Stem Cell Therapy For Acute Ischemic Stroke Patients
Condition: Middle Cerebral Artery Infarction; Anterior Cerebral Artery Infarction
MeSH terms: Ischemic Stroke; Infarction, Middle Cerebral Artery; Infarction, Anterior Cerebral Artery; Infarction
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether patients with subacute ischemic stroke will
      benefit from infusion of patient's own bone marrow derived stem cells.

      Primary Hypothesis: Intravenous injection of bone marrow mononuclear cells at a dose of 30 to
      500 million in patients with subacute ischemic stroke results in reduction of infarct volume
      and improvement of neurological function compared to those without the injection.

      Secondary Hypothesis: Patients receiving more than 100 million Bone marrow derived stem cells
      (BMSC) will have better outcome than those receiving fewer dosages of cells.
    

Detailed description: 
      Background: Stroke accounts for significant disability and there is need for novel treatment
      modality which can improve the functional outcome. In this randomized clinical trial,
      investigators proposed to examine stem cell therapy as a potential therapeutic modality. Stem
      cells in animal stroke models have shown reduction in infarct size and improvement in
      neurological function. Only one human clinical trial with intravenous autologous marrow
      stromal cell therapy of five patients has shown some benefit. The primary objective of this
      phase II study was to explore if there is favourable risk to benefit ratio for autologous
      bone marrow derived mononuclear stem cell therapy (BMSCs) in patients with acute ischemic
      stroke to justify a larger phase III trial.

      Methods & Design: The study recruited 120 men and women aged 18-70 years presenting with
      acute ischemic stroke (7-29 days) and a NIHSS score of ≥ 7 and BI ≤ 50. Following baseline
      assessment (MRI Brain, Whole Body PET scan, EEG brain, CT scan Brain and clinical examination
      including National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), modified
      Rankin Scale (mRS), Glasgow Come Scale (GCS), participants were randomly allocated to two
      groups: conventional management alone (control group); or conventional management and
      autologous intravenous BMSCs transplantation (experimental group). Bone marrow was aspirated
      under local anaesthesia and the isolated BMSCs cells injected intravenously within 4 hours.
      The patients were monitored with hemogram & renal/liver function tests, CT scan brain at 36
      hrs and clinical examination for a week. The patients were followed up to one year with
      periodic MRI brain at 3 months, 6 months, EEG & PET scan at 6 months and 1 year. The primary
      efficacy outcomes were difference between the two groups in the Modified Barthel index score
      and modified Rankin Scale score at six-month post-randomisation. The secondary efficacy
      outcomes are: NIHSS score at six-months and 1 year post-randomisation; and the modified
      Rankin scale score at 3 months and one year post-randomization, and functional status
      measured by barthel index (in binary scale <60 or >60 ) at six months and one year
      post-randomization. Dose response analysis were done by comparing outcomes in patients
      receiving various doses of bone marrow mononuclear cells.

      Discussion: This phase 2 study was aimed to explore if there is a favourable risk-to-benefit
      ratio for stem cell therapy in patients with acute ischemic stroke. Investigators also
      planned to examine whether there is justification for phase III trial of autologous bone
      marrow derived mononuclear stem cell therapy for acute ischemic stroke.
    

Intervention name(s): BMSCs
Intervention type(s): Other
Intervention description(s): 30-500 million Autologous BMSCs will be given intravenously to patients with acute ischemic stroke (onset from 7 to less than 30 days).
Other intervention name(s): Stem cell arm
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Brain attack; stroke; Ischemic stroke; stem cell therapy