form(s) must be obtained before any participant is consented. Any amendment to the protocol
will require review and approval by the IRB before the changes are implemented to the study.
All changes to the consent form(s) will be IRB approved; a determination will be made regarding
whether a new consent needs to be obtained from participants who provided consent, using a
previously approved consent form.
Effective Date: 4/24/2023
End Date:4/23/2024

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1 PROTOCOL SUMMARY
1.1 SYNOPSIS
Title:
The Effects of Incorporated Exoskeletal-Assisted Walking in SCI Acute 
Inpatient Rehabilitation 
Study 
Description:
A randomized controlled trial
Objectives:
Primary Objective:
Primary Objectives: To determine the effects of acute 
inpatient rehabilitation (AIR) with exoskeletal-
assisted walking (EAW) compared with AIR without 
EAW (same total therapy time) on the changes from 
admission to discharge in the International Standards 
for Neurological Classification of Spinal Cord Injury 
(ISNCSCI) upper and lower extremity motor scores, 
Functional Independence Measure (FIM) scores, and 
Spinal Cord Independence Measure (SCIM) scores as 
classified by clinicians. Primary hypothesis: At 
discharge, compared to the baseline data (collected at 
admission), the AIR with EAW group will have 
significantly greater changes in ISNCSCI, FIM, and 
SCIM scores compared to the AIR without EAW 
group.
Secondary 
Objectives:
To determine the effects of AIR with EAW compared 
to AIR without EAW on reducing pain using the 
International Spinal Cord Injury Basic Pain Data Set 
2.0 (ISCIBPDS 2.0) measures where type of pain is 
classified with the Spinal Cord Injury Pain Instrument 
(SCIPI). Secondary hypothesis: At discharge, 
compared with baseline, the AIR with EAW group 
will report significantly more reduction in the average 
intensity of the participant's worst pain over the 
preceding 7 days than the AIR without EAW group.
Tertiary Objectives:
To determine the effects of AIR with EAW compared 
with AIR without EAW on reducing a specific 
systemic inflammatory mediator (C reactive protein, 
CRP). Tertiary hypothesis: At discharge, as compared 
with baseline, the AIR with EAW group will have 
greater reductions in measured values for CRP than 
the AIR without EAW group.
Endpoints:
Primary Endpoint:
The changes from admission to discharge in the 
International Standards for Neurological 
Classification of Spinal Cord Injury (ISNCSCI) 
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upper and lower extremity motor scores, Functional 
Independence Measure (FIM) scores, and Spinal 
Cord Independence Measure (SCIM) scores
Secondary Endpoints: Pain evaluation using the International Spinal Cord 
Injury Basic Pain Data Set 2.0 (ISCIBPDS 2.0) 
measures where the type of pain is classified with the 
Spinal Cord Injury Pain Instrument (SCIPI).
Tertiary Endpoints: 
systemic inflammatory mediator (C reactive protein, 
CRP)
Study 
Population:
Individuals with SCI who stay in the SCI acute inpatient rehabilitation
Phase:
NA
Description of 
Sites/Facilities 
Enrolling 
Participants:
Icahn School of Medicine at Mount Sinai
Description of 
Study 
Intervention:
In the intervention group, participants will receive locomotor training 
provided with an Ekso™ powered exoskeleton. The EAW training will be 
incorporated into the designated therapy times (3 hours of physical therapy 
(PT) and/or occupational therapy (OT)).
Study Duration: 3 years
Participant 
Duration:
Twenty to thirty minute per session, one session a day, equal or more than 3 
sessions/days per week, from enrollment in the study to discharge from the 
acute inpatient rehabilitation. Different participants have different duration of 
participation based on their length of inpatient stay.
Effective Date: 4/24/2023
End Date:4/23/2024

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2 INTRODUCTION
2.1 STUDY RATIONALE
The purpose of this fellowship is to conduct a prospective, randomized controlled trial (RCT) in two 
groups to determine if exoskeletal-assisted walking (EAW) training, incorporated in acute inpatient 
rehabilitation (AIR), is a feasible, safe and efficacious approach to facilitating functional independence 
and reducing pain and inflammatory response in those with a spinal cord injury (SCI) who are candidates 
for locomotor training during AIR.
2.2 BACKGROUND
Paralysis from traumatic SCI results in an abrupt reduction in the level of daily physical activity. 
Depending on the neurological level and completeness of SCI, those with more severe SCI may lose 
neuromuscular control of the upper extremities, trunk, and/or lower extremities which can result in a 
loss of the ability to sit, stand and walk and to perform activities of daily living (ADLs). For people with 
SCI, the ability to walk consistently rank at the top of their priority list for recovery [1, 2]. Most feel that 
their quality of life is lower than it could be without SCI due to difficulties in independently performing 
daily activities, finding a job or vocation, and challenges in participating in all that a community may 
offer [3]. Reductions in physical activity and other physical changes also promote pain in individuals with 
SCI, including the two main subtypes of neuropathic and nociceptive musculoskeletal pain [4]. 
Approximately 80% of people with SCI experience ongoing pain [5], and about 20% of people with SCI 
indicate that this pain interferes with work and daily activities [6]. Furthermore, immobilization and 
paralysis after SCI often leads to a sedentary life style resulting in loss of muscle mass and gain of 
adiposity [7]. This change in ratio of muscle to fat mass predisposes to insulin resistance and the 
development of type II diabetes mellitus as well as to obesity [7-10]. A compromised immune system 
has also been reported to occur after SCI with evidence of increased markers of systemic inflammation, 
including elevated CRP [11-15]. Changes in cholesterol and triglyceride levels as well as 
immunosuppression, such as reduced natural killer, T-cell, and lymphocyte functions, have also been 
reported [11-16]. The inflammatory response may also play an important role in the modulation of pain 
after SCI [17, 18]. Clinical data shows that elevated inflammatory mediators are present in persons with 
acute or chronic SCI, including factors that mediate pain in preclinical models [14, 19-21]. Reductions of 
functional activity and increased pain and
inflammatory response all worsen each other, negatively impacting an individuals' quality of life.
Locomotor training for people with SCI using body weight supported treadmill training (BWSTT) has 
been reported to increase muscle mass [22, 23], improve cardiovascular function [24], decrease 
spasticity [25], decrease pain [26], and preserve bone density [23, 27]. Although walking is considered a 
light intensity physical activity, a number of studies have shown clinically meaningful health benefits 
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from a consistent regimen of walking, in diverse populations including those who are overweight or 
obese [28, 29], postmenopausal [30], and elderly [31, 32]. In people with chronic obstructive pulmonary 
disease and peripheral artery disease, walking impairment has been associated with higher levels of 
systemic inflammatory cytokines [33, 34]. In persons with SCI, consistent exercise has been associated 
with a reduction in inflammatory mediators, e.g. CRP, as is seen in able-bodied people [35]. These data 
support the view that even light physical activity in persons with SCI could have clinically meaningful 
therapeutic effects resulting potentially in a reduction of systemic inflammation.
In theory, adding locomotor training to AIR may have the potential to improve motor recovery and 
functional independence through neuroplasticity. A study has shown that in an animal model locomotor 
training in the acute stage could improve the connectivity of the spinal neurons after SCI, resulting in 
reflex excitability and reduced spasticity [36]. People with SCI who participated in intensive locomotor 
training (five days per week for 8 weeks) using BWSTT within 6 months after SCI had a greater rate of 
improvement in lower-extremity motor scores than those who received this intervention in the chronic 
stage of SCI [37]. Patients also report the desire to begin physical training as soon as possible after acute 
SCI and to continue the inpatient training longer than conventionally available [38].
Powered exoskeletons are a technology that can offer overground locomotion for people with SCI who 
would ordinarily be unable to walk and have been suggested as a way to promote increased function 
and quality of life [39]. In studies pioneered by Dr. Spungen (co-mentor), exoskeletons have been 
studied in the chronic (>6 months post) SCI population for about seven years with preliminary reports 
showing benefits in mobility, health and quality of life (QOL) outcomes [40, 41]. While walking in an 
exoskeleton, people with SCI stand upright with full weight bearing through the feet [41] and walk while 
activating trunk and lower limb muscles. This activation may facilitate improvements in 
neuroconnectivity [39]. EAW has several benefits over BWSTT. It provides ground gait training 
experience that offers the potential benefits of standing and gait training with just one trainer and 
requires less of a constant equipment space allotment in an inpatient rehabilitation setting. EAW also 
possesses the unique potential for use after inpatient discharge to continue training and allow 
functional use in home, work, and community settings.
Previous studies show that EAW can elicit moderate-intensity activity for people with SCI, and 
participants can learn to walk without hands-on physical assistance by another person [40, 42-44]. 
Subjective reports from inpatients who were given the opportunity to use an exoskeleton during AIR in 
Mount Sinai Hospital had comments such as: "it was really great to have the legs moving again", 
"walking helped with regaining trunk support" and resulted in "good sensations in the legs and feet".
Despite the potential functional and health benefits of using EAW training in persons in SCI AIR, there 
are few studies published that have used, or are using an EAW intervention in early inpatient 
rehabilitation for patients with acute/sub-acute SCI. As such, there is a critical gap in knowledge that 
limits the use of EAW across the clinical care spectrum in SCI: we don't know if the EAW can be 
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effectively incorporated in clinical practice and if adding EAW into AIR program is better than traditional 
AIR without EAW. We expect this prospective randomized control trial (RCT) to determine if EAW 
training during AIR is a feasible, safe and efficacious approach to facilitate functional independence and 
to reduce post-SCI pain, as well as inflammation.
2.3 RISK/BENEFIT ASSESSMENT
2.3.1 KNOWN POTENTIAL RISKS
There are several potential risks associated with the EAW and the testing procedures.
1) EAW training has the potential risks of hypotension, falls resulting in bone fracture, muscle soreness,
joint damage, or other musculoskeletal injury, and/or autonomic dysreflexia (AD).
2) Persons using the Ekso may also be at risk for bruising, skin abrasion, pressure sores, soft tissue injury,
or adverse tissue reaction from direct contact of the body with the device. Notable contact points exist
between the sacrum and back pack, hip pads and greater trochanters, shin pads and shins, and with the
straps for the thighs and legs.
3) Other possible risks to exoskeleton use include discomfort, triggered spasms, reflex bowel or bladder
activity, diastolic hypertension and changes in blood pressure and heart rate, or autonomic instability
during use of the device.
4) The person operating the controller could initiate a use error by incorrectly inputting individual
participant specifications which could affect the participant's ability to move correctly with the device
thus increasing risk to the participant.
5) Lastly, the device itself could malfunction due to premature battery failure, interference with other
electrical equipment or devices, electrical shock, or unanticipated operation (stoppage or unintended
movement).
6) Psychological risks could include anxiety (e.g., when you begin walking training), altered mood when
you complete the questionnaires, and depression (e.g., when you end the study).
7) Risk of loss of private information; this risk always exists, but there are procedures in place to
minimize the risk.
2.3.2 KNOWN POTENTIAL BENEFITS
There is no expected benefit to subjects. However, possible benefits may be improving subjects' 
activities of daily living or reducing their pain or systemic inflammation from early intervention of 
walking training using EAW, although it is not guaranteed. These benefits may not continue after 
subjects discharge from the hospital and stop the walking training.
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3 OBJECTIVES AND ENDPOINTS
OBJECTIVES
ENDPOINTS
Primary
To determine the effects of AIR 
with EAW compared with AIR 
without EAW (same total 
therapy time) on the changes 
from admission to discharge in 
the International Standards for 
Neurological Classification of 
Spinal Cord Injury (ISNCSCI) 
upper and lower extremity motor 
scores, Functional Independence 
Measure (FIM) scores, and 
Spinal Cord Independence 
Measure (SCIM) scores as 
classified by clinicians.
ISNCSCI examination results
FIM scores
SCIM scores
Secondary
To determine the effects of AIR 
with EAW compared to AIR 
without EAW on reducing pain 
using the International Spinal 
Cord Injury Basic Pain Data Set 
2.0 (ISCIBPDS 2.0) measures 
where type of pain is classified 
with the Spinal Cord Injury Pain 
Instrument (SCIPI).
Intensity of pain
Tertiary/Exploratory
To determine the effects of AIR 
with EAW compared with AIR 
without EAW on reducing a 
specific systemic inflammatory 
mediator (C reactive protein, 
CRP).
CRP results
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4 STUDY DESIGN
4.1 OVERALL DESIGN
A two-group, single-blinded (raters are not part of intervention) and randomized clinical trial (RCT) with 
stratification for traumatic or non-traumatic injury will be performed. The stratification will help to 
ensure balanced groups prior to randomization.
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5 STUDY POPULATION
5.1 INCLUSION CRITERIA
1. Age 18 years or greater
2. Height between 5'2" and 6'2" (1.6 meters to 1.9 meters)
3. Weight less than 220 pounds (100 kilograms)
4. Near Normal range of motion (ROM), as follows: 1) Hip: more than 5 degrees of extension and 110
degrees of flexion; 2) Knee: Full extension to 110 degrees of flexion; 3) Ankle: at least 0 degree of
dorsiflexion to 25 degrees of plantarflexion
5. Are eligible for locomotor training as part of inpatient rehabilitation
6. Independent with static sitting balance
7. Sufficient function upper extremity strength to manage walking aid (front-wheeled walker, platform
walker, or crutches)
8. Able to follow directions
5.2 EXCLUSION CRITERIA
1. Uncontrolled cardiovascular conditions (i.e. heart failure, angina, hypertension)
2. Inability to sit upright due to orthostatic hypotension
3. Any form of progressive SCI as defined by the physician, such as cancers
4. Upper leg length discrepancy > 0.5" or lower leg discrepancy >0.75"
5. Skin integrity issues in areas that would contact the device or that would likely be made worse by
device use
6. Pregnancy, colostomy, mechanical ventilation
7. Any other medical issue in the judgment of his/her clinicians that might prevent safe standing or
walking
8. Non-English Speaking
9. Cognitive and/or communicative disability (e.g. due to brain injury). Participants must be able to
follow directions
well and demonstrate learning capability.
5.3 STRATEGIES FOR RECRUITMENT AND RETENTION
Prospective subjects will be recruited following admission to the AIR unit at Mount Sinai Hospital. 
Attending physicians and rehabilitation clinicians will identify patients admitted to the unit who may be 
eligible for the study. The informed consent process will be provided to interested and prospective 
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participants. Once the consent form is signed, a research team member and the study physician will 
begin the screening process for the inclusion/exclusion criteria.
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6 STUDY INTERVENTION
6.1 STUDY INTERVENTION(S) ADMINISTRATION
6.1.1 STUDY INTERVENTION DESCRIPTION
Intervention (N=20): In the intervention group, participants will receive locomotor training provided 
with an Ekso™ powered exoskeleton according to the standard of care of AIR at Mount Sinai Hospital 
with the exception that the EAW training will be incorporated into the designated therapy times (3 
hours of physical therapy (PT) and/or occupational therapy (OT)) which will be provided as determined 
by the clinical team from the earliest time they are identified to be able to safely stand, through 
discharge. The goal of EAW intervention is to complete three or more sessions of EAW training a week 
during the AIR period (after enrolling into the study until discharge). One EAW session is defined to have 
at least 20 minutes of uptime in the device (based on data output from EksoTM, device, not including 
donning and doffing time). EAW sessions will include device fitting, instruction for sit-to-stand and 
stand-to-sit maneuvers; balance and fall protection training; and walking on smooth indoor surfaces 
with total or variable device assistance. The clinical team will determine the frequency, duration, and 
intensity of each EAW session based on the participant's response to the previous session.
Control (N=10): In the control group, participants will receive standard of care AIR which includes three 
hours of PT and/or OT per day until they are discharged. This standard of care AIR may include bed 
mobility, balance, strength, gait, transfers, and wheelchair mobility training to improve participants' 
independence in activities of daily living, such as bathing, eating, dressing, grooming, and wheelchair use 
but does not include EAW. The two groups (control and intervention) will have the same total amount of 
therapy time.
6.2 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING
Eligible participants will be randomized into either the intervention group or the control group. In order 
to provide more opportunities for participants to accept EAW training, the intervention group will have 
20 participants, and the control group will have 10 participants.
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7 STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1 DISCONTINUATION OF STUDY INTERVENTION
Subjects may be withdrawn without their consent if it is found that they do not meet eligibility criteria 
for the study, or if during an exoskeleton instruction session, research staff or clinicians have concerns 
about the participant's performance or safety and feel that discontinuing involvement would be in the 
best interest of the participant.
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY
If subjects decide to stop being in the research study, they can contact the Principal Investigator or the 
research staff. There are no early withdrawal procedures that will be required of participants.
Participants may also withdraw their permission for the use and disclosure of any of their protected 
information for research, but they must do so in writing to the Principal Investigator at the address on 
the first page. Even if they withdraw their permission, the Principal Investigator for the research study 
may still use the information that was already collected if that information is necessary to complete the 
research study. Their health information may still be used or shared after their withdraw their 
authorization if they have an adverse event from participating in the research study.
If they decide they don't want their samples and/or data to be used for research anymore, they can 
contact the researcher and ask to have their samples and/or data removed from future use. If any 
samples or data have already been shared without their identity, it won't be possible to retrieve them 
because no one will know who they are.
Samples and data that have already been used will not be affected by their decision. Any samples 
and/or data that are still linked to their identity by a code the researcher has will be withdrawn so that 
no future sharing of their samples and/or data will take place. If their samples have already been 
deposited in an external repository, the study team will request that their samples be removed.
7.3 LOST TO FOLLOW-UP
N/A
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8 STUDY ASSESSMENTS AND PROCEDURES
8.1 EFFICACY ASSESSMENTS
Demographic data:
1.
Age: age of patient in years
2.
Sex: male (M) or female (F)
3.
Race: race of patient
4.
Diagnosis: primary diagnosis of the patient from medical chart (include level of injury from the
International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination
and the completeness of injury from American Spinal Injury Association Impairment Scale (AIS))
at admission and discharge.
5.
Date (or year) of injury: the date of getting the diagnosis
6.
Admission date: the date that the patient starts acute inpatient rehabilitation
7.
Discharge date: the date that the patient discharged
Pain scale: 1) International Spinal Cord Injury Basic Pain Data Set (ISCIBPDS) to identify pain locations, 
average intensity (over the past three days), and influence on daily activities. 2) Spinal Cord Injury Pain 
Instrument (SCIPI) to classify patients' neuropathic or nociceptive pain. ISCIBPDS and SCIPI will be 
performed on the enrollment and discharge dates. 3) Participants' current level of pain before and after 
walking training will be recorded in the walking
session data form.
Walking session results include session date, total up time, total walk time, and total steps. If subjects 
can walk independently 10-meter walking test and Walking Index for Spinal Cord Injury II (WISCI II) will 
be tested. In the 10 MWT, the participant will be asked to walk 10 meters (without the exoskeleton) at 
their fastest, comfortable pace. The time to cover this distance will be timed with a stopwatch. The 20-
item WISCI-II provides a rank-order rating of the ability of a person with SCI to walk 10 meters in relation 
to the severity of impairment. Ratings consider the amount of assistance and the types of assistive 
devices (e.g., leg braces) required to walk. Both the 10 MWT and WISCI II will be evaluated after 
enrollment (within 1-2 days) and before discharge from AIR (±2 days).
The presence and degree of systemic inflammation will be determined by measuring the concentration 
of serum C-reactive protein (CRP). CRP is an acute-phase protein that rises in response to inflammation. 
It is not specific to inflammation caused by SCI. Six ml of blood will be drawn in a red top tube, two times 
(after enrolling into the study and before discharge) for a total of 12 ml of blood over the course of the 
full study for analyses of the inflammatory markers. CRP is routinely measured from patients clinically 
when it is important to assess the degree of inflammation is present. The analysis will compare changes 
in levels of CRP pre- and post-intervention, in both the EAW with AIR or AIR groups.
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8.2 SAFETY AND OTHER ASSESSMENTS
Once the study attending physicians (Drs. Bryce, Escalon, and Huang) and rehabilitation clinicians 
identify potential subjects for the study, they will introduce the study to them and ask their permission 
for referring them to the study team. If they express interest, the study team will approach subjects and 
provide more detailed information about the study to them. If participants agree, the informed consent 
process will be proceeded. 
Once the consent form is signed, research team members and the study physicians (Drs. Bryce, Escalon, 
and Huang) will begin the screening process using the study's inclusion/exclusion criteria. Medical 
record review will also be conducted to identify any other medical concerns that might increase the risks 
associated with participation.
8.3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
8.3.1 DEFINITION OF ADVERSE EVENTS (AE)
There are several potential risks associated with the EAW and the testing procedures.
1) EAW training has the potential risks of falls resulting in bone fracture, muscle soreness, joint damage,
or other musculoskeletal injury, and/or autonomic dysreflexia (AD).
2) Persons using the Ekso may also be at risk for bruising, skin abrasion, pressure sores, soft tissue injury,
or adverse tissue reaction from direct contact of the body with the device. Notable contact points exist
between the sacrum and back pack, hip pads and greater trochanters, shin pads and shins, and with the
straps for the thighs and legs.
3) Lastly, the device itself could malfunction due to premature battery failure, interference with other
electrical equipment or devices, electrical shock, or unanticipated operation (stoppage or unintended
movement).
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)
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.
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8.3.3 ADVERSE EVENT REPORTING
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.
8.3.4 SERIOUS ADVERSE EVENT REPORTING
All AEs and SAEs that occur throughout the study, whether study-related or non-related, will be 
documented and reported to the IRB, as per IRB regulations. AE/SAE report forms will be completed 
within 48 hours throughout the study for each participant. We will keep a running log of all AE/SAEs 
(anticipated and unanticipated) throughout the study. Any SAE will be reported to the IRB within 24 
hours, and the study will be suspended until the study physician states that it is safe to resume the 
study.
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9 STATISTICAL CONSIDERATIONS
9.1 SAMPLE SIZE DETERMINATION
All statistical tests will be 2-sided. The outcome measures will be tested at a 0.05 level of significance. 
SPSS will be used to conduct the statistical analyses. All participants who have EAW sessions will be 
included (regardless of the number of sessions they complete before discharge, but the number and 
reason of missing EAW sessions will be recorded). To test the three main hypotheses of the proposed 
study, the change score of each outcome between baseline and discharge will be calculated. The change 
score will be compared between the intervention and control groups using independent t-test analyses 
(if the outcomes are not normally distributed, Mann-Whitney tests will be used).
Since the primary aim of the study is to compare the improvement of FIM scores between the groups, 
the FIM score results from the preliminary data were used to perform the power analysis for this study. 
In the preliminary data, the mean change in FIM score from the intervention group was 35±12, and the 
control group was 22±13. The effect size of the FIM score change in our preliminary data was 1.07 
(controlling for the different number of participants between the two groups). The power analysis 
showed that using the effect size (1.07) and 0.05 level of significance with two-sided analysis in 
independent t-test, a total of 30 participants will provide the study 80% power.
To account for an expected attrition rate of about 25%, 40 participants will be enrolled. It is expected 
that 30 participants will complete the study (the reasons and number of screening failures and dropouts 
will be recorded).
9.2 STATISTICAL ANALYSES
9.2.1 GENERAL APPROACH
All statistical tests will be 2-sided. The outcome measures will be tested at a 0.05 level of significance. 
SPSS will be used to conduct the statistical analyses. All participants who have EAW sessions will be 
included (regardless of the number of sessions they complete before discharge, but the number and 
reason of missing EAW sessions will be recorded). To test the three main hypotheses of the proposed 
study, the change score of each outcome between baseline and discharge will be calculated. The change 
score will be compared between the intervention and control groups using independent t-test analyses 
(if the outcomes are not normally distributed, Mann-Whitney tests will be used).
In addition to the primary analysis, several secondary analyses will be performed. 1) Each of the 
outcomes will be compared between pre- and post-EAW training using a paired t-test analysis (if the 
outcomes are not normally distributed, Wilcoxon signed-rank test will be used). 2) Analyses will be 
performed to determine the relationships between the change of outcome measures and EAW training 
time (including sessions, up time, walking time, or total number of steps per session and across all 
sessions) using correlation coefficients, regression analyses (stepwise and logistic), analyses of 
covariance, and nonparametric analyses as appropriate. 3) An additional exploratory post
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hoc analyses will be to determine the relationship of participant's' baseline characteristics with 
successful use of the exoskeleton. This post hoc analysis would serve as pilot data to begin to determine 
who is a good candidate for EAW training during AIR for a future study.
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