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Trial registered on ANZCTR


Registration number
ACTRN12612000493842
Ethics application status
Approved
Date submitted
20/04/2012
Date registered
7/05/2012
Date last updated
19/02/2020
Date data sharing statement initially provided
19/02/2020
Date results information initially provided
19/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Alzheimer's disease, cognition and cerebrospinal fluid: Are they associated?
Scientific title
An observational study of Alzheimer's disease, cognition and cerebrospinal fluid: Are they associated?
Secondary ID [1] 279633 0
Nil
Universal Trial Number (UTN)
U1111-1126-5641
Trial acronym
CAPACITY study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 285433 0
Effect of anaesthesia and surgery on cognition 286340 0
Cerebrospinal fluid (CSF) predictors of cognitive change and Alzheimer's diseae 286341 0
Condition category
Condition code
Anaesthesiology 285613 285613 0 0
Anaesthetics
Neurological 285614 285614 0 0
Alzheimer's disease
Mental Health 286586 286586 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is an observational study which will identify if surgery and anaesthesia increase the risk of adverse central nervous system outcomes, including acceleration of the Alzheimer's disease process and subsequent earlier expression. Cognition and function will be measured for 18 months postoperatively to identify any change including signs and symptoms of dementia.
Intervention code [1] 283913 0
Early Detection / Screening
Comparator / control treatment
The effect of anaesthesia and surgery will be assessed by comparing the change in cognition in surgical patients with the change in cognition observed in patients in the AIBL study (without surgical intervention) who have been matched for age, gender, baseline cognition and CSF profile.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 287008 0
To determine the extent to which a pre-operative CSF signature of Alzheimer's disease (amyloid beta 1-42; total-tau and phospho-tau) predicts postoperative cognitive dysfunction (POCD) and increase in clinical dementia rating (CDR) scale in elderly patients who receive general anaesthesia for orthopaedic surgery.
Timepoint [1] 287008 0
Baseline, 3, 12 and 18 months postoperatively
Secondary outcome [1] 297186 0
To identify an association between POCD, Mild Cognitive Impairment (MCI) and dementia. Baseline cognitive and functional data collected at baseline assessment will be compared with 3, 12 and 18 month follow-ups cognitive and functional assessment to measure cognitive outcomes and risk of dementia.
Timepoint [1] 297186 0
Baseline, 3, 12 and 18 months postoperatively
Secondary outcome [2] 297187 0
To identify risk factors for POCD and progressive cognitive decline (MCI and dementia) after anaesthesia and surgery.
Medical history details of risk factors will be collected from the patient at baseline and verified by the patient's medical record.
Timepoint [2] 297187 0
Baseline and 3 months postoperatively
Secondary outcome [3] 380287 0
Exploratory analyses of the blood samples will be undertaken to identify known and unknown biomarkers for cognition and neuronal injury.
Timepoint [3] 380287 0
baseline, 30 min, 6, 24 and 48 hours post surgery.

Eligibility
Key inclusion criteria
Patients aged 60y or more who are scheduled for elective total hip joint replacement (THJR) or total knee joint replacement (TKJR) who do not have neurological deficit; give informed consent; have no contraindication to neuropsychological testing; and reside in accessible proximity to the hospital to enable investigators to administer neuropsychological testing at patients' home.
Minimum age
60 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pre-existing neurological or clinically evident neurovascular disease (eg. stroke); Clnical Dementia Rating score >=1 (exclude frank dementia); anticipated difficulty with neuropsychological assessment, such as English not being the prime language, blindness, deafness; associated medical problems that may lead to significant loss to follow-up (ASA physical status IV or higher); geographical remoteness.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 285144 0
Charities/Societies/Foundations
Name [1] 285144 0
Alzheimer's Australia Dementia Research Foundation Limited
Address [1] 285144 0
1 Frewin Place
Scullin
ACT 2614
Country [1] 285144 0
Australia
Funding source category [2] 287930 0
Government body
Name [2] 287930 0
National Health and Medical Research Council
Address [2] 287930 0
GPO Box 1421
Canberra ACT 2601
Country [2] 287930 0
Australia
Primary sponsor type
Hospital
Name
St. Vincent's Hospital
Address
PO Box 2900
Fitzroy
VIC 3065
Country
Australia
Secondary sponsor category [1] 284008 0
Individual
Name [1] 284008 0
Lisbeth Evered
Address [1] 284008 0
Centre for Anaesthesia and Cognitive Function
Department of Anaesthesia
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Country [1] 284008 0
Australia
Other collaborator category [1] 260761 0
Individual
Name [1] 260761 0
David Scott
Address [1] 260761 0
Centre for Anaesthesia and Cognitive Function
Department of Anaesthesia
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Country [1] 260761 0
Australia
Other collaborator category [2] 260762 0
Individual
Name [2] 260762 0
Brendan Silbert
Address [2] 260762 0
Centre for Anaesthesia and Cognitive Function
Department of Anaesthesia
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Country [2] 260762 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287159 0
St. Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 287159 0
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Ethics committee country [1] 287159 0
Australia
Date submitted for ethics approval [1] 287159 0
01/05/2012
Approval date [1] 287159 0
08/05/2012
Ethics approval number [1] 287159 0
149/11

Summary
Brief summary
The overarching hypothesis for this study is that in older adults who undergo surgery, occult or preclinical Alzheimer’s Disease (AD) increases the risk of adverse central nervous system (CNS) outcomes, including acceleration of the AD disease process itself and subsequent earlier clinical expression. The specific hypotheses are:
1. In older people undergoing elective orthopaedic surgery, the presence of a cerebrospinal fluid (CSF) signature of Alzheimer’s Disease (AD) at baseline will be associated with a greater incidence and or severity of decline in Clinical Dementia Rating scale at 18 months post-operatively, compared with a non-surgical group with a CSF signature of AD and equivalent baseline cognition.
2. At baseline, a CSF signature of AD in surgical patients will be associated with a higher incidence of PostOperative Cognitive Dysfunction (POCD) and functional change at 3, 12, and 18 months post-operatively compared to surgical patients without the CSF AD signature.
3. Individuals classified with POCD will be at higher risk of conversion from cognitively normal to MCI or to dementia, or from MCI to dementia, compared with those who are not classified with POCD.
Trial website
www.cognition.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 33555 0
A/Prof Brendan Silbert
Address 33555 0
St Vincent's Hospital
PO Box 2900
Fitzroy 3065
Vic
Country 33555 0
Australia
Phone 33555 0
+61 9288 4253
Fax 33555 0
Email 33555 0
Brendan.SILBERT@svhm.org.au
Contact person for public queries
Name 16802 0
Dr Lisbeth Evered
Address 16802 0
Centre for Anaesthesia and Cognitive Function
Department of Anaesthesia
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Country 16802 0
Australia
Phone 16802 0
+61 3 9288 2251
Fax 16802 0
+61 3 9288 4255
Email 16802 0
lis.evered@svhm.org.au
Contact person for scientific queries
Name 7730 0
Dr Lisbeth Evered
Address 7730 0
Centre for Anaesthesia and Cognitive Function
Department of Anaesthesia
St. Vincent's Hospital
PO Box 2900
Fitzroy VIC 3065
Country 7730 0
Australia
Phone 7730 0
+61 3 9288 2251
Fax 7730 0
+61 3 9288 4255
Email 7730 0
lis.evered@svhm.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It is intended that the IPD will be made available for this trial but specific details have not yet been ascertained.
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Clinical study report
Ethical approval
Analytic code
How or where can supporting documents be obtained?
Type [1] 6960 0
Study protocol
Citation [1] 6960 0
Link [1] 6960 0
Email [1] 6960 0
lis.evered@svha.org.au
Other [1] 6960 0
Attachment [1] 6960 0
Type [2] 6961 0
Statistical analysis plan
Citation [2] 6961 0
Link [2] 6961 0
Email [2] 6961 0
lis.evered@svha.org.au
Other [2] 6961 0
Attachment [2] 6961 0
Type [3] 6962 0
Informed consent form
Citation [3] 6962 0
Link [3] 6962 0
Email [3] 6962 0
lis.evered@svha.org.au
Other [3] 6962 0
Attachment [3] 6962 0
Type [4] 6963 0
Clinical study report
Citation [4] 6963 0
Link [4] 6963 0
Email [4] 6963 0
lis.evered@svha.org.au
Other [4] 6963 0
Attachment [4] 6963 0
Type [5] 6964 0
Ethical approval
Citation [5] 6964 0
Link [5] 6964 0
Email [5] 6964 0
lis.evered@svha.org.au
Other [5] 6964 0
Attachment [5] 6964 0
Type [6] 6965 0
Analytic code
Citation [6] 6965 0
Link [6] 6965 0
Email [6] 6965 0
lis.evered@svha.org.au
Other [6] 6965 0
Attachment [6] 6965 0
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 6966 0
Evered L, Silbert B, Scott DA, Zetterberg H, Blennow K: Association of Changes in Plasma Neurofilament Light and Tau Levels With Anesthesia and Surgery. JAMA Neurol 2018 doi:10.1001/jamaneurol.2017.4913
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary