Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000989943
Ethics application status
Approved
Date submitted
23/07/2020
Date registered
1/10/2020
Date last updated
1/10/2020
Date data sharing statement initially provided
1/10/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessment of cognitive function and cerebral blood flow in patients undergoing aortic valve intervention
Scientific title
Assessment of cognitive function and cerebral blood flow using transcranial Doppler ultrasound in patients undergoing aortic valve intervention
Secondary ID [1] 301491 0
None
Universal Trial Number (UTN)
U1111-1253-4137
Trial acronym
TAVICOG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aortic Stenosis 317824 0
Transcatheter aortic valve implantation 318701 0
Surgical aortic valve implantation 318702 0
Condition category
Condition code
Cardiovascular 315882 315882 0 0
Diseases of the vasculature and circulation including the lymphatic system
Mental Health 315883 315883 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
We aim to perform a prospective study of the relationship between changes in cerebral blood flow and cognitive function (neurovascular coupling) in a cohort of patients undergoing aortic valve intervention. We aim to assess patients undergoing both transcatheter (TAVI) and traditional surgical aortic valve (SAVI) intervention to document changes in cerebral blood responses following aortic valve replacement by evaluating patients before and within three to six months after their aortic valve procedures. Participants will attend the research clinic at the University of Newcastle on two occasions. Visits will last up to one and a half hours each.

Anthropometric measurements of height, weight and waist circumference will be obtained before the clinic BP is assessed.

A headpiece supporting a transcranial doppler (TCD) ultrasound probe on each temporal region will be fitted to patients. It may take up to 15 minutes to find a signal. The ultrasound will continuously record changes in the blood velocities in the MCA during the cognitive test battery.

Global cognition will be assessed using the Addenbrooke’s Cognitive Examination-III (ACE-III). Trail Making Task will be assessed by pen-paper modality. Spatial Forward Span test. Controlled Oral Word Association Test. Digit Symbol Coding. Psychomotor speed will be assessed using the 9-hole Pegboard Dexterity test. Pattern Comparison Processing Speed Test (NIH-ToolBox). Cognitive testing will take approximately 35 minutes.

After the cognitive tests, the investigator will adjust the ultrasound probes to locate the posterior cerebral arteries. Once a suitable blood flow signal is located, participants will be asked to open and close their eyes as guided by the investigator.

Mood will be assessed using: The Center for Epidemiologic Studies Depression Scale (CES-D) and The State-Trait Anxiety Inventory (STAI). Quality of life will be assessed using the short-form 36 (SF-36).

The visits will be conducted by an experienced Research Assistant, overseen by the Clinical Trials Coordinator.
Intervention code [1] 317798 0
Diagnosis / Prognosis
Comparator / control treatment
We will assess 15 patients undergoing transcatheter aortic valve intervention (TAVI) and 15 patients undergoing surgical aortic valve implantation (SAVI). Participants will not be allocated to these groups by the study. The TAVI group is the 'comparator' group.
Control group
Active

Outcomes
Primary outcome [1] 324088 0
Within-individual pre-post difference in cerebrovascular responsiveness (CVR) to cognitive testing at the level of the middle cerebral artery (MCA) assessed by TCD ultrasound.
Timepoint [1] 324088 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [1] 383727 0
Within-individual pre-post difference in Basal cerebrovascular haemodynamics assessed by TCD ultrasound.
We will measure: maximum BFV, mean BFV, minimum BFV, pulsatility index, cerebrovascular responsiveness (%).
Timepoint [1] 383727 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [2] 383728 0
Within-individual pre-post difference in Cognitive function assessed by the Addenbrooke’s Cognitive Examination-III (ACE-III).
Timepoint [2] 383728 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [3] 383729 0
Within-individual pre-post difference in CVR to photic stimulation assessed by TCD ultrasound.
Mean blood flow velocities in the posterior cerebral arteries will be recorded during 60 sec of eyes open, followed by a 30 sec of eyes shut and 30 sec with eyes open. Responsiveness to photic stimulation will be calculated as the percentage increase of peak mean blood flow velocity over baseline velocity.
Timepoint [3] 383729 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [4] 383731 0
Manual dexterity (psychomotor speed), measured using the NIH Toolbox 9-hole Pegboard Dexterity test. This will be administered by iPad, the iPad will be used to time the tests.
Timepoint [4] 383731 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [5] 384794 0
Within-individual pre-post difference in Cognitive function assessed by cognitive test battery:
Trail Making Task Part A and Part B will be assessed by pen-paper modality.
Timepoint [5] 384794 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [6] 384795 0
Within-individual pre-post difference in Cognitive function assessed by cognitive test battery:
Spatial Forward Span test.
Timepoint [6] 384795 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [7] 384796 0
Within-individual pre-post difference in Cognitive function assessed by cognitive test battery:
Controlled Oral Word Association Test.
Timepoint [7] 384796 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [8] 384797 0
Within-individual pre-post difference in Cognitive function assessed by cognitive test battery:
Digit Symbol Coding: digit-symbol substitution WAIS-III.
Timepoint [8] 384797 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [9] 384798 0
Within-individual pre-post difference in Cognitive function assessed by cognitive test battery:
Pattern Comparison Processing Speed Test (NIH-ToolBox).
Timepoint [9] 384798 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [10] 385944 0
Within-individual pre-post difference in Mood and perceived quality-of-life, measured using: The Center for Epidemiologic Studies Depression Scale (CES-D).
Timepoint [10] 385944 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [11] 385945 0
Within-individual pre-post difference in Mood and perceived quality-of-life, measured using: The State-Trait Anxiety Inventory (STAI).
Timepoint [11] 385945 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [12] 385946 0
Within-individual pre-post difference in Mood and perceived quality-of-life, measured using: The short-form 36 (SF-36).
Timepoint [12] 385946 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [13] 385947 0
Anthropometric measurements of height, weight and waist circumference, measured with scales and tape measures, one wall-mounted.
Timepoint [13] 385947 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [14] 385948 0
Blood pressure, measured by sphygmomanometer.
Timepoint [14] 385948 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)
Secondary outcome [15] 385949 0
HR and Cerebral artery stiffness (extent of arterial hardening) using pulsatility index (TCD).
Timepoint [15] 385949 0
Visit 1 (pre-valve intervention) and Visit 2 (3- 6 months post-valve intervention)

Eligibility
Key inclusion criteria
15 patients with aortic stenosis undergoing surgical aortic valve intervention and 15 patients undergoing transcatheter aortic valve intervention.

Age > 18 years
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to obtain a measurable signal in either left or right MCA.

Uncontrolled hypertension (>160/100mmHg).

Pregnant women and people highly dependent on medical care.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Baseline demographics and clinical data will be collated with differences between the transcatheter (TAVI) and surgical (SAVI) groups compared using Students t-test for continuous variables and chi-square tests for categorical variables.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/10/2020
Actual
Date of last participant enrolment
Anticipated
4/03/2021
Actual
Date of last data collection
Anticipated
4/06/2021
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 16871 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 30521 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 305931 0
Charities/Societies/Foundations
Name [1] 305931 0
John Hunter Hospital Charitable Trust
Country [1] 305931 0
Australia
Primary sponsor type
Individual
Name
Dr Nicholas Collins
Address
Nicholas Collins
Staff Specialist Cardiologist
John Hunter Hospital
Lookout Road.
New Lambton 2305 NSW
Country
Australia
Secondary sponsor category [1] 306383 0
Individual
Name [1] 306383 0
Dr Rachel Wong
Address [1] 306383 0
Clinical Nutrition Research Centre
University of Newcastle
School of Biomedical Sciences & Pharmacy
Medical Sciences Building, MS 514
University Drive, Callaghan, NSW 2308
Country [1] 306383 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306178 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 306178 0
Research Ethics and Governance Unit
Locked bag 1
New Lambton NSW 2305
Ethics committee country [1] 306178 0
Australia
Date submitted for ethics approval [1] 306178 0
29/05/2020
Approval date [1] 306178 0
20/07/2020
Ethics approval number [1] 306178 0
2020/ETH01269
Ethics committee name [2] 306714 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 306714 0
Research & Innovation Services
Research Integrity Unit
The University of Newcastle
Callaghan NSW 2308
Ethics committee country [2] 306714 0
Australia
Date submitted for ethics approval [2] 306714 0
20/07/2020
Approval date [2] 306714 0
21/07/2020
Ethics approval number [2] 306714 0
H-2020-0256

Summary
Brief summary
Aortic stenosis is a common condition caused by a narrowing of the aortic valve that can be resolved by replacing the valve. Traditionally this has been performed with open-heart surgery, which is effective but may be associated with significant complications. Transcatheter aortic valve intervention (TAVI) is an alternative to surgical replacement that has resulted in improved results for patients at high and intermediate risk for surgery. It is understood that surgical valve replacement may negatively affect cognitive function, though the effect of TAVI on cognitive function is less clear; relieving the narrowing improves blood flow to the brain and may improve cognition, however, the procedure may lead to small blood clots being sent to the brain that limit this improvement.
In this study, we are looking to examine whether patients who undergo the different aortic valve procedures may have disturbances in the blood flow in their brain after the procedure and how this affects mental performance. We will use transcranial Doppler ultrasound (TCD) to measure blood flow in the brain during a series of mental tests and compare the results before and after the procedure.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 102982 0
Dr Nicholas Collins
Address 102982 0
Staff Specialist Cardiologist
John Hunter Hospital
c/- 58 Cleary Street
Hamilton NSW 2303
Country 102982 0
Australia
Phone 102982 0
+61 0411987025
Fax 102982 0
Email 102982 0
[email protected]
Contact person for public queries
Name 102983 0
Dr Nicholas Collins
Address 102983 0
Staff Specialist Cardiologist
John Hunter Hospital
c/- 58 Cleary Street
Hamilton NSW 2303
Country 102983 0
Australia
Phone 102983 0
+61 0411987025
Fax 102983 0
Email 102983 0
[email protected]
Contact person for scientific queries
Name 102984 0
Dr Nicholas Collins
Address 102984 0
Staff Specialist Cardiologist
John Hunter Hospital
c/- 58 Cleary Street
Hamilton NSW 2303
Country 102984 0
Australia
Phone 102984 0
+61 0411987025
Fax 102984 0
Email 102984 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8547Study protocol    379981-(Uploaded-20-07-2020-14-55-54)-Study-related document.docx
8548Ethical approval    379981-(Uploaded-20-07-2020-14-56-06)-Study-related document.pdf
8576Ethical approvalUON Registration of External HREC Approval   379981-(Uploaded-23-07-2020-09-41-36)-Study-related document.pdf



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.