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

Phase 2

Completed

• Conditions: Myopia
• Interventions: Drug: 0.9% Sodium-chloride; Drug: 0.1% atropine and 0.01% atropine; Drug: 0.01% atropine

• Registration Number: NCT03911271
• Lead Sponsor: Line Kessel

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-09
• Study First Posted: 2019-04-11
• Study Start: 2019-05-30
• Primary Completion: 2024-04-23
• Study Completion: 2024-04-23
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	0.9% Sodium-chloride	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.
Loading dose	0.1% atropine and 0.01% atropine	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.
Low dose	0.01% atropine	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.

Primary Outcome Measures

Name	Time	Method
Change in axial length	36 months	Treatment group comparison of change in axial length elongation from baseline to 36 months, as measured using IOLMaster 700
Change in spherical equivalent	36 months	Treatment group comparison of change in spherical equivalent from baseline to 36 months, as measured using cycloplegic autorefraction

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Department of Ophthalmology, Rigshospitalet-Glostrup; 🇩🇰 Glostrup, Denmark

Department of Ophthalmology, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Department of Ophthalmology, Vejle Hospital; 🇩🇰 Vejle, Denmark