Combination of Conditioned Medium and Umbilical Cord-Mesenchymal Stem Cells Therapy for Acute Stroke Infarct

Study Overview
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Brief Summary
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The purpose of this study was to determine the effectiveness of a combination of intranasal conditioned medium (CM) with intraparenchymal umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in acute stroke patients to induce neurogenesis.

Detailed Description
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This study has 3 arms namely CM and UC-MSCs treatment, UC-MSCs treatment only, and control. The investigator hypothesized that group of CM and UC-MSCs combination is the optimal treatment to induce neurogenesis in stroke patients.

Official Title
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Safety and Efficacy of Combined Conditioned Medium With Umbilical Cord Mesenchymal Stem Cells as A Novel Strategy for Acute Stroke Infarct

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Biological: Conditioned Medium
* Biological: Umbilical Cord Mesenchymal Stem Cells
* Procedure: Neurologic and Neutrophic Drugs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 25-60 years diagnosed with ischemic stroke acute phase The patient has had a CT scan/MRI of the brain to assess ischemic territory The patient must have an NIH Stroke score of 8-20 The patient or legal assistant has obtained detailed informed consent regarding the study protocol and agreeing to participate in the study Patients with The Glasgow Coma Scale (GCS) score > 8 Patients with Pt-APTT values within normal limits Exclusion Criteria: Patients with recurrent stroke in the 6 months preceding the episode current stroke CT or MRI images show midline shift and bleeding transformation Participate in similar studies using CM and/or UC-MSC Patients who are immunocompromised and/or who are receiving therapy immunosuppressive Patients who cannot have a CT or MRI examination due to their condition Patients with impaired renal and hepatic function after the onset of ischemic stroke: Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) > 5x the upper limit of normal values and a significant increase in urea-creatinine values Patients with a history of malignant tumors or other severe neurologic conditions.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conditioned medium combined with Umbilical cord mesenchymal stem cells treatment<br>Intranasal of 3 cc of conditioned medium each, for 3 days in a row and Intra-parenchymal transplantation of 20x10^6 UC-MSCs | Biological: Conditioned Medium<br>* Intranasal of 3 cc of conditioned medium each, for 3 days in a row<br>* Other names: Secretome;Biological: Umbilical Cord Mesenchymal Stem Cells<br>* Intra-parenchymal transplantation of 20x10^6 UC-MSCs<br>* Other names: Mesenchymal stromal cells;|
| Experimental: Umbilical cord mesenchymal stem cells treatment<br>Intra-parenchymal transplantation of 20x10^6 UC-MSCs | Biological: Umbilical Cord Mesenchymal Stem Cells<br>* Intra-parenchymal transplantation of 20x10^6 UC-MSCs<br>* Other names: Mesenchymal stromal cells;|
| Active Comparator: Standard treatment (control)<br>Neurologic and Neutrophic Drugs | Procedure: Neurologic and Neutrophic Drugs<br>* Such as clopidogrel, piracetam, citicoline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Brain-Derived Neutrophic Factor at one month, 3 months and 6 months after transplantation | Venous blood collection | Before treatment, one month after treatment, 3 months after treatment, and 6 month after treatment | 
| Change from baseline Vascular endothelial growth factor at one month, 3 months and 6 months after transplantation | Venous blood collection | Before treatment, one month after treatment, 3 months after treatment, and 6 month after treatment | 
| Change baseline Magnetic Resonance Imaging at 6 month after transplantation | To observe the brain development (neurogenesis) | Before treatment, 6 month after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The National Institute of Health Stroke Scale (NIHSS) Scoring | The NIH Stroke Scale (NIHSS) is a 15-item scale that is a well-validated and prognostically important measure of stroke-related neurologic deficits in research and clinical care | Before treatment, one month after treatment, 3 months after treatment, and 6 month after treatment | 
| modified Rankin Scale (mRS) | The Modified Rankin Scale (mRS) is used to measure the degree of disability in patients who have had a stroke | Before treatment, one month after treatment, 3 months after treatment, and 6 month after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ischemic stroke, Mesenchymal Stem Cells, Conditioned Medium, Secretome