Safety Study of Human Spinal Cord-derived Neural Stem Cell Transplantation for the Treatment of Chronic SCI
This is a safety study of human spinal cord-derived neural stem cell (HSSC) transplantation for the treatment of chronic spinal cord injury.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label, Multi-site, Safety Study of Human Spinal Cord-derived Neural Stem Cell Transplantation for the Treatment of Chronic SCI|
- The primary objective of the study is to determine the safety of human spinal stem cell transplantation for the treatment of paralysis and related symptoms due to chronic spinal cord injury (SCI) [ Time Frame: The primary outcome measure will be assessed over a 60 month period. ] [ Designated as safety issue: Yes ]The primary outcome measure is the incidence of adverse events in the study population.
- The secondary objective of the study is to evaluate the graft survival in the transplant site by MRI. [ Time Frame: An MRI will be performed at Visits 5, 10, 16, 19 and 24. ] [ Designated as safety issue: Yes ]The secondary outcome measures of the study is to evaluate the ability of HSSC transplantation to positively affect AIS level ISNC SCI motor and sensory index scores, bowel and bladder function, pain, UAB IMR scores, SCIM scores, evoked sensory and motor potentials, and electromyogram (EMG).
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||February 2014|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Surgical implantation of human spinal cord stem cells
Surgical implantation of human spinal cord derived neural stem cells as follows:
Group A1 will consist of 4 patients receiving 1x100000 cells in 10uL/injection x 6 injections.
Group A2 will consist of 4 patients receiving 2x100000 cells in 10ul/injections x 6 injections
Device: Human spinal cord stem cells.
Human spinal cord stem cell implantation in paralysis patients due to a spinal cord injury.
Other Name: spinal cord injury (SCI)
The treatment will consist of removal of spinal instrumentation (in order to allow monitoring of the cell grafts by serial MRI for long-term), followed by laminectomy or laminoplasty of 1-4 vertebral segments overlying the region of spinal cord injury (no laminectomy if previous laminectomy). The dura will be opened midline and direct injections into spinal parenchyma performed. 6 HSSC injections will be administered bilaterally (3 on each side of midline): 2 at rostral and caudal edge of the injury site and 1 into approximately one segment length inferior to the injury site. The injections will target lateral funiculi, the most rostral injection site being in the first segment caudal to the neurological level defined by ISNCSCI examination. Each injection in the first 4 subjects of Group A will consist of 1 x 105 cells in 10μL volume. In the second 4 subjects of Group A, each injection will consist of 2 x 105 cells in 10μL volume:
- Group A1, n=4, T2 - T12: 1 x 105 cells in 10μL/injection x 6 injections
- Group A2, n=4, T2 - T12: 2 x 105 cells in 10μL/injection x 6 injections
Post-operatively, subjects will receive routine standard of care for laminectomy subjects who undergo an intradural procedure. Prior to and after the transplant, subjects will be required to remain on immunosuppressive therapy for 3 months. Immunosuppressive therapy will consist of: 1) basiliximab (Simulect®)) 20mg intravenously (IV) within 2 hours prior to the onset of the surgery, then again at day 4 post transplantation; 2) tacrolimus (Prograf®) initially dosed at a maximum of 0.1 mg/kg divided every 12 hours by mouth (po) on post transplant day 1, and then maintained at a dose that provides a trough serum level of 4-8 ng/ml (adjusted for IV use as necessary); and 3) mycophenolate mofetil (CellCept®) starting from 500mg p.o.
twice daily, progressively increased over 2 weeks to 1.0 gram twice daily as tolerated. The decision to continue immunosuppression therapy will be at the discretion of the site Principal Investigator. Mycophenolate mofetil may be dosed down to half or discontinued prior to the end of the 3-month period if the subject experiences adverse reactions to the immunosuppressive agents. If adverse reactions still persist, the tacrolimus dose can be further reduced in half and then further considered to be discontinued. The Safety Monitoring Board (SMB) will be convened at approximately 1 month (4 weeks) intervals after the first subject and will review the available safety data of all treated subjects. Starting from Week 13 post cell injection, tacrolimus and mycophenolate mofetil will be gradually withdrawn over 2 weeks. During this period and the ensuing weeks and months, the subject's blood will be monitored for the appearance of antibodies against donor cell HLAs. Signs of graft rejection will also be monitored by changes in MRI intensity of the graft area. If antibodies are detected, the immune suppression regimen will be re-instituted and maintained for as long as tolerable by the subject.
Subjects will be assessed for adverse events including pain and infection, motor function, and quality of life. Additional assessments will be made to measure any postoperative changes from baseline in neurologic deficits, neurophysiology, imaging studies, bladder or bowel function, allodynia, and neuropathic pain (see Schedule of Events). Subjects will be followed postoperatively at 2 weeks, monthly for 6 months during the study and at every 6 months thereafter in post-study safety follow-up for total 60 months post stem cell treatment.
|United States, Florida|
|University of Miami|
|Miami, Florida, United States, 33136|
|United States, Georgia|
|Crawford Research Institute, Shepard Center|
|Atlanta, Georgia, United States, 30309|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|