Mesenchymal Stem Cells Transplantation to Patients With Spinal Cord Injury

Study Overview
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Brief Summary
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The study is a phase I/II trial designed to establish the safety and efficacy of intravenous combined with intrathecal administration of autologous bone marrow derived mesenchymal stem cells to patients with spinal cord injury.

Detailed Description
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Spinal cord injury (SCI) is a traumatic disorder resulting in a functional deficit that usually leads to severe and permanent paralysis. Pharmacological and rehabilitation therapies to SCI get limited effect. Another promising therapeutic approaches for SCI is cellular transplantation. Cell types used in SCI therapy include Schwann cells, olfactory ensheathing cells and adult stem cells, such as neural stem cells, umbilical cord blood derived cells, mesenchymal stem cells (MSCs) or induced pluripotent stem cells. There are not yet conclusive evidences on which types of glial or adult stem cells are most effective in SCI treatment. MSC have been shown to promote anatomical and functional recovery in animal models of SCI by promoting tissue sparing ,axonal regeneration, and remyelination. Therapeutic effects of MSCs are primarily due to the secretion of soluble factors and the provision of extracellular matrix that provide protection and support repair. MSC are attractive candidates for transplantation into human patients because they can be easily harvested, expanded and banked, or derived directly from the patient allowing for autologous transplantation, obviating the need for immune suppression. The clinical translation of cellular transplantation strategies requires a safe and efficient means of cellular delivery. In animal models of SCI, the most common delivery is direct injection into the injury site, which allows a defined number of cells to be delivered, but risks further injuring the cord. Less invasive methods for cell delivery have been investigated, including intravascular delivery (intravenous (IV) and intra-arterial) and delivery into the cerebrospinal fluid (intrathecal). These minimally-invasive techniques decrease the risk to the patient and allow delivery of multiple cell doses. Maybe intrathecal administration is superior to IV delivery, cell engraftment and tissue sparing were significantly better after intrathecal delivery, but more researches are needed for get conclusion.

Official Title
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PhaseⅠ/ⅡTrial of Autologous Bone Marrow Derived Mesenchymal Stem Cells to Patients With Spinal Cord Injury.

Conditions
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Spinal Cord Injury

Intervention / Treatment
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* Biological: bone marrow derived mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic spinal cord injury at the thoracic or lumbar level. Age 16 to 60. American Spinal Injury Association Impairment Scale A or B. Time between injury and enrollment greater than 2 weeks and less than 1 year. Patients must have organ function as defined below: total bilirubin within normal institutional limits (NV: 0.0-20.5 umol/L); AST(SGOT)/ALT(SGPT) <2.5 × institutional upper limit of normal AST (NV: 0-35 U/L); ALT (NV: 0-40 U/L) ; Creatinine within normal institutional limits (NV: 53-106 umol/L) or Creatinine clearance >1.25 ml/s for patients with creatinine levels above institutional normal. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients may not be receiving any other investigational agents within 4 weeks of study entry. History of allergic reactions attributed to compounds of similar biologic composition to mesenchymal stem cells. Primary hematologic diseases. Open injuries. Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent. Malignancy within the last 5 years. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (defined as invasive fungal infection and progressive CMV viremia), symptomatic congestive heart failure (NYH class III and IV), unstable angina pectoris, or cardiac arrhythmia. Pregnant or breastfeeding women. HIV-positive patients.

Ages Eligible for Study
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Minimum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC<br>Intravenous combined with intrathecal administration of autologous bone marrow derived mesenchymal stem cells to patients with spinal cord injury. | Biological: bone marrow derived mesenchymal stem cells<br>* Intravenous administration of up to 1x10^6 MSCs per kg; intrathecal administration of up to 1x10^6 MSCs per kg.<br>* Other names: Multipotent Mesenchymal Stromal Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | 1 month after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electromyogram and Electroneurophysiologic test | somatosensory and motor evoked potentials | 1 month after transplantation | 
| Muscle strength assessment | Assessed by the Frankel scale. | 1 month after transplantation | 
| Motor and sensory assessment | Assessed by ASIA score | 1 month after transplantation | 
| Electromyogram and Electroneurophysiologic test | somatosensory and motor evoked potentials | 3 months after transplantation | 
| Muscle strength assessment | Assessed by the Frankel scale. | 3 months after transplantation | 
| Motor and sensory assessment | Assessed by ASIA score | 3 months after transplantation | 
| Electromyogram and Electroneurophysiologic test | somatosensory and motor evoked potentials | 6 months after transplantation | 
| Muscle strength assessment | Assessed by the Frankel scale. | 6 months after transplantation | 
| Motor and sensory assessment | Assessed by ASIA score | 6 months after transplantation | 
| Electromyogram and Electroneurophysiologic test | somatosensory and motor evoked potentials | 12 months after transplantation | 
| Muscle strength assessment | Assessed by the Frankel scale. | 12 months after transplantation | 
| Motor and sensory assessment | Assessed by ASIA score | 12 months after transplantation |