Intravenous Stem Cells After Ischemic Stroke

Study Overview
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Brief Summary
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The main objective of the study is to evaluate feasibility and tolerance of the intravenous injection of autologous mesenchymal stem cells for patients presenting an ischemic stroke (less than 6 weeks).

Detailed Description
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Stroke is the leading cause of acquired adult disability. Except the hospitalization in stroke units, only thrombolysis has been shown to be efficient to treat acute ischemic stroke in the first three hours after the onset. Increasing brain plasticity after stroke represents an important alternative strategy. Cell therapy provides a functional improvement after cerebral ischemia in rodent models. This restorative therapy aims to replace destroyed cerebral tissue with a stem cells graft. Despite these encouraging experiments, we do not know yet the best way of administration of the stem cells, the best dose and the optimal delay of the graft. The pioneer clinical studies failed to reproduce this benefit for patients probably because of the limited number of studied patients. Therefore, more translational studies are needed to improve our knowledge in this promising field. Among different cell sources, mesenchymal (or stromal) stem cells (MSC) derived from bone marrow offer the advantage of arising from a non tumoral and no modified source and are not sources of immunological or ethical problems. Our research project involves a development of cell therapy in a phase IIa clinical trial of feasibility and safety in patients (randomised, controlled, open, with 3 parallel groups).

Official Title
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Cell Therapy by Intravenous Injection of Mesenchymal Stem Cells After Stroke

Conditions
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Ischemia, Stroke

Intervention / Treatment
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* Genetic: Autologous mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: right or left carotid ischemic stroke in the 14 previous days, confirmed by MRI. Persistent neurological deficit (NIHSS >=7). Optimal medical treatment(antithrombotics, antihypertensive, statins). General state compatible with a program of functional rehabilitation. Exclusion Criteria: Severe extensive stroke implying vital prognosis. Severe persistent neurological deficit (NIHSS > 24). Medical history of neurological pathology with a deficit as consequence (Rankin < 3 before stroke). Serious psychiatric disease. Myocardial infarction less than 3 month old. Recurring thromboembolic disease or less than 6 month old. Patient with organ transplantation. Medical history of infection (HIV,HTLV, HBV, HCV). Current immunosuppressive/immunomodulating treatment. Medical history of cancer. Medical history of chemotherapy. Known chronic kidney failure(clearance of creatinin < 90 ml/min/1,73m2). Known hepatic failure(diminution of prothrombin level (TP) not corrigiable with vitamin K). Obesity hinding the bone-marrow sampling in the iliac crest. Pathology implying vital prognosis in the 3 month following stroke. Refusal to participate. Patient unable to give personally his/her consent. Pregnant, parturient and feeding women. Woman in age to procreate who could not receive an effective method of contraception during the study. Participation to another therapeutic clinical trial or in period of exclusion of a therapeutic clinical study. Privation of liberty with a decision of justice or administration, legal protection. Non affiliation to social security.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: 1<br>Control group without intervention nor placebo | |
| Experimental: 2<br>First dose of stem cells | Genetic: Autologous mesenchymal stem cells<br>* Intravenous injection of Mesenchymal Stem Cells in a mixing of physiological salt solution/albumin 4% (volume<100ml) less than 6 weeks after stroke<br>|
| Experimental: 3<br>Second dose of stem cells | Genetic: Autologous mesenchymal stem cells<br>* Intravenous injection of Mesenchymal Stem Cells in a mixing of physiological salt solution/albumin 4% (volume<100ml) less than 6 weeks after stroke<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility and tolerance of the intravenous injection of autologous mesenchymal stem cells in patients with carotid ischemic stroke |  | 2 weeks, 1, 2, 4, 6 months and 1, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and functional effects of the intravenous injection of autologous mesenchymal stem cells in patients with carotid ischemic stroke |  | 2 weeks, 1, 2, 4, 6 months and 1, 2 years | 
| Determination of the most effective dose of stem cells |  | 2 weeks, 1, 2, 4, 6 months and 1, 2 years | 
| To define the best criteria for a future trial (phase III) |  | 2 weeks, 1, 2, 4, 6 months and 1, 2 years | 
| To define the best target population for a future study |  | 2 weeks, 1, 2, 4, 6 months and 1, 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell therapy, Stroke, Neuronal Plasticity, Recovery, Mesenchymal Stem Cells, Transplantation