Safety of Darbepoetin Alfa Treatment in Patients With Severe Traumatic Brain Injury
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to see if the treatment of severely brain injured patients with
      darbepoetin (a long acting form of erythropoietin) will be safe, and will reduce brain damage
      by decreasing harmful levels of chemicals in the brain.
    

Detailed description: 
      Traumatic brain injury (TBI) is a common neurosurgical problem with a high morbidity and
      mortality. Studies interested in defining possible therapeutic targets in TBI have led to an
      appreciation of two phases of injury. These phases are referred to as primary and secondary
      TBI. The primary injury encompasses the immediate insult, diffuse axonal injury, hemorrhage,
      contusion, and primary ischemia. The secondary injury evolves over the post-traumatic period
      and is due to a combination of vasogenic and cytotoxic edema resulting from several processes
      including; glutamate excitotoxicity, disturbance of ionic homeostasis, lipid peroxidation,
      generation of nitric oxide (NO) and free radicals, and release of inflammatory regulators
      such as bradykinin and eicosanoids. It has long been recognized that one of the most
      important factors in the secondary injury process is the indiscriminate release of the
      excitatory neurotransmitter glutamate from neurons and glia. Glutamate excitotoxicity leads
      to substantial intraneuronal release of calcium which in turn mediates the activation of
      phospholipases which generate arachadonic acid, the activation of proteases, and the
      activation of NO, all of which cause neuronal membrane disruption and loss of ionic
      equilibrium. Receptors for erythropoietin (EPOr) are distributed throughout the brain and
      studies have demonstrated that these receptors are not only important in the process of
      development but also in neuroprotection. Treatment with erythropoietin (EPO) protects neurons
      in models of ischemic and traumatic degenerative damage due to exocitotoxins and consequent
      generation of free radicals including NO. EPOr activation also prevents the indiscriminate
      exocytosis of glutamate in a model of chemically induced ischemia on neurons of rat
      hippocampus.

      The hypothesis of this study is that treatment of severely brain injured patients with
      darbepoetin alfa (Aranesp®) will be safe and reduce the cerebrospinal fluid (CSF) levels of
      glutamate within a 96 hour period after traumatic brain injury. This effect is potentially
      mediated through the activation of EPO receptors whose activation prevents the exocytosis of
      glutamate, a known neurocytotoxin, into CSF.
    

Intervention name(s): Darbeopoetin; Normal Saline (Placebo)
Intervention type(s): Drug; Drug
Intervention description(s): The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®). Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio. The treatment group will be given 200 mcg of darbepoetin intravenously. The control group will be given a matching placebo of 1 mL of normal saline.; The treatment group, comprised of ten patients, will receive an intravenous dose of 200 mcg (1 ml) of darbepoetin (Aranesp®). Patients will be randomly assigned to either the treatment group, or the control group in a 2:1 ratio. The treatment group will be given 200 mcg of darbepoetin intravenously. The control group will be given a matching placebo of 1 mL of normal saline.
Other intervention name(s): ARANESP; Placebo
Intervention MeSH terms: Darbepoetin alfa
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neuroprotection; neuron specific enolase; CSF glutamate levels; Darbepoetin Alfa