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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Myopia
• Intervention / Treatment: Drug: 0.1% atropine and 0.01% atropine; Drug: 0.01% atropine; Drug: 0.9% Sodium-chloride

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 Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, DK-8000
    • Department of Ophthalmology, Aarhus University Hospital
  • Glostrup, Denmark, DK-2600
    • Department of Ophthalmology, Rigshospitalet-Glostrup
  • Vejle, Denmark, DK-7100
    • Department of Ophthalmology, Vejle Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Loading dose; 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; 0.1% atropine loading dose for 6 months followed by 0.01% atropine for 18 months; Other Names: Loading dose
Experimental: Low dose; 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; 0.01% atropine for 24 months; Other Names: Low-dose
Placebo Comparator: Placebo; 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; Placebo for 24 months; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Line Kessel
• Collaborators: Aarhus University Hospital; Vejle Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 9, 2019
• First Posted (Actual): April 11, 2019

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Refractive Errors; Myopia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Mydriatics; Atropine
• Other Study ID Numbers: Line Kessel, RH-Glostrup

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No