Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
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
Atrial fibrillation is a common heart rhythm disorder, which increases the lifetime risk of cognitive impairment disorders. Traditionally this was ascribed to blood clots formed during episodes of atrial fibrillation lodging in the brain, however even patients taking anti-coagulants (blood-thinners) without any sort of clot-related stroke are more likely to suffer from dementia and cognitive decline. We propose that the brain blood vessel responsiveness is dysfunctional in atrial fibrillation. To test our hypothesis we will use advanced magnetic resonance imaging techniques to assess brain blood vessel responsiveness in atrial fibrillation patients and matched control participants who have a normal heart rhythm. We will also determine whether brain blood vessel function is rescued in atrial fibrillation after restoring the normal heart rhythm (with [clinically indicated] cardioversion or radiofrequency/ cryo-ablation). These studies will provide novel mechanistic insights into the influence of atrial fibrillation on brain blood vessel function, and may inform the development of therapeutic strategies to offset the insidious effects of atrial fibrillation on the brain.
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.