Excitatory Amino Acids and Activated Microglia After Traumatic Brain Injury: a (R)-[11C]PK11195 PET Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2001 by VU University Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
VU University Medical Center
ClinicalTrials.gov Identifier:
NCT00205582
First received: September 12, 2005
Last updated: November 3, 2005
Last verified: May 2001
  Purpose

Excitatory amino acids may be involved in secondary neuronal damage after traumatic brain injury. The amount of microglia activation is an indirect measure of neuronal damage. Micorglia activation will be measured R)-[11C]PK11195 PET 1 week, 1 month and 6 months after brain injury.


Condition Intervention Phase
Traumatic Brain Injury
Device: Positron Emission Tomography
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: The Role of Excitatory Amino Acids on Neuronal Damage and Outcome After Traumatic Brain Injury: Assessment in Patients Using Microdialysis and (R)-[11C]PK11195 Positron Emission Tomography

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Glasgow coma scale after 6 months

Secondary Outcome Measures:
  • microglia activation

Estimated Enrollment: 20
Study Start Date: May 2001
Estimated Study Completion Date: December 2004
Detailed Description:

Glutamate and aspartate have been identified as the major excitatory neurotransmitters in the central nervous system. A massive increase in the release of these excitatory amino acids (EEA) has been described following traumatic brain injury. The resulting overstimulation of neuronal EAA receptors, particularly the N-Methyl-D-Aspartate (NMDA) receptors, leads to excessive influx of calcium through receptor gated ion-channels, causing metabolic derangement and finally cell death. Although the exact role of EEA in patients who have suffered severe head injury remains to be established, it has been shown that sustained high intracranial pressure (ICP) and poor outcome are significantly correlated to high levels of EEA using microdialysis. Disadvantages of microdialysis are that it can only be used to evaluate a limited part of the brain and that it can only be applied in the acute phase following injury. The same limits also apply to ICP measurements. Therefore, methods which evaluate both the extent and time course of damage in vivo are urgently needed.

Peripheral type benzodiazepine binding sites are a potential candidate for monitoring neuronal damage. They are not normally present in cerebral tissue, but following neuronal damage, the cells involved in the ensuing gliosis show marked expression of these sites.

(R)-PK11195 is a ligand that selectively binds to peripheral type benzodiazepine receptors. Labeled with carbon-11 its uptake can be measured with Positron Emission Tomography (PET). Thus, (R)-[11C]PK11195 PET can be used to monitor in-vivo gliosis after brain injury.

A maximum of twenty patients with traumatic brain injury will be included in this study. A microdialysis probe will be placed in the brain parenchyma to continuously measure EEA until the first PET scan is performed. Several cerebral and haemodynamic parameters, such as ICP and mean arterial blood pressure, will be registered. All patients will receive two Magnetic Resonance Imaging (MRI) scans to evaluate the extent and anatomical localization of cerebral damage. Three (R)-[11C]PK11195 PET scans will be performed: 1 week, 1 month and 6 months after the injury. Outcome will be determined using several outcome scales, including the Glasgow Outcome Scale at six months. In addition, patients will be investigated by repeated neuropsychological examinations.

  Eligibility

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

Inclusion Criteria:

  • 1. Traumatic Brain Injury 2. Age: 18-70 years 3. Haemodynamic and respiratory stable

Exclusion Criteria:

  • 1. Penetrating Skull Damage 2. Pregnancy 3. Hb < 6,5 mmol/l unless patient is known to have no history of cardiovascular disease, in which case a Hb < 5,5 mmol/l, will be the exclusion criterion 4. pH < 7,1 at initial arterial blood analysis 5. Previous neurotrauma 6. Current exposure to radiation in the workplace, or history of participation in nuclear medicine procedures, including research protocols 7. Condition which would exclude a clinical MR scan (e.g. pacemaker, shrapnel, metallic prosthesis)
  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: NCT00205582

Locations
Netherlands
VU University Medical Centre
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Investigators
Principal Investigator: Bart van Berckel, MD; PhD VU University Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00205582     History of Changes
Other Study ID Numbers: 2001/028
Study First Received: September 12, 2005
Last Updated: November 3, 2005
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by VU University Medical Center:
Traumatic Brain Injury
PET
microglia

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Excitatory Amino Acids
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014