Severe traumatic brain injury MedDRA version: 20.0 Level: LLT Classification code 10032349 Term: Other open skull fracture with intracranial injury System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10032350 Term: Other open skull fracture with intracranial injury of other and unspecified nature System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10009630 Term: Closed fracture of vault of skull with intercranial injury of othe
Conditions
Interventions
Product Name: BONE MARROW DERIVED MESENCHYMAL STROMAL CELLS
Product Code: [BM-MSC]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Mesenchymal stromal cells (MSC)
Current Sponsor code:
Sponsors
AZIENDA SOCIO SANITARIA TERRITORIALE MONZA (ASST-MONZA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age: 18-70 years - Clinical frailty index (CFI) 1) - Feasibility of study drug (MSC/placebo) administration within 48 hours from TBI - GCS 40 kg Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: - Motor GCS > 5 at recruitment - High likelihood (>85%) of death in the first 48 h calculated by IMPACT calculator on early admission data - Bilateral mydriasis - Opening ICP > 40 mmHg - Known history of prior brain injury, psychiatric disorder, neurological impairment and/or deficit - Brain penetrating injury - Spinal cord injury - Previous epilepsy requiring anti-convulsant therapy - Severe organ failure (including PaO2/FiO2<200 and shock) - Recent serious infectious process - Cancer - Immunosuppression - Human immunodeficiency virus (HIV) - Positive urine pregnancy test or nursing - Participation in a concurrent interventional study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy and safety of the allogeneic bone marrow derived mesenchymal stromal cells (BM-MSCs) intravenously administered in traumatic brain injured (TBI) patients within 48 h from injury. The study is meant: i)to define if BM-MSCs, administered at dosage of 80 or 160 x 10^6 cells are safe in patients with severe TBI; ii)to define if BM-MSCs, administered at the dosage found to be safe and more promising in terms of activity as revealed by the interim analysis, decrease the plasmatic NFL biomarker of brain damage at 14 days.;Secondary Objective: To assess: i)brain injury evolution and white matter damage by longitudinal neuroimaging (at 4 days, 14 days and 6 months) ii)brain immunomodulatory changes by temporal profiling of circulating biomarkers of brain damage and neuroinflammation iii)clinical outcome by a structured clinical and neuropsychological assessments at both 6 and 12 months;Primary end point(s): 1.Safety: The number of patients experiencing at least one serious adverse drug reaction (SADR) 2.Biological activity: a)The number of responder patients, defined as patients who reaches a percentage NFL increase at 14 days equal or lower than 20% compared to baseline b)The quantitative blood NFL at Day 14 as measured by SIMOA;Timepoint(s) of evaluation of this end point: 14 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of biological activity of intravenous infusions of allogeneic BM-MSCs in terms of modification of the following clinical variable: 1. brain injury evolution and white matter damage by longitudinal advanced MRI (with morphological sequences as T1, T2 as well as FLAIR, SWI, DWI and DTI for quantification of traumatic axonal injury) acutely (4 days) subacutely (14 days) and at 6 months post-TBI to provide a detailed description in atrophy, diffusion and myelin integrity; Assessment of biological activity of intravenous infusions of allogeneic BM-MSCs in terms of modification of the following biological parameters: 1. brain immunomodulatory changes by temporal profiling (daily for 3 days after TBI, at day 7 and 14 and at 1, 6 and 12 months) of circulating biomarkers of: a. structural damage: NFL, GFAP b. neuroinflammation: IL-6, IL-10, TNFalpha c. vascular integrity: MMP9; Assessment of biological activity of intravenous infusions of allogeneic BM-MSCs in terms of modification of the following clinical variable: 3. Clinical outcome by a structured clinical and neuropsychological outcome assessment at both 6 and 12 months, by: a. extended Glasgow Outcome Scale (eGOS) b. quality of life after brain injury test (QOLIBRI, www.qolibrinet.com);Timepoint(s) of evaluation of this end point: At 4 days, 14 days and 6 months after TBI; At baseline, day 3, 7 and 14 and at 1, 6 and 12 months after TBI; At 6 and 12 months after TBI | — |
Countries
Italy
Contacts
Public ContactPrincipal Investigator
Azienda Socio Sanitaria Territoriale di Monza (ASST-MONZA)
Outcome results
None listed