Clinical trial NCT02178657: Intra-arterial Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke
Official title: Intra-arterial Autologous Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke. A Phase II, Open-label, Multicenter, Randomized and Controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke
Keywords: Stroke
Cell therapy
Bone marrow
Lead sponsor: Andalusian Initiative for Advanced Therapies
Sponsor class: OTHER_GOV
First posted: 2014-07-01
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial aims to test that intra-arterial injection of autologous bone marrow mononuclear cells in acute ischemic stroke patients is safe and improves neurological outcomes.

Detailed description: This is a study in which the patients will be included diagnosed of ischemic stroke sharply in the territory of the cerebral average artery that there fulfill criteria of incorporation and none of those of exclusion and that they have signed the informed assent. 76 patients will randomize in proportion 2:1:1 in a group control that will receive only medical conventional treatment and in two groups of intervention that will receive an unique intra-arterial infusion of mononuclear autologous bone marrow stem cells (one group of dose of 2 millions of BMSC for kilogram of weight and another group of dose of 5 millions of BMSC for kilogram of weight). The three groups of patients will be followed for 24 months. The randomization will be stratified depending on the NHSS score. This clinical trial has a voluntary substudy to obtain information on plasma biomarkers.

Eligibility criteria: Inclusion Criteria:

* Patients with middle cerebral artery (MCA) acute ischemic stroke.
* Time of stroke onset is known and treatment can be started between day 1 and 7 of onset.
* DWI-MRI has reliably shown acute MCA ischemic lesions
* Magnetic resonance angiography (MRA) must confirm ipsilateral MCA permeability
* National Institute of Health Stroke Scale score of 6-20 at inclusion
* Age 18-80 years
* Written informed consent has been obtained

Exclusion Criteria:

* Hemorrhagic stroke or symptomatic hemorrhagic transformation
* Lacunar infarction
* Preocclusive stenosis or total occlusion of ipsilateral carotid artery
* Worsening of ≥4 points in National Institute of Health Stroke Scale in the 24 hours previous to inclusion, attributable to edema or hemorrhagic transformation or suspicious of malignant edema
* Decrease of consciousness with a Glasgow Coma Scale of \<8 points
* Patients with present or previous malignant disease during the last 5 years, except for basal cell carcinoma
* Contraindication for MRI or for bone marrow harvest
* Previous diagnosis of neurodegenerative disease
* Acute heart failure
* Hepatic or renal dysfunction (creatinine \>2mg/dL)
* Coagulopathy
* Severe co-morbidity
* Pregnancy, childbearing potential (unless it is certain that pregnancy is not possible) or breast feeding
* Modified Rankin Score (mRS) before stroke of ≥2
* Participation in any clinical trial in the last 3 months

Primary outcomes:
measure: Disability
timeFrame: 6 months
Secondary outcomes:
measure: Mortality
timeFrame: 24 months
Other outcomes:
measure: Functional outcomes
timeFrame: 6 months
measure: Infarct volume
timeFrame: 6 months
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 24 months
measure: Number of Participants with new-onset seizures as a Measure of Safety and Tolerability
timeFrame: 6 months
measure: Functional outcomes
timeFrame: 6 months
Locations:
city: Cadiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Seville
country: Spain
facility: Hospitales Universitarios Virgen del Rocio
city: Seville
country: Spain
facility: Hospitales Universitarios Virgen Macarena
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocio
name: Francisco Moniche, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mancha F, Escudero-Martinez I, Zapata-Arriaza E, Vega-Salvatierra A, Cabezas JA, Lebrato L, Pardo B, De-La-Torre J, Zapata M, Escamilla V, Calderon-Cabrera C, Martin-Sanchez J, Valverde R, Aguera-Morales E, Herrera I, Delgado F, Gamero MA, Perez-Sanchez S, Moya M, Espinosa R, Ortega-Quintanilla J, Gutierrez-Jarrin I, Gonzalez-Garcia A, Montaner J, Moniche F. Circulating microRNA after autologous bone marrow mononuclear cell (BM-MNC) injection in patients with ischemic stroke. J Investig Med. 2020 Mar;68(3):807-810. doi: 10.1136/jim-2019-001161. Epub 2019 Dec 17.
citation: Moniche F, Escudero I, Zapata-Arriaza E, Usero-Ruiz M, Prieto-Leon M, de la Torre J, Gamero MA, Tamayo JA, Ochoa-Sepulveda JJ, Maestre J, Carmona M, Pinero P, Calderon-Cabrera C, Jimenez MD, Gonzalez A, Montaner J. 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. Int J Stroke. 2015 Oct;10(7):1149-52. doi: 10.1111/ijs.12520. Epub 2015 Jun 4.