Dissecting Aneurysm of the Thoracic Aorta Clinical Trial
Official title:
Identification and Quantification of the Effects of a Surgery-induced Peripheral Inflammatory Response on Changes in Drug Efflux Transporter Function in the Brain
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.
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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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02678728 -
Effect of Intraoperative Dexmedetomidine on Lung Protection Following Thoracic Aorta Surgery With Hypothermic Circulatory Arrest: a Randomized Clinical Trial
|
Phase 4 |