Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This prospective clinical study will investigate the ability of different spine imaging characteristics to predict ambulation recovery responsiveness using epidural spinal cord stimulator (SCS) in patients with chronic incomplete spinal cord injury (SCI).
Epidural spinal cord stimulation below the level of injury can restore previously lost lower extremity voluntary motor function for some patients. The goal of this study is to establish whether spine imaging can be utilized as a biomarker to predict which patients will respond to spinal cord stimulation.
Ten patients with chronic spinal cord injury who are scheduled to receive a spinal cord stimulator for refractory chronic pain will be recruited throughout the Mass General Brigham health system. At baseline, participants will undergo a neurologic strength exam, Magnetic Resonance Imaging (MRI) of the spine and brain, electromyography (EMG) of the lower extremities, and will complete a battery of pain, motor function and quality of life questionnaires.
Phase 1: The SCS Optimization phase consists of weekly research visits during the first month post-SCS implant. Settings of the spinal cord stimulator parameters will be modified for activation and optimal voluntary control of lower extremity muscles.
Phase 2: The Individualized Neurorehabilitation phase consists of 4 weekly visits for a 5-month period. Participants will undergo neurorehabilitation with the stimulation settings turned on for motor control. Neurorehabilitation will be individualized and will progressively increase participants' physical activity, including assisted/independent standing, stepping and ambulation within safe limits. Participants will undergo monthly muscle strength and surface EMG testing.
At the end of each research visit or neurorehabilitation session, SCS settings will be adjusted to the original pain management parameters.
At the 6-month follow up participants will undergo a neurologic strength exam, MRI of the spine and brain, EMG of the lower extremities and a battery of questionnaires. After the last follow up visit, participants will have the opportunity to continue a long-term follow up or exit the study. SCS parameters will be adjusted to the pain management settings.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All participants | Experimental | Baseline: participants will undergo lower extremity muscle strength testing, electromyography, spine and brain MRI, and complete a battery of questionnaires All participants will undergo a clinically indicated spinal cord stimulator implanted for refractory chronic pain. SCS Optimization phase consists of weekly research visits for 1 month. SCS parameters will be optimized for voluntary control of lower extremity muscles. Individualized Neurorehabilitation phase consists of 4 x weekly visits for 5-months. With the SCS settings turned on for muscle activation, participants will undergo progressive neurorehabilitation by a spinal cord specialized physical therapist. All participants who complete the 6-month timepoint will be invited to continue long-term follow up. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adjustment of spinal cord stimulation parameters for voluntary motor control | Other | All patients will receive a spinal cord stimulator and undergo adjustment of stimulation parameters for optimal voluntary lower extremity motor control during research visits. Muscle strength will be assessed with the stimulation turned on and off. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-related adverse events | The primary endpoint of this study is the safety of stimulation parameters for motor function assessed with the number of adverse events for the duration of the study. Relatedness of adverse events to treatment is determined by the principal investigator. | 0-6 months after baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle Strength | The ability to restore previously lost voluntary motor function of the lower extremity will be measured with the Medical Research Council (MRC) grade and compared to baseline. MRC grades range from 0 (no visible muscle contraction) to 5 (normal muscle strength against full resistance). A higher grade indicates a better outcome. | 1-6 months after baseline |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joshua I. Chalif, MD, PhD | Contact | 617-525-7378 | jchalif@bwh.harvard.edu | |
| Benjamin R Johnston, MD, PhD | Contact | 617-525-7378 | bjohnston2@mgb.org |
| Name | Affiliation | Role |
|---|---|---|
| Yi Lu, MD, PhD | Brigham and Women's Hospital/Harvard Medical School | Study Chair |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38398403 | Background | Chalif JI, Chavarro VS, Mensah E, Johnston B, Fields DP, Chalif EJ, Chiang M, Sutton O, Yong R, Trumbower R, Lu Y. Epidural Spinal Cord Stimulation for Spinal Cord Injury in Humans: A Systematic Review. J Clin Med. 2024 Feb 14;13(4):1090. doi: 10.3390/jcm13041090. | |
| 30382197 | Background | Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31. |
Not provided
Not provided
Individual participant data will not be shared other than published de-identified data.
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
Not provided
Not provided
All subjects will receive a spinal cord stimulator. Muscle strength will be assessed with the stimulation turned on and off. Parameters for motor function will be assessed with the stimulation turned on and off.
Not provided
Not provided
Not provided
Not provided
|
| Neuroimaging volumetric measures | Assessment of the functional integrity of corticospinal tracts with spine and brain Magnetic Resonance Imaging (MRI) will be performed at baseline and at the last follow up. MRI volumetric measures are quantified in mm^2. | 0-6 months after baseline |
| Voluntary Motor Function | Functional change assessed with the total score on the American Spinal Injury Association Impairment Scale (AIS) of each participant before spinal cord stimulation (SCS) and after SCS augmented with neurorehabilitation therapy. The AIS scale ranges from A (no sensory or motor function is preserved in sacral segments of S4-S5) to E (sensation and motor testing are normal in all segments), with A representing the worst outcome and E representing the best outcome. | 0-6 months after baseline |
| Optimized stimulation amplitude for voluntary motor function | Stimulation amplitude required for voluntary motor function measured in mA (miliAmperes) when supine, assisted/independent standing, stepping, walking. | 1-6 months after baseline |
| Optimized stimulation frequency for voluntary motor function | Stimulation frequency required for voluntary motor function measured in Hz (Hertz) when supine, assisted/independent standing, stepping, walking. | 1-6 months after baseline |
| Optimized stimulation pulse width for voluntary motor function | Stimulation pulse width required for voluntary motor function measured in microseconds when supine, assisted/independent standing, stepping, walking. | 1-6 months after baseline |
| Locomotive ability | Ability to stand, step, or walk either assisted or unassisted assessed with the Walking Index for Spinal Cord Injury II (WISCI II) scale. The WISCI II scale ranges from minimum score of 0 (unable to stand) to maximum score of 20 (ambulates with no devices, brace or assistance). A higher score represents a better outcome. | 1-6 months after baseline |
| Serious adverse events | Serious adverse events related to the post-SCS implant neurorehabilitation therapy. | 1-6 months after baseline |
| 24713270 | Background | Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 May;137(Pt 5):1394-409. doi: 10.1093/brain/awu038. Epub 2014 Apr 8. |
| 30430902 | Background | 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. |
| 30667299 | Background | Darrow D, Balser D, Netoff TI, Krassioukov A, Phillips A, Parr A, Samadani U. Epidural Spinal Cord Stimulation Facilitates Immediate Restoration of Dormant Motor and Autonomic Supraspinal Pathways after Chronic Neurologically Complete Spinal Cord Injury. J Neurotrauma. 2019 Aug 1;36(15):2325-2336. doi: 10.1089/neu.2018.6006. Epub 2019 Mar 6. |
| D014947 | Wounds and Injuries |