Neuroinflammation in Cognitive Decline Post-cardiac Surgery (FOCUS)
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|ClinicalTrials.gov Identifier: NCT04520802|
Recruitment Status : Recruiting
First Posted : August 20, 2020
Last Update Posted : August 20, 2020
|Condition or disease||Intervention/treatment|
|Postoperative Cognitive Dysfunction Coronary Artery Disease Pathophysiology||Diagnostic Test: 18F-DPA-714 PET/CT neuroimaging|
Systemic inflammation can activate the innate immune cells of the brain inducing neuroinflammation, which plays an important role in the pathogenesis of neurodegenerative disease. Major cardiovascular surgery induces a severe systemic inflammatory response.There is growing support that neuroinflammation is a pivotal factor in the development of postoperative cognitive decline (POCD) due to surgery-related systemic inflammation.
Although the neuroinflammatory hypothesis is scientifically accepted, in vivo human data supporting the role of neuroinflammation in severe systemic inflammation such as major surgery are still lacking. In the last decades, several nuclear imaging tracers have been developed that can quantitatively measure microglial and astrocytic activation in vivo, by targeting the mitochondrial 18kDa translocator protein (TSPO).
The investigators hypothesize that cardiac surgery induces a neuroinflammatory response and that its presence is related to acute and long term brain dysfunction postoperatively. This will be studied by pre- and postoperative PET brain imaging using a 18F-DPA-714 tracer targeting TSPO, combined with longitudinal neuropsychological examinations. Structural changes in the brain will be recorded on MRI prior to and after cardiac surgery to enable us to correct for the potentially confounding effects of neurovascular events on cognitive outcomes after CABG surgery.
|Study Type :||Observational|
|Estimated Enrollment :||30 participants|
|Official Title:||Neuroinflammation in Cognitive Decline Post-cardiac Surgery: The FOCUS Study|
|Actual Study Start Date :||February 18, 2019|
|Estimated Primary Completion Date :||September 1, 2021|
|Estimated Study Completion Date :||March 1, 2022|
Patients with postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) surgery
Diagnostic Test: 18F-DPA-714 PET/CT neuroimaging
Patients without postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) surgery
Diagnostic Test: 18F-DPA-714 PET/CT neuroimaging
- Change in TSPO PET tracer uptake at 3-7 days post-surgery [ Time Frame: 3-7 days post-surgery minus preoperative (= day before surgery) ]18F-DPA-714
- Occurrence of postoperative cognitive dysfunction (POCD) [ Time Frame: Baseline (preoperative), postoperative (3-7 days after surgery, 6 weeks and 6 months) ]POCD diagnosis based on neuropsychological assessments including TMT A&B, Stroop I, II, III, WAIS-IV - digit span, LDST, RAVLT, RCFT, RBMT-3 face recognition, LFT and token test. POCD diagnosis is made when patients are newly impaired in one or more cognitive domains (memory, executive functioning, speed of processing and language), or when the average test rating has declined in more than one domain compared to baseline.
- Whole brain TSPO PET tracer uptake pre- and 3-7 days post-surgery [ Time Frame: pre- and 3-7 days post-surgery ]18F-DPA-714
- Pro- and anti-inflammatory in vivo cytokine concentrations [in pg/ml] [ Time Frame: Day before surgery, during surgery (stop extracorporeal circulation (ECC)), after surgery (6 hours after stop ECC, 24 hours after incision, 3-7 days post-surgery and 6 weeks after surgery) ]TNFa, IL6, IL-1B, IL10, IL-1RA
- Ex vivo cytokine production of stimulated monocytes [in ng/10^9 monocytes] [ Time Frame: Day before surgery, 3-7 days and 6 weeks after surgery ]TNFa, IL6, IL1B, MCP1, IL10
- Flowcytometry analysis to study the inflammatory phenotype of the cells [ Time Frame: Day before surgery, 3-7 days and 6 weeks after surgery ]HLA-DR, CCR2, CD11b, CD14, CD16
- Complete blood count [ Time Frame: Day before surgery, during surgery (stop extracorporeal circulation (ECC)), after surgery (6 hours after stop ECC, 24 hours after incision, 3-7 days post-surgery and 6 weeks after surgery) ]including leukocyte differentiation measured on an automated hematology analyzer
- Ex vivo cytokine production of healthy donor monocytes, after exposure to patient serum obtained during CABG surgery [ Time Frame: Perioperatively at stop extracorporeal circulation (ECC) ]Healthy donor monocytes will be exposed to patient serum obtained during surgery, to see whether this changes the ex vivo cytokine producing capacity (TNFa, IL6, IL10)
- Number of newly developed (ischemic and hemorrhagic) brain and vascular wall lesions [ Time Frame: pre- and 3-7 days post-surgery ]
- Delta brain activity in three large scale brain networks involved in stress reactivity on resting-state fMRI [ Time Frame: pre- and 3-7 days post-surgery ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04520802
|Contact: Annemieke M. Peters van Ton, MD||+0031 email@example.com|
|Department of Intensive Care Medicine, Radboud university medical center||Recruiting|
|Contact: Annemieke M. Peters van Ton, MD +0031 243665010 firstname.lastname@example.org|
|Principal Investigator:||Wilson F Abdo, MD PhD||Radboud University|