Safety and Feasibility of Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord

Study Overview
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Brief Summary
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To investigate the feasibility, safety, efficacy and optimal dose of umbilical cord blood mononuclear cell transplant in the treatment of chronic spinal cord injuries.

Detailed Description
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This is an open-label, dose-escalating clinical trial. Three groups of four patients will receive transplants of increasing doses of HLA-matched umbilical cord blood mononuclear cell into the spinal cord. In the fourth group, we will transplant the highest volume of cells that did not increase neurological deficits along with a single bolus of 30mg/kg methylprednisolone sodium succinate. In the fifth group of four subjects, we will inject that volume of cells plus a bolus intravenous dose of 30mg/kg methylprednisolone sodium succinate and a 6-week course of oral lithium carbonate titrated to 0.6-1.0 mM serum levels. All the subjects are encouraged to stand or walk for one hour a day after the cell transplantation. The neurological and walking outcomes will be assessed 1, 2, 6, 24 and 48 weeks after transplantation. The outcomes of the five treatment groups will be compared by analysis of variance and, if possible, correlation with cell dose. Efficacy and safety will be analyzed comparing neurological change scores amongst the five different treatment groups. Loss of motor (>5 points) or sensor scores (>2 points) from baseline pre-treatment levels would be considered deleterious. Increases in scores above baseline would be considered beneficial.

Official Title
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Safety and Feasibility of Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord: an Open-Labeled, Dose-Escalating Clinical Tiral

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Biological: Umbilical Cord Blood Mononuclear Cell
* Drug: Methylprednisolone
* Drug: Lithium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of either gender and 18-60 years old Subjects with chronic spinal cord injury (defined as ≧12 months post-initial SCI surgery) with stable neurological findings for at least 6 months Subject with a current neurological status of ASIA A The neurological level of the subjects is between C5 and T11 The MRI shows that the injured site of the spinal cord is within three vertebral levels and there is no cyst Subjects must be able to read, understand, and complete the Visual Analog Scale Subjects who have voluntarily signed and dated an informed consent form, approved by the appropriate IRB, prior to any study-specific procedures Exclusion Criteria: Significant renal, cardiovascular, hepatic and psychiatric diseases Significant medical diseases or infection (including but not limited to the carrier of hepatitis B virus or HIV) Pregnant or lactating woman Female of childbearing potential and who is unwilling to use an effective contraceptive method while enrolled in the study The MRI shows that the length of spinal cord lesion exceeds three segments or there is cyst in the spinal cord The lesion edge of the spinal cord cannot be determined by imaging technology Unavailability of HLA matched umbilical cord blood cells Any contraindication of laminectomy operation, MPSS and/or lithium carbonate Subject who is currently participating in another investigational study or has been taking any investigational drug within the last 4 weeks prior to screening of this study and finally Any criteria, which, in the opinion of the investigator, suggests that the subject would not be compliant with the study protocol and/or would not be suitable to participant this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>Intraspinal injection of 1.6 million cord blood mononuclear cell | Biological: Umbilical Cord Blood Mononuclear Cell<br>* The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.<br>|
| Active Comparator: Group B<br>Intraspinal injection of 3.2 million cord blood mononuclear cell | Biological: Umbilical Cord Blood Mononuclear Cell<br>* The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.<br>|
| Active Comparator: Group C<br>Intraspinal injection of 6.4 million cord blood mononuclear cell | Biological: Umbilical Cord Blood Mononuclear Cell<br>* The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.<br>|
| Active Comparator: Group D<br>Intraspinal injection of 6.4 million cord blood mononuclear cell plus 30 mg/kg methylprednisolone | Biological: Umbilical Cord Blood Mononuclear Cell<br>* The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.<br>Drug: Methylprednisolone<br>* 30 mg/kg methylprednisolone<br>|
| Active Comparator: Group E<br>Intraspinal injection of 6.4 million cord blood mononuclear cell plus 30 mg/kg methylprednisolone plus 6 week course of oral lithium, titrated to maintain 0.6-1.0 mM serum level | Biological: Umbilical Cord Blood Mononuclear Cell<br>* The cord blood mononuclear cells are obtained from thawed units of HLA-matched human umbilical cord blood. The cells will be slowly injected into the posterior gray matter after laminectomy and opening of the dura.<br>Drug: Methylprednisolone<br>* 30 mg/kg methylprednisolone<br>Drug: Lithium<br>* oral lithium, titrated to maintain 0.6-1.0 mM serum level<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ASIA motor scores and sensory scores |  | 0, 1, 2, 6 24 and 48 weeks | 
| ASIA Impairment Scale grade |  | 0, 1, 2, 6 24 and 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI and Diffusion Tensor Imaging of spinal cord |  | 0, 1, 24 and 48 weeks | 
| Spinal Cord Independence Measure (SCIM) score |  | 0, 6, 24 and 48 weeks | 
| Walking Index of Spinal Cord Injury (WISCI) level |  | 0, 6, 24 and 48 weeks | 
| Modified Ashworth Scale (MAS) of Spasticity |  | 0, 1, 2, 6, 24 and 48 weeks | 
| Visual Analog Scale (VAS) of pain |  | 0, 1, 2, 6, 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injury, cord blood mononuclear cell, Methylprednisolone, Lithium Carbonate