Ex Vivo Cultured Adult Allogenic MSCs in Ischemic Cerebral Stroke

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of intravenous ex vivo cultured adult allogenic mesenchymal stem cells in patients with ischemic cerebral stroke. Patient will be given single intravenous dose of allogenic mesenchymal stem cells 2 million cells/Kg body weight or placebo within 10 days of stroke. Patients will be followed up till 12 months. Safety will be evaluated by type, number and proportion of patients with adverse events. Efficacy will be evaluated by clinical parameters and MRI.

Official Title
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A Randomized, Double Blind, Multicentric, Placebo Controlled, Single Dose, Phase -I/ II Study Assessing The Safety And Efficacy Of Intravenous Ex Vivo Cultured Adult Allogenic Mesenchymal Stem Cells In Patients With Ischemic Cerebral Stroke

Conditions
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Stroke

Intervention / Treatment
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* Biological: Ex vivo cultured adult allogenic MSCs
* Other: Plasmalyte-A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20 and 80 years old MRS equal to or less than 4. Full functional independence before present stroke. Patients will be included within the time frame of 10 days after an acute cerebral ischemic episode. This time period refers to the date of dosing. Neuro-imaging examination showing ischemic cerebral infarct. CT or MRI brain scanning has reliably excluded both intracranial haemorrhage and structural brain lesions which can mimic stroke (e.g. cerebral tumour) Stroke symptoms are to be present for at least 30 minutes and have not improved before treatment. Symptoms must be distinguishable from an episode of generalized ischemia (i.e. syncope), seizure, or migraine disorder. Patients should have motor weakness following the acute cerebral ischemic episode. Able to comply with study procedures for the entire length of the study Exclusion Criteria: Haematological causes of stroke Evidence of intracranial haemorrhage (ICH) on the CT-scan. Severe stroke as assessed clinically (e.g. MRS>4). Subjects who are unlikely to complete the infusion of investigational product and/or are unlikely to undergo active medical management during that period due to a severe clinical condition Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation, intra cranial surgery or radiological evidence of previous cerebral stroke with clinical manifestation. History of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery) Size and location of the cerebral infarct cannot be determined. Comatose / clinically unstable Serious, pre-existing medical conditions such as bleeding disorders (eg. leukopenia, thrombocytopenia) septicemia, TB, hepatic dysfunction (> 2.5 times the ULN of hepatic function tests) and renal dysfunction (Serum creatinine > 2 mg/dl). Disease or impairment that precludes adequate neurological exam Hypo- or hyperglycaemia sufficient to account for the neurological symptoms; the patient should be excluded if their blood glucose is < 3.0 or > 20.0mmol/L. The patient is female and of childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding. Patient is likely to be unavailable for follow-up e.g. no fixed home address Patients with evidence of life threatening infection or life threatening illness (e.g. advanced cancer) or having tested positive for HIV, Hepatitis B, Hepatitis C and VDRL Patient was already dependent in activities of daily living before the present acute stroke Patients who have been included in any other clinical trial within the previous month History of neoplasia or other comorbidity that could impact patient's short-term survival Previous or concomitant treatment with immune modulators or experimental drugs 60 days prior to study enrolment Any condition that in the judgment of the investigator would place the patient under undue risk Sustained systolic BP >220 mmHg, or <80mmHg, or diastolic BP > 140mmHg or <50 mmHg. Patients contraindicated for MRI examination.

Ages Eligible for Study
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Minimum Age: 20 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ex vivo cultured adult allogenic MSCs<br> | Biological: Ex vivo cultured adult allogenic MSCs<br>* Single IV dose of allogenic MSCs<br>|
| Placebo Comparator: Plasmalyte-A<br> | Other: Plasmalyte-A<br>* Single IV dose of Plasmalyte-A<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The type of AE(s), number of AE(s) and proportion of patients with AE(s). |  | 12 Months | 
| Improvement of neurological recovery as assessed by NIH Stroke Scale (NIHSS). |  | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of the Functional recovery - assessed by Barthel's Index for activities of daily living. |  | 12 Months | 
| Improvement of Global outcome as assessed by the Modified Rankin Scale |  | 12 Months | 
| MRI Parameters - Change in infarct size T2 - weighted images and blood flow in infarct area as evaluated by Diffusion Weighted Index |  | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic Cerebral Stroke