Locomotor Function Following Transcutaneous Electrical Spinal Cord Stimulation in Individuals With Hemiplegic Stroke
Phase: NA
Conditions: Stroke
Sponsor: Shirley Ryan AbilityLab

STU#: 00206430 
 
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Official Title of the Study: Locomotor Function Following Transcutaneous Electrical Spinal 
Cord Stimulation in Individuals With Hemiplegic Stroke  
 
NCT Number: NCT03714282 
 
Date of Document: November 19, 2019 
 
 

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PROTOCOL TITLE: Locomotor function following transcutaneous electrical spinal cord 
stimulation in individuals with hemiplegic stroke 
 
PRINCIPAL INVESTIGATOR: 
Elliot J. Roth, MD 
Physical Medicine and Rehabilitation 
312-238-4864 
eroth@sralab.org 
 
VERSION DATE: 
November 19, 2019 
 
STUDY SUMMARY: 
 
Investigational Agent(s)  
(Drugs or Devices) 
Biostim-5 Spinal Stimulator 
IND / IDE / HDE #   
Indicate 
Special Population(s) 
Children  
 Children who are wards of the state  
 Adults Unable to Consent   
 Cognitively Impaired Adults  
 Neonates of Uncertain Viability  
 Pregnant Women  
 Prisoners (or other detained/paroled individuals)  
 Students/Employees  
Sample Size 45 persons with stroke  
Funding Source Shirley Ryan AbilityLab & Frankel Foundation 
Indicate the type of consent 
to be obtained 
Written  
Verbal/Waiver of Documentation of Informed Consent 
Waiver of HIPAA Authorization  
Waiver/Alteration of Consent Process   
Site 
 Lead Site (For A Multiple Site Research Study) 
 Data Coordinating Center (DCC) 
Research Related 
Radiation Exposure 
Yes  
 No  
DSMB / DMC / IDMC 
Yes  
No 
 
 
OBJECTIVES: 
• 
To determine whether transcutaneous spinal cord stimulation combined with ambulation 
training modulates corticospinal locomotor networks in individuals with hemiplegic stroke 
• 
To determine whether transcutaneous spinal stimulation combined with ambulation 
training improves locomotor function in individuals with hemiplegic stroke 
• 
To determine whether transcutaneous spinal stimulation combined with ambulation 
training improves symmetry of gait in individuals with hemiplegic stroke 
• 
To determine whether ambulation efficiency improves with transcutaneous spinal 
stimulation and locomotor training in individuals with hemiplegic stroke  
 

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Our hypothesis is transcutaneous spinal cord stimulation combined with ambulation training in 
persons with hemiplegic stroke will lead to improved: modulation of corticospinal networks, 
locomotor function, symmetry of gait, balance and efficiency compared to ambulation training 
alone.  
 
BACKGROUND: 
 
The use of epidural stimulation has been performed with implanted electrode systems and 
demonstrated effectiveness in human and animal models after spinal cord injury, but this will be 
one of the first studies to investigate the efficacy of a painless and non-invasive method of 
spinal cord stimulation with individuals with hemiplegia due to stroke.  This is significant 
because the transcutaneous epidural stimulation carries less risk (compared to implantation 
procedure) and more individuals suffer from the consequences of stroke compared to spinal 
cord injury. 
 
The use of epidural spinal-cord stimulation was shown to generate locomotion patterning in 
humans after a complete spinal cord injury1.  The intervention may be effective, but the invasive 
and involved procedure is not realistic for incorporation into routine rehabilitation services.  
Recent efforts have induced step-like patterns in patients with a motor complete spinal cord 
injury using non-invasive spinal cord stimulation.  Even more promising is that these individuals 
were able to demonstrate voluntary step-like patterns with continued training.2 These results 
reflect the potential for neuroplasticity modulation through non-invasive spinal stimulation during 
locomotor training for individuals with a disruption between supra and spinal connections.   
 
We would like to explore the use of this device with patients with a single, stroke history that 
resulted in hemiplegia.  The results of this study will help us understand how transcutaneous 
electrical stimulation may improve balance and ambulation in individuals with a stroke. The 
number of people diagnosed with a stroke in the United States is 795,000 per year.  Projections 
estimate that by 2030, there will be an additional 3.4 million adults with a stoke.3 This is a 
significant number of people that may benefit from this training paradigm. 
 
References: 
1. Dimitrijevic MR, Gerasimenko Y, Pinter MM. Evidence for a spinal central pattern 
generator in humans. Ann NY Acad Sci 1998;860:360-376. 
2. Gerasimenko YP, Lu DC, Modaber M, et al. Noninvasive reactivation of motor 
descending control after paralysis. Journal of Neurotrauma. 2015. 32:1968-1980. 
Doi:10.1089/neu.2015.4008. 
3. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics – 2017 
update: a report from the american heart association. Circulation. 2017;135:e1-e458. 
Doi:10.1161/CIR.0000000000000485  
 
STUDY ENDPOINTS: 
Primary endpoint: 
• 
Changed locomotion symmetry reflected by altered symmetry in spatio-temporal 
parameters, and kinematic measures during walking.  
 
Secondary endpoints 
• 
Improved locomotion efficiency in Six Minute Walk Test (6MWT)  
• 
Improved gait speed as measured by the Ten Meter Walk Test (10MWT) at self-selected 
velocity and fastest (safe) velocity 

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• 
Improved gait kinematics reflected by improved symmetry and decreased base of 
support during walking on the the GAITRite electronic walkway 
 
STUDY INTERVENTION(S)  / INVESTIGATIONAL AGENT(S): 
A Transcutaneous Spinal Cord Neurostimulator (BioStim-5) will deliver transcutaneous electrical 
spinal cord stimulation.  It provides constant current stimulation with a range of 0-250 mA 
through self-adhesive electrodes (ValuTrode, Axelgaard Ltd., USA) with a diameter of 3.2 cm 
placed as cathodes on the skin between the spinous processes of the C4 and Co1 vertebrae. In 
addition, two 7.5 × 13 cm self-adhesive electrodes serving as anodes (ValuTrode, Axelgaard 
Ltd., USA) will be placed symmetrically on the skin over the iliac crests. The stimulation 
waveform will consist of biphasic, rectangular 1-ms pulses at a frequency ranged between 0.2 
and 40 Hz, with each pulse filled with a carrier frequency of 5 to 10 kHz. The stimulation 
intensity will vary from 5 to 250 mA and be determined based on participant threshold and 
maximum motor outputs.   
 
PROCEDURES INVOLVED: 
 
Study Design: A randomized control trial.  We are evaluating the effectiveness of 
transcutaneous spinal cord stimulation on ambulation among individuals with hemiplegia due to 
stroke. We will randomly assign participants in the Stroke group into either intervention group A 
or intervention group B.  Intervention group A will receive transcutaneous spinal cord stimulation 
during the intervention visits while intervention Group B will complete the same interventions 
without transcutaneous electrical spinal cord stimulation. However, Group B will receive sham 
stimulation. Healthy control participants will complete assessment visits in order to obtain 
comparative data for various outcome metrics. 
 
STUDY EQUIPMENT 
 
• 
Wearable sensors 
The sensors used will include EMG sensors and Xsens motion capture sensors. The 
wearable sensors will collect the following information: 
• 
Biometric data, including electromyography (EMG) 
• 
Movement data from the limbs including signals from triaxial accelerometers 
(ACC) and gyroscopes (GYR) 
 
• 
Electronic walkway 
The GAITRite electronic walkway contains sensor pads encapsulated in a carpet and 
connected to a computer.  The system can be laid over any flat surface and automates 
measuring temporal and spatial gait parameters.  The GAITRite electronic walkway for the 
study shall be a minimum of 14 feet long.  The GAITRite data capture was chosen as 
measurement of the patient's overall gait quality.  Patients will be asked to walk at a self-
selected speed and a fast, but safe, speed across the GAITRite electronic walkway with 
and without lower extremity orthotics if safe and appropriate during assessment visits and 
during treatment sessions to quantify ambulation symmetry.  
 
• 
Gravity Eliminated locomotion training 
A custom designed apparatus to allow the lower legs to move in a gravity neutral position.  
Participants in the Stroke group are positioned in a side-lying position on their non-paretic 
side.  Participants in the healthy control group will be in a side-lying position on their 
preferred side. Their legs extend off the edge of the mat table.  The upper leg is supported 

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at the shank and the lower leg is placed on a rotating brace attached to a horizontal board 
supported by vertical ropes secured to the ceiling. In this gravity-neutral position, the 
participants will be requested to perform rhythmic stepping-like motions.  
• 
Transcutaneous Spinal Cord Neurostimulator 
A Transcutaneous Spinal Cord Neurostimulator (BioStim-5) will deliver transcutaneous 
electrical spinal cord stimulation.  It provides constant current stimulation with a range of 0-
250 mA through self-adhesive electrodes (ValuTrode, Axelgaard Ltd., USA) with a diameter 
of 3.2 cm placed as cathodes on the skin between the spinous processes of the C4 and 
Co1 vertebrae. In addition, two 7.5 × 13 cm self-adhesive electrodes serving as anodes 
(ValuTrode, Axelgaard Ltd., USA) will be placed symmetrically on the skin over the iliac 
crests. The stimulation waveform will consist of biphasic, rectangular 1-ms pulses at a 
frequency ranged between 0.2 and 40 Hz, with each pulse filled with a carrier frequency of 
5 to 10 kHz. The stimulation intensity will vary from 5 to 250 mA and be determined based 
on participant threshold and maximum motor outputs.   
 
• 
Cosmed K4B2 Metabolic unit 
Cosmed K4B2 (K4B2 Cosmed, Italy) is a portable gas analysis system that measures 
oxygen consumption (VO2) and Carbon-dioxide production (VCO2 ) in a breath by breath 
fashion. K4B2 system consists of a portable unit and battery pack that weighs about 2.4 lbs 
(1100 gm). The portable unit has O2 and CO2 analyzers that are bi-directionally connected 
to a flowmeter and turbine attached to a rubber facemask that is tightly strapped over 
subject’s nose and mouth.  K4B2 requires calibration before every testing session due to 
usage of heated sensors for measurements. Manufacturer’s recommend at least 45 
minutes warm up time for unit under ambient temperature (ideally at 20˚C) before 
calibration. K4B2 calibration involves verifying flowmeter and concentrations of gases with 
labeled concentrations. K4B2 acquires heart rate using a telemetric heart rate sensor that is 
strapped over subject’s thorax. The K4B2 and battery pack can be securely placed in slots 
on a standard harness worn by subject. This harness allows access to buttons on the unit 
on upper back and minimal interference to activities like walking. Data extraction and 
processing is carried using K4B2 custom software. 
 
VISIT SCHEDULE & DESCRIPTION 
 
Visits 1:  Initial screening session 
• 
Obtain voluntary and informed consent  
• 
Inclusion/exclusion criteria checklist reviewed with patient 
• 
Medical history review 
• 
Patient name 
• 
Patient date of birth 
• 
Patient race (voluntary) 
• 
Patient gender 
• 
Date of stroke 
• 
Type and location of stroke 
• 
Paretic/non-paretic limb 
• 
Assistive device use 
• 
Recent surgery/injuries 
• 
Allergies 
• 
Therapy history 

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• 
Current medications 
• 
Emergency contact information 
• 
Personal contact information 
• 
Evaluation of Physical Function 
• 
Active and passive range of motion of bilateral lower extremities 
• 
Assessment of lower extremity spasticity using Modified Ashworth Scale 
• 
Assessment of gait for ataxia and level of independence with Functional 
Ambulation Category 
 
A letter detailing the study procedures and risks will be sent to the subject’s physician or 
clinician to request medical clearance for the subject to participate in the study. Permission to 
contact the participant’s physician or clinician to obtain medical clearance will be obtained 
during the screening process prior to or during Visit 1.  
 
Baseline Assessment Visits 
• 
Standard evaluation of physical function 
• 
Muscle strength assessment using manual muscle testing of lower extremities 
• 
Skin integrity screen  
 
• 
Functional outcome measurements 
• 
Six Minute Walk Test (6 MWT)  
Participants will complete the 6MWT with wearable sensors and Cosmed K4B2 
Metabolic unit to determine participant’s baseline gait efficiency  
• 
Ten Meter Walk Test (10 MWT) 
Participants will complete at their self-selected speed (SSV) and fastest safe velocity 
(FV) three times each with and without lower extremity orthotics if safe and 
appropriate (12 total) with wearable sensors and CosmedK4B2 Metabolic Unit to 
determine baseline gait speed and community ambulation assessment without 
stimulation. Participants will then repeat the assessment up to 12 times with the use 
of transcutaneous electrical spinal cord stimulation to assess for the immediate 
effects of stimulation on gait speed.  
 
• 
Locomotion assessment for inter and intra limb coordination using wearable sensors and 
EMG sensors. Participants will ambulate along Gait Rite electronic walkway to evaluate 
baseline gait pattern at both their self-selected and safe fast gait speed without 
stimulation.  
 
• 
Spinal Motor Evoked Potentials (MEPs) will be obtained at each of the assessment time 
points while stimulating the spinal cord between the spinous processes of C4 and the 
Co1 vertebrae with a single pulse. MEPs are the electromyograph responses of the 
peripheral muscles to electrical stimulation of the spinal cord. MEPs will be used to test 
the integrity of the motor pathways of the spinal cord. 
 
Treatment Sessions 
Each participant will complete up to 24 treatment sessions over the course of 8 weeks.  Each 
treatment session will: 
• 
Intervention Group A (Experimental): 
o 45 minutes of locomotion training with transcutaneous spinal cord stimulation.  
However, the amount of time spent in side-lying locomotion training, treadmill 

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training and overground training will depend on individual tolerance and 
progression.   
• 
Intervention Group B (Control): 
o 45 minutes of locomotion training without transcutaneous spinal cord stimulation, 
but with sham stimulation.  However, the amount of time spent in side-lying 
locomotion training, treadmill training and overground training will depend on 
individual tolerance and progression.   
 
Under all the conditions, the goal is to generate smooth and symmetrical stepping movements.  
The trained research personnel will provide cues (verbal, visual and tactile) to improve 
symmetry of gait and avoid compensatory mechanisms.  The progression in training refers to 
gradually increasing gait speed while maintaining improved gait kinematics.  
 
Follow-up Functional Assessment Visits – Mid point, Post, 3 months Post 
• 
Refer to Baseline Assessment Visit for repeat of assessments 
 
SAFETY MONITORING 
All visits will be under the supervision of a trained researcher and clinician.  Manual assistance 
or cueing will be provided as necessary for safety and balance.  Clinicians will also utilize gait 
belts and overhead harness systems to ensure patient safety during physical activity.  Vital 
signs will be monitored with use of our wearable sensors before, during and after physical 
exertion.  All subjects will be permitted to stop physical activity or rest at any time during the 
study.  In addition, the following patient reports will be used to assess patient participation and 
make adjustments as appropriate.  
• 
Rating of Perceived Exertion (RPE) 
The 15-grade Borg Scale during ambulation training (overground, treadmill and gravity-
eliminated) to monitor RPE.  The intensity will be adjusted to ensure patients do not exceed 
a rating of 17 (very hard). 
• 
Pain scale 
Visual Analogue Scale (VAS) for pain will monitor patient discomfort during non-invasive 
spinal cord stimulation and locomotion training parameters.  This is a 10-point scale.  We 
will stop when the participant states pain that interferes with their safe participation in the 
research. 
 
AUDIO/VIDEO RECORDING/PHOTOGRAPHY 
Video recording and/or pictures of each participant during assessment and training sessions 
may be taken during the training and testing sessions. These items may be used to help 
troubleshoot potential issues for fit or functionality of the device. They may also be used for 
presentations and training of other research personnel. Each Subject may choose to limit if/how 
these items may be used, as indicated during their Consent process. 
 
DATA AND SPECIMEN BANKING 
Data will be collected and kept confidential and compliant with HIPPAA requirements.  All 
personal information and study documentation that can identify participants will be kept secure 
to protect their privacy and will never be shared at any time with any person or entity.  Data 
collected during the study and shared with others will reference participants only by an 
alphanumeric code.  The “master list” linking personal information to the alphanumeric code will 
not be shared.  All data will be captured in electronic format and stored on the secure and 
password protected network and devices managed by the Shirley Ryan AbilityLab.  Electronic 
folders will be private with limited access as determined by the PI. 

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INCLUSION AND EXCLUSION CRITERIA 
Inclusion Criteria: 
• 
Participants are 18 years of age or older 
• 
Participants are at least 4 weeks post stroke 
• 
Participants with hemiplegia secondary to a single stroke 
• 
Functional Ambulation Category of 2 or greater - Patient needs continuous or 
intermittent support of one person to help with balance and coordination. 
• 
Participants are able to provide informed consent 
• 
Participants are not currently receiving regular physical therapy services 
 
Exclusion Criteria:  
• 
Individuals less than18 years of age 
• 
Individuals less than 4 weeks post stroke 
• 
Individuals with ataxia 
• 
Individuals with multiple stroke history 
• 
Currently taking a Selective Serotonin Reuptake Inhibitor (SSRI) or Tricyclic 
antidepressant (TCA) 
• 
Botox injection in lower extremity within the last 4 months 
• 
Modified Ashworth score of 3 or greater in lower extremity  
• 
Pregnancy or nursing 
• 
Pacemaker or anti-spasticity implantable pumps 
• 
Active pressure sores 
• 
Unhealed bone fractures 
• 
Peripheral neuropathies 
• 
Painful musculoskeletal dysfunction due to active injuries or infections 
• 
Severe contractures in the lower extremities 
• 
Medical illness limiting the ability to walk 
• 
Active urinary tract infection 
• 
Clinically significant depression, psychiatric disorders, or ongoing drug abuse 
• 
Metal implants in their spine 
• 
Active cancer or cancer in remission less than 5 years 
 
VULNERABLE POPULATIONS NA 
 
PARTICIPANT POPULATION(S) 
Accrual 
Number: 
Category/Group: 
(Adults/Children 
Special/Vulnerable 
Populations) 
Consented: 
Maximum Number to be 
Consented or 
Reviewed/Collected/Screened 
Enrolled: 
Number to Complete 
the Study or Needed 
to Address the 
Research Question 
Local 
Adults (Stroke 
Group) 
100 consented and screened, 
goal of 45 to complete the full 
protocol 
45 
Study-wide 
Single-Center Study 
0 
0 
Total: 
 
45 
45