G-EO Gait Rehabilitation Training in Progressive Multiple Sclerosis
Phase: NA
Conditions: Progressive Multiple Sclerosis
Sponsor: Indiana University

National MS Society, 
, http://nationalmssociety.org/for-
professionals/researchers/index.aspx 
 
1 
 
 
 
 
 
 
G-EO Gait Rehabilitation Training in 
Progressive Multiple Sclerosis 
 
Study Protocol and Statistical Analysis 
 
 
NCT03980145 
 
 
Date of Last Modification 
 
July 18, 2018 

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, http://nationalmssociety.org/for-
professionals/researchers/index.aspx 
 
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1.0 
Rationale and Specific Aims 
 
The logistic advantages and advanced training capabilities of the G-EO System, as well as the 
benefits reported in other populations, support this strategy as a potentially potent rehabilitation 
tool for restoring and maintaining function in progressive MS. This approach represents a 
paradigm shifting opportunity for improving current clinical practices for patients with 
progressive MS. If successful, this project will provide initial evidence for increasing patient 
access to the G-EO System, and this could be accomplished through “regional technology 
centers” using a rural health-delivery approach.  
 
There are several novel aspects of the proposed trial: (1) the examination of a novel gait 
rehabilitation stimulus (G-EO System) that could alter current clinical practices; (2) the focus on 
patients with progressive MS who have gait impairment (i.e., those who have received minimal 
research attention), which was recently described as the greatest therapeutic challenge facing the 
MS community; and (3) a study design that accounts for standard therapy.  
 
Specific Aims: We propose a single-blinded, randomized pilot trial of electromechanically-
assisted gait training using the G-EO System in patients with progressive MS with gait disability 
(EDSS=4.0-7.5).  
 
Specific Aim 1 will establish the safety and feasibility of gait training using the G-EO System.  
 
Specific Aim 2 will determine the efficacy of gait training using the G-EO System for improving 
mobility, symptomatic, quality of life, and participatory outcomes. 
 
2.0 
Inclusion/Exclusion Criteria 
 
Inclusion criteria  
• 
18-64 years 
• 
Confirmed diagnosis of PPMS or SPMS (this will be confirmed by the referring 
physician) 
• 
EDSS 4.0-7.522 
• 
Stable course of disease-modifying therapy over the past 6 months 
• 
Asymptomatic (i.e., no underlying cardiovascular disease) 
• 
Physician approval for exercise 
• 
Willingness to visit the IU Health Neurosciences Center for testing and training 
 
Exclusion criteria  
• 
Pregnancy 
• 
Current use of dalfampridine (Ampyra®) 
• 
Conventional physical therapy or G-EO training within the past 6 months 
• 
Height <1m or >2m 
• 
Body weight >150 kg 
• 
Contraindications to G-EO gait training (e.g., bone instability) 
 
3.0 
Enrollment/Randomization 
 

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, http://nationalmssociety.org/for-
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A convenience sample of 20 persons with progressive MS will be enrolled for this pilot 
clinical trial. Recruitment will occur through neurologists at the IU Health Neuroscience 
Center. Each participate will be given time to read the consent form or have it read to 
them and to ask questions (see Informed Consent Draft). Consent will be obtained before 
randomization and assessments. The consent process will take place at the Indiana Center 
for Advanced Neurorehabilitation (ICAN) in the Neurorehabilitation and Robotics IU 
Health Neuroscience Center, 355 West 16th Street, Room 1078, Indianapolis, IN 46202 
(317) 963-7050.  
If found eligible for the study and agree to consent to participate, subjects will be 
matched based on disability level (EDSS), and randomized to either conventional 
physical therapy (CPT) group or CPT with G-EO training using a random numbers 
generator and concealed allocation.  
 
4.0 
Study Procedures 
 
Screening 
Potential subjects will be referred to the study via IU Health Physicians who specialize in the 
treatment and management of individuals with Multiple Sclerosis. A member of the research team 
will screen the referral by contacting the physician and confirming they meet the necessary 
inclusion and exclusion criteria. Following confirmation of criteria, potential subjects will be 
contacted by phone to schedule an initial visit for consent and assessment of baseline data.   
 
Assessments 
The study outcomes will be collected by treatment-blinded researchers. All participants on Day 1 
who consent to be in the study will complete the following mobility outcomes: 
1. Spatial and temporal gait kinematics will be assessed using a PKMAS Zeno Walkway 
(Protokinetics). Participants will be asked to walk over a 14 foot pressure mat that will 
capture their gait kinematics and speed. 
2. A 2-minute walk (2MWT) tests to determine walking endurance. Subjects will be asked 
to walk for 2 minutes along a 30m track. Subjects may stop and rest as often as needed.  
3. Balance assessment using the Neurocom Balance Master. Subjects will be asked to stand 
on a balance platform while the load cells in the force-plate measures postural stability 
when challenged. All subjects will be in a safety harness to prevent falling.  
4. Their level of perceived fatigue using the Modified Fatigue Impact Scale. They will 
complete a questionnaire.  
5. Their level of depression using the Hospital Anxiety and Depression Scale. They will 
complete a questionnaire. 
6. Their level of pain assessed by the McGill Pain Questionnaire. They will complete a 
questionnaire. 
7. Their level of health-related quality of life assessed by the Multiple Sclerosis Impact 
Scale-29. They will complete a questionnaire. 
8. Their perceived ability to perform Activities of Daily Living (ADL) using the Late-Life 
Function and Disability Inventory. They will complete a questionnaire. 
Participants who complete the first 6 weeks of training will be asked to complete assessments 1 
thru 3. Participants who complete all 12 weeks of training will be asked to complete all 
assessments one final time.  
 

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Schedule 
Following completion of day 1 assessments, all subjects will be scheduled for the intervention 
phase of the study. Regardless of group allocation, each participant will receive 20 total visits 
scheduled ideally for two times a week for 10 weeks. Following the completion of the first 10 
treatments, all subjects will be asked to complete assessments #1 thru #3 above. Following 
completion of the additional 10 treatments (total of 20 treatment sessions), each subject will 
complete all assessments performed on Day 1. (See Table 1) If a subject cancels a treatment 
session, it will be rescheduled to ensure that all subjects complete the total of 20 treatment 
sessions prior to final testing. If a subject misses three consecutive treatment sessions, they will 
be dropped from the study due to inconsistency in treatment carryover. Cancellations and changes 
in patient scheduling represents a true clinical environment and represents normal clinical patient 
management. Therefore, the emphasis is on total number of treatments (20) and not on total 
number of weeks.  
 
Table 1. Summary Clinical Trials (14-week span) Procedures with Human Subjects. 
Pre-Intervention Phase 
Intervention 
Phase 
Mid Intervention Phase 
Intervention 
Phase 
Post Intervention 
Day 1 
Day 1 
Measurement 
6 weeks 
intervention 
period 
Mid Treatment 
Assessment 
6 weeks 
intervention 
period 
Post Assessment 
 
x Screening of 
Inclusion 
 
x Informed 
consent 
obtained 
 
x Disability 
match and 
random 
assignment to 
CPT or GEO  
 
Outcome 
Measurement 
1. Comfortable 
Walking 
Speed/Mechanics 
 
Trial 1 (14’) 
 
Trial 2 (14’) 
 
Trial 3 (14’) 
2. Walking 
Endurance 
 
2 MWT  
3. Balance 
 
Neurocom 
4. Fatigue 
 Modified 
Fatigue 
Impact Scale 
5. Depression 
 Hospital 
Anxiety and 
Depression 
Scale  
6. Pain 
 McGill Pain 
Questionnaire 
7. Quality of Life 
 MS Impact 
Scale 
8. ADLs  
Treatment 
and control 
group 
2x a week 
 Outcome 
Measurement 
1. Comfortable 
Walking 
Speed/Mechanics 
 
Trial 1 (14’) 
 
Trial 2 (14’) 
 
Trial 3 (14’) 
2. Walking 
Endurance 
 
2 MWT  
3. Balance 
 
Neurocom 
 
Treatment 
and control 
group 
2x a week 
Outcome 
Measurement 
1. Comfortable 
Walking 
Speed/Mechanic
s 
 
Trial 1 (14’) 
 
Trial 2 (14’) 
 
Trial 3 (14’) 
2. Walking 
Endurance 
 
2 MWT  
3. Balance 
 
Neurocom 
4. Fatigue 
 Modified 
Fatigue 
Impact Scale 
5. Depression 
 Hospital 
Anxiety and 
Depression 
Scale  
6. Pain 
 McGill Pain 
Questionnair
e 
7. Quality of Life 
 MS Impact 

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 Late Life 
Function and 
Disability 
Inventory 
Scale 
8. ADLs  
 Late Life 
Function and 
Disability 
Inventory 
 
 
Intervention 
The intervention will be delivered through the Neurorehabilitation and Robotics Clinic by 
three trained Physical Therapists with oversight from Dr. Altenburger. The clinicians 
involved in the delivery of the intervention will not be involved in outcome assessments. 
Participants in both conditions will receive conventional physical therapy (CPT) as usual 
care. Participants in the G-EO training condition will also receive robot-assisted gait 
training. This design will control for attention and social contact, total rehabilitation time, 
and intensity. Both conditions will be delivered at the same frequency (2x/week), 
intensity (40 to 60 minutes), and duration over 12-weeks. Progression will occur by 
increasing the session intensity weekly. Training intensity will be monitored and 
standardized using the Borg Rating of Perceived Exertion38 scale, and will progress from 
‘fairly light’ (11) to ‘somewhat hard’ (13). This prescription is consistent and appropriate 
for individuals with progressive MS with mobility impairment and low fitness levels. 
Progression will occur by increasing the session duration by ~5min/week up to 60 
minutes per session. Total training time includes both CPT and G-EO training for the G-
EO condition (i.e., 30min of CPT + 30min G-EO). Training sessions will not exceed 60 
minutes. We will record all training parameters. Physical therapy training sessions will 
involve: 3-5 minute warm-up, stretching, progressive strength training exercises, and gait 
and balance training. Additional strategies for home exercises, energy conservation, fall 
prevention, and appropriate assistive devices (i.e., orthotics) will be provided universally.  
Conventional physical therapy (CPT): A CPT session will involve a 3-5 minute warm-up, 
stretching, progressive strength training exercises, and gait and balance training.  
 
G-EO training: Using the G-EO System, participants will be secured with the appropriate sized 
harness and attached to an overhead body-weight support system, with feet secured to pressure 
sensitive footplates. Each session will begin with a 3-5 minute warm-up in the continuous passive 
mode (cadence ~40-45 steps/minute). The participant will then be transitioned into the adaptive 
training phase for practicing repetitive floor walking for up to 30 minutes. During this phase, the 
force produced by the robot is modulated to support the effort of the patient in producing a typical 
walking pattern.  
 
Feasibility and Safety 
Feasibility outcomes will involve process, resources, management, and scientific assessment. 
Process metrics will include recruitment, retention, and adherence rates assessed by the 
movement of participants through each stage of the study and training data. Resource metrics will 
include evaluation of the equipment and facilities through feedback from the therapists. Time to 
completion relative to proposed target dates will also be reviewed. Management metrics will 
include data management, documentation of patient progress, record of adverse events, and 

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compliance with approved protocols. Safety will be evaluated through assessment of recorded 
adverse events.  
 
5.0 
Statistical Considerations 
 
Data will be analyzed using IBM SPSS Version 22.0 (IMB Corps., Armonk, NY). Descriptive 
statistics will characterize the sample on demographic, clinical, safety, and feasibility metrics. We 
will compare safety and feasibility between groups using chi-square and t-tests for independent 
samples (Specific Aim 1). The efficacy of the intervention on study variables (Specific Aim 2) will 
be examined using a 2 (Group) by 2 (Time), mixed factor ANOVA. A completers analysis will be 
conducted (i.e., ≥75% of sessions completed). Effect sizes associated with F-statistics will be 
expressed as eta-squared (η2), and effect sizes based on mean differences will be expressed as 
Cohen’s d.