Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier

NCT00878371 | Completed Phase 4

• 1 other identifier: Hall Morphine TAA-01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Dissecting Aneurysm of the Thoracic Aorta

Keywords

morphine; blood brain barrier; surgery induced peripheral inflammatory response

Outcome Measures

Primary Outcomes (1)

• 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.

  CSF and Blood samples will be taken in the OR, post operatively ( every 6 hrs until POD 5 if CSF drain still in place)

Secondary Outcomes (2)

• Correlation between CSF/Plasma ratios of morphine, M3G, M6G and plasma concentration of TNFα and ET-1 over time.

  CSF and Blood samples will be taken in the OR, post operatively ( every 6 hrs until POD 5 if CSF drain still in place)

• Correlation between CSF/plasma ratios for morphine, M3G, M6G and CSF/Plasma ratios for albumin and S-100β over time.

  CSF and Blood samples will be taken in the OR, post operatively ( every 6 hrs until POD 5 if CSF drain still in place)

Study Arms (1)

morphine

OTHER

All patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively

Drug: morphine

Interventions

morphine DRUG

All patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively

morphine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are to undergo elective surgery for thoracic aortic vascular disease requiring insertion of a lumbar CSF drain
• Informed consent will be obtained from the subject or authorized legal representative -

You may not qualify if:

• Unwilling or unable to provide informed consent
• Sensitivity or documented allergy to morphine
• Inability to place lumbar CSF drain
• Dialysis dependent -

Sponsors & Collaborators

• Nova Scotia Health Authority: lead
• Dalhousie University: collaborator

Study Sites (1)

Capital Health- Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H3A7, Canada

Location

Related Publications (3)

• 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. doi: 10.1517/17425255.4.10.1245.

  PMID: 18798696 BACKGROUND

• Roberts DJ, Hall RI, Wang Y, Julien LC, Wood J, Goralski KB. S100B as a biomarker of blood-brain barrier disruption after thoracoabdominal aortic aneurysm repair: a secondary analysis from a prospective cohort study. Can J Anaesth. 2021 Dec;68(12):1756-1768. doi: 10.1007/s12630-021-02110-2. Epub 2021 Sep 27.

  PMID: 34570352 DERIVED

• Wang Y, Goralski KB, Roberts DJ, Landry K, Issa ME, Sleno L, Julien LC, Wood J, Hall RI. An observational study examining the effects of a surgically induced inflammatory response on the distribution of morphine and its metabolites into cerebrospinal fluid. Can J Anaesth. 2017 Oct;64(10):1009-1022. doi: 10.1007/s12630-017-0933-x. Epub 2017 Jul 14.

  PMID: 28710563 DERIVED

MeSH Terms

Interventions

Morphine

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Richard I Hall, MD

  Capital Health- Queen Elizabeth II Health Sciences Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD FRCPC FCCP

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: May 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: June 23, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)