Dissecting Aneurysm of the Thoracic AortaPhase 4NCT00878371
Effects of a Surgery-induced Peripheral Inflammatory Response on the Blood Brain Barrier
A Phase 4 study testing morphine in people with Dissecting Aneurysm of the Thoracic Aorta, run by Nova Scotia Health Authority at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Dissecting Aneurysm of the Thoracic Aorta
- What is being tested?
- morphine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- May 2009to Feb 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 -
Who cannot join
- Unwilling or unable to provide informed consent
- Sensitivity or documented allergy to morphine
- Inability to place lumbar CSF drain
- Dialysis dependent -
Trial locations and contacts
1 site in 1 country.
Canada1 site
Capital Health- Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H3A7
About this study
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.
Read the 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).
- Being tested
- morphine
- Keywords
- morphine, blood brain barrier, surgery induced peripheral inflammatory response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
morphineDrug
All patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively
| Study group | Role | What they receive |
|---|---|---|
| morphine | Other | All patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively Receives: Drug: morphine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: CSF and Blood samples will be taken in the OR, post operatively ( every 6 hrs until POD 5 if CSF drain still in place)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Dissecting Aneurysm of the Thoracic AortaStudies of the same condition, open and under way.
- More trials run by Nova Scotia Health AuthorityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nova Scotia Health Authority
- Sponsor type
- University, hospital or other
- Collaborators
- Dalhousie University
- Responsible party
- Principal investigator, Richard Hall, Nova Scotia Health Authority
- Investigators
- Richard I Hall, MD, Principal investigator, Capital Health- Queen Elizabeth II Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00878371
- Sponsor's protocol ID
- Hall Morphine TAA-01
- Status last verified
- Jun 2016
- First submitted
- 7 Apr 2009
- Last updated
- 23 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: publication in process
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. doi: 10.1517/17425255.4.10.1245.
PubMed 18798696Roberts 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.
PubMed 34570352Wang 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.
PubMed 28710563
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00878371
- Acronym / sponsor ID
- Hall Morphine TAA-01
- Keywords
- morphine, blood brain barrier, surgery induced peripheral inflammatory response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Nova Scotia Health AuthorityUniversity, hospital or other
- Collaborators
- Dalhousie University
- Study start
- May 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 8 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| morphine | Other | Drug: morphineAll patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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 -
Key exclusion criteria (4 listed)
- Unwilling or unable to provide informed consent
- Sensitivity or documented allergy to morphine
- Inability to place lumbar CSF drain
- Dialysis dependent -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| morphineAll patients treated with Morphine during induction after the lumbar drain inserted. Morphine was prescribed as Standard of care post operatively | Drug | morphine |
Primary outcome
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)
2 secondary outcomes
Correlation between CSF/Plasma ratios of morphine, M3G, M6G and plasma concentration of TNFα and ET-1 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)
Correlation between CSF/plasma ratios for morphine, M3G, M6G and CSF/Plasma ratios for albumin and S-100β 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
- Background: PubMed 18798696Roberts 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.
- Derived from this study: PubMed 34570352Roberts 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.
- Derived from this study: PubMed 28710563Wang 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.
- Individual participant dataSharing planned: Yes. publication in process
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard I Hall, MD principal investigator
Capital Health- Queen Elizabeth II Health Sciences Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing morphine in people with Dissecting Aneurysm of the Thoracic Aorta, run by Nova Scotia Health Authority at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00878371, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2016.