Observational Endothelin and Markers of Cellular Apoptosis In CSF Head Injury
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?
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||A Multicenter Observational Study to Evaluate Dynamics of Endothelin and Markers of Cellular Apoptosis in Cerebrospinal Fluid and Plasma in Moderate and Severe Human Head Injury|
|Study Start Date:||July 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00498498
|United States, California|
|University of California, Davis|
|Sacramento, California, United States, 95817|
|Harbor UCLA Medical Center|
|Torrance, California, United States, 90509|
|United States, Florida|
|University of Miami Miller School of Medicine|
|Miami, Florida, United States, 33136|
|United States, Iowa|
|University of Iowa Hospital|
|Iowa City, Iowa, United States, 52242|
|United States, Kentucky|
|University of Kentucky|
|Lexington, Kentucky, United States, 40536|
|United States, Ohio|
|The Mayfield Clinic|
|Cincinnati, Ohio, United States, 45219|
|United States, Tennessee|
|University of Tennessee Health Science Center|
|Memphis, Tennessee, United States, 38163|
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|University Hospital Heidelberg|
|Heidelberg, Germany, D-69120|
|University of Padova Medical School|
|Padova, Italy, 35128|
|Vall d'Hebron University Hospital|
|Barcelona, Spain, 08035|
|Principal Investigator:||John Ward, MD||Virginia Commonwealth University|