Transcutaneous and Epidural Spinal Stimulation for Enabling Motor Function in Humans With Motor Complete Paraplegia

Study Overview
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Brief Summary
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The purpose of this study is to compare transcutaneous electrical spinal stimulation (TESS) and epidural electrical stimulation (EES); in particular, the motor activity enabled by each method and the potential health benefits of each method.

Official Title
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Characterization of Transcutaneous and Epidural Spinal Stimulation for Enabling Motor Function in Humans With Motor Complete Paraplegia

Conditions
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Paraplegia, Spinal, Paraplegia, Complete, Paraplegia; Traumatic

Intervention / Treatment
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* Device: Transcutaneous spinal cord stimulator
* Device: Epidural spinal cord stimulation system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Spinal cord injury due to trauma located between the seventh cervical and tenth thoracic vertebrae American Spinal Injury Association grading scale of A or B (at least 4 each of A and B) below the level of SCI Intact spinal reflexes below the level of SCI At least 1-year post-SCI At least 22 years of age Willing to use medically acceptable methods of contraception, if female and of child-bearing potential Exclusion Criteria Currently a prison inmate, or awaiting trial, related to criminal activity Pregnancy at the time of enrollment DEXA t score <-3.5 at spine and femur head History of chronic and/or treatment resistant urinary tract infection Unhealed decubitus ulcer Unhealed skeletal fracture Untreated clinical diagnosis of depression Presence of joint contractures or an Ashworth spasticity score of 4 Active anti-spasticity medication regimen within 3 months prior to study enrollment Presence of transcranial magnetic stimulation-evoked potentials in leg muscles Non MRI-compatible implanted medical devices. Undergoing, or planning to undergo, diathermy treatment Active participation in another interventional clinical trial Presence of conditions or disorders which require MRI monitoring For EES cohort subjects, a history of coagulopathy or other significant cardiac or medical risk factors for surgery Current use of a ventilator Clinically diagnosed cardiopulmonary complications such as chronic obstructive pulmonary disease, cardiac failure, or heart arrhythmia that contraindicate changes in body position such as supine-to-sit-to-stand activities, prolonged standing, or stepping Mass > 113 kg (250 pounds) History of frequent hypotension characterized by light headedness, or loss of consciousness History of frequent hypertension characterized by headache, or bradycardia History of frequent, severe, autonomic dysreflexia Any illness or condition which, based on the research team's assessment, will compromise with the patient's ability to comply with the protocol, patient safety, or the validity of the data collected during this study.

Ages Eligible for Study
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Minimum Age: 22 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TESS<br>Transcutaneous Electrical Spinal Stimulation (TESS), used during all training sessions. | Device: Transcutaneous spinal cord stimulator<br>* DS8R Electrical Stimulator For Human Research<br>|
| Experimental: EES<br>TESS, used during the initial 6-month training period, followed by Epidural Electrical Stimulation (EES) during the final 6-month training period. | Device: Transcutaneous spinal cord stimulator<br>* DS8R Electrical Stimulator For Human Research<br>Device: Epidural spinal cord stimulation system<br>* Spectra WaveWriter Epidural Spinal Cord Stimulator System with CoverEdge 32 Electrode Surgical Lead<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinematics | Change in measurements of joint angles using video-based, inertial measurement, and/or electromagnetic markers. | Baseline, Month 3, Month 6, End of Month 7, Month 10, Month 13 | 
| Electromyography | Change in measurements of electrical activity at major muscle groups below the level of injury. | Baseline, Month 3, Month 6, End of Month 7, Month 10, Month 13 | 
| Foot pressure | Change in measurements of foot pressure through shoe-insole pressure sensors. | Baseline, Month 3, Month 6, End of Month 7, Month 10, Month 13 | 
| Somatosensory evoked potentials | Change in measurements of change in conduction in the peripheral nerves, cervical and lumbosacral spinal cord, deep brain structures, and sensory cortex, through surface electrodes. | Baseline, Month 6, End of Month 7, Month 13 | 
| Transcranial magnetic stimulation motor evoked potentials | Change in measurements of stimulus intensity required to elicit muscle responses in muscle groups known to elicit optimal motor evoked potential responses, both above and below the level of injury. | Baseline, Month 6, End of Month 7, Month 13 | 
| Monosynaptic spinal reflex testing | Change in measurements of stimulation intensity H and F wave thresholds and maximal responses through surface electrodes. | Baseline, Month 6, End of Month 7, Month 13 | 
| Trunk stability | Change in measurements of trunk stability using the modified functional reach test (mFRT). | Baseline, Month 3, Month 6, End of Month 7, Month 10, Month 13 | 
| Injury severity: American Spinal Injury Association Impairment Scale (AIS) | Change in measurements of impairment of sensory and motor functions using the American Spinal Injury Association Impairment Scale (AIS). Individuals are classified from A (complete spinal cord injury) to E (normal function). 28 dermatomes and 10 key muscles are assessed bilaterally. Results are summed to produce overall sensory and motor scores and are used in combination with evaluation of anal sensory and motor function as a basis for the determination of AIS classification. Sensory scores are rated 0 (sensation absent) to 2 (normal), bilaterally for each of 28 dermatomes. Muscle function is rated 0 (total paralysis) to 5 (active movement, full range of motion against significant resistance) for each myotome. Upper Extremity Motor Subscores and Lower Extremity Motor Subscores are each scored from 0 to 50; the ASIA Motor Score is scored from 0 to 100. The presence of anal sensation and voluntary anal contraction are assessed as a yes/no. | Baseline, Month 6, End of Month 7, Month 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel function | Change in measurements of bowel function utilizing anorectal manometry. | Baseline, Month 6, Month 13 | 
| Bladder function | Change in measurements of bladder function utilizing a urodynamic test consisting of a filling phase and a voiding phase cystometrogram along with perineal patch muscle electromyography. | Baseline, Month 6, Month 13 | 
| Spasticity | Change in measurements of spasticity using the Modified Ashworth Scale (MAS), an assessment which measures resistance during passive soft-tissue stretching of bilateral hip flexors, extensors, adductors, and abductors, knee extensors and flexors, and ankle plantarflexors and dorsiflexors. Scoring is scaled from 0 (no increase in muscle tone) to 4 (affected part[s] rigid in flexion or extension), with higher scores indicating more spasticity. | Baseline, Month 3, Month 6, End of Month 7, Month 10, Month 13 | 
| Bone mineral density | Measurement by dual-energy x-ray absorptiometry (DXA) of change in bone mineral content and bone density. | Baseline, Month 6, Month 13 | 
| Body composition - body fat mass | Measurement by dual-energy x-ray absorptiometry (DXA) of change in regional and total body fat mass. | Baseline, Month 6, End of Month 7, Month 13 | 
| Body composition - lean mass | Measurement by dual-energy x-ray absorptiometry (DXA) of change in regional and total lean mass. | Baseline, Month 6, End of Month 7, Month 13 | 
| Body composition - android and gynoid fat percentage | Measurement by dual-energy x-ray absorptiometry (DXA) of change in regional and total android and gynoid fat percentage. | Baseline, Month 6, End of Month 7, Month 13 | 
| Body composition - android and gynoid fat ratio | Measurement by dual-energy x-ray absorptiometry (DXA) of change in regional and total android to gynoid fat ratio. | Baseline, Month 6, End of Month 7, Month 13 | 
| Body composition - bone mass | Measurement by dual-energy x-ray absorptiometry (DXA) of change in regional and total bone mass. | Baseline, Month 6, End of Month 7, Month 13 | 
| Knee cartilage health | Assessment of change in knee cartilage breakdown using the modified Outerbridge classification or the International Cartilage Repair Society classification, utilizing magnetic resonance imaging (MRI). | Baseline, Month 6; Month 13 for TESS cohort only | 
| Metabolics - CBC | Measurement of changes in complete blood count with differential. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - glucose | Measurement of change in fasting glucose value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - total cholesterol | Measurement of change in total cholesterol value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - HDL cholesterol | Measurement of change in HDL cholesterol value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - calculated LDL cholesterol | Measurement of change in calculated LDL cholesterol value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - triglycerides | Measurement of change in triglycerides value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Metabolics - non-HDL cholesterol | Measurement of change in non-HDL cholesterol value. | Baseline, Month 6, End of Month 7, Month 13 | 
| Spinal structural integrity | Assessment of structural integrity via computerized tomography (CT). | Baseline | 
| Injury severity and potential for spared tissue | Evaluation of severity and possibility of discomplete injury despite complete loss of motor function via MRI. | Baseline | 
| Stimulator array location and migration (EES cohort only) | Evaluation of current array location via CT. | End of Month 7, Month 13 | 
| Patient-reported bowel function (1) | Measurement of change in bowel function using the Neurogenic Bowel Dysfunction Score. Answers to qualitative questions are rated from 0 to 5, with a higher number indicating more problematic symptoms, and totaled for a score which categorizes severity of neurogenic bowel symptoms. | Baseline, Month 6, End of Month 7, Month 13 | 
| Patient-reported bowel function (2) | Measurement of change in bowel function using the International Spinal Cord Injury Bowel Function Basic Data Set (v2.0). Answers to qualitative questions are rated from 0 to 13, with a higher number indicating more problematic symptoms, and totaled for a score which categorizes neurogenic bowel dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Patient-reported bladder function (1) | Measurement of change in bladder function using the Neurogenic Bladder Symptom Score. Answers to qualitative questions are rated from 0 to 5, with a higher number indicating more problematic symptoms, and totaled for a score which categorizes severity of neurogenic bladder symptoms. | Baseline, Month 6, End of Month 7, Month 13 | 
| Patient-reported bladder function (2) | Assessment of change in bowel function using the International Spinal Cord Injury Urodynamic Basic Data Set. Data from various urodynamic variables are aggregated into a single-page format for an abstract overview of bladder dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Male patient-reported sexual function (1) | Assessment of change in sexual function using the International Spinal Cord Injury Male Sexual Function Basic Data Set (v2.0). Data from various male sexual function variables are aggregated into a single-page format for an abstract overview of male sexual dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Male patient-reported sexual function (2) | Measurement of change in erectile dysfunction using the Sexual Health Inventory for Men (SHIM). Answers to qualitative questions are rated from 0 to 5, with a higher number indicating better erectile function, and totaled for a score which categorizes severity of erectile dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Male patient-reported sexual function (3) | Measurement of change in erectile dysfunction using the International Index for Erectile Function (IIEF). Answers to qualitative questions are rated from 0 to 5, with a higher number indicating better erectile function, and totaled for a score which categorizes severity of erectile dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Female patient-reported sexual function (1) | Assessment of change in sexual function using the International Spinal Cord Injury Female Sexual and Reproductive Function Basic Data Set (v2.0). Data from various female sexual and reproductive function variables are aggregated into a single-page format for an abstract overview of female sexual and reproductive dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Female patient-reported sexual function (2) | Measurement of change in sexual function using the Female Sexual Function Index (FSFI). Answers to qualitative questions are rated from 0 to 5, with a higher number indicating better sexual function, and totaled for a score which categorizes severity of sexual dysfunction. | Baseline, Month 6, End of Month 7, Month 13 | 
| Patient-reported quality of life (1): Spinal Cord Injury Secondary Conditions Scale (SCI-SCS) | Measurements of change to quality of life as measured by the Spinal Cord Injury Secondary Conditions Scale (SCI-SCS). Answers to qualitative questions regarding patient activities, independence, and overall quality of life are rated from 0 to 3, with a higher number indicating more significant or chronic problems, and totaled for a score which categorizes patient quality of life. | Baseline, Month 6, End of Month 7, Month 13 | 
| Patient-reported quality of life (2): World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) | Measurement of change to quality of life as measured by the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF). Answers to qualitative questions regarding patient activities, independence, and overall quality of life are rated from 1 to 5, with a higher number indicating a higher concurrence or frequency related to the item in question, and totaled for a score which categorizes patient quality of life. | Baseline, Month 6, End of Month 7, Month 13 |