Intra-arterial Bone-marrow Mononuclear Cells Infusion for Acute Ischemic Stroke

Sponsor

Andalusian Initiative for Advanced Therapies (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02178657

Collaborator

(none)

Enrollment

Locations

Arms

96.4

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Autologous bone marrow mononuclear cell intra-arterial injection	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

76 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Oct 27, 2021

Anticipated Study Completion Date :

Apr 12, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bone marrow transplantation low dose Intra-arterial autologous bone marrow mononuclear cells injection (dose 2x10^6 per kilogram)	Drug: Autologous bone marrow mononuclear cell intra-arterial injection
Experimental: Bone marrow transplantation high dose Intra-arterial autologous bone marrow mononuclear cells injection (dose 5x10^6 per kilogram)	Drug: Autologous bone marrow mononuclear cell intra-arterial injection
No Intervention: Control

Arm

Intervention/Treatment

Experimental: Bone marrow transplantation low dose

Intra-arterial autologous bone marrow mononuclear cells injection (dose 2x10^6 per kilogram)

Drug: Autologous bone marrow mononuclear cell intra-arterial injection

Experimental: Bone marrow transplantation high dose

Intra-arterial autologous bone marrow mononuclear cells injection (dose 5x10^6 per kilogram)

Drug: Autologous bone marrow mononuclear cell intra-arterial injection

No Intervention: Control

Outcome Measures

Primary Outcome Measures

Disability [6 months]
Proportion of patients with modified Rankin Scale scores of 0-2 at 6 months

Secondary Outcome Measures

Mortality [24 months]

Other Outcome Measures

Functional outcomes [6 months]
Functional outcome measure by National Institute of Health Stroke Scale and Barthel at 6 months
Infarct volume [6 months]
Infarct volume change between baseline (DWI) and 6 months (FLAIR)
Number of Participants with Adverse Events as a Measure of Safety and Tolerability [24 months]
Number of Participants with new-onset seizures as a Measure of Safety and Tolerability [6 months]
Functional outcomes [6 months]
Categorical shift in mRS ordinal (0-6) scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Universitario Puerta del Mar	Cadiz	Spain	11009
2	Hospital Universitario Reina Sofía	Córdoba	Spain	14004
3	Hospitales Universitarios Virgen del Rocio	Seville	Spain	41013
4	Hospitales Universitarios Virgen Macarena	Seville	Spain	41071