Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000363886
Ethics application status
Approved
Date submitted
18/02/2021
Date registered
31/03/2021
Date last updated
17/06/2022
Date data sharing statement initially provided
31/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Brain health in atrial fibrillation
Scientific title
Unravelling a clot-less link between atrial fibrillation and dementia - an MRI study of cerebrovascular and cardiac function in adults
Secondary ID [1] 303765 0
None
Universal Trial Number (UTN)
U1111-1245-5413
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial Fibrillation 320831 0
Dementia 321253 0
Condition category
Condition code
Cardiovascular 318654 318654 0 0
Other cardiovascular diseases
Neurological 319035 319035 0 0
Dementias

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a non-therapeutic mechanistic physiological study.

It will study people with atrial fibrillation and healthy people with a normal heart rhythm. They will attend a single preliminary screening visit (~45 min) and a single MRI scan visit (~90 min).

A sub-set of people with atrial fibrillation will be asked to attend a second visit to complete the same assessments undertaken at the MRI scan visit up to 14 days after the restoration of sinus rhythm (clinically indicated). This sub-set will be selected based on participant inability to attend MRI scan visits.

Assessments:

Screening visit-
MRI Safety Screening Form and Health Screening Questionnaires
Delivered by a trained investigator. Delivered face-to-face.
Delivered once. Takes 5-10 min to complete this paper form.

Cognitive function will be assessed using a touch sensitive tablet device.
Delivered by a trained investigator. Delivered face-to-face.
Delivered once. Takes ~20 min to complete this assessment.

MRI scan visit-
Height, weight, and blood pressure
Delivered by a trained investigator. Delivered face-to-face.
Delivered once. Takes 5-10 min to complete this assessment.

Measurement of cerebral blood flow and cerebral metabolic rate for oxygen using MRI
Assessed under baseline/resting conditions, and during neurovacular coupling and CO2 reactivity testing described below. Takes ~10 min to complete this assessment.
Delivered by a trained radiologist and investigator team. Delivered face-to-face.

Neurovascular coupling test in MRI scanner
Participants will view a black/white flickering radial checkerboard visual stimulus alternated with a neutral grey screen baseline.
Delivered by a trained radiologist and investigator team. Delivered face-to-face.
Delivered as 5 x ~30s exposures, separated by ~30 s.
Procedure conducted once per visit.

Cerebrovascular CO2 reactivity
Participants alternate between breathing room air and a premixed gas mixture with a mildly elevated partial pressure of CO2 (5% CO2, 21% O2, balance N2) via a Douglas bag (~2 min).
Delivered by a trained radiologist and investigator team. Delivered face-to-face.
Procedure conducted once per visit.

Cardiac MRI
Conventional ECG-gated retrospective cine cardiac MRI acquisitions will be acquired parallel and perpendicular to the cardiac long-axis.
Delivered by a trained radiologist and investigator team. Delivered face-to-face.
Delivered once per visit. Takes ~15-20 min to complete.
Intervention code [1] 319792 0
Diagnosis / Prognosis
Comparator / control treatment
Healthy control participants with a normal heart rhythm
Control group
Active

Outcomes
Primary outcome [1] 326600 0
Neurovascular coupling as assessed using a MRI scan.
Timepoint [1] 326600 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure
Secondary outcome [1] 392054 0
Cerebrovascular CO2 reactivity as assessed with a MRI scan.
Timepoint [1] 392054 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure
Secondary outcome [2] 393204 0
MRI measurement of cerebral blood flow and cerebral metabolic rate for oxygen assessed under baseline/resting conditions
Timepoint [2] 393204 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure
Secondary outcome [3] 393206 0
ECG-gated retrospective cine cardiac MRI acquisitions
Timepoint [3] 393206 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure
Secondary outcome [4] 393207 0
Cognitive function with interactive quizzes/tests on a touch screen tablet device
Timepoint [4] 393207 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure.
Secondary outcome [5] 393208 0
Blood pressure using a non-invasive brachial artery BP monitor
Timepoint [5] 393208 0
Healthy controls and atrial fibrillation patients will be assessed at a single timepoint of acquisition (i.e., at experimental session). A subset of atrial fibrillation participants will undergo a second observation session up to 14 days post-sinus restoration procedure

Eligibility
Key inclusion criteria
Atrial fibrillation patients
• Chronic AF established on ECG or Holter monitoring
• Men and women
• Aged 18 years and over

A sub-set of atrial fibrillation patients will be studied before and after:
• A clinical decision (i.e., unrelated to the research study) to attempt restoration of sinus rhythm with cardioversion or by radiofrequency/ cryo-ablation has been taken.

Healthy sinus rhythm controls
• Healthy control subjects in sinus rhythm
• Not taking any prescription or over-the-counter medications (other than oral contraceptive pill)
• Men and women
• Aged 18 years and over
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• <18 years old
• Normal contraindications for MRI (e.g., metallic implants)
• Current use of oral nitrates
• Hemodynamically significant valvular heart disease (e.g., stenosis, mechanical valve replacement)
• Severe left ventricular systolic dysfunction
• Recent acute coronary syndrome (<12 months) (e.g., MI, angioplasty, unstable angina)
• Severe respiratory disease (e.g., chronic obstructive pulmonary disease)
• Severe, uncontrolled type II diabetes (e.g., insulin dependent)
• Current cancer diagnosis or complete remission <5 years
• Connective tissue or inflammatory disease (e.g., rheumatoid arthritis, lupus)
• Neurological / psychiatric disease (e.g., stroke, TIA, dementia, Parkisnon’s)
• Current infection or pyrexial illness
• Uncontrolled thyroid disorders
• Hepatic or renal impairment (e.g., eGFR <60)
• Current pregnancy
• Current hormone replacement therapy
• Current user of recreational drugs
• Current abuser of alcohol
• Current smoker
• Body mass index < 18 kg/m2.
• Underlying medical conditions, which in the opinion of the Investigator place the participant at unacceptably high risk for participating in the study
• Inability to fully or appropriately participate in the study

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
For the assessment of normality and homogeneity of distribution of each variable will be performed using the Kolmogorov-Smirnov and Levene’s tests, respectively. Chi-square (X2) test will be used to analyse categorical data. Comparisons between groups will be undertaken using t-tests or an appropriate non-parametric alternative.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/06/2021
Actual
4/05/2022
Date of last participant enrolment
Anticipated
29/02/2024
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
50
Accrual to date
4
Final
Recruitment outside Australia
Country [1] 23478 0
New Zealand
State/province [1] 23478 0
Auckland

Funding & Sponsors
Funding source category [1] 307922 0
Government body
Name [1] 307922 0
Royal Society Te Aparangi - Marsden Fund
Country [1] 307922 0
New Zealand
Primary sponsor type
University
Name
University of Auckland
Address
Private Bag 92019
Auckland 1142
New Zealand
Country
New Zealand
Secondary sponsor category [1] 308639 0
None
Name [1] 308639 0
Address [1] 308639 0
Country [1] 308639 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307920 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 307920 0
Ethics committee country [1] 307920 0
New Zealand
Date submitted for ethics approval [1] 307920 0
Approval date [1] 307920 0
05/03/2020
Ethics approval number [1] 307920 0
20/CEN/30

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108934 0
A/Prof James P Fisher
Address 108934 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 108934 0
New Zealand
Phone 108934 0
+6493737599
Fax 108934 0
Email 108934 0
[email protected]
Contact person for public queries
Name 108935 0
James P Fisher
Address 108935 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 108935 0
New Zealand
Phone 108935 0
+6493737599
Fax 108935 0
Email 108935 0
[email protected]
Contact person for scientific queries
Name 108936 0
James P Fisher
Address 108936 0
Faculty of Medical and Health Sciences
Department of Physiology
University of Auckland
85 Park Road
Grafton
Auckland 1023
Country 108936 0
New Zealand
Phone 108936 0
+6493737599
Fax 108936 0
Email 108936 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?

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.