title: 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: BACKGROUND
  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.
  
  
  OBJECTIVE
  This trial aims to test safety and efficacy of intra-arterial injection of autologous bone marrow mononuclear cell in ischemic stroke patients.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Moniche
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Escudero
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Zapata-Arriaza
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Usero-Ruiz
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Prieto-León
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de la Torre
authors.affiliation: Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: Miguel-Angel
authors.initials: MA
authors.lastname: Gamero
authors.affiliation: Department of Neurology, Hospital Regional de Malaga, Malaga, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Tamayo
authors.affiliation: Department of Neurology, Hospital Reina Sofia, Cordoba, Spain.
authors.forename: Juan-José
authors.initials: JJ
authors.lastname: Ochoa-Sepúlveda
authors.affiliation: Department of Neurology, Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Maestre
authors.affiliation: Department of Hematology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Carmona
authors.affiliation: Department of Radiology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Piñero
authors.affiliation: Department of Hematology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Calderón-Cabrera
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Jimenez
authors.affiliation: Department of Radiology, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Department of Neurology, Hospital Universitario Virgen del Rocío, Seville, Spain.|Instituto de Biomedicina de Sevilla-IBiS, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016026:Bone Marrow Transplantation / Q000379:methods*; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D016037:Single-Blind Method; D020521:Stroke / Q000209:etiology / Q000628:therapy*; D016896:Treatment Outcome; D055815:Young Adult
keywords: bone marrow; cell transplantation; clinical trial; ischemic stroke; mononuclear cell; stem cell