Article Dans Une Revue BMJ Open Année : 2024

Effects of intravascular administration of mesenchymal stromal cells derived from Wharton’s Jelly of the umbilical cord on systemic immunomodulation and neuroinflammation after traumatic brain injury (TRAUMACELL): study protocol for a multicentre randomised controlled trial

1 Hôpital Beaujon [AP-HP]
2 NeuroDiderot (UMR_S_1141 / U1141) - Maladies neurodéveloppementales et neurovasculaires
3 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
4 Département d'épidémiologie, biostatistique et recherche clinique
5 CHU Pitié-Salpêtrière [AP-HP]
6 SHFJ - Service Hospitalier Frédéric Joliot
7 BIOMAPS - LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay
8 NEUROSPIN - Service NEUROSPIN
9 LIB - Laboratoire d'Imagerie Biomédicale [Paris]
10 CATI - Centre d'Acquisition et de Traitement des Images [Paris] = CATI Multicenter Neuroimaging Platform
11 Service de Médecine Nucléaire [Paris 18eme]
12 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
13 GRC 29 - ARPE - Groupe de Recherche Clinique en Anesthésie Réanimation médecine PEriopératoire
14 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
15 Team 6 - U1064 Inserm - CR2TI - Team 6 : Impact of acute inflammation on host pathogen interactions and lung homeostasis
16 Service d'anesthésie et réanimation chirurgicale [Nantes]
17 EVDG - École du Val de Grâce
18 ICM - Institut du Cerveau = Paris Brain Institute
19 CENIR - Plateforme de neuroimagerie CENIR = Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris]
20 AP-HP - Hopital Saint-Louis [AP-HP]
21 MEARY Cell and Gene Therapy Center | Centre MEARY de Thérapie Cellulaire et Génique
22 IAME (UMR_S_1137 / U1137) - Infection, Anti-microbiens, Modélisation, Evolution
23 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
24 HEGP - Hôpital Européen Georges Pompidou [APHP]
25 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Mathieu Boutonnet

Résumé

Introduction : Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Treatments for TBI patients are limited and none has been shown to provide prolonged and long-term neuroprotective or neurorestorative effects. A growing body of evidence suggests a link between TBI-induced neuro-inflammation and neurodegenerative post-traumatic disorders. Consequently, new therapies triggering immunomodulation and promoting neurological recovery are the subject of major research efforts. We hypothesise that repeated intravenous treatment with mesenchymal stromal cells derived from Wharton’s Jelly of the umbilical cord-derived mesenchymal stromal cells ((WJ-UC-MSC) may be associated with a significant decrease of post-TBI neuroinflammation and improvement of neurological status. Methods and analysis : The TRAUMACELL trial is a prospective, national multicentre, phase III, superiority, double-arm comparative randomised (1:1) double-blinded clinical trial. Among patients aged between 18–50, with a severe TBI defined by a Glasgow score less than 12 (within the first 48 hours) with brain traumatic lesion on CT Scan and needing intracranial pressure monitoring, with no other significant organ trauma (abbreviated injury scale<2) and unresponsive to verbal commands after 5 days of sedation discontinuation, 68 will be randomly allocated to receive either WJ-UC-MSC solution or placebo, with three intravenous injections 1 week apart. The primary outcome is the [ 18 F]-DPA-714 signal intensity in corpus callosum measured by dynamic positron emission tomography (PET)-MRI at 6 months after the last injection, blinded to the randomisation arm, to evaluate the post-traumatic neuro-inflammation. Ethics and dissemination : The TRAUMACELL trial has been approved by an independent ethics committee (CPP SUD EST II) and French Medicines Agency (2023-504415-33-00) for all study centres. Participant recruitment will be starting in September 2024. Results will be published in international peer-reviewed medical journals. Trial registration number : NCT06146062 , first posted 24 November 2023 Protocol version identifier TRAUMACELL−V.2.0_20240102

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inserm-04910359 , version 1 (24-01-2025)

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Stéphanie Sigaut, Coralie Tardivon, Alice Jacquens, Michel Bottlaender, Philippe Gervais, et al.. Effects of intravascular administration of mesenchymal stromal cells derived from Wharton’s Jelly of the umbilical cord on systemic immunomodulation and neuroinflammation after traumatic brain injury (TRAUMACELL): study protocol for a multicentre randomised controlled trial. BMJ Open, 2024, 14 (12), pp.e091441. ⟨10.1136/bmjopen-2024-091441⟩. ⟨inserm-04910359⟩
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