Stroke
Conditions
Keywords
Cell therapy, stem cell, transplantation, graft, recovery, repair, stroke, msesenchymal stem cell, regenerative
Brief summary
Stroke is the second leading cause of death in the world population. When not fatal, stroke often results in disability, and secondary health problems affecting not only patients but also their families. Building on emerging preclinical and pilot clinical evidences, RESSTORE will focus on the clinical assessment of regenerative cell therapy to improve stroke recovery and patients quality of life.
Interventions
DRUGAdipose derived Stem Cell
4 doses
OTHERplacebo
placebo
Sponsors
Horizon 2020 - European Commission
University Grenoble Alps
Servicio Madrileño de Salud, Madrid, Spain
St. Anne's University Hospital Brno, Czech Republic
Andaluz Health Service
University of Glasgow
University of Eastern Finland
Etablissement Français du Sang
Tampere University
Histocell SL, Spain
Oy Medfiles Ltd
Institut National de la Santé Et de la Recherche Médicale, France
Hospices Civils de Lyon
Association Groupe ESSEC
NOVADISCOVERY SAS, France
Finovatis
Centre Hospitalier Universitaire de Besancon
Assistance Publique - Hôpitaux de Paris
University Hospital, Toulouse
University Hospital, Bordeaux
University Hospital, Caen
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Servicio de Salud de Castilla La Mancha, Albacete, Spain
Servicio Gallego de Salud
Pirkanmaa Hospital District, Tampere, Finland
Hospital Vall d'Hebron
Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
CH Sainte-Anne, Paris, France
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
* Dose escalation from 1.10\^6 cells/kg to 3.10\^6 cells/kg (phase 1a, non randomized, open-label); * Effect-dose: 3.10\^6 cells/kg + placebo (phase 1b, randomized, double blind); Phase Ia: n = 15 patients; Phase Ib: n = 80 patients
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion criteria are similar in the phase 1a (RESSTORE 1a, Toxicity study) and in the phase 1b (RESSTORE 1b, Dose-effect study). * Male or female \> 18-year-old * Hemispheric ischemic stroke (\> 1.5 cm on 2 imaging slices) (i.e. non lacunar stroke) Admitted to the stroke unit within the first 24h after stroke onset * Patient must be included within 1st and 2nd day after stroke onset (signature of informed consent and randomization) (i.e. between 24 hours and 48 hours from stroke onset) and must be able to receive investigation treatment within the first week. * NIHSS \> or equal to 7 including motor score (upper, lower limbs and hand) \> or equal to 3 * No decompressive craniectomy procedure planned or performed * Patient able to follow a rehabilitation program * Modified Rankin scale = 0 before stroke onset * Obtained signed informed consent from patient or legally acceptable representative * Negative pregnancy test for women of child-bearing age. Non Inclusion Criteria: Non-inclusion criteria are similar in the phase 1a (RESSTORE 1a, Toxicity study) and the phase 1b (RESSTORE 1b, Dose-effect study). * Contraindication for MRI * Coma (score of 2 or more on item 1a of the NIHSS related to awareness) * Evidence on neuroimaging (CT or MRI) of a brain tumour, cerebral oedema with midline shift and a clinically significant compression of ventricles, cerebellar or brainstem infarction, or subarachnoid haemorrhage, or intracerebral parenchymal hematoma (petechial small haemorrhages are NOT a non-inclusion criteria) * Severe leucoariosis * Previous stroke * Active endocarditis, pneumonia, AIDS, active hepatic disease due to HBV or HCV (a controlled infection is NOT a non-inclusion criteria) * Active inflammatory and/or auto-immune diseases (such as Crohn disease, lupus, rheumatoid polyarthritis, renal or liver immune pathology) * History of cancer * Pre-existing dementia * A health status, any clinical condition (eg, short life expectancy, and coexisting disease) or other characteristic that precludes appropriate diagnosis, treatment, or follow-up in the trial * Surgical or endovascular procedure planned in the following 3 months * Pregnancy / Breast feeding (women of childbearing age should have a negative pregnancy test prior to inclusion) * Patients who are participating in another therapeutic trial or who have previously participated in a biotherapy trial * Non-membership to a social security scheme * Inability or unwillingness of the individual or their legal guardian/representa tive to provide written informed consent, according to national regulations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia (Toxicity study) | 7 days after stroke onset | cell-related serious adverse event |
| Phase Ib (Dose-effect study) | 6 months after stroke onset | modelling the dose-effect |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functionnal recovery | through study completion (2 years) | NIHSS Evolution (0-42) over 2 years |
| Post stroke handicap | through study completion (2 years) | Modified Rankin scale (0-6) over 2 years |
| Blood biomarkers for stroke recovery | at 6 months post-stroke | selection of candidate biomarkers for stroke recovery |
| fMRI recovery | at 6 months post-stroke | activation fMRI and resting state fMRI at 6 months after stroke |
| Motor recovery | over 6 months post-stroke | Fugl Meyer score (0-226) assessed by physiotherapist over 6 months post-stroke |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability | through study completion (2 years) | Adverse events report and mortality over 2 years |
Countries
France
Contacts
Primary ContactZaza Putkaradze, PharmD
Backup ContactJulien Colombat
Outcome results
None listed