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Observational Endothelin and Markers of Cellular Apoptosis In CSF Head Injury

This study has been completed.
Sponsor:
Collaborator:
Solvay Pharmaceuticals
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00498498
First received: July 9, 2007
Last updated: November 15, 2011
Last verified: November 2011
  Purpose

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?

Condition
Cerebrovascular Trauma
Neurohormones
Cellular Apoptosis
Endothelin System

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Biospecimen Retention:   Samples Without DNA

CSF, plasma


Enrollment: 51
Study Start Date: July 2007
Study Completion Date: December 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498498

Locations
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
Germany
University Hospital Heidelberg
Heidelberg, Germany, D-69120
Italy
University of Padova Medical School
Padova, Italy, 35128
Spain
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
Sponsors and Collaborators
Virginia Commonwealth University
Solvay Pharmaceuticals
Investigators
Principal Investigator: John Ward, MD Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00498498     History of Changes
Other Study ID Numbers: S001.2, S001, S001.1, S001.2
Study First Received: July 9, 2007
Last Updated: November 15, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
severe head injury
Endothelin
CSF
Plasma
Cellular Apoptosis

Additional relevant MeSH terms:
Cerebrovascular Trauma
Craniocerebral Trauma
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Trauma, Nervous System
Vascular Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on November 25, 2014