Postoperative DeliriumTURBONCT04523909
Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery
An observational study of Postoperative Delirium and Postoperative Cognitive Dysfunction, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Observational prospective pilot study to analyze the trajectory of neuroinflammatory protein expression in cerebrospinal fluid (CSF) in relation to systemic compartment in patients undergoing thoracic aortic surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Delirium, Postoperative Cognitive Dysfunction, Thoracic Aortic Aneurysm
- What is being tested?
- Trajectory of neuroinflammatory proteins in CSF and blood
- How many people
- 100 participants
- Where
- 1 siteNetherlands
- Study dates
- 18 Dec 2017to 1 Dec 2026
- How long will I take part?
- 2 Weeks
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients undergoing thoracic aortic surgery who will therefore receive an external lumbar drain as a standard of care procedure.
Who may be able to join
- Competent patients ≥ 18 years
- Patients who will undergo thoracic aortic surgery and will therefore receive an external lumbar drain as a standard of care procedure.
Who cannot join
- Patients with meningitis/encephalitis/brain abscess within the last 6 months
- Patients with other neurological conditions: brain injury (acute stroke, brain trauma or cerebral haemorrhage) within the last 3 months, known brain tumours, neurodegenerative disease or known pre-existing cognitive impairment (to a degree that would be compatible with mild cognitive impairment or more).
- Brain or spinal surgery within the last 3 months
- Active infection <2 weeks before surgery
- Patients who object against storage of their body material for scientific reasons
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Department of Intensive Care Medicine, Radboud university medical center
Nijmegen, 6500HB
Wilson F. Abdo, MD, PhD, 0243617273, f.abdo@radboudumc.nl
About this study
Official title: Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery: the TURBO Study
Observational prospective pilot study to analyze the trajectory of neuroinflammatory protein expression in cerebrospinal fluid (CSF) in relation to systemic compartment in patients undergoing thoracic aortic surgery.
The aim of this study is to identify and unravel the biochemical (neuroinflammatory) pathways involved in postoperative delirium.
Patient undergoing thoracic aortic surgery will have an external lumbar drain (ELD) in situ on the day before surgery. This ELD remains in place during and three days after surgery to reduce the risk on periprocedural spinal cord ischemia. Paired measurements of CSF and blood will be analyzed.
Read the detailed description
Major (cardiovascular) surgery is frequently associated with cerebral dysfunction postoperatively. Major surgical procedures account for substantial systemic inflammatory activation. Interestingly, animal models have shown that surgery rather than anaesthetics trigger a neurocognitive decline. An increase of pro-inflammatory cytokines and activation of immune cells mediate this post operative cognitive decline. There is growing support that systemic inflammation can activate the innate immune system of the brain leading to inflammation in the brain ('neuroinflammation'). This neuroinflammation is suggested to play a pivotal role in postoperative delirium and postoperative cognitive decline due to surgery-related systemic inflammation. However little evidence is available on the extend of the neuroinflammation and which biochemical pathways are dysregulated in the brain after surgery.
Thoracic aortic surgery offers the unique opportunity to study the trajectory of protein expression in CSF prior to and after surgery in a non-invasive matter. It is standard of care that an external lumbar drain (ELD) is placed the day prior to surgery and this ELD will remain in place during three postoperative days.
To advance the understanding of the impact of major surgery to the brain, the investigators wish to study the trajectory of protein expression prior to and after thoracic aortic surgery.
- Being tested
- Trajectory of neuroinflammatory proteins in CSF and blood
- Medical subject headings
- Emergence Delirium, Postoperative Cognitive Complications, Aortic Aneurysm, Thoracic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trajectory of neuroinflammatory proteins in CSF and bloodDiagnostic test
Kinetics of neuroinflammatory markers in CSF and blood
| Study group | Role | What they receive |
|---|---|---|
| Thoracic aortic surgery patients | Not described Receives: Diagnostic Test: Trajectory of neuroinflammatory proteins in CSF and blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Trajectory of the concentration of a panel of inflammatory proteins in CSF
Changes in CSF cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.
Measured: 9 timepoints: Baseline (immediately before surgery); Start extracorporeal circulation; Stop extracorporeal circulation (ECC); 2 hours (h) after stop ECC; 4h after stop ECC; 6h after stop ECC; 24h after baseline; 48h after baseline; 72h after baseline
Secondary outcomes (7)
Trajectory of the concentration of a panel of inflammatory proteins in plasma
Changes in plasma cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.
Measured: 9 timepoints: Baseline to 72 hours after surgery
Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio
CSF/Plasma albumine ratios will be measured for all timepoints where paired CSF/plasma samples are present
Measured: 9 timepoints: Baseline to 72 hours after surgery
Occurence of postoperative delirium
Yes or No
Measured: 14-day incidence of delirium
Trajectory of brain injury markers in CSF
Changes in brain injury markers will be determined (including NFL, S100B, GFAP, UCHL1, NSE)
Measured: 9 timepoints: Baseline to 72 hours after surgery
Trajectory of brain injury markers in plasma
Changes in brain injury markers will be determined (including S100B, GFAP, UCHL1, NSE)
Measured: 9 timepoints: Baseline to 72 hours after surgery
Changes in ex vivo cytokine production after whole blood stimulation
TNF-a,IL6, IL10
Measured: 5 timepoints: Baseline to 48 hours after surgery
Changes in mHLA-DR expression
monocytic HLA-DR expression assessed by flowcytometry
Measured: 5 timepoints: Baseline to 48 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start18 Dec 2017
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative DeliriumStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
- Target duration
- 2 Weeks
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilson F. Abdo, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04523909
- Sponsor's protocol ID
- CMO 2017-3774
- Acronym
- TURBO
- Status last verified
- Mar 2023
- First submitted
- 6 May 2019
- Last updated
- 31 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery: the TURBO Study
- ClinicalTrials.gov ID
- NCT04523909
- Acronym / sponsor ID
- TURBO / CMO 2017-3774
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 18 Dec 2017 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 24 Aug 2020 (actual)
- 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.
Observational prospective pilot study to analyze the trajectory of neuroinflammatory protein expression in cerebrospinal fluid (CSF) in relation to systemic compartment in patients undergoing thoracic aortic surgery.
The aim of this study is to identify and unravel the biochemical (neuroinflammatory) pathways involved in postoperative delirium.
Patient undergoing thoracic aortic surgery will have an external lumbar drain (ELD) in situ on the day before surgery. This ELD remains in place during and three days after surgery to reduce the risk on periprocedural spinal cord ischemia. Paired measurements of CSF and blood will be analyzed.
Detailed description
Major (cardiovascular) surgery is frequently associated with cerebral dysfunction postoperatively. Major surgical procedures account for substantial systemic inflammatory activation. Interestingly, animal models have shown that surgery rather than anaesthetics trigger a neurocognitive decline. An increase of pro-inflammatory cytokines and activation of immune cells mediate this post operative cognitive decline. There is growing support that systemic inflammation can activate the innate immune system of the brain leading to inflammation in the brain ('neuroinflammation'). This neuroinflammation is suggested to play a pivotal role in postoperative delirium and postoperative cognitive decline due to surgery-related systemic inflammation. However little evidence is available on the extend of the neuroinflammation and which biochemical pathways are dysregulated in the brain after surgery.
Thoracic aortic surgery offers the unique opportunity to study the trajectory of protein expression in CSF prior to and after surgery in a non-invasive matter. It is standard of care that an external lumbar drain (ELD) is placed the day prior to surgery and this ELD will remain in place during three postoperative days.
To advance the understanding of the impact of major surgery to the brain, the investigators wish to study the trajectory of protein expression prior to and after thoracic aortic surgery.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Weeks
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thoracic aortic surgery patients | – | Diagnostic Test: Trajectory of neuroinflammatory proteins in CSF and blood |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients undergoing thoracic aortic surgery who will therefore receive an external lumbar drain as a standard of care procedure.
Key inclusion criteria (2 listed)
- Competent patients ≥ 18 years
- Patients who will undergo thoracic aortic surgery and will therefore receive an external lumbar drain as a standard of care procedure.
Key exclusion criteria (5 listed)
- Patients with meningitis/encephalitis/brain abscess within the last 6 months
- Patients with other neurological conditions: brain injury (acute stroke, brain trauma or cerebral haemorrhage) within the last 3 months, known brain tumours, neurodegenerative disease or known pre-existing cognitive impairment (to a degree that would be compatible with mild cognitive impairment or more).
- Brain or spinal surgery within the last 3 months
- Active infection <2 weeks before surgery
- Patients who object against storage of their body material for scientific reasons
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 |
|---|---|---|
| Trajectory of neuroinflammatory proteins in CSF and bloodKinetics of neuroinflammatory markers in CSF and blood | Diagnostic test | Thoracic aortic surgery patients |
Primary outcome
Trajectory of the concentration of a panel of inflammatory proteins in CSF
Time frame: 9 timepoints: Baseline (immediately before surgery); Start extracorporeal circulation; Stop extracorporeal circulation (ECC); 2 hours (h) after stop ECC; 4h after stop ECC; 6h after stop ECC; 24h after baseline; 48h after baseline; 72h after baseline
Changes in CSF cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.
7 secondary outcomes
Trajectory of the concentration of a panel of inflammatory proteins in plasma
Time frame: 9 timepoints: Baseline to 72 hours after surgery
Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio
Time frame: 9 timepoints: Baseline to 72 hours after surgery
Occurence of postoperative delirium
Time frame: 14-day incidence of delirium
Trajectory of brain injury markers in CSF
Time frame: 9 timepoints: Baseline to 72 hours after surgery
Trajectory of brain injury markers in plasma
Time frame: 9 timepoints: Baseline to 72 hours after surgery
Changes in ex vivo cytokine production after whole blood stimulation
Time frame: 5 timepoints: Baseline to 48 hours after surgery
Changes in mHLA-DR expression
Time frame: 5 timepoints: Baseline to 48 hours after surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Postoperative Delirium and Postoperative Cognitive Dysfunction, run by Radboud University Medical Center at 1 site in Netherlands.
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 5 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: looking for participants now, as of the sponsor's last update on 31 Mar 2023. 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 Netherlands. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wilson F. Abdo, MD, PhD (+31243617273, f.abdo@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Trajectory of the concentration of a panel of inflammatory proteins in CSF (time frame: 9 timepoints: Baseline (immediately before surgery); Start extracorporeal circulation; Stop extracorporeal circulation (ECC); 2 hours (h) after stop ECC; 4h after stop ECC; 6h after stop ECC; 24h after baseline; 48h after baseline; 72h after baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Mar 2023.