Intrathecal Transplantation of UC-MSC in Patients With Early Stage of Chronic Spinal Cord Injury

Study Overview
=================
Brief Summary
-----------------
This study aim to evaluate the safety and efficacy of intrathecal transplantation of allogeneic umbilical cord derived mesenchymal stem cells (UC-MSC) for treatment of different phrases of spinal cord injury. Here, the history of spinal cord injury is divided into three periods, Sub-acute SCI, Early stage of chronic SCI, and Late stage of chronic SCI, which is 2W-2M, 2M-12M, and more than 12M after injury, respectively. The purpose is to investigate whether the patients with spinal cord injury benefit from UC-MSC transplantation, and then find out the best time for SCI treatment. In this part of the study, the investigators will treat patients with early stage of chronic spinal cord injury with UC-MSC transplantation or placebo.

Detailed Description
-----------------
Spinal cord injury (SCI), damage to any part of the spinal cord or nerves, often causes permanent neurofunction deficit, including strength, sensation and other body functions below the site of injury. WHO reported 15-40/million people suffer from SCI each year, about 250,000 to 500,000 people. The majority of SCI victims are young patients, who are at the time of working age. As a result of that, SCI not only affects the physical and psychological health of those patients, but also bring huge economic burden to their families, as well as the society. The current treatments for SCI mainly include surgical operation, neuroregenerative medicine, physical therapy, chinese acupuncture and so on. However, none of these methods are efficient enough to make any functional recovery of neurological injury in patients, and most patients will have to face paraplegia or tetraplegia. The most challenge of SCI treatment are reported to be regeneration of axon and rewiring of the damaged spinal cord. The properties of strong proliferation and differentiation make stem cell transplantation possible to replace the damage axon and rebridge the injury spinal cord. Currently, evidences from animal experiments and pilot clinical studies have reported that umbilical cord mesenchymal stem cells transplantation was a potential method to treat spinal cord injury, but its safety and efficacy remain controversial. This study will conduct a multicenter, randomized, controlled trial for UC-MSC transplantation for the treatment of different phrases of SCI, including sub-acute, early stage, and late stage of chronic SCI. These three trials will investigate the safety and efficacy of intrathecal transplantation of UC-MSC in patients with SCI treatment. The study will be conducted at 3 hospitals in China, covering eastern, southern and western of Chinese mainland. The primary outcome is the changes of motor and sensory assessment before and after intervention using American Spinal Injury Association (ASIA) Score Scale. Secondary outcomes will include International Association of Neural Restoration Spinal Cord Injury Functional Rating Scale (IANR-SCIRFS), electromyogram test, residual urine test and adverse events. The enrolled participants will be followed up at baseline, 1, 3, 6 and 12 months after UC-MSC transplantation. Besides, the samples of serum and cerebrospinal fluid will be collected, before and after treatment, to explore the potential mechanism of UC-MSC transplantation for the treatment of SCI. The results of this study will, for the first time, provide high level of evidence as to the relative safety and efficacy of UC-MSC transplantation for the treatment of spinal cord injury.

Official Title
-----------------
The Effect of Intrathecal Transplantation of Umbilical Cord Mesenchymal Stem Cells in Patients With Early Stage of Chronic Spinal Cord Injury：A Multicenter, Randomized, Controlled Trial

Conditions
-----------------
Spinal Cord Injuries

Intervention / Treatment
-----------------
* Drug: Umbilical Cord Mesenchymal Stem Cells
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 to 65 Traumatic spinal cord injury ASIA Impairment Scale A-D Participants who understand and sign inform consent Duration of injury from 2 months to 12 months Exclusion Criteria: Traumatic spinal cord injury with brain injury Non-traumatic spinal cord injury caused by spinal tumors, myelitis, demyelination, spinal vascular malformation, etc. with Ankylosing spondylitis with Malignant tumors with Neurodegenerative diseases, or any neuropathies with Hematologic diseases, or blood coagulation disorder with Hepatic dysfunction, renal dysfunction Ongoing or active infectious diseases Pregnancy, or lactation women Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent Not agree to take part in clinical trial or can't finish follow up Previous history of MSCs therapy Participation in another clinical trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A 2:1 ratio of randomization (intervention group:control group) was used.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Umbilical Cord Mesenchymal Stem Cells<br>Intrathecal Transplantation of Umbilical Cord Mesenchymal Stem Cells, 1*10^6 cells/kg, once a month for 4 months | Drug: Umbilical Cord Mesenchymal Stem Cells<br>* Intrathecal Transplantation of Umbilical Cord Mesenchymal Stem Cells<br>* Other names: UC-MSC;|
| Placebo Comparator: Control<br>Sham operation and 10ml saline as placebos, once a month for 4 months | Drug: Placebos<br>* Placebos: Saline，Sham operation<br>* Other names: Sham operation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in American Spinal Injury Association (ASIA) Score Scale | Changes in motor and sensory scores assessed by the ASIA score scale (total score range from 0 to 324, higher values represent a better outcome) | Baseline, 1 month, 3 months, 6 months and 12 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in International Association of Neural Restoration Spinal Cord Injury Functional Rating Scale (IANR-SCIRFS) | Changes in motor and sensory scores assessed by IANR-SCIRFS scale (total score range from 0 to 51, higher values represent a better outcome) | Baseline, 1 month, 3 months, 6 months and 12 months post-treatment | 
| Changes in electromyogram test | Changes in electromyogram test | Baseline, 6 months and 12 months post-treatment | 
| Changes in residual urine | Changes in residual urine measured by ultrasound test (volume of urine in mL, lower values represent a better outcome) | Baseline, 6 months and 12 months post-treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
spinal cord injury, umbilical cord mesenchymal stem cells