The primary objective of this study is to evaluate the functional recovery based on Barthel index (BI) and modified Rankin Scale (mRS) while the secondary objectives are to assess the survival and re-admission rate as well as to investigate the inflammatory response in a subclinical study within 1 year of Neuroncell-EX infusion in participants with acute ischemic stroke.
Background: Ischemic stroke is a serious cerebrovascular disease with high morbidity and disability worldwide. Despite the great efforts that have been made, the prognosis of stroke patients remains unsatisfactory. Mesenchymal stem cells (MSCs) therapy is an emerging treatment studied in various medical conditions including autoimmune, inflammatory as well as central nervous system diseases. The mechanism of MSCs in the treatment of ischemic stroke involved with immune regulation, neuroprotection, angiogenesis, and neural circuit reconstruction. A large number of preclinical data have proved the feasibility of MSCs in the treatment of stroke where the administration of MSCs can alleviate neurological deficits. Similarly, a number of clinical trials have also proved the effectiveness and safety of MSCs in the treatment of stroke. Among these is a phase 2, single-center, assessor-blinded randomized controlled study by investigators using bone marrow-derived MSCs in patients with subacute middle cerebral artery infarct. The investigators demonstrated the safety, tolerability, and efficacy of intravenous infusion of MSCs with significant improvement in median infarct volume (Law et al., 2021). Objective: To determine the efficacy of intravenous infusion of allogeneic Cytopeutics umbilical cord mesenchymal stem cells (Neuroncell-EX) in participants with acute ischemic stroke. Study Design: This is a phase II-III double-blind randomized controlled study involving 80 participants, diagnosed with acute ischemic stroke admitted to HCTM-UKM. Investigational treatment arm (Group A-MSCs) consist of 40 participants will receive Neuroncell-EX whereas control treatment arm (Group B-Control) consist of 40 participants will receive placebo. Both groups will also receive standard medical care for acute stroke. Efficacy assessments will include Barthel index (BI) and modified Rankin Scale (mRS), Functional Magnetic Resonance Imaging (fMRI) and blood tests including biomarkers within 12 months follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
80
Intravenous infusion of Neuroncell-EX (2 million UCMSCs per kg body weight) on day 1 and day 14 plus standard medical care.
Intravenous infusion of Placebo (normal saline) on day 1 and day 14 plus standard medical care.
Hospital Canselor Tuanku Muhriz UKM
Cheras, Kuala Lumpur, Malaysia
RECRUITINGBarthel Index (BI)
Functional recovery after stroke onset is measured by the Barthel Index (BI). BI score from 0-100, higher scores mean better outcome. The investigators measure and compare the BI score for ischemic stroke patients who received Neuroncell-EX and control treatments.
Time frame: Baseline, 6 weeks, 3 months, 6 months and 12 months
Modified Rankin Scale
Functional recovery after stroke onset is measured by the modified Rankin Scale (mRS). mRS is a 7 point (0-6) ranking scale to assess neurological disability. A score of 0 indicates normal functions with no symptoms while higher scores indicates more severe neurological disability.The investigators measure and compare the mRS score for ischemic stroke patients who received Neuroncell-EX and control treatments.
Time frame: Baseline, 6 weeks, 3 months, 6 months and 12 months
Number of participants with adverse events due to umbilical cord-derived mesenchymal stem cells infusion as assessed by clinical examination.
Presence or absence of any adverse events due to the umbilical cord-derived mesenchymal stem cells (UC-MSCs) infusion, sepsis, organ failure (clinically apparent or subclinical), hospitalization, cancers and death during the study period based on clinical examination.
Time frame: Baseline, day 1, day 14, 6 weeks, 3 months, 6 months and 12 months
Survival and Re-admission rate
Survival and re-admission rate
Time frame: Baseline, day 1, day 14, 6 weeks, 3 months, 6 months and 12 months
Blood inflammatory markers before and after umbilical cord derived mesenchymal stem cell infusion based on subclinical analysis.
Biomarkers concentration: Interleukin-6 (IL-6), interleukin-2 (IL-2), matrix metalloproteinase-9 (MMP-9), tumour necrosis factor alpha (TNFα), interleukin-1beta (IL-1β), vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), Interleukin-1 receptor antagonist protein (IL-1Ra) and transforming growth factor beta 1 (TGF-β1).
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Time frame: Baseline, 6 months and 12 months