MesenchymAl stromal cells for Traumatic bRain Injury (MATRIx): a study protocol for a multicenter, double-blind, randomised, placebo-controlled phase II trial

Intensive Care Medicine Experimental

Methodologies

Elisa R. Zanier¹  Francesca Pischiutta¹  Paolo Gritti²  Eliana Rulli³  Giuseppe Gaipa⁴  Daniela Belotti⁴  Francesca Elli⁵  Nino Stocchetti⁶  Tommaso Zoerle⁶  Alessia Vargiolu⁷  Gianpaolo Basso⁸  Giuseppe Citerio⁹ 

[1] Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy;Department of Anesthesia, Emergency and Critical Care Medicine, ASST Ospedale Papa Giovanni XXIII, Bergamo, Italy;Department of Clinical Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy;M. Tettamanti Research Center, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy;Neurological Intensive Care Unit, Department of Neurosciences, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy;Neuroscience Intensive Care Unit, Department of Anaesthesia and Critical Care, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy;Department of Pathophysiology and Transplants, University of Milan, Milan, Italy;School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy;School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy;Department of Neurosciences, Neuroradiology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy;School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy;Neurological Intensive Care Unit, Department of Neurosciences, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy;

关键词: Traumatic brain injury;    Mesenchymal stromal cells;    Cell therapy;    Neurogenesis and synaptic plasticity;    Inflammation;   

DOI  :  10.1186/s40635-023-00535-1

 received in 2023-05-26, accepted in 2023-07-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTraumatic 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/designThe 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.DiscussionOverall, 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.

【 授权许可】

CC BY   
© The Author(s) 2023. corrected publication 2023

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