Ignite Creation Date:
2024-05-05 @ 9:23 PM
Last Modification Date:
2024-10-26 @ 10:03 AM
Study NCT ID:
NCT00878371
Status:
COMPLETED
Last Update Posted:
2016-06-23
First Post:
2009-04-07
Brief Title:
Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier
Sponsor:
Nova Scotia Health Authority
Organization:
Nova Scotia Health Authority
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2016-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Barriers 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 eg Alzheimers 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 mechanisms by which inflammation alters blood brain barrier efflux transport of morphine M3G and M6G
Functions of the Blood Brain Barrier in animals have been studied Human studies with multiple causes of inflammation eg Alzheimers 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 mechanisms by which inflammation alters blood brain barrier efflux transport of morphine M3G and M6G
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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None