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Trial registered on ANZCTR


Registration number
ACTRN12621000563864
Ethics application status
Approved
Date submitted
18/03/2021
Date registered
13/05/2021
Date last updated
4/04/2024
Date data sharing statement initially provided
13/05/2021
Date results information initially provided
4/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of low dose atropine eye drops on eye-related changes at near focal distances in children and young adults
Scientific title
Effect of low dose atropine eye drops on ocular changes during accommodation in children and young adults with myopia
Secondary ID [1] 303604 0
Nil known
Universal Trial Number (UTN)
U1111-1265-8438
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Progressive myopia 320974 0
Condition category
Condition code
Eye 318781 318781 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive 0.025% atropine sulphate eye drops (preserved with 0.1% benzalkonium chloride), taken as one drop in each eye, once daily (at night before sleep), for a duration of 7 days (+/- 3 days). The duration of treatment will be 7 days, however will be allowed to vary by +/- 3 days dependent upon participant availability to attend.

Adherence to the intervention will be maintained through regular daily text messages reminding the participants to take the dose, and will be assessed by weighing the bottle and the solution before dispensation and after the treatment period.
Intervention code [1] 319890 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326761 0
Accommodation-induced variation in ocular biometry. Measurements of the left eye will be captured using an optical biometer (Zeiss IOLMaster 700) at accommodation demands of 0, 2, 4, and 6 D, presented using a Badal optometer.
Timepoint [1] 326761 0
Visit 2: 4-10 days post-commencement of intervention
Primary outcome [2] 326762 0
Accommodation-induced variation in higher order aberrations (HOA's). HOA's of the left eye will be measured using a Hartmann-Shack wavefront aberrometer (Imagine Eyes IRX3) at accommodation demands of 0, 2, 4, and 6 D, presented using a Badal optometer.
Timepoint [2] 326762 0
Visit 2: 4-10 days post-commencement of intervention
Primary outcome [3] 326874 0
Accommodation-induced variation in retinal image quality, determined from the HOA's. Measurements of the left eye will be caputured using a Hartmann-Shack wavefront aberrometer (Imagine Eyes IRX3) at accommodation demands 0, 2, 4, and 6 D presented using a Badal optometer.
Timepoint [3] 326874 0
Visit 2: 4-10 days post-commencement of intervention
Secondary outcome [1] 392811 0
Choroidal thickness. Measurements of the left eye will be captured using a spectral-domain optical coherence tomographer (SD-OCT) (Nidek RS-3000).
Timepoint [1] 392811 0
Visit 2: 4-10 days post-commencement of intervention
Secondary outcome [2] 394066 0
Accommodation-induced variation in refractive power, determined from the HOA's.. Measurements of the left eye will be caputured using a Hartmann-Shack wavefront aberrometer (Imagine Eyes IRX3) at accommodation demands 0, 2, 4, and 6 D presented using a Badal optometer.
Timepoint [2] 394066 0
Visit 2: 4-10 days post-commencement of intervention
Secondary outcome [3] 394068 0
Accommodation-induced variation in pupil diameter, measured using a Hartmann-Shack wavefront aberrometer (Imagine Eyes IRX3) at accommodation demands 0, 2, 4, and 6 D presented using a Badal optometer.
Timepoint [3] 394068 0
Visit 2: 4-10 days post-commencement of intervention

Eligibility
Key inclusion criteria
Healthy myopic children, adolescents, and young adults aged 6 to 25 years and with a myopic refractive error between -0.50 and -5.00 DS, and no greater than 1.00 D of astigmatism or anisometropia. Participants will currently be corrected with spectacles or contact lenses.
Minimum age
6 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Current or previous use of myopia control treatments (atropine, OrthoK, peripheral defocus soft contact lenses or spectacle lenses)
• Amblyopia or strabismus
• Stereopsis of 200 seconds of arc or greater
• Monocular amplitude of accommodation of less than 8 D
• Best corrected visual acuity (BCVA) poorer than 0.1 logMAR in both eyes, or greater than 1 line (0.1 logMAR) difference in VA between eyes
• History of ocular surgery
• History of significant ocular infection or injury
• Known allergy to atropine, tropicamide, or benzalkonium chloride (BAK)
• Known angle closure glaucoma, or temporal VH ratio <0.3:1 in either eye
• Intraocular pressure greater than 21 mmHg in either eye
• Current use of: anticholinergics, antiglaucoma medications, antimyasthenics, potassium drugs, carbachol/physostigmine/pilocarpine, no CNS depressants (such as antiemetics, phenothiazines, or barbiturates).
• History of Down's syndrome, spastic paralysis, or brain damage.

Study design
Purpose of the study
Treatment
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)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
Minimum total sample sizes were determined using G*Power based on a repeated-measures analysis of variance with an alpha-error probability of 0.05 to achieve statistical power of 0.8. Data collected to date were preliminarily analysed to approximate effect size for the accommodation-induced changes in the key variables between visits (i.e. before and after low dose atropine use). A minimum total sample size of 20 participants will be required. Attrition rates have been low during recruitment thus far, therefore, 22 participants will be recruited to account for attrition due to screening failures or drop-out.

A series of linear mixed model (LMM) analyses using a “restricted maximum likelihood” strategy and a “variance components” matrix covariance structure will be undertaken for each of the primary outcome parameters (ocular biometry, higher order aberrations, refractive power vectors, and retinal image quality), using fixed factors of accommodation demand (cyclopleged, 0, 2, 4, and 6 D) and treatment condition (baseline measurements and measurements following use of 0.025% atropine eye drops). Where there is an interaction between accommodation demand and treatment condition, a post-hoc MM analysis with the same fixed factors will be undertaken using the change in each parameter from the baseline, cycloplegic measurement captured at the first visit.

A one-way repeated-measures multivariate analysis of variance (RM-MANOVA) using the Hotelling’s Trace test statistic will be undertaken to evaluate change in choroidal thickness at various locations, pre- and post-treatment with 0.025% atropine eye drops. All regional locations will be included as dependent variables, with treatment as the independent variable. If the RM-MANOVA reveals a significant overall difference in choroidal thickness, post-hoc comparisons between the pre- and post-treatment measurements will be undertaken using a Sidak correction for multiple comparisons.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
24/05/2021
Actual
16/07/2021
Date of last participant enrolment
Anticipated
1/12/2023
Actual
1/03/2024
Date of last data collection
Anticipated
22/12/2023
Actual
9/03/2024
Sample size
Target
30
Accrual to date
Final
31
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 33443 0
4059 - Kelvin Grove

Funding & Sponsors
Funding source category [1] 308137 0
Charities/Societies/Foundations
Name [1] 308137 0
Children's Hospital Foundation
Country [1] 308137 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
2 George Street
Brisbane City QLD 4000
Country
Australia
Secondary sponsor category [1] 308746 0
None
Name [1] 308746 0
Address [1] 308746 0
Country [1] 308746 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308015 0
Queensland University of Technology (QUT) Human Research Ethics Committee
Ethics committee address [1] 308015 0
Office of Research Ethics and Integrity
Level 4, 88 Musk Avenue
Kelvin Grove QLD 4059
Ethics committee country [1] 308015 0
Australia
Date submitted for ethics approval [1] 308015 0
01/04/2021
Approval date [1] 308015 0
14/05/2021
Ethics approval number [1] 308015 0
2021000204

Summary
Brief summary
Low dose atropine eye drops (in varying concentrations from 0.01% to 0.1% ) are a treatment strategy that has shown promise to slow or halt myopia (short-sightedness) progression in children in a dose-dependent manner, with a minimum concentration of 0.025% has been recommended for use in children as a balance between efficacy and the side effect profile. Recent studies have demonstrated that there is an increase in eye length (distance from the cornea to retina) and higher order aberrations (HOA’s; optical imperfections which degrade the image quality of the eye), and a decrease in retinal image quality when children focus their eyes at close distances. Atropine is known to reduce the focusing ability of the eye, however the effect of low dose atropine on changes in eye length, HOA's, and image quality during near focus in myopic children remains unknown and it is possible that atropine alters these changes, which may contribute to its effect in slowing myopia progression.

The primary objective of this project is to examine the effect of nightly dosing of 0.025 atropine sulfate eye drops for approximately 7 nights on the changes in eye length, HOA's, focal power, pupil diameter, and image quality in myopic children during near focusing. This research is expected to provide greater understanding of the effect of low dose atropine on the focusing mechanism of the eye and associated eye changes, in addition to the potential mechanisms underpinning the myopia control effect of low dose atropine eye drops.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 109238 0
Dr Rohan Hughes
Address 109238 0
School of Clinical Sciences (Optometry and Vision Science), Queensland University of Technology. Victoria Park Road, Kelvin Grove QLD 4059
Country 109238 0
Australia
Phone 109238 0
+61 731385732
Fax 109238 0
Email 109238 0
rp.hughes@qut.edu.au
Contact person for public queries
Name 109239 0
Dr Rohan Hughes
Address 109239 0
School of Clinical Sciences (Optometry and Vision Science), Queensland University of Technology. Victoria Park Road, Kelvin Grove QLD 4059
Country 109239 0
Australia
Phone 109239 0
+61 731385732
Fax 109239 0
Email 109239 0
rp.hughes@qut.edu.au
Contact person for scientific queries
Name 109240 0
Dr Rohan Hughes
Address 109240 0
School of Clinical Sciences (Optometry and Vision Science), Queensland University of Technology. Victoria Park Road, Kelvin Grove QLD 4059
Country 109240 0
Australia
Phone 109240 0
+61 731385732
Fax 109240 0
Email 109240 0
rp.hughes@qut.edu.au

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.