Clinical Plan of Ischemic Stroke

Study Overview
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Brief Summary
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Stroke is the main cause of adult health damage. 20% of stroke survivors need institutional care after 3 months, and up to 30% of them have severe or permanent disability. Stem cells are a kind of pluripotent cells with the ability of self replication. The self-renewal and differentiation characteristics of mesenchymal stem cells, as well as cytokine secretion effect and immune characteristics, provide the possibility for mesenchymal stem cells to treat ischemic stroke. After the infusion of mesenchymal stem cells, the secretion of soluble media including growth factors and cytokines may be the main mechanism of mesenchymal stem cells.

Detailed Description
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Stroke is the main cause of adult health damage. 20% of stroke survivors need institutional care after 3 months, and up to 30% of them have severe or permanent disability. Stem cells are a kind of pluripotent cells with the ability of self replication. The self-renewal and differentiation characteristics of mesenchymal stem cells, as well as cytokine secretion effect and immune characteristics, provide the possibility for mesenchymal stem cells to treat ischemic stroke. After the infusion of mesenchymal stem cells, the secretion of soluble media including growth factors and cytokines may be the main mechanism of mesenchymal stem cells. The main purpose of this study was to evaluate the safety and tolerance of intravenous injection of ischemia tolerant human allogeneic bone marrow mesenchymal stem cells in patients with ischemic stroke. The secondary objective was to evaluate the clinical efficacy of ischemic tolerant human allogeneic bone marrow mesenchymal stem cells in the treatment of ischemic stroke patients with neurological dysfunction.

Official Title
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A Multicenter, Blind, Randomized, Placebo-controlled Phase I / IIA Study to Evaluate the Safety, Tolerability, and Initial Efficacy of a Single Injection of Ischemia Tolerant Human Allogeneic Bone Marrow Mesenchymal Stem Cells in Patients With Ischemic Stroke

Conditions
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Stroke

Intervention / Treatment
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* Biological: it-hMSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female ≥ 18 years old; The history showed that the last clinical diagnosis of ischemic stroke was more than 6 months; The results of MRI at the first diagnosis and at the time of selection indicated that there was ischemic stroke and dysfunction; There was no significant improvement in neurological function or functional defect 2 months before the study; There is serious neurological dysfunction related to the diagnosis in Article 2, which leads to the subjects need the assistance of others to walk, or cannot complete the general activities of daily living independently; NIHSS score was 6-20; The life expectancy is more than 12 months; Before treatment, the patient received standard medical care for secondary prevention of ischemic stroke, including but not limited to appropriate blood pressure and cholesterol control measures, use of antiplatelet drugs or anticoagulants (except prohibited cases); Be able to understand and provide the signed informed consent, or ask the designated legal guardian or spouse to make the above decision voluntarily on behalf of the subjects; It is reasonable to expect that patients will receive standard medical care for secondary prevention of ischemic stroke and participate in safety follow-up of all plans; Organ function determined according to the following criteria: Serum AST ≤ 2.5 × Upper normal limit (ULN); Serum alanine aminotransferase (ALT) ≤ 2.5 × Normal upper limit; Total serum bilirubin ≤ 1.5 × Normal upper limit; In subjects without antithrombotic therapy, prothrombin time (PT) and partial thrombokinase time (PTT) ≤ 1.25 × Normal upper limit; Serum albumin ≥ 3.0g/dl; Absolute neutrophil count (ANC) ≥ 1500/ μ L； Platelets ≥ 150000/ μ L； Hemoglobin ≥ 9.0g/dl; Serum creatinine ≤ 1.5 × Normal upper limit; Serum amylase or lipase were in normal range. Exclusion Criteria: History of epilepsy; History of tumor; History of brain tumor and brain trauma; hepatitis B, five surface antigens, e antigens, e antibodies and core antibodies were positive for any one, positive for hepatitis C virus antibody, positive for syphilis serum antibody or HIV positive. Myocardial infarction occurred within 6 months before the trial; Suffering from any other medical disease with clinical significance, or with abnormal mental or laboratory results, the researcher or the sponsor determines that participating in the trial will bring safety risks to the subjects; Imaging examination showed subarachnoid hemorrhage or intracerebral hemorrhage in the past 12 months; Participate in another study on the use of test drug or equipment within 3 months before treatment; Participated in other stem cell therapy related research; History of drug or alcohol abuse in the past year; Women who are known to be pregnant, breast-feeding or have a positive pregnancy test (to be tested during the screening process) or plan to be pregnant during the trial; Allergic to cattle and pork products.

Ages Eligible for Study
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Minimum Age: 18 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: 3 arms for phase 1, and 3 arms for pashe 2
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose group<br>0.5 × 10 ^ 6 / kg (body weight) of it-hMSC per person | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|
| Experimental: Middle dose group<br>1 × 10 ^ 6 / kg (body weight) of it-hMSC per person | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|
| Experimental: High dose group<br>2 × 10 ^ 6 / kg (body weight) of it-hMSC per person | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|
| Experimental: Highest dose cell group<br>Highest dose of it-hMSC | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|
| Experimental: Sub high dose cell group<br>Sub high dose of it-hMSC | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|
| Placebo Comparator: placebo group<br>placebo | Biological: it-hMSC<br>* Different doses of it-hMSC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and serious adverse events rate | Safety and tolerability of it-hMSC treatment | In 12 months | 
| Rate of clinical significant changes in laboratory | Safety and tolerability of it-hMSC treatment | In 12 months | 
| Rate of abnormal neurological physical examination results | Safety and tolerability of it-hMSC treatment | In 12 months | 
| Rate of imaging changes | Safety and tolerability of it-hMSC treatment | In 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of NIHSS scores | The improvement of neurological function was evaluated by neurological | 1、3、6、9、12 months after treatment | 
| Change of BI scores | The improvement of neurological function was evaluated by neurological | 1、3、6、9、12 months after treatment | 
| Change of mRS scores | The improvement of neurological function was evaluated by neurological | 1、3、6、9、12 months after treatment | 
| Change of MMSE scores | The improvement of neurological function was evaluated by neurological | 1、3、6、9、12 months after treatment | 
| Change of GDS scores | The improvement of neurological function was evaluated by neurological | 1、3、6、9、12 months after treatment |