Clinical trial NCT03570450: Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1
Official title: Regenerative Stem Cell Therapy for Stroke in Europe 1
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Stroke
Keywords: Cell therapy
stem cell
transplantation
graft
recovery
repair
stroke
msesenchymal stem cell
regenerative
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Horizon 2020 - European Commission
name: University Grenoble Alps
name: Servicio Madrileño de Salud, Madrid, Spain
name: St. Anne's University Hospital Brno, Czech Republic
name: Andaluz Health Service
name: University of Glasgow
name: University of Eastern Finland
name: Etablissement Français du Sang
name: Tampere University
name: Histocell SL, Spain
name: Oy Medfiles Ltd
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Hospices Civils de Lyon
name: Association Groupe ESSEC
name: NOVADISCOVERY SAS, France
name: Finovatis
name: Centre Hospitalier Universitaire de Besancon
name: Assistance Publique - Hôpitaux de Paris
name: University Hospital, Toulouse
name: University Hospital, Bordeaux
name: University Hospital, Caen
name: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
name: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Servicio de Salud de Castilla La Mancha, Albacete, Spain
name: Servicio Gallego de Salud
name: Pirkanmaa Hospital District, Tampere, Finland
name: Hospital Vall d'Hebron
name: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta
name: CH Sainte-Anne, Paris, France
First posted: 2018-06-27
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase Ia (Toxicity study)
timeFrame: 7 days after stroke onset
measure: Phase Ib (Dose-effect study)
timeFrame: 6 months after stroke onset
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
timeFrame: through study completion (2 years)
measure: Functionnal recovery
timeFrame: through study completion (2 years)
measure: Post stroke handicap
timeFrame: through study completion (2 years)
measure: Motor recovery
timeFrame: over 6 months post-stroke
measure: fMRI recovery
timeFrame: at 6 months post-stroke
measure: Blood biomarkers for stroke recovery
timeFrame: at 6 months post-stroke
Other outcomes:
Locations:
city: Grenoble
country: France
facility: CHU Grenoble Aples
Study officials:
affiliation: University Hospital Grenoble-Alpes
name: Olivier Detante, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: