- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04523909
Trajectory of Neuroinflammatory Markers in Cerebrospinal Fluid Prior to and After Thoracic Aortic Surgery (TURBO)
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Wilson F. Abdo, MD, PhD
- Phone Number: +31243617273
- Email: f.abdo@radboudumc.nl
Study Locations
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-
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Nijmegen, Netherlands, 6500HB
- Recruiting
- Department of Intensive Care Medicine, Radboud university medical center
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Contact:
- Wilson F. Abdo, MD, PhD
- Phone Number: 0243617273
- Email: f.abdo@radboudumc.nl
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Thoracic aortic surgery patients
|
Kinetics of neuroinflammatory markers in CSF and blood
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Trajectory of the concentration of a panel of inflammatory proteins in plasma
Time Frame: 9 timepoints: Baseline to 72 hours after surgery
|
Changes in plasma cytokine concentrations will be determined (including IL6, IL8, IL10, MCP-1, IL1RA and CX3CL1) between timepoints described below.
|
9 timepoints: Baseline to 72 hours after surgery
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Trajectory of blood-CSF barrier disruption based on CSF/Plasma albumine ratio
Time Frame: 9 timepoints: Baseline to 72 hours after surgery
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CSF/Plasma albumine ratios will be measured for all timepoints where paired CSF/plasma samples are present
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9 timepoints: Baseline to 72 hours after surgery
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Occurence of postoperative delirium
Time Frame: 14-day incidence of delirium
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Yes or No
|
14-day incidence of delirium
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Trajectory of brain injury markers in CSF
Time Frame: 9 timepoints: Baseline to 72 hours after surgery
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Changes in brain injury markers will be determined (including NFL, S100B, GFAP, UCHL1, NSE)
|
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
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Changes in brain injury markers will be determined (including S100B, GFAP, UCHL1, NSE)
|
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
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TNF-a,IL6, IL10
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5 timepoints: Baseline to 48 hours after surgery
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Changes in mHLA-DR expression
Time Frame: 5 timepoints: Baseline to 48 hours after surgery
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monocytic HLA-DR expression assessed by flowcytometry
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5 timepoints: Baseline to 48 hours after surgery
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CMO 2017-3774
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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