Autologous Human Schwann Cells in Peripheral Nerve Repair

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) augmentation of nerve autograft repair in participants with severe peripheral nerve injury (PNI). For humans with acute severe PNI, the hypothesis is that augmentation of nerve autograft repair with ahSCs can potentially enhance axonal regeneration and myelin repair and thus improve functional recovery.

Official Title
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The Safety and Efficacy of Autologous Human Schwann Cell (ahSC) Augmentation of Nerve Autografts After Severe Peripheral Nerve Injury (PNI)

Conditions
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Peripheral Nerve Injuries

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 severe sciatic nerve injury, brachial plexus injury, and/or major injury at the upper or lower extremity with nerve loss within previous year; Peripheral nerve injury with large gap (5 - 10 cm) between healthy nerve endings; Between the ages of 18 and 65 years at last birthday; Exclusion Criteria: Persons unable to safely undergo an MRI (may include persons with an implanted device or metallic fragments which may interfere with MRI safety); Persons with pre-existing conditions that would preclude satisfactory sural nerve harvest (may include amputation or major injury to lower limb, or disease affecting the sural nerve); Persons with severe peripheral nerve injury gap length > 10 cm in length; Persons with history of radiation or local cancer in area of nerve injury, including primary tumors of the nerve; Pregnant women or a positive pregnancy test in those women with reproductive potential prior to transplantation; Presence of disease that might interfere with participant safety, compliance, or evaluation of the condition under study; History of active substance abuse; Persons allergic to gentamicin; Persons who test positive for HIV or Hepatitis B or C virus;

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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous human Schwann cells<br>All participants will receive autologous human Schwann cells harvested from their own sural nerve. | Biological: autologous human Schwann cells<br>* Schwann cells harvested from the sural nerve and debrided, injured sciatic nerve of the participant will be autologously transplanted along sural nerve autografts wrapped in a collagen matrix<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with reported adverse events (AEs) | The number of participants with reported AEs will be evaluated to assess safety. Using CTCAE v4.0 grading scale, all AEs that are Grade 3 or higher with treating physician's attribution of probable or definite relation to intervention will be included. | 12 months post-transplantation | 
| Number of participants with reported cell product culture test failure | Using sterility testing, the number of participants with reported cell product culture test failure will be evaluated. | 12 months post-transplantation | 
| Change in muscle strength scale grade of affected limb muscles | The Medical Research Council (MRC) scale for muscle strength grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle. | from baseline to 12 months post-transplantation | 
| Sensory recovery scale grade of affected dermatomes | Assessment of pin-prick and two point discrimination in areas previously anesthetic in the distal distribution of the nerve injury. | from baseline to 12 months post-transplantation | 
| Change in pain scores | The Douleur Neuropathique 4 (DN4) questionnaire estimates the probability of neuropathic pain, based on 10 items. Seven items related to pain quality are based on an interview and 3 items are based on clinical examination. | from baseline to 12 months post-transplantation | 
| Change in pain characteristics (location, intensity, and description) | Assessed by a pain diagram which identifies areas of pain with descriptors. An intensity scale from 0 (no pain) to 10 (most intense pain imaginable) is used to rate the overall intensity of pain at the time of assessment. | from baseline to 12 months post-transplantation | 
| Number of participants with reported tumorigenesis or unexpected changes in nerve structure | Tumorigenesis and/or unexpected changes in the nerve structure will be determined by evaluation of magnetic resonance imaging (MRI). | 2 years post-transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle strength scale grade of affected limb muscles | The Medical Research Council (MRC) scale for muscle strength grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle. | from baseline to 5 years | 
| Sensory recovery scale grade of affected dermatomes | Assessment of pin-prick and two point discrimination in areas previously anesthetic in the distal distribution of the nerve injury. | from baseline to 5 years | 
| Change in pain scores | The Douleur Neuropathique 4 (DN4) questionnaire estimates the probability of neuropathic pain, based on 10 items. Seven items related to pain quality are based on an interview and 3 items are based on clinical examination. | from baseline to 5 years post-transplantation | 
| Change in pain characteristics (location, intensity, and description) | Assessed by a pain diagram which identifies areas of pain with descriptors. An intensity scale from 0 (no pain) to 10 (most intense pain imaginable) is used to rate the overall intensity of pain at the time of assessment. | from baseline to 5 months post-transplantation | 
| Nerve-graft continuity | Ultrasound will be used to assess nerve-graft continuity. | 2 weeks post-transplantation |