MesenchymAl stromal cells for Traumatic bRain Injury (MATRIx): a study protocol for a multicenter, double-blind, randomised, placebo-controlled phase II trial.
Cell therapy
Inflammation
Mesenchymal stromal cells
Neurogenesis and synaptic plasticity
Traumatic brain injury
Journal
Intensive care medicine experimental
ISSN: 2197-425X
Titre abrégé: Intensive Care Med Exp
Pays: Germany
ID NLM: 101645149
Informations de publication
Date de publication:
25 Aug 2023
25 Aug 2023
Historique:
received:
26
05
2023
accepted:
07
07
2023
medline:
25
8
2023
pubmed:
25
8
2023
entrez:
24
8
2023
Statut:
epublish
Résumé
Traumatic brain injury (TBI) is a significant cause of death and disability, with no effective neuroprotective drugs currently available for its treatment. Mesenchymal stromal cell (MSC)-based therapy shows promise as MSCs release various soluble factors that can enhance the injury microenvironment through processes, such as immunomodulation, neuroprotection, and brain repair. Preclinical studies across different TBI models and severities have demonstrated that MSCs can improve functional and structural outcomes. Moreover, clinical evidence supports the safety of third-party donor bank-stored MSCs in adult subjects. Building on this preclinical and clinical data, we present the protocol for an academic, investigator-initiated, multicenter, double-blind, randomised, placebo-controlled, adaptive phase II dose-finding study aiming to evaluate the safety and efficacy of intravenous administration of allogeneic bone marrow-derived MSCs to severe TBI patients within 48 h of injury. The study will be conducted in two steps. Step 1 will enrol 42 patients, randomised in a 1:1:1 ratio to receive 80 million MSCs, 160 million MSCs or a placebo to establish safety and identify the most promising dose. Step 2 will enrol an additional 36 patients, randomised in a 1:1 ratio to receive the selected dose of MSCs or placebo. The activity of MSCs will be assessed by quantifying the plasmatic levels of neurofilament light (NfL) at 14 days as a biomarker of neuronal damage. It could be a significant breakthrough if the study demonstrates the safety and efficacy of MSC-based therapy for severe TBI patients. The results of this trial could inform the design of a phase III clinical trial aimed at establishing the efficacy of the first neurorestorative therapy for TBI. Overall, the MATRIx trial is a critical step towards developing an effective treatment for TBI, which could significantly improve the lives of millions worldwide affected by this debilitating condition. Trial Registration EudraCT: 2022-000680-49.
Sections du résumé
BACKGROUND
BACKGROUND
Traumatic brain injury (TBI) is a significant cause of death and disability, with no effective neuroprotective drugs currently available for its treatment. Mesenchymal stromal cell (MSC)-based therapy shows promise as MSCs release various soluble factors that can enhance the injury microenvironment through processes, such as immunomodulation, neuroprotection, and brain repair. Preclinical studies across different TBI models and severities have demonstrated that MSCs can improve functional and structural outcomes. Moreover, clinical evidence supports the safety of third-party donor bank-stored MSCs in adult subjects. Building on this preclinical and clinical data, we present the protocol for an academic, investigator-initiated, multicenter, double-blind, randomised, placebo-controlled, adaptive phase II dose-finding study aiming to evaluate the safety and efficacy of intravenous administration of allogeneic bone marrow-derived MSCs to severe TBI patients within 48 h of injury.
METHODS/DESIGN
METHODS
The study will be conducted in two steps. Step 1 will enrol 42 patients, randomised in a 1:1:1 ratio to receive 80 million MSCs, 160 million MSCs or a placebo to establish safety and identify the most promising dose. Step 2 will enrol an additional 36 patients, randomised in a 1:1 ratio to receive the selected dose of MSCs or placebo. The activity of MSCs will be assessed by quantifying the plasmatic levels of neurofilament light (NfL) at 14 days as a biomarker of neuronal damage. It could be a significant breakthrough if the study demonstrates the safety and efficacy of MSC-based therapy for severe TBI patients. The results of this trial could inform the design of a phase III clinical trial aimed at establishing the efficacy of the first neurorestorative therapy for TBI.
DISCUSSION
CONCLUSIONS
Overall, the MATRIx trial is a critical step towards developing an effective treatment for TBI, which could significantly improve the lives of millions worldwide affected by this debilitating condition. Trial Registration EudraCT: 2022-000680-49.
Identifiants
pubmed: 37620640
doi: 10.1186/s40635-023-00535-1
pii: 10.1186/s40635-023-00535-1
pmc: PMC10449745
doi:
Types de publication
Journal Article
Langues
eng
Pagination
56Subventions
Organisme : FRRB
ID : "Unmet medical needs"
Organisme : FRRB
ID : proposal number 3440227
Organisme : Italian Ministry of Health
ID : Bando di Ricerca Finalizzata 2021
Organisme : Italian Ministry of Health
ID : proposal number RF-2021-12372642
Informations de copyright
© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.
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