Low-dose Atropine for the Prevention of Myopia Progression in Danish Children

Study Overview
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Brief Summary
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Myopia (nearsightedness) is increasing in prevalence throughout the world. It is associated with a risk of potentially blinding complications such as retinal detachment and myopic maculopathy. There is a direct association between the degree of myopia and the risk of complications. Myopia develops in childhood and during adolescence. To prevent higher degrees of myopia, we need to halt disease progression in children and teenagers. Low-dose atropine eye drops have been shown to reduce myopia progression by 50% in Asian populations but its effect in non-Asian populations is unknown. The aim of this study is to investigate if low-dose atropine can reduce myopia progression in Danish children and teenagers. The study is an investigator initiated randomized clinical trial conducted as a collaboration between three Danish Eye Departments covering all of Denmark.

Detailed Description
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The main hypotheses tested in this study are: 0.01% atropine one drop nightly reduces the progression of childhood myopia in Danish children. 0.01% atropine one drop nightly is safe and with no significant side effects. A 6-month loading dose of 0.1% atropine followed by a 0.01% atropine maintenance dose is superior to single 0.01% atropine. 0.1% atropine one drop nightly is safe and has tolerable side effects. The rebound effect after stopping both atropine regimens is limited. Choroidal thickness is a predictor for the progression of childhood myopia.

Official Title
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Low-dose Atropine for the Prevention of Myopia Progression in Danish Children - a Randomized, Double-masked, Multicenter, 36-month Prospective 1:1:1 Study of Safety and Efficacy of 0.1% Atropine Loading Dose to Single 0.01% Atropine and Placebo

Conditions
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Myopia

Intervention / Treatment
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* Drug: 0.1% atropine and 0.01% atropine
* Drug: 0.01% atropine
* Drug: 0.9% Sodium-chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged ≥6-<9 years: myopia ≤-1 (spherical power) in at least one eye Children aged ≥9-≤12 years: myopia ≤-2 (spherical power) in at least one eye Cylinder less than 1.5 diopters Exclusion Criteria: Myopia related to retinal dystrophies Collagen syndroms (Ehlers-Danlos syndrome, Marfan syndrome and Stickler syndrome) Other ocular pathology (e.g., amblyopia, strabismus) Previous eye surgery Previous use of agents thought to affect myopia progression, e.g. atropine, pirenzepine or 7-methylxanthine (metabolite of caffeine and theobromine) and orthokeratology contact lenses Known allergy to atropine or any of the contents of the trial medication (active and in-active ingredients) used in the study Non-compliance to eye examinations Serious systemic health troubles (e.g., cardiac or respiratory illness) and developmental disorders and delays

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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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Loading dose<br>In phase 1 (treatment phase), the participants (n=50) will receive 0.1% atropine loading dose for 6 months followed by 0.01 % atropine for 18 months. The eye drops are administered as one eye drop daily in each eye at bedtime. In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | Drug: 0.1% atropine and 0.01% atropine<br>* 0.1% atropine loading dose for 6 months followed by 0.01% atropine for 18 months<br>* Other names: Loading dose;|
| Experimental: Low dose<br>In phase 1 (treatment phase), the participants (n=50) will receive 0.01 % atropine for 24 months. The eye drops are administered as one eye drop daily in each eye at bedtime. In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | Drug: 0.01% atropine<br>* 0.01% atropine for 24 months<br>* Other names: Low-dose;|
| Placebo Comparator: Placebo<br>In phase 1 (treatment phase), the participants (n=50) will receive placebo eye drops for 24 months. The eye drops are administered as one eye drop daily in each eye at bedtime. In phase 2 (washout phase), treatment will be stopped and the participants monitored for 12 months. | Drug: 0.9% Sodium-chloride<br>* Placebo for 24 months<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in axial length | Treatment group comparison of change in axial length elongation from baseline to 36 months, as measured using IOLMaster 700 | 36 months | 
| Change in spherical equivalent | Treatment group comparison of change in spherical equivalent from baseline to 36 months, as measured using cycloplegic autorefraction | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects and reactions | Treatment group comparison of adverse effects and reactions | 36 months | 
| Change in choroidal thickness | Treatment group comparison of change in choroidal thickness from baseline to 36 months, as measured using optical coherence tomography (OCT) | 36 months | 
| Change in ocular biometry | Treatment group comparison of change in ocular biometry (i.e. keratometry, anterior chamber depth, lens thickness, vitreous axial distance) from baseline to 36 months | 36 months | 
| Change in higher-order aberrations | Treatment group comparison of change in higher-order aberrations from baseline to 36 months | 36 months |