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Postoperative Cognitive DysfunctionFOCUSNCT04520802

Neuroinflammation in Cognitive Decline Post-cardiac Surgery

An observational study of Postoperative Cognitive Dysfunction and Coronary Artery Disease, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Major cardiovascular surgery is associated with postoperative cognitive decline (POCD), with a deterioration in memory, attention and speed of information processing. A multifactorial pathophysiology is presumed but this study focuses on the role of (neuro)inflammation in the development of POCD after coronary artery… Read more about this study

Who is it for?
Ages 50 years and older
What is being tested?
18F-DPA-714 PET/CT neuroimaging
How many people
15 participants
Where
1 siteNetherlands
Study dates
18 Feb 2019to 1 Jul 2022
Phase
Observational
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 50 years and older
  • All sexes
  • Adult, Older adult

Study population: Patients >50 years that are planned to undergo elective coronary artery bypass grafting (CABG) surgery by the cardiothoracic surgery department of the Radboud university medical center in Nijmegen (NL).

Who may be able to join

  • Age > 50 years
  • Planned for on-pump coronary artery bypass grafting surgery
  • High-affinity binder or mixed-affinity binders based on rs6971 polymorphism for TSPO
  • Chronic use of statins (defined as pre-hospital use)

Who cannot join

  • Previous cardiac surgery.
  • Pregnancy or wish to become pregnant within 2 weeks after PET-CT scan
  • Contra-indication to undergo a PET/CT or MRI scan, including claustrophobia.
  • Low-affinity binder based on rs6971 polymorphism for TSPO, or unable to determine rs6971 polymorphism.
  • Patients with cognitive disorders that have not recovered enough to be able to understand the study leaflets and information for participation.
  • Brain or spinal surgery within the last 6 months.
Show all 22Show fewer
  • Meningitis or brain infection within the last 6 months.
  • Pre-existing dementia or neurodegenerative disease or cognitive impairment interfering with the ability to understand informational material about this research project.
  • Presence of a CSF catheter or shunt.
  • Patients with known brain tumors.
  • Patients with brain injury (e.g. acute stroke, or subarachnoid hemorrhage) within the last 6 months.
  • Severe brain trauma in previous medical history.
  • Chronic (>2 weeks) use of immunosuppressive agents (see table 3.3.A).
  • Concomitant diseases resulting in severe immunosuppression (e.g. HIV).
  • Auto-immune or auto-inflammatory disease
  • Active infection < 2 weeks prior to inclusion (defined as fever >38.5 or antibiotic treatment)
  • Kidney failure, defined by a MDRD-GFR<15 ml/min/1.73m2
  • Known contrast allergy for gadolinium
  • Chronic use of neuroleptics, defined as pre-hospital use.
  • Patients that do not speak Dutch or have disabilities that prevent accurate delirium diagnosis.
  • Analphabetic patients.
  • No written informed consent obtained.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Department of Intensive Care Medicine, Radboud university medical center

    Nijmegen, 6500HB

Other trials in Netherlands

About this study

Official title: Neuroinflammation in Cognitive Decline Post-cardiac Surgery: The FOCUS Study

Major cardiovascular surgery is associated with postoperative cognitive decline (POCD), with a deterioration in memory, attention and speed of information processing. A multifactorial pathophysiology is presumed but this study focuses on the role of (neuro)inflammation in the development of POCD after coronary artery bypass grafting (CABG) surgery.

Read the detailed description

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.

Being tested
18F-DPA-714 PET/CT neuroimaging
Medical subject headings
Postoperative Cognitive Complications, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 18F-DPA-714 PET/CT neuroimagingDiagnostic test

    • Pre- and postoperative neuroimaging using 18F-DPA-714 PET/CT and brain MRI.
    • Longitudinal neuropsychological examinations (up to 6 months postoperatively)
    • Blood samples are drawn to assess the severity of the systemic inflammatory response
Study groups in NCT04520802
Study groupRoleWhat they receive
POCDPatients with postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) surgery
Receives: Diagnostic Test: 18F-DPA-714 PET/CT neuroimaging
no POCDPatients without postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) surgery
Receives: Diagnostic Test: 18F-DPA-714 PET/CT neuroimaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in TSPO PET tracer uptake at 3-7 days post-surgery

    18F-DPA-714

    Measured: 3-7 days post-surgery minus preoperative (= day before surgery)

Secondary outcomes (9)

  1. Occurrence of postoperative cognitive dysfunction (POCD)

    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.

    Measured: Baseline (preoperative), postoperative (3-7 days after surgery, 6 weeks and 6 months)

  2. Whole brain TSPO PET tracer uptake pre- and 3-7 days post-surgery

    18F-DPA-714

    Measured: pre- and 3-7 days post-surgery

  3. Pro- and anti-inflammatory in vivo cytokine concentrations [in pg/ml]

    TNFa, IL6, IL-1B, IL10, IL-1RA

    Measured: 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)

  4. Ex vivo cytokine production of stimulated monocytes [in ng/10^9 monocytes]

    TNFa, IL6, IL1B, MCP1, IL10

    Measured: Day before surgery, 3-7 days and 6 weeks after surgery

  5. Flowcytometry analysis to study the inflammatory phenotype of the cells

    HLA-DR, CCR2, CD11b, CD14, CD16

    Measured: Day before surgery, 3-7 days and 6 weeks after surgery

  6. Complete blood count

    including leukocyte differentiation measured on an automated hematology analyzer

    Measured: 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)

  7. Ex vivo cytokine production of healthy donor monocytes, after exposure to patient serum obtained during CABG surgery

    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)

    Measured: Perioperatively at stop extracorporeal circulation (ECC)

  8. Number of newly developed (ischemic and hemorrhagic) brain and vascular wall lesions

    Measured: pre- and 3-7 days post-surgery

  9. Delta brain activity in three large scale brain networks involved in stress reactivity on resting-state fMRI

    Measured: pre- and 3-7 days post-surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Aug 2020
  2. Study start18 Feb 2019
  3. Primary completion1 Jul 2022
  4. Study completion1 Jul 2022

Resources

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
Other
Time perspective
Prospective
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04520802
Sponsor's protocol ID
NL.57785.091.16
Other IDs
2016-002016-40, CMO 2016-2598, 2016
Acronym
FOCUS
Status last verified
Mar 2023
First submitted
3 Jul 2020
Last updated
31 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Peters van Ton AM, Duindam HB, van Tuijl J, Li WW, Dieker HJ, Riksen NP, Meijer FA, Kessels RP, Kohn N, van der Hoeven JG, Pickkers P, Rijpkema M, Abdo WF. Neuroinflammation in cognitive decline post-cardiac surgery (the FOCUS study): an observational study protocol. BMJ Open. 2021 May 11;11(5):e044062. doi: 10.1136/bmjopen-2020-044062.

    PubMed 33980522

Questions about this trial

What is this clinical trial studying?

An observational study of Postoperative Cognitive Dysfunction and Coronary Artery Disease, 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 4 inclusion and 22 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 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?

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?

Change in TSPO PET tracer uptake at 3-7 days post-surgery (time frame: 3-7 days post-surgery minus preoperative (= day before surgery)). 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 NCT04520802, which also lists 1 linked publication.

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.

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