Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000887572
Ethics application status
Approved
Date submitted
1/06/2023
Date registered
22/07/2024
Date last updated
19/10/2024
Date data sharing statement initially provided
22/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Detecting early eye changes in diabetic children using Optical Coherence Tomography Angiography (OCTA)
Scientific title
Investigation of Optical Coherence Tomography Angiography (OCTA) as a non-invasive technique to detect early retinal microvascular dysfunction in children with Diabetes Mellitus
Secondary ID [1] 312242 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
diabetes mellitus 329953 0
diabetic retinopathy 329954 0
Condition category
Condition code
Eye 326857 326857 0 0
Diseases / disorders of the eye
Metabolic and Endocrine 326879 326879 0 0
Diabetes

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Both Diabetes Mellitus (DM) and healthy participants will be required to attend annual visits at the Lions Eye Institute for 5 years (inclusive of enrolment visit). Visits will be approximately 3 hours in duration.

During these visits visual and imaging assessments as described below will be performed by study staff:

Ocular history and changes to ocular signs/symptoms – takes about 5 minutes
Relevant ocular history will be recorded. After the first visit, any changes to ocular history since the previous visit will be recorded.

Demographics – takes about 2 minutes
Date of birth and sex will be recorded at Visit 1.

Use of ACE inhibitor or ARB medications
We will record use of specific medications called ACE (angiotensin converting enzyme) inhibitors or ARBs (angiotensin receptor blockers). If the child is diabetic, information will be requested from the Western Australian Children’s Diabetes Database.

Height and Weight- takes about 3 minutes
height and weight will be measured.

Blood Pressure- takes about 7 minutes
blood pressure will be measured once. The child will be asked to sit down on a chair and rest for 5 minutes before the reading is taken

Visual Acuity- takes about 20 minutes
Visual Acuity will be checked by assessing ability to see letters of different sizes on a chart at a distance.

Measurement of Intraocular (eye) pressure - takes about 2 minutes
The intraocular pressure of the eyes will be checked. A small instrument lightly touches the front of the eye to measure pressure.

Pupil dilation
Standard of care eye drops will be used to dilate the pupils.

Visual function test: this will take about 5 minutes
Participants are shown a series of patterns on a provided iPad that contain either 1, 2 or 3, black (OFF) or white (ON) squares that are superimposed on a textured background. The participant needs to indicate the number of squares that are present, by selecting a push button on the tablet screen. This will continue for 2 mins per eye.

Optical Coherence Tomography (OCT) – this will take about 10 minutes
The participant will position themselves on a chair with their chin on a chin rest and look into the device. This device takes scans which are used to assess the health of the back of the eye (the retina).

Optical Coherence Tomography Angiography (OCTA) – this will take about 50 minutes
This device takes scans which allow the research doctor to collect information about the blood vessels in the retina of your child’s eyes. Images will be taken on two devices. One is the current clinical standard, the other is a specially designed OCTA device for research.

Colour Fundus photography – this will take about 30 minutes
The participant will position themselves on a chair with their chin on a chin rest and look into the device. This camera takes a picture of the back of the eye (fundus). It is taken on two machines, one is a “normal view” and the other is an “ultra wide view”.

Dilated Ophthalmic examination – take about 5 minutes
Examination of the structures in the front, middle and back parts of the eyes. To examine the back of the eye they will be dilated (as described above) and a magnifying instrument will be used to see into the back of the eye.

Blood and urine tests – kidney function
5 mL of blood and a urine sample will be collected at each visit to assess markers related to kidney function.

Additional Blood sample – general markers
An additional 10mL of your blood will be collected at each visit to assess general markers such as the amount of glucose in the blood, lipid profile and full blood count. If the patient is diabetic and has had these blood tests done within the last 3 months of their visit at the PCH clinic, we will not collect this additional blood sample and use these results instead.

A novel method of quantifying retinal perfusion is being investigated by calculating the Coefficient of Variation measure (CV). The CV method using OCTA to estimate retinal perfusion is non-invasive as it does not require injection of any tracer/contrast element and requires no specific or specialised equipment or tools. A standard commercial OCTA machine is used so the experience is identical to having a normal OCTA scan which is very well tolerated, the patient is asked to fixate on a light and a scan is completed within seconds. The primary difference for this CV method being that instead of a single OCTA scan we take repeated OCTA scans over several minutes of the same eye and calculate intensity differences between each blood vessel on these repeated scans to estimate retinal perfusion variability represented as a CV value. This retinal perfusion is hypothesised to be compromised in pathologic states and there is no discomfort at all for patients having these repeated OCTA scans. The specific methodology for this is described in our recent publication (Yu, DY., Mehnert, A., Balaratnasingam, C. et al. An assessment of microvascular hemodynamics in human macula. Sci Rep 13, 7550 (2023). https://doi.org/10.1038/s41598-023-33490-8)
Intervention code [1] 326065 0
Not applicable
Comparator / control treatment
healthy participants who do not have diabetes mellitus
Control group
Active

Outcomes
Primary outcome [1] 334712 0
Change in Coefficient of Variation (CV) measure between non-DM children and DM children without diabetic retinopathy (DR),

CV measure is Coefficient of Variation measure and is calculated as described in "Description of intervention(s) / exposure" with repeated OCTA scans.

Timepoint [1] 334712 0
2 year follow-up and 4 year follow-up post enrolment
Primary outcome [2] 334717 0
Severity of DR determined by CV measure derived from OCTA
Timepoint [2] 334717 0
2 year follow-up and 4 year follow-up post enrolment
Primary outcome [3] 338705 0
Severity of diabetic nephropathy determined by CV measure derived from OCTA
Timepoint [3] 338705 0
2 year follow-up and 4 year follow-up post enrolment
Secondary outcome [1] 421869 0
ON and OFF pathway function using a visual assessment delivered via a tablet/iPad
Timepoint [1] 421869 0
2 year follow-up and 4 year follow-up post enrolment

Eligibility
Key inclusion criteria
Diabetic Participants:
Children aged 10-18 diagnosed with diabetes Type 1 or 2
Participant or parent/guardian willing and able to provide informed consent
Participant in the Western Australian Children's Diabetes Database
grading of "no retinopathy" per ETDRS classification
normal urine and serum kidney biomarkers

Healthy Participants:
Aged 10-18
Participant or parent/guardian willing and able to provide informed consent
Normal visual acuity, retinal images and no history of ocular disease
normal urine and serum kidney biomarkers and Hb1Ac
Minimum age
10 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
For both healthy and diabetic participants:

1.Abnormal results from serum or urine kidney biomarker samples as determined by the study doctor

2.Presence or history of any clinically significant disease or condition, or taking medications that in the opinion of the investigator may affect participant safety or affect the outcome of the investigation
.
3.Participants, who in the opinion of the investigator are not likely to complete the study for whatever reason

4.For healthy participants only - abnormal Visual Acuity or retinal colour photography images, history of ocular disease (including refractive error greater than -2D dioptres of myopia or +3 dioptres of hyperopia); Abnormal urine kidney biomarkers or HbA1c.

Study design
Purpose
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/11/2024
Actual
Date of last participant enrolment
Anticipated
24/08/2026
Actual
Date of last data collection
Anticipated
18/08/2031
Actual
Sample size
Target
401
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 313812 0
Charities/Societies/Foundations
Name [1] 313812 0
Stan Perron Charitable Foundation
Country [1] 313812 0
Australia
Funding source category [2] 313820 0
Charities/Societies/Foundations
Name [2] 313820 0
Perth Eye Foundation
Country [2] 313820 0
Australia
Funding source category [3] 313821 0
Charities/Societies/Foundations
Name [3] 313821 0
Channel 7 Telethon Trust
Country [3] 313821 0
Australia
Primary sponsor type
Hospital
Name
Lions Eye Institute
Address
2 Verdun Street, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 315655 0
None
Name [1] 315655 0
Address [1] 315655 0
Country [1] 315655 0
Other collaborator category [1] 282675 0
Hospital
Name [1] 282675 0
Perth Children's Hospital
Address [1] 282675 0
15 Hospital Ave, Nedlands WA 6009
Country [1] 282675 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312973 0
Children and Adolescent Health Services Human Research Ethics Committee
Ethics committee address [1] 312973 0
Ethics committee country [1] 312973 0
Australia
Date submitted for ethics approval [1] 312973 0
14/02/2023
Approval date [1] 312973 0
27/03/2023
Ethics approval number [1] 312973 0
RGS0000005753

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

Contacts
Principal investigator
Name 126542 0
Prof Chandra Balaratnasingam
Address 126542 0
Lions Eye Institute, 2 Verdun Street, Nedlands WA, 6009
Country 126542 0
Australia
Phone 126542 0
+61 08 9381 0751
Fax 126542 0
Email 126542 0
[email protected]
Contact person for public queries
Name 126543 0
Tammy Corica
Address 126543 0
Lions Eye Institute, 2 Verdun Street, Nedlands WA, 6009
Country 126543 0
Australia
Phone 126543 0
+61 08 9381 0829
Fax 126543 0
Email 126543 0
[email protected]
Contact person for scientific queries
Name 126544 0
Chandra Balaratnasingam
Address 126544 0
Lions Eye Institute, 2 Verdun Street, Nedlands WA, 6009
Country 126544 0
Australia
Phone 126544 0
+61 08 9381 0751
Fax 126544 0
Email 126544 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
IPD will not be available outside of the investigational site. The IPD will only be available to the Principal Investigator, research team and approved collaborators.


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.