A Study of Allogeneic Mesenchymal Bone Marrow Cells in Subjects With Ischemic Stroke

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of allogeneic adult mesenchymal bone marrow cells administered intravenously to patients with ischemic stroke.

Detailed Description
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Stroke remains a major global healthcare problem. Recent data compiled by the American Heart Association (AHA) for 2008 show that the annual incidence of new or recurrent stroke in the United States is about 780,000, with approximately 600,000 of these strokes being first attacks. Among adults age 20 and older, the estimated prevalence of stroke in 2005 was 5.8 million in the United States, resulting in >150,000 deaths annually, with 4.8 million stroke survivors alive today. Stroke ranks as the country's third leading cause of death, behind only cancer and heart disease. The only approved treatments of acute ischemic stroke involve restoring blood flow to the affected region by using thrombolytics or mechanical devices that physically remove clots. However, the use of thrombolytics is limited due to the therapeutic window of < 3-6 hours post onset of stroke symptoms such that only a small fraction of stroke patients receive this therapy. Following the completion of a stroke, there is little therapy to offer patients to promote recovery other than physical, occupational, and speech therapy. Allogeneic mesenchymal stem cells have been used in a number of clinical trials for different indications demonstrated the safety of allogeneic mesenchymal stem cell treatment. In addition to their ability to differentiate into multiple different cell types that would be contributory to the recovery and repair of the brain by replacing destroyed cells, mesenchymal stem cells also secrete angiogenins, cytokines and trophic factors that can support and stimulate multiple other cell types. The cascade of cellular events following the release of these cytokines and trophic factors would also potentially lead to beneficial effects by restoring blood supply, by rescuing cells at risk, and by stimulating the remaining cell populations to repair and propagate new cells and synaptic connections.

Official Title
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A Phase I/II, Multi-Center, Open-Label Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Allogeneic Mesenchymal Bone Marrow Cells to Subjects With Ischemic Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Biological: Allogeneic adult mesenchymal bone marrow stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of ischemic stroke for longer than 6 months Brain CT/MRI scan at initial diagnosis and at enrollment consistent with ischemic stroke No substantial improvement in neurologic or functional deficits for the 2 months prior to enrollment NIHSS score between 6-20 Life expectancy greater than 12 months Prior to treatment patient received standard medical care for the secondary prevention of ischemic stroke Adequate organ function as defined by the following criteria: Exclusion Criteria: History of uncontrolled seizure disorder History of cancer within the past 5 years. History of cerebral neoplasm Positive for hepatitis B, C or HIV Myocardial infarction withing six months of study entry Findings on baseline CT suggestive of subarachnoid or intracerebral hemorrhage within past 12 months. Allergies to Bovine or Porcine 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stem cells<br>All subjects will receive allogeneic adult mesenchymal bone marrow stem cells | Biological: Allogeneic adult mesenchymal bone marrow stem cells<br>* Patients will receive intravenously one dose of 0.5-1.5 million cells per kg of allogeneic adult mesenchymal bone marrow stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be the safety of treatment with aMBMC during the twelve-month study period. | The primary endpoint will be the safety of treatment with aMBMC during the twelve-month study period as determined by the incidence and severity of adverse events, clinically-significant changes on clinical laboratory tests, vital signs, physical and neurologic examinations. | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale Score. | The change from the baseline in National Institutes of Health Stroke Scale score will be calculated at 1, 3, 6, 9, 12 months post-treatment, as available: | 12 months | 
| Mini Mental Status Exam score. | The change from the baseline in Mini Mental Status Exam score will be calculated at 1, 3, 6, 9, 12 months post-treatment, as available. | 12 month | 
| Barthel Index Score. | The change from the baseline in Barthel Index score at 1, 3, 6, 9, 12 months post-treatment, as available. | 12 month | 
| The Geriatric Depression Scale Score. | The change from baseline in the Geriatric Depression Scale score at 1, 3, 6, 9, 12 months post-treatment, as available. | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic, adult, stem, cells, stroke, ischemic