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Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1

Primary Purpose

Stroke

Status

Recruiting

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Adipose derived Stem Cell

placebo

About this trial

This is an interventional treatment trial for Stroke focused on measuring Cell therapy, stem cell, transplantation, graft, recovery, repair, stroke, msesenchymal stem cell, regenerative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHU Grenoble AplesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

Adipose derived Stem Cells - 1.10^6cells/kg

Adipose derived Stem Cells - 2.10^6cells/kg

Adipose derived Stem Cells - 2,5.10^6cells/kg

Adipose derived Stem Cells - 3.10^6cells/kg

placebo

Arm Description

ADSC, single, IV, 1.10^6cells/kg

ADSC, single, IV, 2.10^6cells/kg

ADSC, single, IV, 2,5.10^6cells/kg

ADSC, single, IV, 3.10^6cells/kg

Placebo

Outcomes

Primary Outcome Measures

Phase Ia (Toxicity study)

cell-related serious adverse event

Phase Ib (Dose-effect study)

modelling the dose-effect

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability

Adverse events report and mortality over 2 years

Functionnal recovery

NIHSS Evolution (0-42) over 2 years

Post stroke handicap

Modified Rankin scale (0-6) over 2 years

Motor recovery

Fugl Meyer score (0-226) assessed by physiotherapist over 6 months post-stroke

fMRI recovery

activation fMRI and resting state fMRI at 6 months after stroke

Blood biomarkers for stroke recovery

selection of candidate biomarkers for stroke recovery

Full Information

NCT ID

NCT03570450

First Posted

April 18, 2018

Last Updated

July 25, 2023

Sponsor

University Hospital, Grenoble

Collaborators

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, Medfiles CRO, Finland, 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, Servizo Galego de Saude, Santiago de Compostela, Spain, Pirkanmaa Hospital District, Tampere, Finland, Hospital Vall d'Hebron, Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta, CH Sainte-Anne, Paris, France

1. Study Identification

Unique Protocol Identification Number

NCT03570450

Brief Title

Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1

Official Title

Regenerative Stem Cell Therapy for Stroke in Europe 1

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 2, 2018 (Actual)

Primary Completion Date

July 1, 2025 (Anticipated)

Study Completion Date

July 1, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Grenoble

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke

Keywords

Cell therapy, stem cell, transplantation, graft, recovery, repair, stroke, msesenchymal stem cell, regenerative

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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

ParticipantInvestigator

Allocation

Randomized

Enrollment

95 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Adipose derived Stem Cells - 1.10^6cells/kg

Arm Type

Experimental

Arm Description

ADSC, single, IV, 1.10^6cells/kg

Arm Title

Adipose derived Stem Cells - 2.10^6cells/kg

Arm Type

Experimental

Arm Description

ADSC, single, IV, 2.10^6cells/kg

Arm Title

Adipose derived Stem Cells - 2,5.10^6cells/kg

Arm Type

Experimental

Arm Description

ADSC, single, IV, 2,5.10^6cells/kg

Arm Title

Adipose derived Stem Cells - 3.10^6cells/kg

Arm Type

Experimental

Arm Description

ADSC, single, IV, 3.10^6cells/kg

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Adipose derived Stem Cell

Other Intervention Name(s)

ADSC

Intervention Description

4 doses

Intervention Type

Other

Intervention Name(s)

placebo

Intervention Description

placebo

Primary Outcome Measure Information:

Title

Phase Ia (Toxicity study)

Description

cell-related serious adverse event

Time Frame

7 days after stroke onset

Title

Phase Ib (Dose-effect study)

Description

modelling the dose-effect

Time Frame

6 months after stroke onset

Secondary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability

Description

Adverse events report and mortality over 2 years

Time Frame

through study completion (2 years)

Title

Functionnal recovery

Description

NIHSS Evolution (0-42) over 2 years

Time Frame

through study completion (2 years)

Title

Post stroke handicap

Description

Modified Rankin scale (0-6) over 2 years

Time Frame

through study completion (2 years)

Title

Motor recovery

Description

Fugl Meyer score (0-226) assessed by physiotherapist over 6 months post-stroke

Time Frame

over 6 months post-stroke

Title

fMRI recovery

Description

activation fMRI and resting state fMRI at 6 months after stroke

Time Frame

at 6 months post-stroke

Title

Blood biomarkers for stroke recovery

Description

selection of candidate biomarkers for stroke recovery

Time Frame

at 6 months post-stroke

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zaza Putkaradze, PharmD

Phone

0476767842

Ext

+33

zputkaradze@chu-grenoble.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Julien Colombat

Phone

04 76 76 56 09

Ext

+33

ArcPromoteur@chu-grenoble.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Olivier Detante, MD PhD

Organizational Affiliation

University Hospital Grenoble-Alpes

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Grenoble Aples

City

Grenoble

ZIP/Postal Code

38043

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Olivier Detante, MD PhD

Phone

04 76 76 57 89

Ext

+33

odetante@chu-grenoble-alpes.fr

First Name & Middle Initial & Last Name & Degree

Zaza Putkaradze, PharmD

Phone

0476767842

Ext

+33

zputkaradze@chu-grenoble.fr

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Regenerative Stem Cell Therapy for Stroke in Europe 1-RESSTORE1

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