Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1

Study Overview
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Brief Summary
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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.

Official Title
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Regenerative Stem Cell Therapy for Stroke in Europe 1

Conditions
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Stroke

Intervention / Treatment
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* Drug: Adipose derived Stem Cell
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adipose derived Stem Cells - 1.10^6cells/kg<br>ADSC, single, IV, 1.10^6cells/kg | Drug: Adipose derived Stem Cell<br>* 4 doses<br>* Other names: ADSC;|
| Experimental: Adipose derived Stem Cells - 2.10^6cells/kg<br>ADSC, single, IV, 2.10^6cells/kg | Drug: Adipose derived Stem Cell<br>* 4 doses<br>* Other names: ADSC;|
| Experimental: Adipose derived Stem Cells - 2,5.10^6cells/kg<br>ADSC, single, IV, 2,5.10^6cells/kg | Drug: Adipose derived Stem Cell<br>* 4 doses<br>* Other names: ADSC;|
| Experimental: Adipose derived Stem Cells - 3.10^6cells/kg<br>ADSC, single, IV, 3.10^6cells/kg | Drug: Adipose derived Stem Cell<br>* 4 doses<br>* Other names: ADSC;|
| Placebo Comparator: placebo<br>Placebo | Other: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ia (Toxicity study) | cell-related serious adverse event | 7 days after stroke onset | 
| Phase Ib (Dose-effect study) | modelling the dose-effect | 6 months after stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability | Adverse events report and mortality over 2 years | through study completion (2 years) | 
| Functionnal recovery | NIHSS Evolution (0-42) over 2 years | through study completion (2 years) | 
| Post stroke handicap | Modified Rankin scale (0-6) over 2 years | through study completion (2 years) | 
| Motor recovery | Fugl Meyer score (0-226) assessed by physiotherapist over 6 months post-stroke | over 6 months post-stroke | 
| fMRI recovery | activation fMRI and resting state fMRI at 6 months after stroke | at 6 months post-stroke | 
| Blood biomarkers for stroke recovery | selection of candidate biomarkers for stroke recovery | at 6 months post-stroke | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell therapy, stem cell, transplantation, graft, recovery, repair, stroke, msesenchymal stem cell, regenerative