Intra-arterial Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke

Study Overview
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Brief Summary
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This trial aims to test that intra-arterial injection of autologous bone marrow mononuclear cells in acute ischemic stroke patients is safe and improves neurological outcomes.

Detailed Description
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This is a study in which the patients will be included diagnosed of ischemic stroke sharply in the territory of the cerebral average artery that there fulfill criteria of incorporation and none of those of exclusion and that they have signed the informed assent. 76 patients will randomize in proportion 2:1:1 in a group control that will receive only medical conventional treatment and in two groups of intervention that will receive an unique intra-arterial infusion of mononuclear autologous bone marrow stem cells (one group of dose of 2 millions of BMSC for kilogram of weight and another group of dose of 5 millions of BMSC for kilogram of weight). The three groups of patients will be followed for 24 months. The randomization will be stratified depending on the NHSS score. This clinical trial has a voluntary substudy to obtain information on plasma biomarkers.

Official Title
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Intra-arterial Autologous Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke. A Phase II, Open-label, Multicenter, Randomized and Controlled Clinical Trial.

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Autologous bone marrow mononuclear cell intra-arterial injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with middle cerebral artery (MCA) acute ischemic stroke. Time of stroke onset is known and treatment can be started between day 1 and 7 of onset. DWI-MRI has reliably shown acute MCA ischemic lesions Magnetic resonance angiography (MRA) must confirm ipsilateral MCA permeability National Institute of Health Stroke Scale score of 6-20 at inclusion Age 18-80 years Written informed consent has been obtained Exclusion Criteria: Hemorrhagic stroke or symptomatic hemorrhagic transformation Lacunar infarction Preocclusive stenosis or total occlusion of ipsilateral carotid artery Worsening of ≥4 points in National Institute of Health Stroke Scale in the 24 hours previous to inclusion, attributable to edema or hemorrhagic transformation or suspicious of malignant edema Decrease of consciousness with a Glasgow Coma Scale of <8 points Patients with present or previous malignant disease during the last 5 years, except for basal cell carcinoma Contraindication for MRI or for bone marrow harvest Previous diagnosis of neurodegenerative disease Acute heart failure Hepatic or renal dysfunction (creatinine >2mg/dL) Coagulopathy Severe co-morbidity Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding Modified Rankin Score (mRS) before stroke of ≥2 Participation in any clinical trial in the last 3 months

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bone marrow transplantation low dose<br>Intra-arterial autologous bone marrow mononuclear cells injection (dose 2x10^6 per kilogram) | Drug: Autologous bone marrow mononuclear cell intra-arterial injection<br> <br> |
| Experimental: Bone marrow transplantation high dose<br>Intra-arterial autologous bone marrow mononuclear cells injection (dose 5x10^6 per kilogram) | Drug: Autologous bone marrow mononuclear cell intra-arterial injection<br> <br> |
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability | Proportion of patients with modified Rankin Scale scores of 0-2 at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Cell therapy, Bone marrow