Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001234707
Ethics application status
Approved
Date submitted
2/09/2022
Date registered
13/09/2022
Date last updated
7/04/2024
Date data sharing statement initially provided
13/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing cardiovascular diseases through the eye
Scientific title
Non-invasive assessment of cardiovascular disease in adults via retinal blood vessel imaging using polarisation sensitive optical coherence tomography
Secondary ID [1] 307903 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ACE (Assessing Cardiovascular diseases through the Eye)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cardiovascular diseases 327537 0
Coronary artery disease 327538 0
Hypertension 327539 0
Condition category
Condition code
Cardiovascular 324639 324639 0 0
Coronary heart disease
Cardiovascular 324640 324640 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- Name: Retinal imaging using polarisation-sensitive optical coherence tomography (PS-OCT). A custom-made PS-OCT system will be used in the trial to image the retinas of patients.

- The aim of the study is to establish a normative database for low-cost non-invasive screening based on PS-OCT measurement to accurately screen for coronary artery disease (CAD) through the eye. PS-OCT is an extension of standard optical coherence tomography (OCT), a non-contact imaging method that provides high-resolution, three-dimensional images of biological tissues, in vivo and in real-time. The OCT signal depends on differences in the index of refraction of the tissue to reflect and backscatter and it uses low-coherence interferometry to depth resolve the reflections. OCT has revolutionized the sensitivity and specificity of diagnosis, follow up and response to treatment in almost all fields of clinical practice involving primary ocular pathologies and secondary ocular manifestations in systemic diseases like diabetes mellitus, hypertension, vascular and neurological diseases.
This trial is designed to reflect the potential of the method as an alternative low-cost and non-invasive screening method to screen for cardiovascular diseases in particular CAD. For the trial, two cohorts of subjects will be recruited. The first cohort consists of patients with CAD who have undergone cardiac computed tomography angiography (CCTA) or Invasive coronary angiography (ICA). The second cohort consists of age- and gender-matched healthy individuals without a history of CAD or cardiovascular diseases. The PS-OCT imaging of the patients is expected to be performed within six months of previous cardiac imaging.

- What and how the intervention works: a combination of vessel wall birefringence (as an indication of tissue integrity) and thickness measurement has been used to diagnose hypertension. While the birefringence of the blood vessel walls in patients with hypertension is lower than those without hypertension, the thickness experiences an increase.

- The imaging will be done by PS-OCT experts (Hadi Afsharan and Barry Cense who are experienced biomedical engineers, have imaged tens of subjects, and analysed the PS-OCT data of up to 50 eyes.). Participants will be recruited by a cardiovascular specialist, professor Girish Dwwedi and his associated group.

- Method of imaging: the participant will be asked to sit in front of our PS-OCT system and look at a fixation target. The target helps to stabilize the eye, and it also points the eye into the right direction so that we can image the largest blood vessels around the optic nerve head. A head and chin rest is also designed in the system so the participant can rest their head while performing the imaging. There are two stages of imaging; one for calibrating our system, and one for recording the images from the retina. Before each stage, we need a few seconds to make sure that the system is aligned and the light beam entering the eye is centred on the pupil, because this provides the best image quality. Furthermore, quick processing will be done after the calibration stage to assure that the image quality is high enough for the analysis to be performed. While in most cases the calibration stage will be done only one time per time, for some patients this stage may be performed twice if the image quality is not sufficient. If the image quality is still not sufficient after repeating the calibration, then the imaging session will be terminated. Based on our experience, we expect that the whole procedure will not take more than 20 minutes.

The imaging will be performed at Fiona Stanly Hospital, Perth, Western Australia.

- Imaging will be done once for each participant, however, two or more images may be recorded in a single imaging session. There is also no need to monitor participant compliance or adherence to the intervention.

- No tailoring, modification or personalised intervention is planned.
Intervention code [1] 324363 0
Early detection / Screening
Comparator / control treatment
The Control group in the study is the individuals who do not have any signs of cardiovascular diseases and diabetes.
Control group
Active

Outcomes
Primary outcome [1] 332492 0
Birefringence of the retinal blood vessel assessed for CAD patients using PS-OCT
Timepoint [1] 332492 0
Cumulative data will be assessed at the conclusion of the study which is expected to be two years after the first participant imaging
Primary outcome [2] 332493 0
The thickness of the retinal blood vessel assessed for CAD patients using PS-OCT
Timepoint [2] 332493 0
Cumulative data will be assessed at the conclusion of the study which is expected to be two years after the first participant imaging
Primary outcome [3] 332494 0
Birefringence of the retinal blood vessel assessed for healthy people using PS-OCT
Timepoint [3] 332494 0
Cumulative data will be assessed at the conclusion of the study which is expected to be two years after the first participant imaging
Secondary outcome [1] 413584 0
assessment of the integrity of the blood vessels for CAD patients and healthy participants using blood vessel wall birefringence index (BBI) determined by PS-OCT data.
Timepoint [1] 413584 0
Cumulative data will be assessed at the conclusion of the study which is expected to be two years after the first participant imaging
Secondary outcome [2] 413729 0
The thickness of the retinal blood vessel assessed for healthy people using PS-OCT (primary outcome)
Timepoint [2] 413729 0
Cumulative data will be assessed at the conclusion of the study which is expected to be two years after the first participant imaging

Eligibility
Key inclusion criteria
Age 18 years or older
Willing to give consent.
No cataract or corneal opacity.
For the patients (first cohort): patients who have undergone or are expected to undergo coronary angiography.
• For the healthy subjects (second cohort): people who have not been diagnosed with coronary artery disease and are deemed to be healthy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Patients unable to provide written informed consent.
- Cognitive impairment
- Patients with very poor vision or who have too many cataracts, as these are likely to obstruct the imaging beam, leading to images with insufficient signal-to-noise for analysis.
- Patients who are not able to fixate.
- For some other reason retinal imaging is not feasible.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Participants will be grouped as healthy and non-healthy and all will be imaged with the same imaging technique (same PS-OCT machine)
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
To find the minimum sample size, a conservative approach was taken where an expected sensitivity of 70% and a maximum confidence interval width of W equal to 10% were chosen. Based on the recent statistics reported by CDC, the prevalence of coronary artery disease is about 20%. Given these numbers, the minimum required sample size is 403 samples. Given the fact that two eyes will be imaged for every subject, the number of subjects should be around 200. This number of subjects seems sufficient for the trial study since for each of the images recorded from each eye, four different blood vessels near the optic nerve head will be analysed, accumulating the number of blood vessels to 800. In addition to 200 patients, 200 healthy age-matched subjects will be imaged.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2023
Actual
4/12/2023
Date of last participant enrolment
Anticipated
1/01/2025
Actual
Date of last data collection
Anticipated
1/01/2025
Actual
Sample size
Target
400
Accrual to date
20
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 23100 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 38455 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 312176 0
Self funded/Unfunded
Name [1] 312176 0
Dr Girish Dwevidi
Country [1] 312176 0
Australia
Primary sponsor type
Individual
Name
Hadi Afsharan
Address
The University of Western Australia, 35 Stirling street, Crawley, Western Australia, 6009
Country
Australia
Secondary sponsor category [1] 313701 0
None
Name [1] 313701 0
Address [1] 313701 0
Country [1] 313701 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311561 0
South Metropolitan Health Service Human Research Ethics Committee (EC00265)
Ethics committee address [1] 311561 0
Level 2, Education Building, Fiona Stanley Hospital
14 Barry Marshall Parade
MURDOCH Western Australia 6150
Ethics committee country [1] 311561 0
Australia
Date submitted for ethics approval [1] 311561 0
20/10/2022
Approval date [1] 311561 0
19/12/2022
Ethics approval number [1] 311561 0

Summary
Brief summary
Cardiovascular (CV) disease including coronary artery disease (CAD) is the leading global cause of morbidity and mortality, Early diagnosis of CAD can help to manage the disease. Invasive coronary angiography (ICA) is a common diagnostic test used to detect CAD, but ICA provides no direct assessment of plaque burden, is costly, and also exposes patients to potentially serious complications such as stroke, coronary dissection, and local access site complications.

Recently, we showed that polarisation-sensitive optical coherence tomography (PS-OCT) can be used to non-invasively assess the structure of retinal blood vessel wall tissue in-vivo (https://opg.optica.org/boe/viewmedia.cfm?uri=boe-12-7-4340&html=true). Retinal blood vessels share structure and function with the heart, making them an interesting non-invasive proxy for coronary artery disease.

The objective of the trial is to develop an accurate low-cost tool based on the assessment of retinal blood vessel wall tissue through PS-OCT measurements that can non-invasively screen for cardiovascular diseases, particularly for CAD.
Trial website
Trial related presentations / publications
Public notes
This trial is designed to examine whether the PS-OCT instrument can quantitatively measure any changes in the retinal blood vessel wall thickness and birefringence in a group of patients diagnosed with CAD when compared to healthy age-matched subjects. We have already established the method as described in (https://opg.optica.org/boe/viewmedia.cfm?uri=boe-12-7-4340&html=true) and collected 22 volunteer subjects to begin a feasibility study on hypertension.

Contacts
Principal investigator
Name 121546 0
Dr Hadi Afsharan
Address 121546 0
The University of Western Australia,
35 Stirling Hwy, Crawley WA 6009
Country 121546 0
Australia
Phone 121546 0
+61 414484181
Fax 121546 0
Email 121546 0
[email protected]
Contact person for public queries
Name 121547 0
Hadi Afsharan
Address 121547 0
The University of Western Australia,
35 Stirling Hwy, Crawley WA 6009
Country 121547 0
Australia
Phone 121547 0
+61 8 6488 2317
Fax 121547 0
Email 121547 0
[email protected]
Contact person for scientific queries
Name 121548 0
Hadi Afsharan
Address 121548 0
The University of Western Australia,
35 Stirling Hwy, Crawley WA 6009
Country 121548 0
Australia
Phone 121548 0
+61 8 6488 2317
Fax 121548 0
Email 121548 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
No individual data will not be available. No individual images will be released. The collected images will be used to extract polarisation properties such as the thickness and birefringence of the blood vessels.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17109Informed consent form  [email protected]



Results publications and other study-related documents

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