The Safety of ahSC in Chronic SCI With Rehabilitation

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of autologous human Schwann cell (ahSC) transplantation in participants with chronic SCI. This trial design is phase I, open label, unblinded, non-randomized, and non-placebo controlled multiple injury cohorts.

Detailed Description
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For humans with chronic SCI, we hypothesize that axons might show improved function if myelin repair is induced with the implantation of ahSC. In addition spinal cord cavitation may be reduced, and neural sprouting and plasticity may be enhanced via neurotrophic effects. In this trial, subjects will receive fitness conditioning and rehabilitation prior to transplantation in order to validate the stability of their neurological baseline and enhance their ability to undergo surgery with few complications. They will also receive fitness conditioning and rehabilitation post-transplantation to maintain health and promote neuronal activity and potential neuroplasticity. Trial enrollment will target 2 cohorts. The first cohort will be thoracic (T) level 2-12 ASIA Impairment Scale (AIS) grade A, B, or C (n = up to 4), the second cohort will be cervical (C) level 5 through T1 AIS A, B, or C (n = up to 6). Two (2) participants with AIS grade A will be enrolled prior to enrolling a participant with AIS B or C, applicable to both cohorts. Participants will be monitored throughout a 6 month post-transplantation evaluation period for occurrence of AEs (acute, delayed, and/or cumulative), as well as for changes in clinical status and neurological status. Safety and efficacy assessments will be performed at weeks 1 and 2 post-transplantation and months 2 and 6 post-transplantation.

Official Title
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The Safety of Autologous Human Schwann Cells (ahSC) in Subjects With Chronic Spinal Cord Injury (SCI) Receiving Rehabilitation

Conditions
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Spinal Cord Injury, Paraplegia, Quadriplegia, Tetraplegia

Intervention / Treatment
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* Biological: Autologous human Schwann cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persons with traumatic SCI that occurred a minimum of 12 months prior to enrollment; Between the ages of 18 and 65 at last birthday; SCI between spinal levels C5-T12 as defined by the most caudal level of intact motor and sensory function on the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI); ASIA Impairment Scale (AIS) grade A, B, or C at time of enrollment; Lesion length less than or equal to 3 cm and lesion volume less than or equal to 2 cc, as approximated by MRI. Exclusion Criteria: Persons unable to safely undergo an MRI; Persons with penetrating injury of the spinal cord or complete transection of the cord, as identified by MRI; Persons with severe, uncorrected post-injury spinal deformity and/or spinal cord inadequately decompressed; Persons with a cavity structure that would preclude successful transplantation, as identified by MRI; Persons with syringomyelia - defined as patients with progressively enlarging cysts on T2 weighted images with associated neurological decline; Persons with pre-existing conditions that would preclude satisfactory sural nerve harvest; Intolerance to functional electrical stimulation of muscles; Exercise induced abnormalities; Range of motion of the upper or lower extremities outside functional limits for targeted fitness and rehabilitation activities; Evidence of bone or joint pathology that adversely influences participation in the fitness and rehabilitation activities; Fracture, dislocation, or extremity instruments (implanted or external) that adversely influences participation in the fitness and rehabilitation activities; Unhealed pressure ulcer; History of documented seizures, stroke, brain tumor, serious head injury, or any other intracranial problem that could increase the risk of seizures during motor evoked potentials testing; Pregnant women or a positive pregnancy test in those women with reproductive potential prior to enrollment; Presence of disease that might interfere with participant safety, compliance, or evaluation of the condition under study; Body Mass Index (BMI) ≥ 35; History of active substance abuse; Persons who are current participants in any interventional trial; Persons with a history of prior intrathecal or intraspinal cell therapy for SCI; Persons allergic to gentamicin; Persons who test positive for HIV or Hepatitis B or C virus; Persons with lab values significantly outside of the upper and lower limits; Persons who can independently ambulate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ahSC transplantation<br>Autologous human Schwann cells | Biological: Autologous human Schwann cells<br>* Schwann cells harvested from the sural nerve of the participant will be autologously transplanted into the epicenter of the participant's spinal cord injury.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International Standards of Neurological Classification of Spinal Cord Injury |  | Change from Baseline at 6 months | 
| Magnetic Resonance Imaging of spinal cord |  | Change from Baseline at 6 months | 
| Neuropathic Pain Symptoms Inventory |  | Change from Baseline at 6 months | 
| ISCI Basic Pain dataset version2 |  | Change from Baseline at 6 months | 
| Pain Diagram |  | Change from Baseline at 6 months | 
| Quantitative Sensory Testing |  | Change from Baseline at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spinal Cord Independence Measure III |  | Change from Baseline at 6 months | 
| SCI-Functional Index Computer Adaptive Testing |  | Change from Baseline at 6 months | 
| 10-Meter Walk Test |  | Change from Baseline at 6 months | 
| 2-Minute Walk Test |  | Change from Baseline at 6 months | 
| Timed Up and Go |  | Change from Baseline at 6 months | 
| Timed Stair Climb |  | Change from Baseline at 6 months | 
| Capabilities of Upper Extremity Questionnaire |  | Change from Baseline at 6 months | 
| ISCI Upper Extremity Basic dataset |  | Change from Baseline at 6 months | 
| ISCI Basic Bowel dataset |  | Change from Baseline at 6 months | 
| ISCI Basic Lower Urinary Tract dataset |  | Change from Baseline at 6 months | 
| ISCI Basic Male and Female Sexual Function datasets |  | Change from Baseline at 6 months | 
| ISCI Quality of Life dataset |  | Change from Baseline at 6 months | 
| Motor Evoked Potentials |  | Change from Baseline at 6 months | 
| Somatosensory Evoked Potentials |  | Change from Baseline at 6 months | 
| Sympathetic Skin Response |  | Change from Baseline at 6 months | 
| Graded Strength Test |  | Change from Baseline at 6 months | 
| 1-Repetition Maximum |  | Change from Baseline at 6 months | 
| Head-up Tilt |  | Change from Baseline at 6 months | 
| Guy Farrar Subject Global Impression of Change |  | Change from Baseline at 6 months | 
| Modified Ashworth Scale |  | Change from Baseline at 6 months | 
| Pendulum Test |  | Change from Baseline at 6 months | 
| Spinal Cord Assessment Tool for Spastic reflexes |  | Change from Baseline at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schwann cells