Allogenic Mesenchymal Stem Cell Derived Exosome in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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Administration of cell-free exosomes derived from mesenchymal stem cell (MSCs) can be sufficient to exert therapeutic effects of intact MSCs after brain injury. In this study we aim to assay the administration of MSC derived exosome on improvement of disability of patients with acute ischemic stroke

Detailed Description
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Exosomes derived from multipotent mesenchymal stromal cells (MSCs) promote neurovascular remodeling and functional recovery after stroke. Animal study has shown that Exosome treatment markedly increased the number of newly formed doublecortin (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial cells) cells. Based on previous literature, intravenous administration of MSC-generated exosomes post stroke improves functional recovery and enhances neurite remodeling, neurogenesis, and angiogenesis and represents a novel treatment for stroke. Also some studies have presented which miR-124-Loaded Exosomes ameliorate the brain Injury by promoting neurogenesis. So in present study we aim to assess improving patients with acute ischemic stroke who received MSC derived exosome

Official Title
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Safety and Efficacy of Allogenic Mesenchymal Stem Cells Derived Exosome on Disability of Patients With Acute Ischemic Stroke: a Randomized, Single-blind, Placebo-controlled, Phase 1, 2 Trial

Conditions
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Cerebrovascular Disorders

Intervention / Treatment
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* Biological: exosome


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female acute ischemic patients aged 40-80 years with symptoms of acute cerebral infarction of less than 24h from stroke onset. Patients with infarct size 3*3 Patients with a measurable focal neurological that must persist to the time of treatment without clinically meaningful improvement. Patients must have computerized tomography (CT) and / or magnetic resonance imaging (MRI) compatible with the clinical diagnosis of acute ischemic stroke in the territory of the middle cerebral artery before being included in the study. Patients must have a score on the NIH Stroke Scale 8-24, and mRS ≤ 1 Women of childbearing age should have a negative pregnancy test performed prior to inclusion Obtaining informed consent signed Exclusion Criteria: Comatose patients. brain tumour, cerebral oedema with compression of ventricles, cerebellar infarction or brainstem, or intraventricular, intracerebral or subarachnoid haemorrhage. alcohol use Active infectious disease, including HIV, hepatitis B, Hepatitis . patients with dementia. Specify clinical conditions Patients who are participating in another clinical trial. Inability or unwillingness of individual for giving written informed consent.

Ages Eligible for Study
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Minimum Age: 40 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: exosome or vesicle<br>CVA patients who have disability, will receive total protein of allogenic MSC-generated exosome transfected by miR-124, one month after attack, via Stereotaxis/Intraparanchymal | Biological: exosome<br>* allogenic mesenchymal stem cells derived exosome enriched by miR-124<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | deteriorating stroke, stroke recurrences, brain oedema, seizures, hemorrhagic transformation | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| measurement of Modified Ranking Scale | measure the degree of disability in Stroke patients. score was recorded from 0-6. 0 No symptoms at all No significant disability despite symptoms; able to carry out all usual duties and activities Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance Moderate disability; requiring some help, but able to walk without assistance Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Severe disability; bedridden, incontinent and requiring constant nursing care and attention Dead | 12 months |