Pilot Study of Powered Exoskeleton Use for Gait Rehabilitation in Individuals With Multiple Sclerosis
Phase: NA
Conditions: Multiple Sclerosis, Gait Disorders, Neurologic
Sponsor: The Cleveland Clinic

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Pilot study of Powered Exoskeleton Use for Gait Rehabilitation in Individuals with Multiple Sclerosis 
PI:  
 
 
Francois Bethoux 
Co-investigators: 
Matthew Sutliff 
 
 
 
Randy Karim 
 
 
 
Robert Bermel 
Date: April 17, 2019 
Version: 1.0 
 
Background 
Powered exoskeletons are approved by the FDA to assist in the rehabilitation of persons with spinal cord 
injury and post-stroke hemiplegia, but not multiple sclerosis (MS). We are aware of only one pilot study 
of a powered exoskeleton (ReWalk®) in MS. Thirteen persons with MS and EDSS 5.5 to 7.0 were 
enrolled, and 5 were able to tolerate the device. Skin issues were the most frequent adverse event.  
Qualitative improvement of sitting, standing, and walking posture was noted in those who used the 
device consistently. We are not aware of any study of the EksoBionics GT exoskeleton in MS. 
Device 
The EksoGT is a powered motorized orthosis intended to enable individuals who are experiencing 
muscular or neurological conditions affecting their lower extremities to perform ambulatory functions 
such as gait training. (See Figures 1 and 2.) It consists of a fitted metal brace that supports the legs, feet, 
and torso. It is adjustable to accommodate different length segments and different hip widths. Typically, 
a physical therapist straps the patient’s feet, legs, and torso into the device. Soft goods (pads, spacers, 
straps, and supports) are available for bracing and adapting to various body types. The straps and soft 
goods are specifically designed to prevent pressure points or other skin issues. There is also a link (Don-
Doff Link) just below each hip joint, which permits abducting the legs while seated to facilitate donning 
and doffing the device.   
 
 
Figure 1: The EksoGT in use during gait training 
of an SCI patient. 
 
 
Figure 2: The EksoGT structure and general 
dimensions. 
 
The EksoGT manipulates the patient’s legs and waist to stand up, walk over level ground, and then to sit 
down. Battery powered motors drive knee and hip joints. The batteries are designed to last for 

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approximately three hours of normal use. The patient is required to assist with balance and body 
positioning using a cane, crutches, or walker, which are provided with the device. The physical therapist 
operates the device and monitors the patient to ensure balance is maintained. The device is operated in 
various modes. In some modes, steps are triggered with the attached user interface. In other modes, 
steps are triggered when the machine is in certain target postures. In other modes, the therapist may 
adjust the level of assistance provided so that, if the patient has some residual strength, the patient 
performs some of the walking motion with their own muscles. 
The EksoGT has a number of features to ensure patient safety. It is equipped with mechanical hard stops 
at the limits of healthy Participant ranges of motion to prevent powering the joint of the user to a 
position that the joint cannot reach. The actuated range of motion at the hip is -20° to 135° and the 
actuated range for the knee is 0° to 120°. Not all of this range of motion is needed in normal walking; 
however the ranges of these joints were selected to provide for other necessary functions such as 
standing and sitting. At the ankle the device is passive, with springs to resist sagittal plane motion, and 
locked in the other degrees of freedom. The range of motion provided at the ankle is from -10° to 20° 
dorsiflexion with hard stops at the limits of this range to protect the user and a setting to specify the 
neutral angle. 
Redundant position sensing on all of the actuated joints ensures that the motors are always controlled 
using reliable sensor information. In addition, the device has numerous sensor, motor, and software 
monitoring systems.  If any abnormality is detected (i.e. excess joint speed or force, or if redundant 
sensors do not agree) the device enters a safe mode, which prevents continued walking and enables the 
physical therapist to safely remove the patient. The device is also equipped with fail-safe brakes on the 
actuated knee joints, such that if the device loses power or is shut down for any reason the knees will 
continue to support the patient. Finally, an emergency disable button is available to instantly shut down 
the device for any reason. This is implemented via hardware, so it is effective even during a software 
malfunction.   
All study physical therapists will be trained to using the study device by the manufacturer. The training 
will be conducted at our facility. 
Aims 
1. To assess the feasibility and safety of using the EksoBionics GT exoskeleton for gait training in patients 
with relapsing or progressive MS and severe mobility limitations (EDSS 5-5 – 7.5). 
2. To collect preliminary efficacy outcomes on gait and walking for the purpose of designing a larger 
clinical trial of the EksoBionics GT exoskeleton for gait training in patients with MS. 
Methods 
Design: uncontrolled pre-post intervention study 
Participants:  
Sample size: up to 15 participants will be enrolled, with the goal of 5 participants completing the study 
period. 
 
 

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Inclusion/exclusion criteria 
Inclusion criteria 
Exclusion criteria 
 
Diagnosis of MS per 2017 revised 
McDonald criteria 
 
EDSS score 5.5-7.5 (moderate to severe 
walking disability)  
 
Cleared for gait training with the study 
device by the study treating physician 
 
Device-Specific Criteria 
 
Involved in a standing program or must 
be able to tolerate at least 15 min upright 
without signs or symptoms of orthostatic 
hypotension 
 
Weigh 220 pounds (100kg) or less 
 
Be able to fit into the Ekso device: 
 
Between approximately 5’0” and 6’4” tall 
(really depends on leg measurements) 
 
Sufficient diaphragmatic strength such 
that respiration is not compromised with 
exercise 
 
Assessed by physical therapy: 
 
Standing hip width of approximately 18” 
or less 
 
Have near normal range of motion in 
hips, knees and ankles 
 
Sufficient upper extremity strength to 
use a front wheeled walker by manual 
muscle testing (minimum triceps strength 
bilaterally of 3/5, shoulder abduction and 
flexion/extension of 4/5 OR as discussed 
during demo, 2 normally functioning 
limbs such as in hemiplegia) 
 
 
MS exacerbation, severe acute 
comorbidity or surgery less than 90 days 
prior to enrollment 
 
Diagnosed with osteoporosis or history of 
long bone fractures since diagnosis 
 
Safety concern due to neurologic 
impairments (e.g. upper extremity 
weakness, visual loss) or comorbidities 
(e.g. cardiac, respiratory) 
 
Other neurologic or non-neurologic 
condition interfering with walking 
 
< 1 month since previous intensive gait 
training regimen or initiation of 
treatment that can affect walking (e.g. 
medication for spasticity) 
 
Planned change in medications that may 
affect walking during the study period 
 
Uncontrolled or severe orthostatic 
hypotension that limits standing 
tolerance 
 
Active heterotrophic ossification (HO), 
hip dysplasia, or uncontrolled hip/knee 
axis abnormalities 
 
Score <22 on the Mini-Mental State 
Examination or deemed to have cognitive 
impairment precluding safe training with 
the device during the screening and 
training process 
 
Colostomy 
 
Pregnancy 
 
Unresolved deep vein thrombosis 
 
Uncontrolled autonomic dysreflexia 
 
Currently involved in another 
rehabilitation study 
 
Assessed by physical therapy: 
 
Severe spasticity that prevents joint 
motion (severe stiffness or rigidity) in 
proximal lower extremity muscles, 
including hip adductors and knee 
flexors/extensors.  
 
Hip flexion contracture greater than ~17° 
 
Knee flexion contracture greater than 12° 

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 
Unable to achieve neutral ankle 
dorsiflexion with passive stretch (achieve 
neutral with up to 12° knee flexion) 
 
Leg length discrepancy greater than 0.5” 
for upper leg, greater than 0.75” for 
lower leg 
 
Spinal instability (TLSO may be worn in 
device with physician clearance) 
 
Severe muscular or skeletal pain 
 
Open skin ulcerations on buttocks or 
other body surfaces in contact with 
exoskeleton or harness 
 
Shoulder extension ROM < 50° excludes 
using crutches during sit to stand or vice 
versa. (Walking with crutches permitted, 
sit <> stand would be done with walker.) 
 
Data collected 
Demographic and clinical data: age, sex, duration of MS symptoms in years, MS course (relapsing or 
progressive), use of assistive device to walk indoors / outdoors (none, unilateral, bilateral), Body Mass 
Index, concomitant medications 
Screening 
Expanded Disability Status Scale 
Mini-Mental State Examination 
Safety 
Adverse events during or between rehabilitation 
sessions (particularly falls and musculoskeletal 
pain) 
Pain severity on Numeric Pain Rating Scale and 
pain location 
Feasibility 
Percentage of patients who complete at least 
75% of the training sessions. 
Percentage of patients who drop out of the study 
Acceptability 
assistive device subscale of the Quebec 
User Evaluation of Satisfaction with Assistive 
Technology questionnaire v.2 
(https://www.sralab.org/rehabilitation-
measures/quebec-user-evaluation-satisfaction-
assistive-technology ) 
Efficacy (tested without device) 
Spasticity (Modified Ashworth Scale) 
Hip flexor strength (handheld dynamometer) 
Gait parameters : 
- 
GAITRite system (overground gait mat): 
velocity, cadence, step length, step 
width, double support time (averaged 
between left and right when appropriate) 
- 
CAREN system (treadmill with harness): 
gait kinematics 

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Timed 25 Foot Walk 
2-minute Walk Test 
MS Walking Scale-12 
 
The Expanded Disability Status Scale (EDSS) is a comprehensive, quantitative neurological examination, 
and is the most widely used measure of MS-related disability for clinical and research purposes. The 
order of the exam may vary slightly among providers, but generally the patient undergoes a complete 
neurologic examination, then completes up to a 500 meter walk (with or without an assistive device) 
which involves walking the length of our 50 meter clinic hallway 10 times. The examiner notes the 
distance the patient is able to walk, along with the presence of an assistive device, if applicable. 
The Mini Mental State Examination (MMSE) is an 11-question measure that tests five areas of cognitive 
function: orientation, registration, attention and calculation, recall, and language. Widely used in clinical 
practice, the MMSE will be administered in this study to screen for severe cognitive impairment that 
precludes safe participation. 
The Numeric Pain Rating Scale evaluates pain by asking the patient to situate the severity of pain 
experienced on a 0-10 level scale (from no pain to maximal pain). In addition, the patient will be asked 
to report the location of the pain. A publication from a cross-sectional study using the NRS on 236 MS 
patients with pain proposed the following cutoff scores: 0-2 : mild, 3-5 : moderate,  6-10 : severe.1 Pain 
will be assessed as a safety measure. 
The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) questionnaire v.2 is a 
new outcome measurement instrument designed to evaluate a person’s satisfaction with his or her 
assistive technology device. It can be used with adolescents, adults and elderly persons who as a result 
of a physical or sensory impairment have acquired an assistive technology device. The QUEST 2.0 was 
created for assistive technology practitioners and researchers.  As a clinical tool, the QUEST 2.0 provides 
practitioners with a means of collecting satisfaction data that can be used to document the real-life 
benefits of assistive technology and to justify the need for these devices. As a research tool, it can be 
used to compare satisfaction data with other outcome measures such as clinical results, quality of life, 
functional status, cost factors and comfort 
The Modified Ashworth Scale (MAS): the Ashworth scale, first published in 1964, grades resistance to 
passive mobilization on a 5-level ordinal scale. The psychometric properties of the Ashworth scale are 
well documented, and even though this tool has been criticized for its lack of inter-rater reliability, it is 
still the most widely used measure of spasticity in clinical trials. The modified version of the Ashworth 
scale, which allows one intermediate grade, will be used for this study. We will evaluate the following 
muscle groups: hip adductors, knee flexors, and knee extensors. The MAS scores for all muscle groups in 
both legs will be averaged.  
Hip Flexor Strength will be measured bilaterally with a hand-held dynamometer (the Lafayette Manual 
Muscle Testing System, Lafayette IN). This device provides a digital display of the force generated by 
active muscle contraction. Two measurements of peak strength will be taken on each side, and the 
average of the measurements will be calculated. Hand-held dynamometry was found more reproducible 
and sensitive to change than the manual muscle test grading system. 

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Phone 
pre-
screening 
Screening 
Device fit 
Enrollment 
Baseline 1 
 
End of 
Treatment 
Evaluation 
Follow-up 
Evaluation 
Phone 
safety / 
adherence 
visit 
The GAITRite electronic walkway is a computerized gait analysis system consisting of a 30-foot mat with 
embedded sensors and a data acquisition and processing software. The GAITRite has been used to 
analyze gait patterns in various neurologic populations, including MS. The spatiotemporal gait 
parameters analyzed include stride length, double support time, base of support (step width), and the 
functional ambulation profile (FAP) score. 
The Computer Assisted Rehabilitation ENvironment (CAREN) system is installed in the Mellen Center 
building and routinely used for patient care and clinical research. The hardware includes: a 6 degrees of 
freedom motion base on which sits a 3-meter diameter platform with a dual belt instrumented 
treadmill; a 10-camera real-time motion capture system; a 120-degree cylindrical screen projection 
system with surround sound; wireless EMG and 3 high-speed cameras. The CAREN system creates an 
immersive virtual environment with real-time feedback loop, causing the system to respond to subject 
motion. The software allows to define inputs, perturbations and sensory disturbances, for research and 
training purposes. Gait data is continuously recorded and analyzed offline using the Gait Off-Line 
Analysis Tool. The CAREN system is staffed with two trained operators, who are also developers for the 
system. 
The Timed 25 Foot Walk (T25FW) is part of the Multiple Sclerosis Functional Composite (MSFC), an 
outcome measure for MS therapeutic trials. This test has been widely used to measure walking speed in 
MS. The patient is instructed to walk 25 feet as quickly as possible, but safely. Two trials are conducted, 
and the average time is calculated. 
The 2-Minute Walk (2MW) has been validated in cardiovascular and respiratory disease, in lower limb 
amputation, and has been used in neurorehabilitation trials in stroke 6 and multiple sclerosis. The 
subject is asked to walk as far as possible and as fast as possible (but safely) for 2 minutes in a 50-meter 
hallway. The timer will not be stopped if the patient takes brief rest periods during the walk. If the test is 
discontinued before 2 minutes, either by patient request or evaluator decision, the time and reason for 
stopping will be noted. 
The MS Walking Scale-12 (MSWS-12) is a disease-specific instrument gathering subject-reported 
information about the impact of MS on their walking ability, designed for use in clinical practice and 
clinical research. The MSWS-12 contains 12 questions with a recall period of 2 weeks. The psychometric 
properties of the MSWS-12 have been extensively evaluated in diverse MS populations in both 
community and hospital settings, with demonstration of internal consistency, high reliability and 
validity, and good generalizability. 
Evaluation schedule 
 
 
 
 
 
 
2 +/- 1 weeks 
8 weeks 
4 +/- 2 weeks 
T1 
T2
T3
Treatment 

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All assessments will be performed at T1, T2, and T3. In addition, a phone visit will be conducted 4 +/- 1 
weeks after treatment initiation to review adverse events, adherence to treatment sessions, and any 
comments / questions the participants may have. 
All participants will be invited to participate in the T2 assessment visit, even if they have decided to 
terminate treatment for various reasons.  
Treatment 
The rehabilitation treatment will consist of 3 sessions per week for 8 weeks, for a total of 24 sessions. 
Missed sessions will be made up if possible. Each session will be scheduled for 60 minutes, and will 
consist of stretching, overground gait training, and gait training with the study device. Rest periods will 
be provided as necessary during the training visits. 
Statistical analysis 
Patient characteristics will be summarized using frequencies and percentages for categorical factors and 
means and standard deviations or medians and quartiles for continuous measures.  The percentage of 
participants meeting established MDC or MCID for any of the outcome measures will also be calculated. 
Change over time in functional outcomes will be evaluated using linear mixed effect models.  In these 
models, each functional measure will be the outcome and time point will be the predictor.  Repeated 
measures within subject will be models assuming an autoregressive or spatial correlation structure.  
Estimated changes with 95% confidence intervals will be summarized for each measure.  Outcomes 
measured bilaterally will be averaged for analysis primarily.  Incidences and types of adverse events will 
be summarized overall and by time period.  Adherence to training sessions will be summarized 
descriptively using means and standard deviation and the percentage of patients achieving minimum 
completion standards will also be described.  Analysis will be performed using SAS software (version 9.4, 
Cary, NC).