High Intensity Training for Neurological Injury Using Overground Exoskeletons in Inpatient Rehabilitation
Phase: NA
Conditions: Spinal Cord Injuries
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 High Intensity Training for Neurological Injury Using Overground Exoskeletons in 
Inpatient Rehabilitation 
 
NCT04973852 
 
Version Date: 10/17/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
Protocol Title: 
High Intensity Training for Neurological Injury Using Overground 
Exoskeletons in Inpatient Rehabilitation 
 
Principal Investigator: 
Shuo-Hsiu Chang, Ph.D. 
 
Co-Investigator: 
Marcie Kern, PT, MS 
 
Population: 
Human subjects (male and female), age 18 years or older, who have a 
confirmed diagnosis of spinal cord injury or cerebrovascular accident. 
Number of Sites: 
1. TIRR Memorial Hermann 
 
Study Duration: 
1 year 
 
Subject Duration: 
2 weeks 
 
 
GENERAL INFORMATION 
Recovery of walking ability remains one of the most important predictors of quality of 
life in patients with neurological conditions such as spinal cord injury (SCI) and cerebrovascular 
accident (CVA). Not only is gait an essential activity of daily living, but it can also help minimize 
many of the secondary complications seen as a result of sedentary lifestyles due to neurological 
injuries, such as cardiovascular deconditioning and bone mass loss. With advanced robotic 
technology, robotic exoskeletons in neurological rehabilitation have gained attention and have 
become more popular for mobility and gait training. One of the most important advantages of 
robotic exoskeleton-assisted gait training is that the robot is powered and operated by motors 
and actuators that promote repetitive movement, such as bipedal movement in walking for a 
sustained period, and enable the achievement of maximal practice effects during retraining. 
Therefore, this type of gait training has the potential to induce neuroplasticity by modulating 
neuronal excitability and connectivity at the spinal and supraspinal level, thereby improving 
walking and the quality of life of individuals with mobility impairments. 
Based on the concept of neuroplasticity, it is important to consider intensity and 
variability in the recovery of walking after neurological injury. It is unclear whether using 
exoskeleton technology following task-specific gait training combined with 
high aerobic intensity practice can achieve neuromotor behavior changes or gains 
in functional recovery improvement such as walking. Therefore, the purpose of this study is to 
determine whether high-intensity locomotor training can safely be achieved while utilizing 
overground robotic exoskeletons. We hypothesize that subjects can safely achieve high 
cardiovascular intensity (70-80% heart rate reserve) gait training utilizing the overground 
exoskeleton. We also hypothesize subjects will demonstrate improvement in overground 
walking ability after receiving high-intensity gait training sessions in the exoskeleton. 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
BACKGROUND INFORMATION 
The impaired ability to walk independently is a significant consequence after 
neuromuscular injuries resulting in substantial limitation in mobility and performance of daily 
activities, thus restricting full participation and home and community re-integration.1, 2, 3 This 
contributes to an extremely limited number of steps taken per day, and often leads to a 
sedentary lifestyle.4 Further, a sedentary lifestyle contributes to secondary medical problems 
such as diabetes, obesity, osteoporosis/osteopenia, urinary, pulmonary, and cardiovascular 
disease.5-8 Walking, therefore, is not only an important activity of daily living but also helps to 
reduce secondary complications and improve the overall quality of life.9-10 
Historically therapy was limited to teaching compensatory strategies. Evidence is now 
growing to support the ability of the nervous system to adapt after injury.12 Emerging research 
indicates that the intentional massed practice of activity-based training may promote neural 
plasticity and cortical reorganization and subsequent recovery of walking ability after 
neurological injury.13-18 Moreover, studies have shown that placing the body in a load-bearing 
position and moving the lower limbs in a repetitive stepping pattern leads to improved 
locomotor recovery.19-21 
One example of locomotor training is the use of bodyweight supported treadmill 
training (BWSTT) to drive changes in spinal cord pathways by increasing the excitability of the 
spinal cord leading to the recovery of movements controlled below the level of injury.22, 
23 In BWSTT, a bodyweight support system allows for unweighting of the body while using a 
treadmill to provide repetitive stepping. An alternative method for achieving load-bearing, 
repetitive stepping in an overground environment is the use of lower extremity robotic 
exoskeletons. This locomotor training technique requires less energy expenditure and physical 
strain for the clinician while still providing repetitive stepping in a full load-bearing position. 
Robotic exoskeletons, such as Ekso® by Eksobionics, have been developed and approved 
by the FDA for rehabilitation after neurological injury. These devices are worn outside of the 
body and can move an individual's legs via motors in the hip and knee joints. The users of the 
exoskeleton must be both physically and cognitively engaged in advancing the limb. The 
benefits of utilizing robotic exoskeleton for gait include 1) Opportunity for maximizing the 
effects of massed practice, task-specific training by producing large numbers of repetitions 
without demanding intensive physical labor of trainers. The anticipated improvements could be 
maximized by the active engagement in consciousness by the individual 24; 2) Potential 
promotion of neural plasticity with subsequent recovery of walking ability after neurological 
injury 25-30, and 3) Creating an environment that will support ideal gait kinematics and speed, 
optimize joint loading, and provide accurate sensory cues to promote spinal and cortical 
neuroplasticity in an overground environment.25 
New evidence is developing that demonstrates, along with repetition, it is important to 
consider intensity and variability in recovery of walking after neurological injury.31-37 Intensity 
can be evaluated as power, time, frequency, or repetitions. The growing body of 
literature describes the high intensity, measured as power, to increase neuromuscular, 
cardiovascular, and metabolic demands on the body to promote neurological 
recovery. Specifically looking at recovery of gait, locomotor training modalities that maximize 
stepping at high intensities with a variability of the task have led to significant improvements in 
walking compared to conventional therapy. 32, 36, 38, 40 Individuals post SCI and CVA have been 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
able to successfully achieve high aerobic intensities (70-80% heart rate reserve) during 
gait training sessions without adverse reactions.35, 39 For this proposed study, we will set 
variables of time and frequency as those that can be reasonably achieved during standard of 
care in an acute rehabilitation setting. Repetitions of steps will be logged; however, the 
primary measure for power will be aerobic intensity. 
Typically, high-intensity training protocols involved the use of bodyweight supported 
treadmill systems, unweighting machines, and stepping overground. Overground exoskeletons 
offer the opportunity for individuals to receive full weight-bearing while working on 
stepping. However, it is unknown if an individual utilizing an exoskeleton can work hard 
enough to reach high aerobic intensity levels. Therefore, we propose the investigation of 
performing task-specific gait training at high-intensity levels in an exoskeleton to achieve 
greater gains in the neurological recovery of walking. 
 
OBJECTIVES 
The purpose of this study is to determine the feasibility and potential efficacy to 
implement high cardiovascular intensity training parameters (70-80% heart rate reserve) with 
the use of overground wearable robotic exoskeletons in an inpatient rehabilitation setting for 
locomotor recovery. 
Specific Aim 1: To determine whether it is feasible to achieve high-intensity locomotor 
training sessions at 70-80% of subjects' heart rate reserve using an overground wearable 
robotic exoskeleton. We hypothesize that all subjects will successfully achieve targeted heart 
rate for at least 50% of the treatment session (>25 min of 45 min of activity in the 
exoskeleton) in 3 out of 5 sessions, without adverse reactions. 
Specific Aim 2: To investigate the potential functional improvements in gait after 
receiving high-intensity locomotor training with an overground exoskeleton. We hypothesize 
subjects will demonstrate improvement in overground walking ability, measured on the 10- 
meter walk test and six-minute walk test, after participation in high-intensity locomotor training 
with an overground exoskeleton. 
 
STUDY DESIGN 
A pre-post design with outcomes monitored before and after participation in high- 
intensity gait training intervention with an overground robotic exoskeleton will be used. 
 
Study Population 
We plan to enroll up to 20 human subjects (male and female), age 18 years or 
older, admitted to inpatient rehabilitation with a confirmed diagnosis of cerebrovascular 
accident (CVA) or motor incomplete spinal cord injury (SCI), classified by the American Spinal 
Injury Association Impairment Scale (AIS) grades C or D. 
Potential subjects will be recruited from the TIRR Memorial Hermann inpatient 
rehabilitation facility. Subjects will be excluded if they lack sufficient range of motion at lower 
extremity preventing the achievement of normal stepping kinematics, are unable to physically 
fit within the exoskeleton, have evidence of an unstable spine, presence of lower extremity or 
pelvic fractures, or other conditions limiting weight-bearing into legs, history of severe 
neurological disorder other than CVA or SCI, difficulty completing forms written in English 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
or following verbal instructions provided in English, use of mechanical ventilation for 
respiratory support. See the chart for all inclusion and exclusion criteria. 
 
Inclusion Criteria 
Exclusion Criteria 
• Male or female â‰¥18 
years of age 
• Able to achieve adequate fit 
within the exoskeleton 
• Diagnosis of CVA or motor 
incomplete SCI (AIS C or D) 
• Sufficient range of motion 
to attain normal, reciprocal 
gait pattern, and transition 
from normal sit to stand or 
stand to sit 
• Intact skin on all surfaces in 
contact with device and 
load-bearing surfaces 
• Weight <220 pounds 
• Pregnancy 
• Spinal instability 
• Unhealed limb or pelvic fractures or any condition 
restricting weight-bearing in limbs 
• Diagnosis of other neurological injuries other than CVA 
or SCI 
• Uncontrolled spasticity (3 on Modified Ashworth Scale) 
• Colostomy 
• Decreased range of motion or contractures in legs (>10° 
at hips, knees, or ankles) 
• Uncontrolled autonomic dysreflexia 
• Unresolved deep vein thrombosis 
• Inability to tolerate standing due to cardiovascular 
issues or orthostatic hypotension 
• Inability to follow 3 step commands 
• Severe comorbidities: active infections, heart, lung, or 
circulatory conditions 
• Pressure sores, impaired skin integrity 
• Use of mechanical ventilation for respiratory support 
Procedures 
The study will require subjects to participate in 7 visits. The initial visit will be a 
screening visit and baseline assessment (2 hours), followed by five intervention visits (1.5 hours 
each) and a post-assessment (1 hour). These sessions are additional to the subjects regular 
inpatient rehabilitation plan of care. 
After informed consent is provided, the subject will participate in a screening 
evaluation and baseline assessment, which will include assessment of skin integrity, hip, knee, 
and ankle range of motion, and spasticity, functional mobility, measurements to ensure the 
individual will safely fit inside the robotic exoskeletons and cardiopulmonary measurements 
(blood pressure, heart rate). 
Subjects will then participate in 5 high-intensity gait training sessions utilizing Ekso® 
exoskeleton. Intervention sessions will be performed at TIRR Memorial Hermann and will occur 
in addition to the subject's daily scheduled 3 hours of therapy. Each training session will last up 
to 60 minutes in the Exoskeleton and will be completed within 14 days. Training will focus on 
walking in the Ekso®. The goal of each session is to achieve high-intensity stepping, maintaining 
heart rate (HR) within 70-80% of heart rate reserve (HRR), or a Rating of Perceived Exertion 
(RPE) of 15-17. Target HR ranges will be calculated using age-predicted maximum heart rate 
(HRmax = 208 - [0.7 * age]) and the Karvonen formula (target HRR = 0.7 * [HRmax - HRrest) +  
HRrest). Heart rate and RPE will be monitored continuously and recorded every 5 minutes 
throughout the session. There will always be at least one trainer present during the 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
training sessions to provide assistance as needed for safety. After completing five intervention 
sessions, subjects will participate in a post-assessment evaluation for functional mobility 
measurements. 
We will also measure subjects’ heart rate during standard of care physical therapy 
sessions. Subjects will be asked to wear a heart rate monitor for up to 5 therapy sessions. 
 
Outcome Measures 
• Seated dynamic reach: We will assess a subject’s stability with the Modified Functional 
Reach, measuring the maximum distance an individual can reach forward from a seated 
position. We will average three trials. 
• Gait Speed: The 10 Meter Walk Test (10MWT) will assess the subject's self-selected and 
fast gait speeds. Four marks will be placed on the ground at 0, 2, 12, and 14 
meters. Subjects will walk a total of 14 meters, where the middle 10 meters (between 
marks at 2 and 12 meters) will be timed and recorded as their gait speed. Subjects will 
complete two attempts at their self-selected pace and two at their fastest pace. 
• Spatial-temporal gait parameters: The GAITRite pressure map will be used during the 
10MWT. This pressure map will digitally record the subject's footprints' placement and 
pressure as they walk over it during the 10MWT. This data will calculate temporospatial 
gait parameters, such as swing and stance times, lengths, widths, etc. 
• Walking endurance: The 6 Minute Walk Test (6MWT) will measure the distance subjects 
can walk over six minutes. Subjects will walk along a 100-foot hallway as many times as 
they can in 6 minutes. Subjects are allowed to rest as needed; however, the timer 
continues to run for 6 minutes consecutively, whether they are standing or walking. 
• Metabolic expenditure during walking: Oxygen consumption will be calculated on a 
breath-by-breath basis measured by a portable metabolic system (Cosmed 
K4b2).  During the testing, the subject will wear a face mask at all times and will be 
asked to breathe normally. Subjects will also wear a heart rate monitor. This task will be 
performed during the 10MWT and 6MWT. 
• Heart rate: We will measure heart rate using a wearable heart rate sensor (Polar® 
H10) that captures continuous heart rate data via Bluetooth technology. Data collected 
during pre and post assessments, during exoskeleton sessions and overground physical 
therapy sessions. 
 
PHOTOGRAPHY and VIDEOTAPING 
We would like to obtain photographs and video during the exoskeleton training sessions. The 
goal of the photography and videotaping will be used for educational purposes when 
presenting results of this study. The photographs will be used to demonstrate what exoskeleton 
training looks like. The identity of subjects will not be revealed in the photograph. If a 
photograph or video is used, a black box will be placed in front of subjects face to protect their 
identity. Any photographs and videos taken during the study will be saved on a locked 
computer in a file labeled with the subjects research number and no other identifying 
information. 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
DATA and SAFETY MONITORING 
We will use following strategies to prevent some expected events for this study: 
1) Loss of confidentiality or privacy 
Information obtained for this study will be kept private to the extent allowed by law. However, 
research information may be shared with the University of Texas Health Science Center at 
Houston Institutional Review Board (IRB), the research physician investigator, the research staff 
and others who are responsible for ensuring compliance with laws and regulations related to 
research. The study will be performed at TIRR Memorial Hermann. Data will be collected on 
paper forms which will be kept in a locked room in a locked filing cabinet in the research office 
in UT Health Motor Recovery Laboratory at the TIRR NeuroRecovery Research Center. To allow 
for data analysis, data will be de-identified and entered into an excel spreadsheet. All 
computers are password protected and therefore, only authorized persons have the access to 
the electronic files saved in computers and will adhere to TIRR Memorial Hermann standards. 
2) Loss of saved electronic data after a computer crash 
All original data will be maintained on paper data collection forms. De-identified data may be 
entered into computer for data analysis. A standard procedure of electronic file backup is 
established and enforced by the PI. All file backups are routinely performed in the local hard 
drive. However, if there are other unanticipated problems which occur during and after data 
collection: the original paper version of the data will be maintained in the locked file cabinet. 
3) Loss of balance or fall from testing 
One research team member will remain next to the subject as long as the subject is donned in 
the exoskeleton robot to prevent loss of balance or fall whether sitting or standing. If a fall or 
significant loss of balance occurs, one staff physician will be notified immediately. All adverse 
events will be reported per CPHS protocol. 
4) Possible skin irritation 
Local skin irritation, bruising, swelling, or temporary discomfort following wearing of the 
exoskeleton may occur. Prior to donning the exoskeleton subjects skin will be inspected by a 
licensed Physical Therapist for baseline, and compared after doffing exoskeleton. Any 
differences will be recorded and followed up with the study physician accordingly. All adverse 
events will be reported per CPHS protocol. 
5) Muscular soreness or fatigue 
Borg Rating of Perceived Exertion Scale (Borg) will be administrated periodically throughout the 
intervention sessions. Subject will be provided with rest period as needed, in particular if BORG 
rating 17. 
6) Bone Fracture 
The risk of fracture to the subject is no greater with the use of exoskeleton than conventional 
weight bearing and walking therapy. 
STATISTICS 
The proposed study is a single-arm, pilot study; therefore, no data is available to 
calculate the sample size. This study's data will allow for performing power analysis to 
determine the effect size and sample size for future studies. 
Descriptive analysis will be used to analyze the heart rate variables, such as the number 
of minutes the target heart rate is met during the training and the heart rate- time relationship 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
during a typical session. Paired t-tests will be used to compare dependent variables (i.e., 
functional assessment) between baseline and post-training. The significant level is set at 0.05. 
 
ETHICS 
The study will be performed under the prevue and in accordance with the rules set by 
the Committee for the Protection of Human Subjects (UT IRB). Potential subjects will be 
identified by physiatrists and physical therapists working on the inpatient wards at The Institute 
for Rehabilitation and Research (TIRR) Memorial Hermann. Once identified, the potential 
subjects will be approached and asked if they wish to discuss a study utilizing exoskeletons 
(Robotic suits worn on the outside of the body) for individuals with CVA or SCI. It will also be 
explained that choosing not to inquire further about the study will in no way jeopardize the 
relationship with anyone at TIRR or in the Memorial Hermann system. Once the potential 
subject agrees he/she will be introduced to either the Principal Investigator or the study 
coordinator. Once the potential subject agrees to discuss the study, the individual and anyone 
that the potential subject wishes to accompany him/her will go into a private room to discuss 
the contents of the consent form with either the Principal Investigator or study 
coordinator. After the consent is reviewed in its entirety, and after allowing ample time for 
questions, either the Principal Investigator or the study coordinator will give the potential 
subject time to discuss the study with whomever the potential subject cares to discuss the 
study with. If the subject agrees to enroll in the study, the Principal Investigator or study 
coordinator will review the informed consent form with the subject in its entirety. 
 
DATA HANDLING and RECORD KEEPING 
The subjects name and demographic information will be collected prior to testing. Each 
subject will be assigned an identification number which will be used from this point forward. 
All measurements will be stored according to the identification number. All research materials 
will be kept in a locked file cabinet in the research office. All computers are password 
protected and only authorized persons have the access to the electronic files saved in 
computers. Paper data will be stored in the UT Health Motor Recovery Laboratory research 
office at TIRR NeuroRecovery Research Center in a locked file cabinet. Access to the file cabinet 
will be given to the Primary Investigator and authorized team members. All electronic data 
stored on the hard drive of the desktop machine will be password protected and available only 
to the authorized research team members. Identifiable data will be stored for 5 years after the 
study is completed. Stored files will be deleted from the portable hard drive after 5 years as 
well. Identifiable data will be shredded at the end of 5 years after the completion of the study. 
 
 
 
QUALITY CONTROL and ASSURANCE 
To ensure research integrity, standard written procedures for all tests will be 
established by the Principle Investigator and the Study Coordinator who will then assess each 
team members competence for research conduction on a regular basis. Therefore, the testing 
protocol will be consistent throughout the entire data collection for this study. 

IRB NUMBER: HSC-MS-21-0262 
IRB APPROVAL DATE: 10/17/2023 
 
COSTS, REIMBURSEMENTS and COMPENSATION 
Subjects will receive $100 for participation in this study. Subjects will receive $20 at the 
completion of each exoskeleton intervention. 
 
FUTURE STUDIES 
Subject will be asked to answer a question regarding their interest in being contacted in 
the future to participate in other studies. Subjects will be given the choice to say yes or no if 
they agree to be contacted in the future regarding other projects. 
 
PUBLICATION PLAN 
The results of this study will be used for presentation at national conferences and 
publications in peer-reviewed journals. 
 
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