Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to determine if bone marrow harvest, BMMNC separation, and
      re-infusion in adults with acute severe TBI is safe and will improve functional outcome.

      12/09/2015 Update: The study is closed to new enrollment and all follow-up visits have been
      completed. Data analysis is underway.
    

Detailed description: 
      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. Over the past 10
      years there has been a growing body of literature supporting the use of various progenitor
      cell types to treat acute neurological injuries such as TBI and stroke. Neural stem cells
      (adult and embryonic), mesenchymal stromal and multipotent adult progenitor cells, and bone
      marrow mononuclear cells (from which MSC and MAPCs are derived) have all shown efficacy in
      pre-clinical models of TBI/stroke through various mechanisms; however, few groups believe
      that true neural replacement and integration are the putative mechanisms involved in the
      observed efficacy. More likely is that the progenitor cell populations are modifying the
      regional response to injury (inflammatory/reparative vs. regenerative), resulting in improved
      functional outcomes. Our primary hypothesis is that bone marrow mononuclear cell (BMMNC)
      autologous transplantation after TBI is safe (harvest and infusion related toxicity) after
      TBI. Our secondary hypothesis is that functional outcomes measures will improve after BMMNC
      infusion, (3) BMMNC infusion will reduce BBB permeability, (4) BMMNC is neuroprotective and
      preserves grey matter and white matter volumes after TBI.

      Patients, ages18 to 55 years old, admitted to Memorial Hermann Hospital Trauma Center with
      Glasgow Coma Scores (GCS) of 5 to 8 will be screened. Those patients meeting
      inclusion/exclusion criteria (or their Legal Authorized Representative [LAR]) will be offered
      consent to participate. This is a dose-escalation study consisting of 4 cohorts including a
      control group (5 subjects/cohort). The first five subjects will not undergo the bone marrow
      harvest procedure; though they will be followed and treated the same as the other study
      participants and complete all follow-up procedures. Subjects 6-10 will receive the lowest
      dose target of 6X106 mononuclear cells/kilogram body weight. Subjects 11-15 will receive
      9x106 mononuclear cells/kilogram body weight, and lastly Subjects 16-20 will receive 12X106
      mononuclear cells/kilogram body weight. The study is NOT powered to detect functional
      measures of efficacy. However, estimates can be made regarding potential treatment effect
      sizes to allow rational power analyses for the follow-on Phase II study. This study should
      determine if bone marrow harvest, BMMNC separation, and reinfusion is safe in adults with
      acute, severe TBI.
    

Intervention name(s): autologous bone marrow mononuclear cells
Intervention type(s): Biological
Intervention description(s): bone marrow harvest (5ml/kg of body weight) performed within 36 hours of injury, followed by single intravenous infusion of bone marrow mononuclear cells.
Other intervention name(s): BMMNCs
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Traumatic Brain Injury; TBI; stem cells