Zinc and Post-Operative Cognitive Dysfunction

NCT04369157 | Withdrawn DMC

• 1 other identifier: RDG-006
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

A decline in cognitive abilities following surgery (POCD: Post-Operative Cognitive Dysfunction) affects up to 47% of patients undergoing a surgical procedure. Risk factors include age, previous depression, alcohol and drug use, smoking, cognitive impairment as well as pre-operative biochemical and haematological abnormalities. Inflammation has been proposed as a potential cause, however, there is little empirical and clinical evidence in this area to determine aetiology or reduce risk of incidence. Zinc is an important metal for brain function, with deficiency associated with poorer cognitive outcomes. In relation to POCD, biomarker studies have revealed that levels of a zinc-alpha-2-glycoprotein (AZGP1) were lower in patients with POCD. AZGP1 is a multifunctional glycoprotein implicated in cell adhesion, immune response, transmembrane transport and cellular proliferation. Microglia, the immune cells of the brain, are highly sensitive to changes in zinc which have been proposed to contribute to neurodegenerative disease as well as POCD. However, whilst animal studies looking at the effects of zinc on cognition have been promising, robust human trials are lacking. This research aims to establish the role of zinc in POCD by determining associations between zinc status, inflammation, cognitive function, and biomarkers of POCD risk and incidence. This will be achieved by gathering clinical and cognitive data from a sample of older adults undergoing surgery. Blood samples will be taken pre and post-operatively to establish zinc status and plasma concentrations of biomarkers of POCD risk and incidence. Pre and post-operative cognitive assessments will also be conducted to measure memory and executive function. Incidence of POCD will be determined via neurological assessment according to diagnostic criteria. Should associations between zinc status, POCD biomarkers, inflammation, cognitive performance and POCD incidence be established, not only would it lead to future work to investigate potential mechanisms of action as well as intervention studies looking to support zinc status, optimising early identification of individuals who may be at higher risk of developing POCD should lead to better patient outcomes.

Conditions

Cognitive Dysfunction

Outcome Measures

Primary Outcomes (6)

• Baseline zinc status as a predictor of POCD incidence 1-3 days post-operation

  Concentration of zinc in plasma/serum at baseline as a predictor for development of POCD 1-3 days post operation

  1-3 days post operation

• Baseline zinc status as a predictor of POCD incidence at follow-up

  Concentration of zinc in plasma/serum at baseline as a predictor for development of POCD at follow-up

  One month post operation

• POCD risk biomarker as a predictor of POCD incidence 1-3 days post operation

  Concentration of POCD risk biomarker AZGP1 in plasma/serum at baseline as a predictor for development of POCD 1-3 days post operation

  1-3 days post operation

• POCD risk biomarker as a predictor of POCD incidence at follow-up

  Concentration of POCD risk biomarker AZGP1 in plasma/serum at baseline as a predictor for development of POCD at follow-up

  One month post operation

• Baseline cognitive function (global Z score) as a predictor of POCD incidence 1- 3 days post operation

  Baseline cognitive function (global Z score) as a predictor for development of POCD 1-3 days post operation

  1-3 days post operation

• Baseline cognitive function (global Z score) as a predictor of POCD incidence at follow-up

  Baseline cognitive function (global Z score) as a predictor for development of POCD at follow-up

  One month post operation

Secondary Outcomes (22)

• Baseline zinc status as a predictor of cognitive function (global Z score) 1-3 days

  1-3 days post operation

• Baseline zinc status as a predictor of cognitive function (global Z score) at follow-up

  One month post operation

• Current zinc status and incidence of POCD 1-3 days post operation

  1-3 days post operation

• Current zinc status and incidence of POCD at follow-up

  One month post operation

• Current zinc status and cognitive function (global Z score) 1-3 days post operation

  1-3 days post operation

Study Arms (1)

Elective surgery group

Patients undergoing hip/knee replacements or colorectal surgery will be recruited and tested on 3 occasions: pre-op, post-op and at follow-up. POCD status will be determined at post-op and follow up. Cognitive function, zinc status, POCD biomarkers and inflammatory markers will be measured on all 3 occasions.

Procedure: Elective surgery

Interventions

Elective surgery PROCEDURE

Patients will be scheduled to undergo elective orthopaedic (knee/hip replacement) or colorectal surgery.

Elective surgery group

Eligibility Criteria

• Age: 60 Years - 100 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged over 60 years scheduled to undergo elective orthopaedic or colorectal surgery at the Royal Berkshire Hospital

You may qualify if:

• Aged 60 years or over
• Able to provide fully informed consent
• Scheduled to undergo orthopaedic (knee/hip replacement) or colorectal surgery
• English as their primary language

You may not qualify if:

• Under 60 years of age
• Unable to provide fully informed consent
• English not their primary language
• Not electing to undergo any surgery or surgery that is not a knee or hip replacement, or colorectal surgery

Sponsors & Collaborators

• University of Reading: lead
• Royal Berkshire NHS Foundation Trust: collaborator

Study Sites (2)

School of Psychology and Clinical Languages, University of Reading

Reading, Berkshire, RG6 6AL, United Kingdom

Location

Royal Berkshire Hospital

Reading, Berkshrie, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma or serum samples processed to remove DNA, to determine zinc status and POCD biomarkers.

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Elective Surgical Procedures

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Claire Williams, PhD

  University of Reading

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: April 30, 2020
• Study Start: January 1, 2021
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: June 29, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available on request following publication of the findings.
• Access Criteria: Data will be shared at the discretion of the Principle Investigator.

Locations

GB (2)