Autologous Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation in the Treatment of Ischemic Stroke

Study Overview
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Brief Summary
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This study is to evaluated the safety and efficacy of BMSCs transplantation in the treatment of ischemic stroke, so as to provide a basis for future clinical application of BMSCs transplantation in the treatment of ischemic stroke.

Detailed Description
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Routine treatment: 1.1. If arterial plaque is found, use lipid-lowering therapy (routine dose of atorvastatin or rosuvastatin). If no plaque is found, use atorvastatin or rosuvastatin based on the maintenance of normal blood lipid; 1.2. If venous thrombosis or arterial plaques are found in the lower limbs, use dabigatran to prevent platelet aggregation; if no vascular problems are found in the lower limbs, use aspirin or clopidogrel to prevent platelet aggregation; 1.3. During the treatment, cerebrovascular stenosis (non responsible vessels) can be treated intravascularly; 1.4. The use of neurotrophic drugs is prohibited during the study; 1.5. Elevated homocysteine was treated with mecobalamin and folic acid; 1.6. Hypertension, diabetes and other basic diseases receive routine treatment, and the combined medication is recorded in the case report form. Grouping: 2.1. BMSCs group: BMSCs were transplanted on the basis of routine treatment: the transplanted cells were injected intravenously and transplanted in two times, with a dose of 1 × 106 / kg body weight, each volume of 80ml ± 5ml, and the time interval between two transplants was 1 week; 2.2. Routine treatment group: only receiving routine treatment;

Official Title
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A Randomized, Open and Routine Parallel Controlled Clinical Study on the Safety and Efficacy of Autologous Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation in the Treatment of Ischemic Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Biological: Transplantation of self BMSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-65 years old in the rehabilitation period of cerebral infarction (including subacute stage, chronic stage and sequelae stage, with onset time ≤ 3 years), regardless of gender; Definite cerebral infarction in the blood supply area of middle cerebral artery confirmed by imaging; There are clear neurological deficits, such as motor and cognitive dysfunction (National Institutes of Health Stroke Scale 7 < NIHSS < 21 points); Those who agree to take effective contraceptive measures during the study period, and women of childbearing age have negative pregnancy test; Sign the informed consent of the patient and agree to participate in all visits, examinations and treatments as required by the study protocol. Exclusion Criteria: Lacunar cerebral infarction; Acute cerebral infarction, onset time < 2 weeks; Mild ischemic stroke or mild neurological impairment or severe ischemic stroke, with coma; Patients with moyamoya disease, vascular malformation, hemangioma and carotid stenosis exceeding 70%; Patients with severe heart valve disease or confirmed intractable atrial fibrillation; Complicated with intracranial hemorrhage or tumor; Patients with cerebral infarction caused by blood system diseases, or those with previous blood history or family history of blood diseases; Any one of 5 items of hepatitis B virus (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody and syphilis spiral physical examination; Those with severe respiratory or circulatory system or liver and kidney dysfunction who cannot tolerate treatment and examination; Severe febrile disease or viral disease in the past 12 weeks; Malignant tumor; Those who have a previous history of autoimmune diseases or a family history of autoimmune diseases; Previous history of drug allergy; Pregnant or lactating women; Those who are participating or have participated in this study or participated in other clinical trials within 12 weeks before enrollment; Other circumstances that the investigator considers inappropriate for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Routine treatment group<br>No special measures were taken and routine treatment was adopted | |
| Experimental: BMSCs group<br>BMSCs were transplanted on the basis of routine treatment: the transplanted cells were injected intravenously and transplanted in two times at a dose of 1 × 106/kg body weight, each volume was 80ml ± 5ml, and the time interval between two transplants was 1 week | Biological: Transplantation of self BMSCs<br>* Bone marrow was collected, cultured in vitro and injected back into the body<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in National Institutes of Health Stroke Scale (NIHSS) score from baseline after the first transplant. | The difference in National Institutes of Health Stroke Scale (NIHSS) score from baseline at week 96 ±30 days after the first transplant. | 96 weeks ±30 days after the first transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference from baseline in National Institutes of Health Stroke Scale (NIHSS) score after the first transplantation | The difference from baseline in National Institutes of Health Stroke Scale (NIHSS) score at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Improvement rate of the modified Barthel Index Rating Scale score from baseline after the first transplant | Improvement rate of the modified Barthel Index Rating Scale score from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Improvement rate of the modified Barthel Index Rating Scale score from baseline | Improvement rate of the modified Barthel Index Rating Scale score from baseline at 96 weeks ±30 days after the first transplant | 96 weeks ±30 days after the first transplantation | 
| Improvement rate of Fugl-Meyer scale score from baseline after the first transplantation | Improvement rate of Fugl-Meyer scale score from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Improvement rate of Fugl-Meyer scale score from baseline after the first transplantation | Improvement rate of Fugl-Meyer scale score from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| Improvement rate of Simple Mental State Examination Scale (MMSE) score | Improvement rate of Simple Mental State Examination Scale (MMSE) score from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Improvement rate of Simple Mental State Examination Scale (MMSE) score | Improvement rate of Simple Mental State Examination Scale (MMSE) score from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline after the first transplantation | The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline after the first transplantation | The time course of the left abductor pollicis brevis and right abductor pollicis brevis of the motor evoked potential decreased from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential after the first transplantation | MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential after the first transplantation | MT increase rate from baseline in the left abductor Pollicis brevis and right abductor pollicis brevis of the motor evoked potential at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline after the first transplantation | The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline after the first transplantation | The time course of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) decreased from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) after the first transplantation | Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) after the first transplantation | Rate of increase from baseline amplitude of the upper limb sensory evoked potential N9(left), N11(left), N20(left), N9(right), N11(right), N20(right) at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| Changes in CTA from baseline after the first transplantation | Changes in CTA from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Changes in CTA from baseline after the first transplantation | Changes in CTA from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| Changes in CTP from baseline after the first transplantation | Changes in CTP from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation | 
| Changes in CTP from baseline after the first transplantation | Changes in CTP from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Changes in mRS Scores from baseline after the first transplantation | Changes in mRS Scores from baseline at 48 weeks ±15 days after the first transplantation | 48 weeks ±15 days after the first transplantation | 
| Changes in mRS Scores from baseline after the first transplantation | Changes in mRS Scores from baseline at 96 weeks ±30 days after the first transplantation | 96 weeks ±30 days after the first transplantation |