Predicting the Risk of Post-operative Delirium: Use of Neuropsychology, Serum and CSF Biomarkers and Genetics to Predict Risk of Post-operative Delirium

Delirium Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02299037
• Other study ID #: 09069PP-OPMS
• Status: Active, not recruiting
• Start date: March 2012
• Est. completion date: February 2025

Study information

• Verified date: December 2023
• Source: Belfast Health and Social Care Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the study is to determine if pre-operative neuropsychological characteristics, apolipoprotein E4 status and/or cerebrospinal fluid (CSF) and serum biomarkers can predict those most at risk of post-operative delirium. Patients over the age of 65 years undergoing elective primary hip or knee arthroplasty in Musgrave Park Hospital are invited to take part. Participants undergo a pre-operative neuropsychological assessment which is repeated 6-12 weeks post-operatively at the time of surgical review appointment. At the time of surgery advantage is taken of the necessary venous cannulation and spinal anaesthetic to gain venous blood and CSF samples respectively. Venous blood is also sampled post-operatively. Patients are assessed daily for delirium, using the Confusion Assessment Method, until discharge. The association between delirium and subsequent cognitive decline is now well established in the literature. It is not yet clear whether this is solely because delirium following elective surgery indicates a previously unrecognised neurodegenerative process or whether the delirium itself exerts an additional pathophysiological insult. In order to investigate this, a follow-up study of these participants, approximately 8 years later is currently being conducted. Neuropsychological assessment and venous blood sampling will be repeated with consenting participants. Furthermore, the significance of subtle symptoms, not sufficient to fulfil the criteria for delirium and known as subsyndromal delirium, in relation to cognitive function years later will be analysed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 316
• Est. completion date: February 2025
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• living at home
• undergoing primary, elective hip or knee arthroplasty
• spinal anaesthetic with intrathecal diamorphine anticipated

Exclusion Criteria:

• neurological, hearing or visual disability affecting ability to participate in study
• known neurodegenerative condition eg dementia, Parkinson's disease, multiple sclerosis

Related Conditions & MeSH terms

• Delirium

Locations

Country	Name	City	State
United Kingdom	Centre for Public Health, Queen's University Belfast	Belfast

Sponsors (1)

Lead Sponsor	Collaborator
Belfast Health and Social Care Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of inpatient post-operative delirium as measured using the confusion assessment method (CAM)		Day 1 post-operatively
Primary	Incidence of inpatient post-operative delirium as measured using the confusion assessment method (CAM)		Day 2 post-operatively
Primary	Incidence of inpatient post-operative delirium as measured using the confusion assessment method (CAM)		Day 3 post-operatively
Primary	Performance on the Mini-Mental Status Examination (MMSE; Folstein MF, Folstein SE et al. 1975).	A 30 point scale pre-operatively and at follow-up 7-8 years later.	8 year follow-up
Primary	Performance on the Executive Clock Drawing Task (CLOX 1 & 2; Royall, Cordes et al. 1998).	A 24 point scale pre-operatively and at follow-up 7-8 years later.	8 year follow-up
Primary	Performance on the Controlled Oral Word Association Test (COWAT; Benton, A.L. Hamsher, K. Sivan, A.B. 1983).	A test which measures both phonemic and semantic fluency. One point is awarded for each word generated (within the task parameters) within one minute. A total of five categories are assessed. Performance pre-operatively and at follow-up 7-8 years later will be compared.	8 year follow-up
Primary	Performance on the Stroop Colour and Word Test (Golden 1978).	This test features 100 items, the score reflects how many words were correctly identified in 45 seconds. A total of five categories are assessed. Performance pre-operatively and at follow-up 7-8 years later will be compared.	8 year follow-up
Primary	Colour Trails 1&2 (D'Elia, Satz et al. 1996).	Performance is measured in the time taken (seconds) taken to successfully complete this test. Performance pre-operatively and at follow-up 7-8 years later will be compared.	8 year follow-up
Primary	New York Paragraph Recall Test (Kluger, Ferris et al. 1999).	This test is scored based on the number of correctly recalled sections of the story. There are two recall conditions - immediate recall, assessed immediately following the reading of the paragraph and delayed recall, performance assessed five minutes following conclusion of the story. Each condition can earn a maximum of 21 points. Performance pre-operatively and at follow-up 7-8 years later will be compared.	8 year follow-up
Primary	Weighted Composite Summary Cognitive Measure at 7-8 year Follow-up	This weighted composite summary cognitive measure will be calculated based on the work of Inouye et al (Inouye, Marcantonio et al. 2016). This will be calculated (using outcome measures 4-9 above), for two time points 1) using preoperative scores and 2) using follow-up study visit scores. With the follow-up study visit scores being our primary outcome measure. The cognitive tests used in this study are similar to those utilised by the General Cognitive Performance score (Jones, Rudolph et al. 2010) and in deriving these scores we intend to use locally available normative data from representative samples, namely the Irish longitudinal studies (The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) and The Irish Longitudinal Study on Ageing (TILDA)).	8 year follow-up
Secondary	Performance on the Mini-Mental Status Examination (MMSE; Folstein MF, Folstein SE et al. 1975).	Performance on this 30 point scale pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	Performance on the Executive Clock Drawing Task (CLOX 1 & 2; Royall, Cordes et al. 1998).	Performance on this 24 point scale pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	Performance on the Controlled Oral Word Association Test (COWAT; Benton, A.L. Hamsher, K. Sivan, A.B. 1983).	A test which measures both phonemic and semantic fluency. One point is awarded for each word generated (within the task parameters) within one minute. A total of five categories are assessed. Performance pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	Performance on the Stroop Colour and Word Test (Golden 1978).	This test features 100 items, the score reflects how many words were correctly identified in 45 seconds. A total of five categories are assessed. Performance pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	Colour Trails 1&2 (D'Elia, Satz et al. 1996).	Performance is measured in the time taken (seconds) taken to successfully complete this test. Performance pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	New York Paragraph Recall Test (Kluger, Ferris et al. 1999).	This test is scored based on the number of correctly recalled sections of the story. There are two recall conditions - immediate recall, assessed immediately following the reading of the paragraph and delayed recall, performance assessed five minutes following conclusion of the story. Each condition can earn a maximum of 21 points. Performance pre-operatively and at follow-up 6-12 weeks later will be compared.	6-12 weeks post-surgery
Secondary	Weighted Composite Summary Cognitive Measure at 6-12 Week Follow-Up	This weighted composite summary cognitive measure will be calculated based on the work of Inouye et al (Inouye, Marcantonio et al. 2016). This will be calculated (using outcome measures 11-16 above), for two time points 1) using preoperative scores and 2) using follow-up study visit scores at 6-12 weeks post-operatively. With the follow-up study visit scores being our primary outcome measure. The cognitive tests used in this study are similar to those utilised by the General Cognitive Performance score (Jones, Rudolph et al. 2010) and in deriving these scores we intend to use locally available normative data from representative samples, namely the Irish longitudinal studies (The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) and The Irish Longitudinal Study on Ageing (TILDA)).	6-12 weeks post-surgery
Secondary	Incidence of mild cognitive impairment and dementia at the time of follow-up study visit	Diagnosed using appropriate criteria (Albert, DeKosky et al., 2011, McKhann, Knopman et al., 2011).	8 year follow-up