Spinal Cord Injury Epidural Stimulation

Study Overview
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Brief Summary
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This is a feasibility study to test the use of epidural stimulation to restore volitional function previously lost due to spinal cord injury. Previous studies conducted in animal models, performed elsewhere and here at Mayo Clinic, have shown that direct electrical stimulation of the spinal cord increases the excitability of spared neuronal connections within the site of injury, thereby enhancing signal transmission and allowing recovery of previously lost volitional function. Recently, epidural electrical stimulation of the lumbosacral spinal cord in four individuals with spinal cord injury (SCI) has restored motor and autonomic function below the level of injury. Despite positive results, further translational research is needed to validate these findings. The goal of this proposal is to perform epidural stimulation to restore volitional function in patients with SCI. In two patients, we will implant an epidural stimulator onto the dorsal aspect of the lumbosacral spinal cord dura mater. Patients will undergo a structured program of daily physical rehabilitation, treadmill step training, and epidural stimulation to recover motor, sensory, and autonomic function.

Official Title
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A Feasibility Study: Epidural Stimulation to Enable Volitional Movement After Chronic Complete Paralysis in Humans.

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Device: Epidural Stimulator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable medical condition without *cardiopulmonary disease or *dysautonomia that would contraindicate standing or stepping with body weight support training No current anti-spasticity medication regimen Non-progressive spinal cord injury between the vertebral levels of C7 & T10 American Spinal Injury Association grading scale of A or B Sensory evoked potentials are either not present or have a bilateral delay Segmental reflexes remain functional below the lesion At least 2-years post-injury. Exclusion Criteria: Pregnancy at time of enrollment Failure to obtain consent Prisoners Children (age less than 21) Any patient identified as unsuitable for this protocol by the Mayo study team Skeletal fracture Osteoporosis with Dual-energy X-ray absorptiometry (DEXA) t score ≤-3.5 Uncontrolled urinary tract infections Presence or history of frequent decubitus ulcers Clinical depression Drug abuse Painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore, or urinary tract infection that might interfere with stand or step training Current anti-spasticity medication regimen Voluntary motor response present in leg muscles Volitional control during voluntary movement attempts in leg muscles as measured by electromyography (EMG) activity Brain influence on spinal reflexes as measured by EMG activity Recordable motor evoked potential in the lower limbs with transcranial magnetic stimulation Implanted cardiac pacemaker Implanted defibrillator Other implanted metallic or active body worn medical electronic device such as an insulin pump *Cardiopulmonary disease that would result in exclusion from the study will be defined as clinically diagnosed chronic obstructive pulmonary disease, cardiac failure, and heart arrhythmia that would contraindicate sudden changes in body position such as sit-to-stand and stepping *Excessive and uncontrolled autonomic dysreflexia characterized by symptomatic hypotension, light headedness and hypertension, flushing and bradycardia. Additionally blood pressure monitoring will be available at all times during rehabilitation and assessment times.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br>Subjects will be implanted with an epidural stimulator onto the dorsal aspect of the lumbosacral spinal cord dura mater. Patients will undergo a structured program of daily physical rehabilitation, treadmill step training, and epidural stimulation to recover motor, sensory, and autonomic function. The total estimated time for the intervention is 66 weeks. | Device: Epidural Stimulator<br>* Subjects will be implanted with an epidural stimulator onto the dorsal aspect of the lumbosacral spinal cord dura mater. Patients will undergo a structured program of daily physical rehabilitation, treadmill step training, and epidural stimulation to recover motor, sensory, and autonomic function.<br>* Other names: Medtronic Restore ULTRA 97712;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of time for which subject can sit unassisted on the edge of a mat table |  | Approximately 50 weeks after implantation | 
| Assessment of volitional movement of lower limbs |  | Approximately 50 weeks after implantation | 
| Subject's ability to coordinate stepping on a treadmill will be measured using biomechanical and electrophysiological analyses |  | Approximately 50 weeks after implantation | 
| Duration of time for which subject can stand weight bearing with minimal assistance provided as needed. |  | Approximately 50 weeks after implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in volitional movement restoration via NeuroRecovery scale |  | baseline, approximately 50 weeks after implantation | 
| Change of bladder function, as measured by the Neurogenic Bladder Symptom Score questionnaire |  | baseline, approximately 50 weeks after implantation | 
| Change in sexual function as measured by the Sexual Function Questionnaire |  | baseline, approximately 50 weeks after implantation | 
| Change in body thermoregulatory capacity as measured by thermoregulatory sweat testing |  | baseline, approximately 50 weeks after implantation | 
| Change in lean body mass |  | baseline, approximately 50 weeks after implantation | 
| Change in bone density |  | baseline, approximately 50 weeks after implantation | 
| Change in sense of wellbeing as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire |  | baseline, approximately 50 weeks after implantation | 
| Change in sitting balance via functional reach test |  | baseline, approximately 50 weeks after implantation | 
| Change in spasticity via Ashworth spasticity test |  | baseline, approximately 50 weeks after implantation | 
| Change in ability of performing basic activities of daily life via spinal cord independence measure |  | baseline, approximately 50 weeks after implantation | 
| Change in total body fat |  | baseline, approximately 50 weeks after implantation | 
| Change in bowel function as measured by the Neurogenic Bowel Dysfunction Score questionnaire |  | baseline, approximately 50 weeks after implantation |