Clinical trial NCT00875654: Intravenous Stem Cells After Ischemic Stroke
Official title: Cell Therapy by Intravenous Injection of Mesenchymal Stem Cells After Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemia
Stroke
Keywords: Cell therapy
Stroke
Neuronal Plasticity
Recovery
Mesenchymal Stem Cells
Transplantation
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Commissariat A L'energie Atomique
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2009-04-03
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of the study is to evaluate feasibility and tolerance of the intravenous injection of autologous mesenchymal stem cells for patients presenting an ischemic stroke (less than 6 weeks).

Detailed description: Stroke is the leading cause of acquired adult disability. Except the hospitalization in stroke units, only thrombolysis has been shown to be efficient to treat acute ischemic stroke in the first three hours after the onset. Increasing brain plasticity after stroke represents an important alternative strategy. Cell therapy provides a functional improvement after cerebral ischemia in rodent models. This "restorative" therapy aims to replace destroyed cerebral tissue with a stem cells graft. Despite these encouraging experiments, we do not know yet the best way of administration of the stem cells, the best dose and the optimal delay of the graft. The pioneer clinical studies failed to reproduce this benefit for patients probably because of the limited number of studied patients. Therefore, more translational studies are needed to improve our knowledge in this promising field. Among different cell sources, mesenchymal (or stromal) stem cells (MSC) derived from bone marrow offer the advantage of arising from a non tumoral and no modified source and are not sources of immunological or ethical problems.

Our research project involves a development of cell therapy in a phase IIa clinical trial of feasibility and safety in patients (randomised, controlled, open, with 3 parallel groups).

Eligibility criteria: Inclusion Criteria:

* right or left carotid ischemic stroke in the 14 previous days, confirmed by MRI.
* Persistent neurological deficit (NIHSS \>=7).
* Optimal medical treatment(antithrombotics, antihypertensive, statins).
* General state compatible with a program of functional rehabilitation.

Exclusion Criteria:

* Severe extensive stroke implying vital prognosis.
* Severe persistent neurological deficit (NIHSS \> 24).
* Medical history of neurological pathology with a deficit as consequence (Rankin \< 3 before stroke).
* Serious psychiatric disease.
* Myocardial infarction less than 3 month old.
* Recurring thromboembolic disease or less than 6 month old.
* Patient with organ transplantation.
* Medical history of infection (HIV,HTLV, HBV, HCV).
* Current immunosuppressive/immunomodulating treatment.
* Medical history of cancer.
* Medical history of chemotherapy.
* Known chronic kidney failure(clearance of creatinin \< 90 ml/min/1,73m2).
* Known hepatic failure(diminution of prothrombin level (TP) not corrigiable with vitamin K).
* Obesity hinding the bone-marrow sampling in the iliac crest.
* Pathology implying vital prognosis in the 3 month following stroke.
* Refusal to participate.
* Patient unable to give personally his/her consent.
* Pregnant, parturient and feeding women.
* Woman in age to procreate who could not receive an effective method of contraception during the study.
* Participation to another therapeutic clinical trial or in period of exclusion of a therapeutic clinical study.
* Privation of liberty with a decision of justice or administration, legal protection.
* Non affiliation to social security.

Primary outcomes:
measure: feasibility and tolerance of the intravenous injection of autologous mesenchymal stem cells in patients with carotid ischemic stroke
timeFrame: 2 weeks, 1, 2, 4, 6 months and 1, 2 years
Secondary outcomes:
measure: Clinical and functional effects of the intravenous injection of autologous mesenchymal stem cells in patients with carotid ischemic stroke
timeFrame: 2 weeks, 1, 2, 4, 6 months and 1, 2 years
measure: Determination of the most effective dose of stem cells
timeFrame: 2 weeks, 1, 2, 4, 6 months and 1, 2 years
measure: To define the best criteria for a future trial (phase III)
timeFrame: 2 weeks, 1, 2, 4, 6 months and 1, 2 years
measure: To define the best target population for a future study
timeFrame: 2 weeks, 1, 2, 4, 6 months and 1, 2 years
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Neuroradiology/MRI, University Hospital of Grenoble
city: Grenoble
country: France
facility: Stroke Unit, University Hospital of Grenoble
city: Grenoble
country: France
facility: Tissular and cell therapy unit, UniversityHospitalof Grenoble
Study officials:
affiliation: University Hospital, Grenoble
name: Olivier Detante, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jaillard A, Hommel M, Moisan A, Zeffiro TA, Favre-Wiki IM, Barbieux-Guillot M, Vadot W, Marcel S, Lamalle L, Grand S, Detante O; (for the ISIS-HERMES Study Group). Autologous Mesenchymal Stem Cells Improve Motor Recovery in Subacute Ischemic Stroke: a Randomized Clinical Trial. Transl Stroke Res. 2020 Oct;11(5):910-923. doi: 10.1007/s12975-020-00787-z. Epub 2020 May 27.
citation: Hannanu FF, Goundous I, Detante O, Naegele B, Jaillard A. Spatiotemporal patterns of sensorimotor fMRI activity influence hand motor recovery in subacute stroke: A longitudinal task-related fMRI study. Cortex. 2020 Aug;129:80-98. doi: 10.1016/j.cortex.2020.03.024. Epub 2020 Apr 17.