Intra-Arterial Bone Marrow Mononuclear Cells (BM-MNCS) Transplantation in Acute Ischemic Stroke (IBiS Trial): Protocol of a Phase II, Randomized, Dose-Finding, Controlled Multicenter Trial

RATIONALE: No neuroprotective or neurorestorative therapies have been approved for ischemic stroke. Bone marrow mononuclear cell intra-arterial transplantation improves recovery in experimental models of ischemic stroke. AIMS: This trial aims to test safety and efficacy of intra-arterial injection of autologous bone marrow mononuclear cell in ischemic stroke patients. DESIGN: Multicenter, prospective, phase II, randomized, controlled (non-treated group as control), assessor-blinded clinical trial. Seventy-six stroke patients will be enrolled. Patients fulfilling clinical and radiological criteria (e.g. age between 18 and 80 years, middle cerebral artery ischemic stroke with a National Institutes of Health Stroke Scale score of 6-20 within one- to seven-days from stroke onset and no lacunar stroke) will be randomized to intervention or control group (1 : 1). Bone marrow harvest and intra-arterial injection of autologous bone marrow mononuclear cell will be done in the intervention group with two different doses (2 × 10(6) /kg or 5 × 10(6) /kg in 1 : 1 proportion). Patients will be stratified at randomization by National Institutes of Health Stroke Scale score. Patients will be followed up for two-years. STUDY OUTCOMES: The primary outcome is the proportion of patients with modified Rankin Scale scores of 0-2 at 180 days. Secondary outcomes include National Institutes of Health Stroke Scale and Barthel scores at six-months, infarct volume, mortality, and seizures. DISCUSSION: This is the first trial to explore efficacy of different doses of intra-arterial bone marrow mononuclear cell in moderate-to-severe acute ischemic stroke patients. The trial is registered as NCT02178657.