Mesenchymal Stromal Cells for Traumatic Brain Injury
Status:
Recruiting
Trial end date:
2026-12-01
Target enrollment:
Participant gender:
Summary
Traumatic Brain Injury (TBI) is an alteration of brain function caused by an external force.
Long-term mortality in TBI is substantial, TBI survivors can develop chronic progressive
disabilities and have a life expectancy shortened by 6 years. Treatment consists in
supportive therapy directed at prevention of second insults, but no neuroprotective therapy
is available. Given the multifaceted nature of TBI, mesenchymal stromal cells (MSCs) are an
ideal candidate: they release multiple soluble factors shown to ameliorate the injury
microenvironment through immunomodulatory, protective, reparative and regenerative processes.
Preclinical data across a range of different TBI models and injury severities show that human
MSCs improve outcome through pleiotropic mechanisms of protection and repair. Thus, data
indicate MSCs as strong therapeutic candidate and support a clinical study in TBI.
Aim: the study is designed to assess the safety and the efficacy of the MSCs, intravenously
administered in severe TBI patients within 48h from injury. The study will be conducted in a
stepwise manner. Step 1 will enroll 36 patients (randomized 1:1:1 in arms 80 x 10^6 MSCs vs
160 x 10^6 MSCs vs placebo) to define safety, and will allow to select the most promising
dose. Step 2 will enroll 30 patients (1:1 in arms MSCs selected dose vs placebo) to define
the MSC activity based on the quantification of the plasmatic levels of the neurofilament
light (NFL) at 14 days, as biomarker of neuronal damage.
Secondary objectives are aimed to assess:
1. brain injury evolution and white matter damage by longitudinal neuroimaging (at 4 days
and 14 days post-TBI and at 6 months)
2. brain immunomodulatory changes by temporal profiling of circulating biomarkers of brain
damage and neuroinflammation (daily for 3 days after TBI, at day 7 and 14, and at 1, 6
and 12 months)
3. clinical outcome by a structured clinical and neuropsychological assessment at both 6
and 12 months
Methods: a multicenter, double blind, randomized, placebo-controlled, adaptive phase II dose
finding study.
Duration of the study: 36 months (24 of enrolment and 12 of follow up).
Funding: Fondazione Regionale per la ricerca Biomedica, FRRB (Call "Unmet medical needs",
proposal number 3440227) and Italian Ministry of health (Ministero della Salute, Bando di
Ricerca Finalizzata 2021; proposal number RF-2021-12372642).
Phase:
Phase 2
Details
Lead Sponsor:
Fondazione IRCCS San Gerardo dei Tintori
Collaborators:
A.O. Ospedale Papa Giovanni XXIII Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Istituto di Ricerche Farmacologiche Mario Negri IRCCS