Biomarkers Associated With Postoperative Cognitive Dysfunction

Cognitive Impairment Clinical Trial

Official title:

Feasibility Study of the Use of Biomarkers to Detect Perioperative Brain Injury: the Association Between Serum Neurofilament Light Chains, Tau Proteins, Continuous Intra-operative Electroencephalography, and the Development of Post Operative Cognitive Dysfunction After Surgery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05464355
• Other study ID #: PID16101
• Secondary ID: 302168Protocol v
• Status: Recruiting
• Start date: January 5, 2023
• Est. completion date: November 2029

Study information

• Verified date: December 2023
• Source: University of Oxford
• Contact: Martyn Ezra
• Phone: +44 1865572878
• Email: martyn.ezra[@]ndcn.ox.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Loss of cognitive function after major surgery is a significant risk in older people. It can occur acutely in the days after surgery as delirium or in months to years later as a persistent reduction in brain function termed neurocognitive decline. Together these conditions are called post operative cognitive dysfunction (POCD). They can be acutely distressing for patients and are associated with other problems after surgery. The causes of post operative cognitive dysfunction are poorly understood. Studies have been limited by a lack of biomarkers to predict which patients are at high risk of developing POCD. Research suggests silent strokes occurring during surgery and different sensitivities to anaesthetic medicines are associated with POCD. The project consists of a feasibility study to investigate markers that might predict people over 65 years old getting POCD. The first biomarker is a non-invasive monitor of anaesthetics effects on brain function called electroencephalography (EEG): The investigators will identify which EEG patterns predict delirium within five days surgery. The second set of biomarkers are two blood tests of proteins that increase after strokes: these are neurofilament light chains and tau proteins. The investigators will establish if these can be used to predict having POCD up to one year after surgery and long term cognitive impairment up to 5 years after surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: November 2029
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• Greater than or equal to 65 years of age
• Having elective non-cardiac surgery under general anaesthesia
• Anticipated to have at least 48 hours of inpatient admission
• Able & willing to give informed consent

Exclusion Criteria:

• Unable to participate in neurocognitive assessments
• Presence of delirium prior to surgery
• Contraindication to use of EEG electrodes (e.g. known allergy to a component of the electrodes)
• Known history of severe traumatic brain injury
• Learning disability specifically with a known structural brain lesion
• Known history of dementia
• Participants undergoing operations on the carotid artery

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction
• Cognitive Impairment
• Delirium
• Postoperative Cognitive Complications
• Postoperative Cognitive Dysfunction

Intervention

Procedure:
• Intraoperative electroencephalography recording
Intraoperative electroencephalography measurements, a non-invasive routine monitoring device used during anaesthesia to measure the brain's electrical activity
• Neurofilament light chain measurement
Measurement of the level of neurofilament light chain in a blood sample
• Tau protein measurement
Measurement of the level of tau protein in a blood sample

Locations

Country	Name	City	State
United Kingdom	Royal Berkshire NHS Foundation Trust	Reading	Berkshire

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Oxford University Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility to conduct the study	The total number of participants who are successfully recruited, receive the study procedures and complete both 90 day and 1 year follow up after surgery.	1 year after surgery
Secondary	Postoperative delirium incidence and severity	Postoperative delirium identified as being present according to a positive result using 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and severity according to the absolute value on the 3D-CAM-Severity which is a scale converting the 3-Minute Diagnostic Interview for Confusion Assessment Method into a scale from 0-7. Higher scores are associated with worse outcome.	Up to 5 days after surgery
Secondary	Days alive and at home up to 90 days after surgery	The number of days a participant is alive and how many are spent at home after surgery	90 days after surgery
Secondary	Change in neurofilament light chains and tau proteins levels pre- to post operatively	Measurements of the level of the biomarkers neurofilament light chain and tau protein in plasma	Up to 2 days after surgery
Secondary	Postoperative neurocognitive dysfunction and severity	Cognitive impairment measured on Montreal Objective Cognitive Assessment administered by telephone. The scale is 0-22 with higher scores representing better outcome.	Up to 1 year after surgery
Secondary	Long term cognitive impairment	Incidence of new diagnosis in primary or secondary care of dementia or mild cognitive impairment	Up to 5 years after surgery