Treatment of Adult Severe Traumatic Brain Injury Using Autologous Bone Marrow Mononuclear Cells.

摘要

Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for adults following severe TBI (Glasgow Coma Scale < 9) is estimated to be 33%. There is currently no therapy to reverse the primary injury associated with TBI. There has been a growing body of literature supporting the use of various progenitor cell types to treat acute neurological injuries such as TBI. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC infusion, (1) BMMNC infusion will reduce BBB permeability, and (2) BMMNC is neuroprotective and preserves grey and white matter volumes after TBI. This is a dose-escalation study consisting of 4 cohorts including a control group (5 subjects/cohort). Subjects in the control group will not undergo the bone marrow harvest procedure and will receive only the standard of care for TBI patients. All subjects (including those in the control group), will be followed for safety, have plasma & CSF (if available) collected for neuroinflammatory markers. The 1 & 6 month follow-up visits include physical and neurological exams, neuropsych, & functional outcome tests, blood sample for routine labs and neuroinflammatory markers, & a DTMRI. As of 31 May 2014, 20 subjects have been enrolled (5 control, 15 treatment). All subjects had in-patient plasma & CSF (when available) collected for neuroinflammatory markers. Seventeen subjects have completed the study including one control group subject who was lost to follow-up after discharge. The three remaining subjects have completed the 1-month visit and have 6-month end of study visits scheduled. Per protocol, the medical monitor has reviewed all subject records and no serious adverse events related to the BMMNC infusion have been reported. The DSMB met on 10 January 2014 and reviewed safety data on the 17 subjects enrolled in the study at the time. No subject safety issues were identified and the DSMB recommended the study continue as in with no protocol modifications. Our most clinical monitor visit was 11 March 2014.