Effect of Mesenchymal Stem Cells(MSCs) Transplantation for Acute Cerebral Infarction Patients

Study Overview
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Brief Summary
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This is a placebo controlled, randomized, double blinded study including Phase 1 and Phase 2. Phase I study is a safety assessment and Phase 2 study is incline to assess effectiveness of MSCs. Potential subjects must be screened and consented before enrolled. The primary objective of this study is to determine the effects of early intravenous infusion of allogeneic human umbilical cord mesenchymal stem cells (HucMSCs or MSCs used in the following section) for patients with acute ischemic stroke. Eligible patients will receive a single dose of MSCs or placebo within 24 hours after stroke. Patients will be followed for 2 years post infusion for safety and efficacy (change in neurological symptoms and quality of life). Assessments will occur during transplantation and at 3,7, 14 days and1,3, 6, 12, 18 and 24 months after infusions of stem cells.

Detailed Description
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In Phase 1 study, the eligible patients of acute cerebral infarction within 7 days after onset will be randomized to MSCs group or control group and receive intravenous MSCs 2 x 10^6/kg or placebo as a single dose, respectively. Each group will enroll 10 patients and patients will be followed for 2 years to observe the adverse events and evaluate the safety of MSCs for acute ischemic stroke patients. The safety and preliminary effectiveness of MSCs in the treatment of acute cerebral infarction will be summarized after all patients of Phase 1 study were followed for 3 months post infusion, and the report will be submit to the academic committee and the ethics committee to evaluate before approval to begin the Phase 2 study. In Phase 2 study, 100 patients with acute infarction within 24 hours after onset will be enrolled and randomized to MSCs group or control group. Patients will have baseline laboratory examinations and cerebral image (MRI or CTP). Enrolled patients will receive intravenous infusion of 2*10^6/kg MSCs or placebo for a single dose and follow for 24 months to assess the adverse events, neurological functional recovery and quality of life.

Official Title
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Effect of Human Umbilical Cord Mesenchymal Stem Cells(MSCs) Transplantation for on Prognosis of Acute Cerebral Infarction Patients

Conditions
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Infarction, Middle Cerebral Artery, Infarction, Anterior Cerebral Artery, Cerebral Infarction, Stroke, Ischemic, Acute Stroke, Brain Infarction, Infarction, PCA, Infarction, Posterior Circulation, Brain

Intervention / Treatment
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* Biological: human umbilical cord mesenchymal stem cells
* Biological: Placebo
* Other: standardized treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke; Age 18 80y; 4≤NIHSS score≤18（including limb score≥2）and modified Rankin scale 0-1 before this cerebral ischemic stroke; patients and their families understand and will cooperate within the whole process of study, and sign informed consent; any of following items：①acute cerebral infarction confirmed by cerebral CT perfusion or non-contrast computed tomographic scan < 7 days after onset or ②acute cerebral infarction confirmed by cerebral MR image < 7 days after onset Exclusion Criteria: accompanied by hematological disease, severe infection, liver dysfunction (ALT>3*ULN), kidney dysfunction (Scr >2*ULN), cardiac dysfunction (NYHA grade III or IV); Disturbance of consciousness, mental illness, cognitive impairment and other diseases that may affect informed consent and evaluation of study. Malignancy history or found to associate cancer after this stroke Pregnant or lactating women, or women have fertility requirements within 2 years; Accompanied by immunodeficiency diseases or autoimmune diseases; Life expectancy is less than 2 years; Participated in other clinical trial within 6 months; Patients received Chinese traditional medicine after onset of this stroke; Patients with allergic predisposition; Mental implantation or other reasons cannot tolerate magnetic resonance imaging; Cannot follow up regularly or unwilling to sign informed consent; Other situations not suitable for enrollment judged by the researchers;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: placebo controlled, randomized, double blinded
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MSCs group<br>The people in this group will receive intravenous MSCs 2 x 10^6/kg as a single dose and standardized treatment of acute ischemic stroke. | Biological: human umbilical cord mesenchymal stem cells<br>* The MSCs was intravenous transplanted to acute cerebral infarction patients as a single dose.<br>Other: standardized treatment<br>* standardized treatment<br>|
| Placebo Comparator: control group<br>The people in this group will receive placebo and standardized treatment of acute ischemic stroke. | Biological: Placebo<br>* Placebo<br>Other: standardized treatment<br>* standardized treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | include tumorigenesis, death, pulmonary embolism, allergy, newly cerebrovascular events and other adverse events to evaluate the safety of MSCs for acute ischemic stroke patients | 24 months post transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the National Institutes of Health Stroke Scale (NIHSS) of 3 months | The NIHSS neurologic examination includes 15 individual elements that measure motor and sensory function, language and speech production, vision, level of consciousness and attention, and neglect. The scores of each element are summed (range from 0 to 42) to evaluate the severity of neurological deficits. The more higher score means the more severe neurological dysfunction. | 3 months post transplantation | 
| the Barthel index (BI) of 3 months | The BI (range from 0 to 100) are used to assess the difference of activities of daily living between two groups. the score ≤40 means severe dependence， score 41 60 means moderate dependence, score 61 99 means mild dependence and score 100 means independence. | 3 months post transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute cerebral infarction ,Mesenchymal Stem Cells,prognosis