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

November 3, 2005 updated by: Amsterdam UMC, location VUmc

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU University Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Glasgow coma scale after 6 months

Secondary Outcome Measures

Outcome Measure
microglia activation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Investigators

  • Principal Investigator: Bart van Berckel, MD; PhD, Amsterdam UMC, location VUmc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2001

Study Completion

December 1, 2004

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

November 4, 2005

Last Update Submitted That Met QC Criteria

November 3, 2005

Last Verified

May 1, 2001

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2001/028

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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