Efficacy and Safety of hUC-MSCs and hUCB-MSCs in the Treatment of Chronic Spinal Cord Injury

Study Overview
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Brief Summary
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There is evidence that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) can differentiate into oligodendrocytes and neurons, and improve the recovery of nerve function, which strongly suggests the feasibility and effectiveness of hUCB-MSCs as an intervention treatment for spinal cord injury. At present, there are only a few clinical centers in which hUCB-MSCs transplantation for treatment of chronic spinal cord injury has been performed and a certain degree of efficacy has been achieved. However, this has not been supported by systematic standardized randomized controlled trials. Therefore, the investigators design a prospective, randomized, open-label, parallel, controlled trial to evaluate the efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs)/hUCB-MSCs to treat spinal cord injury. The primary objective of this study was to investigate whether hUC-MSCs)/hUCB-MSCs transplantation can improve the locomotor function of patients with spinal cord injury. The secondary objectives were to investigate whether hUC-MSCs)/hUCB-MSCs transplantation can improve the muscle tension of patients with spinal cord injury and investigate the complications and safety of hUC-MSCs)/hUCB-MSCs transplantation.

Detailed Description
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Patient recruitment will be performed via information dissemination on bulletin boards to advertise the study among patients at the clinics and wards of the First Affiliated Hospital of Dalian Medical University, China. Patients interested in participation in this study or their legal guardians contact the project manager via telephone. Patients will be screened according to the inclusion and exclusion criteria after providing signed informed consent. Eligible patients with chronic spinal cord injury will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs (provided by Cell Bank of Stem Cell Clinical Research Institute, The First Affiliated Hospital of Dalian Medical University). The primary outcome measure of this study is neurologic function scores, including ASIA (American Spinal Injury Association) motor score, ASIA sensory score, ASIA impairment scale (ASIA classification), and acupuncture score. These scores will be used to evaluate the recovery of nerve function after spinal cord injury and determine the therapeutic efficacy and persistence. The secondary outcome measures of this study include Walking Index of Spinal Cord Injury (WISCI), Spinal Cord Independence Measure (SCIM), Kunming Locomotion Scale (KLS), Modified Ashworth Scale (MAS), and Visual Analogous Scale (VAS) scores and the incidence of adverse reactions. At 1, 3, 6 and 12 months after treatment, patients will be followed up to evaluate the efficacy and safety of hUC-MSCs)/hUCB-MSCs transplantation in the treatment of spinal cord injury.

Official Title
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Efficacy and Safety of hUC-MSCs and hUCB-MSCs in the Treatment of Chronic Spinal Cord Injury: a Prospective, Randomized, Open-label, Parallel, and Controlled Clinical Study

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Other: Stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at 20-65 years, of either gender; Patients with radiologically confirmed chronic spinal cord injury, with over 1 year of disease history; Patients having no change in ASIA motor score, ASIA sensory score, ASIA impairment scale (ASIA classification) score, and acupuncture score within 6 months and no change in recovery of neurological function; Patients with spinal cord injury who have been relieved of spinal cord compression injury or hematoma clearance; Patients with trauma-caused spinal cord injury accompanied by neurological deficits (sensory, motor, and autonomic dysfunction); Patients who have been subjected to electromyography and urodynamics examination to determine the denervation below the level of spinal cord injury and the function of the detrusor muscle; Patients with normal results of routine blood, urine, and stool tests, blood biochemical parameters, coagulation function, immune indices, electrocardiography and chest radiograph findings, and negative results of human immunodeficiency viruses and syphilis antibody Provision of written informed consent; approval by hospital ethics committee Exclusion Criteria: Patients with consciousness disorder, lumbosacral infection, or other complications; Patients with spinal cord injury caused by spinal cord compression, syringomyelia, subacute combined degeneration of spinal cord, spinal vascular disease, arachnoiditis of spinal cord, radiation myelopathy, amyotrophic lateral sclerosis, multiple sclerosis, or neuromyelitis optica; Patients with cerebrovascular disease, peripheral neuropathy, history of epilepsy, pregnancy, lactation, diabetes mellitus, mental disorders or other factors that affect the clinical treatment of spinal cord injury; Patients with serious cardiopulmonary disease, liver and kidney function damage, and other serious basic diseases; Patients wearing a metal internal fixator (except titanium alloy) or a pacemaker in the body; Patients with poor compliance who are unable to complete the study process or who are not considered suitable for the study by the investigators; Decline to participate in this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: participants are assigned to one of two or more groups in parallel for the duration of the study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Rehabilitation control group<br>Routine rehabilitation treatment for chronic spinal cord injury and Intravenous injection of 100 mL 0.9% saline solution. | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUC-MSCs intravenous administration group<br>intravenous administration of 100 mL of cell suspension containing 5×107 hUC-MSCs | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUC-MSCs lumbar administration group<br>lumbar administration of a solution prepared by 5 mL of cell suspension containing 5×107 hUC-MSCs and 5 mL of cerebrospinal fluid | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUC-MSCs local administration group<br>hUC-MSCs (100,000 cells/μL) were injected via 4 points in the edge of injured spinal cord (2 points in the upper edge and 2 points in the lower edge), 16 μL hUC-MSCs/point. | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUCB-MSCs intravenous administration group<br>intravenous administration of 100 mL of cell suspension containing 5×107 hUCB-MSCs | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUCB-MSCs lumbar administration group<br>lumbar administration of a solution prepared by 5 mL of cell suspension containing 5×107 hUCB-MSCs and 5 mL of cerebrospinal fluid | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|
| Experimental: hUCB-MSCs local administration group<br>hUCB-MSCs (100,000 cells/μL) were injected via 4 points in the edge of injured spinal cord (2 points in the upper edge and 2 points in the lower edge), 16 μL hUCB-MSCs/point. | Other: Stem cell transplantation<br>* The eligible patients with chronic spinal cord injury included in this study will receive intravenous, lumbar, and local administration of hUC-MSCs/hUCB-MSCs and routine rehabilitation treatment. At 1, 3, 6 and 12 months after treatment, patients will be followed up and evaluated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurologic function score | ASIA motor score, ASIA sensory score, ASIA impairment scale (ASIA classification), and acupuncture score will be obtained to evaluate the recovery of nerve function after spinal cord injury and determine the therapeutic efficacy and persistence. | Change from Baseline at 12 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Walking Index of Spinal Cord Injury (WISCI) | To evaluate walking ability | Change from Baseline at 12 months after treatment | 
| Spinal Cord Independence Measure (SCIM) | To evaluate ability of daily activities after spinal cord injury | Change from Baseline at 12 months after treatment | 
| Kunming Locomotion Scale (KLS) | To evaluate walking ability | Change from Baseline at 12 months after treatment | 
| Modified Ashworth Scale (MAS) | 0-4 score, to evaluate spasticity | Change from Baseline at 12 months after treatment | 
| Visual Analogous Scale (VAS) | To evaluate the degree of pain | Change from Baseline at 12 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injuries, Cord Blood Stem Cell Transplantation, Pain, Human