Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001210369
Ethics application status
Approved
Date submitted
15/08/2017
Date registered
18/08/2017
Date last updated
5/04/2023
Date data sharing statement initially provided
5/04/2023
Date results information initially provided
5/04/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Does cerebral perfusion impact on cognitive function following intervention for carotid artery stenosis?
Scientific title
Does cerebral perfusion impact on cognitive function following intervention for carotid artery stenosis?
Secondary ID [1] 292665 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
carotid artery stenosis 304406 0
cognition 304407 0
Condition category
Condition code
Cardiovascular 303736 303736 0 0
Diseases of the vasculature and circulation including the lymphatic system
Mental Health 303737 303737 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Cerebral perfusion (as measured by cerebral blood flow on transcranial doppler, cerebral oximetry on near-infrared spectroscopy, and magnetic resonance imaging with arterial spin labelling protocols and diffusion weighted imaging), and cognitive function (as measured by CogState, DKEFS Verbal Fluency test, and Stroop test) will be measured pre-intervention/1 week post-intervention/4 weeks post-intervention/3 months post-intervention in patients who undergo either carotid endarterectomy for high-grade carotid artery stenoses for stroke risk reduction (under current algorithms and evidence for carotid intervention). Cerebrovascular reserve as per Ringelstein calculations will also be measured pre-intervention/4 weeks post-intervention/3 months post-intervention using hypocapnic (baseline minus 6mmHg EtCO2), room air, 3% CO2 inhalation, and 6% CO2 inhalation.
Intervention code [1] 298901 0
Not applicable
Comparator / control treatment
Healthy age and education matched subjects with or without out high-grade carotid stenoses will undergo the above listed measurements at 4 time points equivalent to those undergoing carotid intervention - baseline measurement (equivalent to pre-intervention), 1-2 weeks post-baseline (equivalent to 1 week post-intervention), 4-6 weeks post-baseline (equivalent to 4 weeks post-intervention), and 3-4 months post-baseline (equivalent to 3 months post-intervention).
Control group
Active

Outcomes
Primary outcome [1] 303104 0
Cognitive function as measured by CogState battery, DKEFS Verbal Fluency test, Stroop test; measured as a composite.
Timepoint [1] 303104 0
Pre-intervention (approx 1 week pre), 1 week post-intervention, 4 weeks post-intervention, 3 months post-intervention
Primary outcome [2] 303108 0
Cerebral perfusion as measured by MRI arterial spin labelled protocol
Timepoint [2] 303108 0
Pre-intervention (approx 1 week pre), 1 week post-intervention
Primary outcome [3] 303110 0
Cerebrovascular reactivity as measured by transcranial doppler of middle cerebral artery flows, with four stimuli (hypocapnic ie baseline minus 6mmHg EtCO2, baseline at room air, 3% CO2, 6% CO2), calculated as per Ringelstein's equation.
Timepoint [3] 303110 0
Pre-intervention (approx 1 week pre), 1 week post-intervention, 4 weeks post-intervention, 3 months post-intervention
Secondary outcome [1] 337892 0
Quality of life as measured by WHO-QOL questionnaire
Timepoint [1] 337892 0
Pre-intervention, 1 week post-intervention, 4 weeks post-intervention, 3 months post-intervention.
Secondary outcome [2] 337898 0
Mood as measured by POMS-A questionnaire, administered immediately prior to cognitive testing
Timepoint [2] 337898 0
Pre-intervention, 1 week post-intervention, 4 weeks post-intervention, 3 months post-intervention.

Eligibility
Key inclusion criteria
Patients 45-89 years of age planned for carotid endarterectomy or carotid artery stenting of high-grade carotid stenoses for stroke risk reduction.
Healthy control group: 45-89 years of age, age and education matched volunteers/spouses.
Minimum age
45 Years
Maximum age
89 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Non-English speaking
Functional impairment impeding physical ability to participate in cognitive testing
Diagnosed dementia
Haemorrhagic stroke
Stroke post-operatively
On neuro-modulating drugs

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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/08/2017
Actual
18/08/2017
Date of last participant enrolment
Anticipated
31/10/2019
Actual
31/10/2019
Date of last data collection
Anticipated
31/01/2020
Actual
10/01/2020
Sample size
Target
66
Accrual to date
Final
68
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 8808 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 8809 0
St John of God Hospital, Subiaco - Subiaco
Recruitment hospital [3] 8810 0
Mount Hospital - Perth
Recruitment postcode(s) [1] 16931 0
6009 - Nedlands
Recruitment postcode(s) [2] 16932 0
6008 - Subiaco
Recruitment postcode(s) [3] 16933 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 297300 0
Other Collaborative groups
Name [1] 297300 0
Heart Research Institute
Country [1] 297300 0
Australia
Funding source category [2] 297307 0
Hospital
Name [2] 297307 0
Sir Charles Gairdner Hospital
Country [2] 297307 0
Australia
Funding source category [3] 297308 0
University
Name [3] 297308 0
School of Science (Exercise and Sports Science), University of Western Australia
Country [3] 297308 0
Australia
Funding source category [4] 300191 0
Commercial sector/Industry
Name [4] 300191 0
WL Gore & Associates
Country [4] 300191 0
Australia
Funding source category [5] 300192 0
Commercial sector/Industry
Name [5] 300192 0
Boston Scientific
Country [5] 300192 0
Australia
Funding source category [6] 300193 0
Commercial sector/Industry
Name [6] 300193 0
Abbott Medical
Country [6] 300193 0
Australia
Funding source category [7] 300194 0
University
Name [7] 300194 0
Curtin University
Country [7] 300194 0
Australia
Primary sponsor type
Individual
Name
Dr Shirley Jansen
Address
Dept of Vascular and Endovascular Surgery
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, Perth
WA 6009
Country
Australia
Secondary sponsor category [1] 296272 0
Individual
Name [1] 296272 0
Dr Chi Ho Ricky Kwok
Address [1] 296272 0
Dept of Vascular and Endovascular Surgery
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands, Perth
WA 6009
Country [1] 296272 0
Australia
Secondary sponsor category [2] 296273 0
Individual
Name [2] 296273 0
Winthrop Professor Daniel Green
Address [2] 296273 0
School of Science (Exercise and Sports Science)
University of Western Australia (M408)
35 Stirling Highway
Crawley, Perth
Western Australia 6009
Country [2] 296273 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298408 0
Human Research Ethics Committee, Sir Charles Gairdner Hospital
Ethics committee address [1] 298408 0
Sir Charles Gairdner Hospital
Level 2, A Block, Hospital Avenue, NEDLANDS WA 6009
Ethics committee country [1] 298408 0
Australia
Date submitted for ethics approval [1] 298408 0
30/11/2014
Approval date [1] 298408 0
11/02/2015
Ethics approval number [1] 298408 0
RGS0000001708

Summary
Brief summary
The link between carotid artery disease and stroke is well defined in severe carotid artery stenosis. The link between carotid artery disease, cerebral perfusion, and cognitive function, is less well characterised, particularly in the absence of clinical stroke. Characterising the relationship between carotid stenosis, cerebral perfusion, and cognitive function is relevant to 1). understanding the role of carotid intervention in improving cerebral perfusion and cognitive function and, thereby, dementia prevention; 2). reconsidering the threshold for intervention in those patients who are judged ‘asymptomatic’ by current criteria (whereby indications for intervention are based on stroke risk reduction); and 3). examining whether the two distinct forms of intervention for carotid stenosis (carotid endarterectomy and carotid artery stenting) have different impacts on cognitive function. Alongside our study of the impact of intervention for carotid stenosis and cognition, we will also examine relationships between changes in cognition and quality of life. If improvement in cerebral perfusion and cognitive function in patients treated for asymptomatic carotid artery stenosis can be demonstrated, this would impact significantly on decision making and treatment for these patients with respect to the prevention of cognitive decline.

The overarching aim of this research is to determine whether changes in cognitive function occur in older adults following intervention for carotid artery stenosis.

The primary objectives are to investigate whether:
1) carotid endarterectomy (CEA) improves cognitive function in patients with symptomatic and asymptomatic carotid artery stenosis,
2) changes in cognitive function following CEA are related to changes in cerebral blood flow and cerebrovascular reserve (CVR) in patients with symptomatic and asymptomatic carotid artery stenosis,
4) changes in cognitive function following CEA are related to findings on MRI, and specifically, on arterial spin-labelled cerebral perfusion imaging,
5) changes in cognitive function following CEA are independent of changes in mood scores,
6) changes in cognitive function following CEA are related to changes in quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76994 0
Dr Chi Ho Ricky Kwok
Address 76994 0
Dept of Vascular and Endovascular Surgery
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands
WA 6009
Country 76994 0
Australia
Phone 76994 0
+61 8 6457 3333
Fax 76994 0
+61 8 6457 2298
Email 76994 0
[email protected]
Contact person for public queries
Name 76995 0
Dr Ricky Kwok
Address 76995 0
Dept of Vascular and Endovascular Surgery
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands
WA 6009
Country 76995 0
Australia
Phone 76995 0
+61 8 6457 3333
Fax 76995 0
+61 8 6457 2298
Email 76995 0
[email protected]
Contact person for scientific queries
Name 76996 0
Dr Ricky Kwok
Address 76996 0
Dept of Vascular and Endovascular Surgery
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands
WA 6009
Country 76996 0
Australia
Phone 76996 0
+61 8 6457 3333
Fax 76996 0
+61 8 6457 2298
Email 76996 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
deidentified cognitive and perfusion data
When will data be available (start and end dates)?
From publication until Jan 2027.
Available to whom?
Upon request with a sound proposal, as determined by primary sponsor
Available for what types of analyses?
To achieve aims of approved proposal
How or where can data be obtained?
Request initially via email [email protected]


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.