Eccentric Motor Training With Neuromodulation and Biomarkers for Rehabilitation Readiness in Subacute SCI

Brief Summary

Detailed Description

SCI group: Individuals 3 months (+/-2 months) after SCI will be randomized into standard of care control group or augmented rehabilitation group (DownHill training with STIMulation = dhSTIM group). The study statistician will produce the randomization schedule with varying permuted blocks of size 3 and 6. The randomization schedule will be uploaded to REDCap for randomization of subjects at the time of enrollment into the study. The dhSTIM group will have cerebrospinal fluid (CSF) and blood collected and analyzed. These will be collected for research purposes only by the study's experienced proceduralist unless it is being collected clinically within the required timeframe for the study. CSF is collected via lumbar puncture under guided fluoroscopy which is a standardized technique to collect CSF and minimizes risks. If not enough CSF is collected on the first attempt, a second attempt may be required which is not expected due to the use of guided fluoroscopy but may occur in standard practice. Based on inflammatory status relative to healthy controls, the dhSTIM group will be directed to a Go group - immediate start at \~3 months) or No Go Group - delayed start at \~6 months. All SCI groups (dhSTIM Go, dhSTIM No Go, SOC) will also continue with regular outpatient therapy. The augmented rehabilitation groups and healthy controls will undergo MRI. The dhSTIM training will be a 12-week downhill training program combined with Xcite electrical stimulation 3 times a week. Participants will walk downhill on a treadmill with a harness for body weight support and trainers assisting as needed. All SCI groups (dhSTIM Go, dhSTIM No Go, SOC) will participate in pre, post, and 4 week follow-up assessments as follows: Biomechanical analysis will include kinematics, kinetics, and electromyography (EMG) while on the treadmill. Clinical outcome measures will include: American Spinal Injury Association (ASIA) Impairment scale (AIS), International standards for neurological classification of spinal cord injury (ISNCSCI), Autonomic Standards Assessment Form, Neuromuscular Recovery Scale, Neuropathic Pain Symptom Inventory, Pain Numeric Rating Scale, Spinal Cord Injury Independence Measure (SCIM3), 6 minute walk test (MWT), 10 meter walk test (MWT). Clinical outcome measures conducted as standard measures will be collected will be accessed via medical record when available. If absent from the medical record, they will be collected by a rater blind to group assignment. Leg strength will also be measured using the Biodex system. An additional MRI scan will be obtained at the end of the 12 week training period for the dhSTIM GO and dhSTIM No Go groups. Healthy Control Group: Healthy participants from the community will volunteer for the CSF and blood collection by the study's experienced proceduralist. CSF will be collected from at least half of the healthy controls prior to enrolling participants with SCI to provide a sample of normal levels of inflammatory genes and concentration of microglia-like cells as a baseline. CSF is collected for research purposes only via lumbar puncture under guided fluoroscopy which is a standardized technique to collect CSF and minimizes risks. If not enough CSF is collected on the first attempt, a second attempt may be required which is not expected due to the use of guided fluoroscopy but may occur in standard practice. When possible, they will also participate in one MRI scan of the brain and spinal cord. Due to MRI restrictions, some healthy controls may only be able to participate in biomarkers collection, some to only participate in MRI scans and some to participate in both types of collection. Individuals for the healthy control group will be enrolled until a total of n=10 +1 for biomarkers and n=10+1 for MRI is reached. One additional individual is allocated to account for dropouts. If there no individuals are able to take part in both MRI and fluid biomarker collection, then up to n=22 healthy controls will be enrolled.

Primary Outcomes

Secondary Outcomes

• Change from baseline in International Standards for Neurological Classification of SCI (ISNCSCI): motor scores(12 weeks)
• Change from 12 weeks to 16 weeks in International Standards for Neurological Classification of SCI (ISNCSCI): motor scores(16 weeks)
• Change from baseline in ASIA Impairment Scale (AIS)(12 weeks)
• Change from 12 weeks to 16 weeks in American Spinal Injury Association (ASIA) Impairment Scale (AIS)(16 weeks)
• Change from baseline in International Standards for Neurological Classification of SCI (ISNCSCI): sensory scores(12 weeks)
• Change from 12 weeks to 16 weeks in International Standards for Neurological Classification of SCI (ISNCSCI): sensory scores(16 weeks)
• Change from 12 weeks to 16 weeks on Autonomic Standards Assessment Form(16 weeks)
• Change from baseline in 6 Minute Walk Test (6MWT)(12 weeks)
• Change from 12 weeks to 16 weeks in 6 Minute Walk Test (6MWT)(16 weeks)
• Change from baseline in 10 Meter Walk Test(12 weeks)
• Change from baseline in International Standards for Neurological Classification of SCI (ISNCSCI): neurological level of injury (NLI)(12 weeks)
• Change from 12 weeks to 16 weeks in Neuropathic Pain Symptom Inventory (NPSI) scale(16 weeks)
• Change from 12 weeks to 16 weeks in Numeric Pain Rating Scale (NPRS)(16 weeks)
• Change from baseline in Strength Testing(12 weeks)
• Change from 12 weeks to 16 weeks in International Standards for Neurological Classification of SCI (ISNCSCI): neurological level of injury (NLI)(16 weeks)
• Change from baseline on Autonomic Standards Assessment Form(12 weeks)
• Change from 12 weeks to 16 weeks in 10 Meter Walk Test(16 weeks)
• Change from baseline in Spinal Cord Independence Measure III (SCIM3) score(12 weeks)
• Change from baseline in Numeric Pain Rating Scale (NPRS)(12 weeks)
• Change from 12 weeks to 16 weeks in kinetics during weight acceptance(16 weeks)
• Change from 12 weeks to 16 weeks in Spinal Cord Independence Measure III (SCIM3) score(16 weeks)
• Change from 12 weeks to 16 weeks in Strength Testing(16 weeks)
• Change from baseline in electromyography of eccentric acting muscles at 12 weeks(12 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: knee range of motion(16 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: knee acceleration(16 weeks)
• Change from baseline on Neuromuscular Recovery Scale (NRS) score(12 weeks)
• Change from 12 weeks to 16 weeks on Neuromuscular Recovery Scale (NRS) score(16 weeks)
• Change from baseline in Neuropathic Pain Symptom Inventory (NPSI) scale(12 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: hip range of motion(16 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: ankle range of motion(16 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: hip acceleration(16 weeks)
• Change from 12 weeks to 16 weeks in kinematics during weight acceptance: ankle acceleration(16 weeks)