Spinal Cord Injury Epidural Stimulation

• ClinicalTrials.gov Identifier: NCT02592668
• Recruitment Status: Completed
• First Posted: October 30, 2015
• Last Update Posted: April 13, 2020
• Sponsor: Mayo Clinic
• Collaborators: University of California, Los Angeles; Reneu Health Inc.; Bel13ve in Miracles Foundation; The Craig H. Neilsen Foundation; National Center for Advancing Translational Sciences (NCATS)
• Information provided by (Responsible Party): Kristin Zhao, PhD, Mayo Clinic

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injury	Device: Epidural Stimulator	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Device Feasibility
• Official Title: A Feasibility Study: Epidural Stimulation to Enable Volitional Movement After Chronic Complete Paralysis in Humans.
• Actual Study Start Date: January 4, 2016
• Actual Primary Completion Date: September 14, 2018
• Actual Study Completion Date: February 11, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active stimulation; 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; 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.; Other Name: Medtronic Restore ULTRA 97712

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change in volitional movement restoration via NeuroRecovery scale [ Time Frame: baseline, approximately 50 weeks after implantation ]
2. Change of bladder function, as measured by the Neurogenic Bladder Symptom Score questionnaire [ Time Frame: baseline, approximately 50 weeks after implantation ]
3. Change in sexual function as measured by the Sexual Function Questionnaire [ Time Frame: baseline, approximately 50 weeks after implantation ]
4. Change in body thermoregulatory capacity as measured by thermoregulatory sweat testing [ Time Frame: baseline, approximately 50 weeks after implantation ]
5. Change in lean body mass [ Time Frame: baseline, approximately 50 weeks after implantation ]
6. Change in bone density [ Time Frame: baseline, approximately 50 weeks after implantation ]
7. Change in sense of wellbeing as measured by the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire [ Time Frame: baseline, approximately 50 weeks after implantation ]
8. Change in sitting balance via functional reach test [ Time Frame: baseline, approximately 50 weeks after implantation ]
9. Change in spasticity via Ashworth spasticity test [ Time Frame: baseline, approximately 50 weeks after implantation ]
10. Change in ability of performing basic activities of daily life via spinal cord independence measure [ Time Frame: baseline, approximately 50 weeks after implantation ]
11. Change in total body fat [ Time Frame: baseline, approximately 50 weeks after implantation ]
12. Change in bowel function as measured by the Neurogenic Bowel Dysfunction Score questionnaire [ Time Frame: baseline, approximately 50 weeks after implantation ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

University of California, Los Angeles

Reneu Health Inc.

Bel13ve in Miracles Foundation

The Craig H. Neilsen Foundation

National Center for Advancing Translational Sciences (NCATS)

Investigators

• Principal Investigator: Kristin D. Zhao, Ph.D.; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

Publications:

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.

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. Erratum In: Nat Med. 2018 Oct 23;:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kristin Zhao, PhD, Kristin D. Zhao, Ph.D., Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02592668
• Other Study ID Numbers: 15-000510; UL1TR000135 ( U.S. NIH Grant/Contract )
• First Posted: October 30, 2015
• Last Update Posted: April 13, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System