Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1 (RESSTORE 1)

Regenerative Stem Cell Therapy for Stroke in Europe 1

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Other: placebo; Drug: Adipose derived Stem Cell

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zaza Putkaradze, PharmD; Phone Number: +33 0476767842; Email: zputkaradze@chu-grenoble.fr
• Study Contact Backup: Name: Julien Colombat; Phone Number: +33 04 76 76 56 09; Email: ArcPromoteur@chu-grenoble.fr

Study Locations

• France
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble Aples
    • Contact: Olivier Detante, MD PhD; Phone Number: +33 04 76 76 57 89; Email: odetante@chu-grenoble-alpes.fr
    • Contact: Zaza Putkaradze, PharmD; Phone Number: +33 0476767842; Email: zputkaradze@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: Assistance Publique - Hôpitaux de Paris; Hospices Civils de Lyon; Institut National de la Santé Et de la Recherche Médicale, France; University Hospital, Bordeaux; Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta; University Hospital, Caen; Centre Hospitalier Universitaire de Besancon; University Hospital, Toulouse; Etablissement Français du Sang; Tampere University; Andaluz Health Service; University of Eastern Finland; 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; University of Glasgow; St. Anne's University Hospital Brno, Czech Republic; University Grenoble Alps; Hospital Vall d'Hebron; Servicio Madrileño de Salud, Madrid, Spain; Horizon 2020 - European Commission; Histocell SL, Spain; Medfiles CRO, Finland; Association Groupe ESSEC; NOVADISCOVERY SAS, France; Finovatis; Servicio de Salud de Castilla La Mancha, Albacete, Spain; Servizo Galego de Saude, Santiago de Compostela, Spain; Pirkanmaa Hospital District, Tampere, Finland; CH Sainte-Anne, Paris, France
• Investigators: Principal Investigator: Olivier Detante, MD PhD, University Hospital Grenoble-Alpes

Publications and helpful links

Helpful Links

• website

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2018
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: June 15, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 25, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: stroke; recovery; stem cell; transplantation; Cell therapy; graft; repair; msesenchymal stem cell; regenerative
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 38RC17.312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No