Observational Endothelin and Markers of Cellular Apoptosis In CSF Head Injury
Condition: Cerebrovascular Trauma; Neurohormones; Cellular Apoptosis; Endothelin System
MeSH terms: Craniocerebral Trauma; Cerebrovascular Trauma
Study type: Observational

Summary: 
      The goal of this study is to answer the following questions:

        -  What is the time course of the expected changes in endothelin levels during the first
           two weeks after injury and how does this relate to outcome?

        -  What is the relation between endothelin levels (big ET-1 and ET-1) in plasma and
           cerebrospinal fluid and type of injury, from CT scans and GCS?

        -  What is the relation between endothelin levels (big ET-1 and ET-1) in plasma and
           cerebrospinal fluid and outcome measurements like GOSE, ICP and CT scans?

        -  What is the relation between neurohormones related to the neutral endopeptidase (NEP)
           (ANP, BNP and cGMP) in plasma and cerebrospinal fluid and type of injury, from CT scans
           and GCS?

        -  What is the relation between endothelin levels (big ET-1 and ET-1) in plasma and
           cerebrospinal fluid and markers for apoptosis?
    

Detailed description: 
      Severe traumatic brain injury (TBI) remains a critical problem in the United States and
      throughout the world. Advances in critical care of the TBI patient has resulted in improved
      outcome. However, despite these efforts, half of the patients with severe brain injury die or
      are left with severe disability. Thus, the need for a pharmaceutical agent to blunt the
      cascade of neurotoxins released with mechanical head trauma and improve outcome is critically
      important. One of these neurotoxins is endothelin, a potent vasoactive peptide, which is
      considered to play a major role in TBI, particularly with subarachnoid hemorrhage and
      concomitant vasospasm. However, relatively little is known regarding the up-regulation of
      this toxin after head injury. Thus, the purpose of this observational study is to document
      the levels of endothelin in cerebrospinal fluid and plasma of patients with brain injury over
      a 14 day period. Aliquots of CSF and blood will be obtained at 12 hour intervals as long as a
      ventriculostomy for sampling of CSF is required for routine management. Additional
      information regarding the severity of injury, CT pathology, intracranial pressure, neurologic
      assessment, CSF biomarkers, and transcranial doppler ultrasound will also be collected. The
      study will be implemented among 12 centers,8 in the U.S.A and 3 in Europe and 1 in Canada,
      providing an average of approximately 5 patients per center over a period of 7 months. The
      study may be extended based on an interim analysis of endothelin levels at various injury
      severity levels. Data will be collected and coordinated by the American Brain Injury
      Consortium utilizing a web-based entry system. Following the completion of accrual a final
      report will be assembled by the ABIC which will serve as the basis for scientific publication
      and provide reference data for future development of clinical trials utilizing the endothelin
      system.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Fifty patients will be enrolled in this trial. Subjects will be eligible who have severe
        traumatic brain injury (the majority of patients) or moderate TBI together with lesions on
        CT scans sufficient to warrant placement of ventriculostomy catheter.
      
Biospecimen description: 
      CSF, plasma
    
Keywords: severe head injury; Endothelin; CSF; Plasma; Cellular Apoptosis