Safety of Autologous Stem Cell Treatment for Traumatic Brain Injury in Children
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine if bone marrow progenitor cell (BMPC) autologous
      transplantation in children after isolated traumatic brain injury is safe and will improve
      functional outcome.
    

Detailed description: 
      Traumatic brain injury (TBI) contributes to 50% of all trauma deaths. The mortality rate for
      children following severe TBI (Glasgow Coma Scale < 9) ranges from 14-24%. There is currently
      no therapy to reverse the primary injury associated with TBI. Bone marrow precursor cells
      (BMPC) or bone marrow mononuclear cellular fractions of bone marrow contain mesenchymal stem
      cells (MSC) and hematopoetic stem cells (HSC). These cells are a component of bone marrow
      that preferentially migrate to the site of brain injury and differentiate into neurons and
      cell supporting elements, improving functional outcome in animals. The primary objective of
      this study is to determine if BMPC harvest and autologous transplantation is safe in children
      after TBI. The secondary objective is to determine if late functional outcome is improved
      with BMPC autologous transplantation compared to age and severity matched concomitant
      controls. Safety will be determined by monitoring cerebral and systemic hemodynamics during
      harvest and transplantation, neurologic events (seizure, change in GCS, stroke), local site
      inflammation/injury, and secondary organ injury. Late outcomes will be determined using
      age-corrected Glasgow Outcome Scores, and a battery of functional outcome measures. In vitro,
      an aliquot of cells harvested from patients will be studied for labeling with
      magnetodendrimers as a feasibility study, and these cells will not be reinfused into the
      patients. The primary endpoint is to assess the safety of autologous BMPC
      harvest/transplantation in the acute injury phase (hospital stay) and the secondary endpoint
      is to assess efficacy through 1 and 6 month post-injury follow-up. The rationale for the use
      of autologous BMPC transplantation is based on a large volume of in vitro and in vivo animal
      data (see background and significance section). The rationale for using children as the
      primary population is that children have a greater neurologic plasticity with a unique injury
      pattern when compared to adults. Children are more likely to have isolated TBI that is more
      diffuse and less likely to be secondary to extra-axial fluid collections. Patients aged 5-14
      years old with GCS of 5-8 will be considered for enrollment into the study. Within 24-36
      hours of injury, enrolled patients will undergo bone marrow harvest/BMPC separation and
      re-infusion. Daily monitoring of the safety outcomes measures and long term neurologic
      outcomes will be performed. This study should determine if bone marrow harvest, BMPC
      separation, and reinfusion is safe in children after severe TBI.
    

Intervention name(s): Autologous bone marrow precursor cell harvest and transplant
Intervention type(s): Drug
Intervention description(s): Bone marrow harvest (3 ml/kg of body weight) performed between 12 and 30 hours post injury, followed by single intravenous infusion of bone marrow progenitor cells - target dose is 6x10^6 mononuclear cells/kg body weight, administered within 36 hours of injury
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Traumatic Brain Injury; Stem Cell