Clinical trial NCT02592668: Spinal Cord Injury Epidural Stimulation
Official title: A Feasibility Study: Epidural Stimulation to Enable Volitional Movement After Chronic Complete Paralysis in Humans.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injury
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of California, Los Angeles
name: Reneu Health Inc.
name: Bel13ve in Miracles Foundation
name: The Craig H. Neilsen Foundation
name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2015-10-30
Enrollment: 2
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Duration of time for which subject can sit unassisted on the edge of a mat table
timeFrame: Approximately 50 weeks after implantation
measure: Assessment of volitional movement of lower limbs
timeFrame: Approximately 50 weeks after implantation
measure: Subject's ability to coordinate stepping on a treadmill will be measured using biomechanical and electrophysiological analyses
timeFrame: Approximately 50 weeks after implantation
measure: Duration of time for which subject can stand weight bearing with minimal assistance provided as needed.
timeFrame: Approximately 50 weeks after implantation
Secondary outcomes:
measure: Change in volitional movement restoration via NeuroRecovery scale
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change of bladder function, as measured by the Neurogenic Bladder Symptom Score questionnaire
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in sexual function as measured by the Sexual Function Questionnaire
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in body thermoregulatory capacity as measured by thermoregulatory sweat testing
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in lean body mass
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in bone density
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in sense of wellbeing as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in sitting balance via functional reach test
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in spasticity via Ashworth spasticity test
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in ability of performing basic activities of daily life via spinal cord independence measure
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in total body fat
timeFrame: baseline, approximately 50 weeks after implantation
measure: Change in bowel function as measured by the Neurogenic Bowel Dysfunction Score questionnaire
timeFrame: baseline, approximately 50 weeks after implantation
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Kristin D. Zhao, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grahn PJ, Lavrov IA, Sayenko DG, Van Straaten MG, Gill ML, Strommen JA, Calvert JS, Drubach DI, Beck LA, Linde MB, Thoreson AR, Lopez C, Mendez AA, Gad PN, Gerasimenko YP, Edgerton VR, Zhao KD, Lee KH. Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia. Mayo Clin Proc. 2017 Apr;92(4):544-554. doi: 10.1016/j.mayocp.2017.02.014.
citation: Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Nov;24(11):1677-1682. doi: 10.1038/s41591-018-0175-7. Epub 2018 Sep 24.
citation: Calvert JS, Grahn PJ, Strommen JA, Lavrov IA, Beck LA, Gill ML, Linde MB, Brown DA, Van Straaten MG, Veith DD, Lopez C, Sayenko DG, Gerasimenko YP, Edgerton VR, Zhao KD, Lee KH. Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis. J Neurotrauma. 2019 May 1;36(9):1451-1460. doi: 10.1089/neu.2018.5921. Epub 2018 Dec 15.
citation: Gill ML, Linde MB, Hale RF, Lopez C, Fautsch KJ, Calvert JS, Veith DD, Beck LA, Garlanger KL, Sayenko DG, Lavrov IA, Thoreson AR, Grahn PJ, Zhao KD. Alterations of Spinal Epidural Stimulation-Enabled Stepping by Descending Intentional Motor Commands and Proprioceptive Inputs in Humans With Spinal Cord Injury. Front Syst Neurosci. 2021 Jan 28;14:590231. doi: 10.3389/fnsys.2020.590231. eCollection 2020.