Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier
Tracking Information | |||||||||
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First Received Date ICMJE | April 7, 2009 | ||||||||
Last Updated Date | August 2, 2012 | ||||||||
Start Date ICMJE | May 2009 | ||||||||
Estimated Primary Completion Date | December 2012 (final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
The primary outcome variables are the correlation between the ratio of CSF/plasma morphine , morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) levels and the plasma concentration of IL-6 over time. [ Time Frame: CSF and Blood samples will be taken in the OR, post operatively ( every 6 hrs until POD 5 if CSF drain still in place) ] [ Designated as safety issue: No ] | ||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | Complete list of historical versions of study NCT00878371 on ClinicalTrials.gov Archive Site | ||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Outcome Measures ICMJE | |||||||||
Original Other Outcome Measures ICMJE | |||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier | ||||||||
Official Title ICMJE | Identification and Quantification of the Effects of a Surgery-induced Peripheral Inflammatory Response on Changes in Drug Efflux Transporter Function in the Brain | ||||||||
Brief Summary | The purpose for this study is to determine if surgery (repair of descending thoracic aneurysm) causes a temporary decrease in the Blood Brain Barrier's ability to remove drugs from the brain back into the blood. The Blood Brain Barrier surrounds the brain and the spinal cord. This Blood Brain Barrier acts as a filter and allows some things to cross into the brain and allows other matter to be removed. Studies have shown the Blood Brain Barrier is affected by inflammation. Functions of the Blood Brain Barrier in animals have been studied. Human studies with multiple causes of inflammation (e.g. Alzheimer's, Epilepsy, trauma and severe infections in critically Hypothesis: Surgically-induced inflammation will temporarily reduce blood-brain barrier drug efflux transporter function in proportion to the degree of inflammation. The investigators anticipate that inflammation-mediated reductions in drug transporter function will be reflected by an increased cerebral spinal fluid (CSF) concentration of morphine (a PGP substrate) and M3G and M6G (MRP1 substrates). The corresponding in vitro studies will allow us to elucidate the mechanism(s) by which inflammation alters blood brain barrier efflux transport of morphine, M3G and M6G. |
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Detailed Description | Study Objectives: To determine the role of surgery-induced inflammation on the transport of morphine and its metabolites, M3G and M6G, across the blood-brain barrier. Study phase: IV Study Design: This is a sequential enrolment study design in which elective surgical patients presenting for repair of an ascending thoracic aneurysm and fitted with a CSF drain as part of their standard of care will be approached for permission to draw blood samples at specified times during their hospital course. Concomitantly, samples of CSF will be collected from the CSF drainage system (CSF is normally wasted). Morphine will be used as the primary analgesic agent (this is within the standard of care). Samples will be collected at specified time intervals for 5 days or until the CSF drain is removed (whichever comes first). Samples collected will be analysed for morphine, its 3- and 6- glucuronide metabolites, inflammatory cytokines, markers of CNS injury and anatomical integrity of the BBB. Area under the concentration vs. time curve will be calculated and the effect on morphine metabolism and penetration across the BBB will be determined using a repeated measures analysis of variance technique (as used in our previous study). |
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Study Type ICMJE | Interventional | ||||||||
Study Phase | Phase 4 | ||||||||
Study Design ICMJE | Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
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Condition ICMJE | Dissecting Aneurysm of the Thoracic Aorta | ||||||||
Intervention ICMJE | Procedure: Repair of descending thoracic aneurysm and morphine
Elective surgical patients undergoing repair of a descending thoracic aortic aneurysm, requiring insertion of a cerebral spinal fluid (CSF) drain and receiving Morphine as their primary analgesic agent can be enrolled |
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Study Arm (s) | |||||||||
Publications * | Roberts DJ, Goralski KB. A critical overview of the influence of inflammation and infection on P-glycoprotein expression and activity in the brain. Expert Opin Drug Metab Toxicol. 2008 Oct;4(10):1245-64. Review. | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE | 30 | ||||||||
Estimated Completion Date | December 2012 | ||||||||
Estimated Primary Completion Date | December 2012 (final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||||||
Ages | |||||||||
Accepts Healthy Volunteers | No | ||||||||
Contacts ICMJE |
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Location Countries ICMJE | Canada | ||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT00878371 | ||||||||
Other Study ID Numbers ICMJE | Hall Morphine TAA-01 | ||||||||
Has Data Monitoring Committee | No | ||||||||
Responsible Party | Richard Hall, Capital District Health Authority, Canada | ||||||||
Study Sponsor ICMJE | Capital District Health Authority, Canada | ||||||||
Collaborators ICMJE | |||||||||
Investigators ICMJE |
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Information Provided By | Capital District Health Authority, Canada | ||||||||
Verification Date | August 2012 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |