The Safety of ahSC in Chronic SCI With Rehabilitation

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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury; Tetraplegia; Quadriplegia; Paraplegia
• Intervention / Treatment: Biological: Autologous human Schwann cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• 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
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Persons with traumatic SCI that occurred a minimum of 12 months prior to enrollment;
2. Between the ages of 18 and 65 at last birthday;
3. 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);
4. ASIA Impairment Scale (AIS) grade A, B, or C at time of enrollment;
5. 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:

1. Persons unable to safely undergo an MRI;
2. Persons with penetrating injury of the spinal cord or complete transection of the cord, as identified by MRI;
3. Persons with severe, uncorrected post-injury spinal deformity and/or spinal cord inadequately decompressed;
4. Persons with a cavity structure that would preclude successful transplantation, as identified by MRI;
5. Persons with syringomyelia - defined as patients with progressively enlarging cysts on T2 weighted images with associated neurological decline;
6. Persons with pre-existing conditions that would preclude satisfactory sural nerve harvest;
7. Intolerance to functional electrical stimulation of muscles;
8. Exercise induced abnormalities;
9. Range of motion of the upper or lower extremities outside functional limits for targeted fitness and rehabilitation activities;
10. Evidence of bone or joint pathology that adversely influences participation in the fitness and rehabilitation activities;
11. Fracture, dislocation, or extremity instruments (implanted or external) that adversely influences participation in the fitness and rehabilitation activities;
12. Unhealed pressure ulcer;
13. 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;
14. Pregnant women or a positive pregnancy test in those women with reproductive potential prior to enrollment;
15. Presence of disease that might interfere with participant safety, compliance, or evaluation of the condition under study;
16. Body Mass Index (BMI) ≥ 35;
17. History of active substance abuse;
18. Persons who are current participants in any interventional trial;
19. Persons with a history of prior intrathecal or intraspinal cell therapy for SCI;
20. Persons allergic to gentamicin;
21. Persons who test positive for HIV or Hepatitis B or C virus;
22. Persons with lab values significantly outside of the upper and lower limits;
23. Persons who can independently ambulate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: ahSC transplantation; Autologous human Schwann cells	Biological: Autologous human Schwann cells; Schwann cells harvested from the sural nerve of the participant will be autologously transplanted into the epicenter of the participant's spinal cord injury.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Maher JL, Anderson KD, Gant KL, Cowan RE. Development and deployment of an at-home strength and conditioning program to support a phase I trial in persons with chronic spinal cord injury. Spinal Cord. 2021 Jan;59(1):44-54. doi: 10.1038/s41393-020-0486-7. Epub 2020 Jun 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): August 12, 2019
• Study Completion (Actual): August 12, 2019

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: February 2, 2015
• First Posted (Estimate): February 3, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Schwann cells
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Paralysis; Spinal Cord Injuries; Quadriplegia; Paraplegia
• Other Study ID Numbers: 20140846