Observational Endothelin and Markers of Cellular Apoptosis In CSF Head Injury

Cerebrovascular Trauma Clinical Trial

— Endothelin  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00498498
• Other study ID #: S001.2
• Secondary ID: S001S001.1S001.2
• Status: Completed
• Phase: N/A
• First received: July 9, 2007
• Last updated: November 15, 2011
• Start date: July 2007
• Est. completion date: December 2009

Study information

• Verified date: November 2011
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: December 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained before collection of blood and CSF is commenced.

• TBI diagnosed by history, clinical examination with GCS of 8 or less, and head CT scan and placement of ventriculostomy catheter

• Patients with GCS 9 -12 who undergo placement of a ventriculostomy because of the severity of the CT lesion may be included

• Patients will be enrolled in the study within the first 8 hours after injury

• At least one reactive pupil after injury

• Age 18-70

Exclusion Criteria:

• Life expectancy of less than 8 hours as determined by the investigator

• Associated spinal cord injury

• Patients with penetrating head injury will be excluded

• Inability to establish ventriculostomy drainage

• Severe cardiac or hemodynamic instability consistent with point #1 above

• blood pressure less than 65mmHg mean, will be an exclusion criteria.

• Receipt of any known investigational drug within 30 days prior to this study

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cellular Apoptosis
• Cerebrovascular Trauma
• Craniocerebral Trauma
• Endothelin System
• Neurohormones

Locations

Country	Name	City	State
Germany	University Hospital Heidelberg	Heidelberg
Italy	University of Padova Medical School	Padova
Spain	Vall d'Hebron University Hospital	Barcelona
United States	The Mayfield Clinic	Cincinnati	Ohio
United States	University of Iowa Hospital	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky
United States	University of Tennessee Health Science Center	Memphis	Tennessee
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of California, Davis	Sacramento	California
United States	Harbor UCLA Medical Center	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Solvay Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Spain,