Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI)
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is:

        1. To assess the safety and feasibility of minocycline administration after TBI in a dose
           escalation study at two different doses over 7 days.

        2. To assess the pharmacokinetic characteristics of two different dosing regimens of
           minocycline in TBI patients, the effect on biochemical markers of neuroprotective
           mechanisms, and effect on neurobehavioral and functional outcome.

        3. To begin initial assessment of the efficacy of minocycline as a therapeutic agent for
           severe human TBI.
    

Detailed description: 
      The purpose of this preliminary study is to test the hypothesis that administration of
      minocycline to humans with moderate and severe TBI is both safe and feasible in the acute
      post-injury setting, and to characterize its disposition and effects on biomarkers of
      traumatic CNS injury in a Phase IIa trial. The data collected will serve as the basis for a
      larger Phase IIb clinical trial in a randomized placebo-controlled parallel group design, to
      investigate further its potential safety and efficacy as a therapeutic agent for severe human
      TBI.

      Tetracycline derivatives, including doxycycline and minocycline, have been shown to be
      neuroprotective when given after traumatic brain injury (TBI) and ischemia in rodents. In
      particular, reduced lesion volume and improved neurological outcome have been demonstrated
      following minocycline treatment of TBI. The proposed mechanism for these observations is
      multifactorial, and includes inhibition of microglial activation, caspase-mediated apoptosis,
      and the excitotoxic N-methyl-D-aspartic acid (NMDA) pathway. Because comparable inflammatory,
      excitotoxic and apoptotic pathways have also been implicated in human TBI, we hypothesize
      that administration of minocycline will confer neuroprotection after moderate to severe TBI
      in that milieu as well, with the potential for significant clinical benefit. Minocycline is
      highly lipophilic, and thus penetrates the human central nervous system (CNS). In addition,
      it has been shown to be safe when used in non-traumatic human neurological disorders.
    

Intervention name(s): Minocycline
Intervention type(s): Drug
Intervention description(s): Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.
Other intervention name(s): Minocin
Intervention MeSH terms: Minocycline
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Traumatic Brain Injury; Minocycline; Outcome