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

Abstract

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 × 106/kg or 5 × 106/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.