Autologous Human Schwann Cells in Peripheral Nerve Repair

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Peripheral Nerve Injuries
• Intervention / Treatment: Biological: autologous human Schwann cells

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous human Schwann cells; All participants will receive autologous human Schwann cells harvested from their own sural nerve.	Biological: autologous human Schwann cells; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: W. Dalton Dietrich
• Collaborators: The Miami Project to Cure Paralysis
• Investigators: Principal Investigator: Allan Levi, MD, PhD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2019
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: June 24, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 26, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 18, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Peripheral Nerve Injuries
• Other Study ID Numbers: 20190453

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No