Low-dose Atropine Eye Drops to Reduce Progression of Myopia in Children in the United Kingdom

Study Overview
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Brief Summary
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Short-sightedness, also called myopia, makes objects in the distance, such as the television, look blurred. This is caused by the eye growing too long, something that usually happens while children are also getting taller. People with myopia can see better with glasses or contact lenses, but this doesn't stop their eyes continuing to become more short-sighted. The CHAMP UK study is investigating a type of eye drop called atropine that might help to stop myopia getting worse as children get older.

Detailed Description
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The study hypothesis is that low dose atropine eye drops will reduce the progression of short-sightedness in children compared with placebo eye drops. This is a randomised controlled trial which will be conducted across four Clinical Research Facilities associated with higher education institutions in the UK. It is a double masked trial, that is, neither the participant or the research team will know what treatment the participants are receiving. 289 children aged 6-12 years with short-sightedness will be recruited to the trial. They will be randomly chosen to receive either atropine eye drops or placebo eye drops on a 2:1 basis. Therefore, 193 participants will receive atropine eye drops, 96 participants will receive placebo eye drops. Potential participants will be referred either by their high street optician or their parents will refer them directly. The study will be advertised on local radio. Potential participants will be invited to attend a baseline screening visit. Written informed consent and written informed assent will be obtained from the parent and child prior to undertaking any assessments. Potential participants will undergo a number of assessments similar to what is conducted by the high street optician or eye clinic to determine if they are eligible to participate. These include: assessment of near and distance vision, reading speed and different measurements of the eye using instruments. An eye drop will be put into each eye for some of these assessments. These drops cause a short-term increase in pupil size, which may last for 12-24 hours, and make close up vision (through their glasses) blurry for up to four hours, and may make them more sensitive to bright light. Participants will also be asked about their quality of life and their daily activities such as screen time, playing outside and reading. Participants will be instructed in the use of the eye drops. They will put one drop in each eye daily for 24 months. The atropine eye drops contain 0.01% atropine sulphate. Placebo eye drops have been chosen as the comparator group as there is no alternative treatment for this condition. Participants will be given a six month supply of eye drops at each visit (except the last visit at 24 months). This will include seven bottles as each bottle can only be used for 28 days after opening. Participants will have a further four visits to the research facility for the assessments to be repeated. This will be every six months, therefore five visits in total (baseline, 6 months, 12 months, 18 months and 24 months). It is anticipated that each visit will last approximately 1-2 hours. Children will be offered the opportunity to rest between assessments. At these follow up visits, in addition to the assessments, they will be asked about their tolerability of the eye drops. Also, five years after randomisation, the investigators will post a questionnaire to participants and ask details of any possible complications and adverse events. The investigators will also request information from their optometrist regarding their eye health, distance vision and refractive error data. The primary outcome is the change in the severity of short-sightedness after 24 months. This will be measured using a machine called an autorefractor.

Official Title
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Low-dose Atropine Eye Drops to Reduce Progression of Myopia in Children: a Multi-centre Placebo Controlled Randomised Trial in the United Kingdom

Conditions
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Myopia

Intervention / Treatment
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* Drug: Atropine Sulfate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6-12 years (at the time of consenting) Myopia of -0.5D or greater (spherical equivalent refractive error) in both eyes Best-corrected distance visual acuity (BCDVA) 0.20 logMAR or better in both eyes Exclusion Criteria: Children with other ocular morbidities Myopia of -10D or greater in either eye Astigmatism of 2D or higher in either eye Amblyopia Significant health problems that can compromise the ability to attend research visits or complete the trial Other factors that may compromise the ability to attend the research appointments Parents or children with poor understanding of the English language Children enrolled in other interventional trials Allergy or hypersensitivity to atropine or excipients

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre, randomised, double-masked, placebo-controlled superiority trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group (Atropine 0.01%)<br>The intervention group will receive 0.01% atropine sulfate eye drops, administered once daily for two years. | Drug: Atropine Sulfate<br>* Atropine sulfate 0.01% eye drops which consist of 10mls of a clear colourless solution of atropine sulfate 0.01% w/v and benzalkonium chloride 0.01% w/v in sterile water.<br>|
| Placebo Comparator: Placebo Group<br>The control group will receive placebo eye drops, administered once daily for two years. | Other: Placebo<br>* Placebo eye drops which consist of 10mls of a clear colourless solution of benzalkonium chloride 0.01% w/v in sterile water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spherical equivalent refractive error (i.e. myopia severity) | Spherical equivalent refractive error (i.e., myopia severity) of both eyes measured by autorefractor under cycloplegia (adjusted for baseline). | Baseline - 24-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central axial length | Measured using a laser biometer at central fixation conditions. | Baseline - 24-months | 
| Best corrected distance visual acuity (BCdVA) (uniocular and binocular) | Assessed using the logMAR ETDRS chart. This is a standard letter chart used in research to ensure accuracy and validity of the acuity measurements and has been shown to be repeatable in children. | Baseline - 24-months | 
| Near visual acuity (uniocular and binocular) | Tested using near logMAR ETDRS at 40 cm. | Baseline - 24-months | 
| Reading speed | Measured with the Wilkins Rate of Reading test. | Baseline - 24-months | 
| Pupil diameter | Measured using an autorefractor. | Baseline - 24-months | 
| Accommodation | Measured prior to the instillation of cycloplegia using the autorefractor. The measures will be taken monocularly in each eye and binocularly (minimum 3 measurements per condition). The accommodation response (accommodation lag) will be determined by calculating the difference between the Accommodation Response (AR = near MSE (autorefractor)) and the Accommodation Stimulus. | Baseline - 24-months | 
| Spectacle correction | Current spectacle prescription. | Baseline - 24-months | 
| Eye drop tolerability | Assessed using a 4-point scale to quantify, from the point of view of the participant, (1) local irritation/stinging associated with eye drop instillation; (2) photophobia; and (3) difficulties reading and writing. | Baseline - 24-months | 
| Adverse event rates and allergic reactions rates | All AEs will be assessed for seriousness, causality, severity and if the adverse event is related to the study drug, for expectedness. | Baseline - 24-months | 
| Quality of Life: measured using the EQ-5D-Y | The EQ-5D-Y evaluates five dimensions of a child's health (mobility, looking after myself, doing usual activities, having pain or discomfort and feeling worried, sad or unhappy) using three levels (no problems, some problems and a lot of problems). Each response results in a one-digit number, which can be tallied up for the five dimensions. Participants will then indicate their overall health on a visual analogue scale from 0 (worst health you can imagine) to 100 (best health you can imagine). | Baseline - 24-months |