Clinical trial NCT02354625: The Safety of ahSC in Chronic SCI With Rehabilitation
Official title: The Safety of Autologous Human Schwann Cells (ahSC) in Subjects With Chronic Spinal Cord Injury (SCI) Receiving Rehabilitation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Spinal Cord Injury
Paraplegia
Quadriplegia
Tetraplegia
Keywords: Schwann cells
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: The Miami Project to Cure Paralysis
First posted: 2015-02-03
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: International Standards of Neurological Classification of Spinal Cord Injury
timeFrame: Change from Baseline at 6 months
measure: Magnetic Resonance Imaging of spinal cord
timeFrame: Change from Baseline at 6 months
measure: Neuropathic Pain Symptoms Inventory
timeFrame: Change from Baseline at 6 months
measure: ISCI Basic Pain dataset version2
timeFrame: Change from Baseline at 6 months
measure: Pain Diagram
timeFrame: Change from Baseline at 6 months
measure: Quantitative Sensory Testing
timeFrame: Change from Baseline at 6 months
Secondary outcomes:
measure: Spinal Cord Independence Measure III
timeFrame: Change from Baseline at 6 months
measure: SCI-Functional Index Computer Adaptive Testing
timeFrame: Change from Baseline at 6 months
measure: 10-Meter Walk Test
timeFrame: Change from Baseline at 6 months
measure: 2-Minute Walk Test
timeFrame: Change from Baseline at 6 months
measure: Timed Up and Go
timeFrame: Change from Baseline at 6 months
measure: Timed Stair Climb
timeFrame: Change from Baseline at 6 months
measure: Capabilities of Upper Extremity Questionnaire
timeFrame: Change from Baseline at 6 months
measure: ISCI Upper Extremity Basic dataset
timeFrame: Change from Baseline at 6 months
measure: ISCI Basic Bowel dataset
timeFrame: Change from Baseline at 6 months
measure: ISCI Basic Lower Urinary Tract dataset
timeFrame: Change from Baseline at 6 months
measure: ISCI Basic Male and Female Sexual Function datasets
timeFrame: Change from Baseline at 6 months
measure: ISCI Quality of Life dataset
timeFrame: Change from Baseline at 6 months
measure: Motor Evoked Potentials
timeFrame: Change from Baseline at 6 months
measure: Somatosensory Evoked Potentials
timeFrame: Change from Baseline at 6 months
measure: Sympathetic Skin Response
timeFrame: Change from Baseline at 6 months
measure: Graded Strength Test
timeFrame: Change from Baseline at 6 months
measure: 1-Repetition Maximum
timeFrame: Change from Baseline at 6 months
measure: Head-up Tilt
timeFrame: Change from Baseline at 6 months
measure: Guy Farrar Subject Global Impression of Change
timeFrame: Change from Baseline at 6 months
measure: Modified Ashworth Scale
timeFrame: Change from Baseline at 6 months
measure: Pendulum Test
timeFrame: Change from Baseline at 6 months
measure: Spinal Cord Assessment Tool for Spastic reflexes
timeFrame: Change from Baseline at 6 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Allan Levi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Miami
name: James Guest, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.