The Safety of ahSC in Chronic SCI With Rehabilitation

• ClinicalTrials.gov Identifier: NCT02354625
• Recruitment Status: Completed
• First Posted: February 3, 2015
• Last Update Posted: August 14, 2019
• Sponsor: W. Dalton Dietrich
• Collaborator: The Miami Project to Cure Paralysis
• Information provided by (Responsible Party): W. Dalton Dietrich, University of Miami

Tracking Information

• First Submitted Date: January 29, 2015
• First Posted Date: February 3, 2015
• Last Update Posted Date: August 14, 2019
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: August 12, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2015)

• International Standards of Neurological Classification of Spinal Cord Injury [ Time Frame: Change from Baseline at 6 months ]
• Magnetic Resonance Imaging of spinal cord [ Time Frame: Change from Baseline at 6 months ]
• Neuropathic Pain Symptoms Inventory [ Time Frame: Change from Baseline at 6 months ]
• ISCI Basic Pain dataset version2 [ Time Frame: Change from Baseline at 6 months ]
• Pain Diagram [ Time Frame: Change from Baseline at 6 months ]
• Quantitative Sensory Testing [ Time Frame: Change from Baseline at 6 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 2, 2015)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Spinal Cord Injury
• Paraplegia
• Quadriplegia
• Tetraplegia

Intervention

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.

Study Arms

Experimental: ahSC transplantation

Autologous human Schwann cells

Intervention: Biological: Autologous human Schwann cells

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 8, 2019): 8
• Original Estimated Enrollment (submitted: February 2, 2015): 10
• Actual Study Completion Date: August 12, 2019
• Actual Primary Completion Date: August 12, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02354625
• Other Study ID Numbers: 20140846
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: W. Dalton Dietrich, University of Miami
• Original Responsible Party: Same as current
• Current Study Sponsor: W. Dalton Dietrich
• Original Study Sponsor: Same as current
• 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

• PRS Account: University of Miami
• Verification Date: August 2019