Low-Dose Atropine for Treatment of Myopia (MTS1)

Low-Dose Atropine for Treatment of Myopia (Myopia Treatment Study)

Study Objectives

The objectives for this randomized trial are:

1. To determine the efficacy of daily low-dose atropine (0.01%) for slowing myopia progression over a two-year treatment period in children aged 5 to less than 13 years (Primary Outcome On-Treatment).
2. To determine the efficacy of atropine treatment on myopia progression 6 months following cessation of low-dose atropine treatment (Secondary Outcome Off-Treatment).

Synopsis of Study Design The current study is designed as an efficacy study, making effort to maximize adherence to treatment group assignments. After a run-in phase during which all participants are treated with daily artificial tear eyedrops for 2-4 weeks (and glasses are updated if required) to assess their ability to adhere to daily eye drops, participants are randomly assigned to daily atropine or placebo for 24 months, followed by 6 months off treatment.

Study Overview

• Status: Completed
• Conditions: Myopia
• Intervention / Treatment: Drug: Atropine; Other: Placebo Eyedrops

Detailed Description

Study Objectives

The objectives for this randomized trial are:

1. To determine the efficacy of daily low-dose atropine (0.01%) for slowing myopia progression over a two-year treatment period in children aged 5 to less than 13 years with myopia -1.00 to -6.00D at the time of enrollment (Primary Outcome On-Treatment).
2. To determine the efficacy of atropine treatment on myopia progression 6 months following cessation of low-dose atropine treatment (Secondary Outcome Off-Treatment).

Synopsis of Study Design The current study is designed as an efficacy study, making effort to maximize adherence to treatment group assignments. After a run-in phase during which all participants are treated with daily artificial tear eyedrops for 2-4 weeks (and glasses are updated if required) to assess their ability to adhere to daily eye drops, participants are randomly assigned to daily atropine or placebo for 24 months, followed by 6 months off treatment.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Eye Center Dept of Ophthalmology
  • Idaho
    • Boise, Idaho, United States, 83702
      • St Luke's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Illinois College of Optometry
    • Chicago Ridge, Illinois, United States, 60415
      • Ticho Eye Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02453
      • Boston Children's Hospital Waltham
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Pediatric Ophthalmology Associates, Inc.
    • Poland, Ohio, United States, 44514
      • Eye Care Associates, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean A. McGee Eye Institute, University of Oklahoma
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center - Vanderbilt Eye Institute
  • Texas
    • Houston, Texas, United States, 77204
      • University of Houston College of Optometry
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Rocky Mountain Eye Care Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 5 years to <13 years at time of enrollment. Children within 4 weeks of their 13th birthday are not eligible.

• Refractive error meeting the following by cycloplegic autorefraction:

  • Myopia -1.00D to -6.00D spherical equivalent (SE) in both eyes
  • Astigmatism <=1.50D in both eyes
  • Anisometropia <1.00D SE
• Gestational age ≥ 32 weeks.
• Birth weight >1500g.
• Parent understands the protocol and is willing to accept randomization to atropine or placebo.
• Is willing to participate in a 2 to 4 week run-in phase using daily artificial tear eyedrops.
• Able to return in 2 to 4 weeks for possible randomization.
• Parent has a phone (or access to phone) and is willing to be contacted by Investigator's site staff.
• Relocation outside of the area of an active PEDIG site within next 32 months is not anticipated.

Exclusion Criteria:

• Current or previous myopia treatment with atropine, pirenzepine or other anti-muscarinic agent.
• Current or previous use of bifocals, progressive-addition lenses, or multi-focal contact lenses.
• Current or previous use of orthoK, rigid gas permeable, or other contact lenses being used to reduce myopia progression.
• Known atropine allergy.
• Abnormality of the cornea, lens, central retina, iris or ciliary body.
• Current or prior history of manifest strabismus, amblyopia, or nystagmus.
• Prior eyelid, strabismus, intraocular, or refractive surgery.
• Down syndrome or cerebral palsy.

• Females who are pregnant, lactating, or intending to become pregnant within the next 30 months.

  • A negative urine pregnancy test will be required for all females who have experienced menarche.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atropine Group; 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops	Drug: Atropine; Daily 0.01% atropine eyedrops; Other Names: Low-Dose Atropine
Placebo Comparator: Placebo Group; Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops	Other: Placebo Eyedrops; Daily placebo eyedrops

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error.	The primary analysis will be a treatment group comparison of change from baseline to 24-months in spherical equivalent refractive error (SER), as measured by a masked examiner using cycloplegic autorefraction (on-treatment comparison). The mean of the three readings from autorefraction in each eye will be calculated and then the mean of both eyes for each participant will be used for the analysis. The treatment group difference (atropine - placebo) and a 95% confidence interval will be calculated based on the model estimates at 24 months.	At 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent	Treatment group comparison of change from baseline to 30 months in spherical equivalent in each eye as measured by a masked examiner using cycloplegic autorefraction (off-treatment comparison). Calculated based on the model estimates at 24 months.	At 30 months

Collaborators and Investigators

• Sponsor: Jaeb Center for Health Research
• Collaborators: National Eye Institute (NEI); Pediatric Eye Disease Investigator Group
• Investigators: Study Chair: Michael X Repka, MD, MBA, Wilmer Eye Institute; Study Chair: Katherine K Weise, OD, MBA, University of Alabama Birmingham Pediatric Eye Care, Birmingham Health Care

Publications and helpful links

General Publications

• Repka MX, Weise KK, Chandler DL, Wu R, Melia BM, Manny RE, Kehler LAF, Jordan CO, Raghuram A, Summers AI, Lee KA, Petersen DB, Erzurum SA, Pang Y, Lenhart PD, Ticho BH, Beck RW, Kraker RT, Holmes JM, Cotter SA; Pediatric Eye Disease Investigator Group. Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial. JAMA Ophthalmol. 2023 Aug 1;141(8):756-765. doi: 10.1001/jamaophthalmol.2023.2855.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): September 12, 2022

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Myopia; atropine
• 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; Pharmaceutical Solutions; Mydriatics; Ophthalmic Solutions; Atropine
• Other Study ID Numbers: MTS1; 2U10EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.
• IPD Sharing Time Frame: After completion of the protocol and publication of the primary manuscript, the data will be made available for the duration of the grant and any future grants.
• IPD Sharing Access Criteria: Users accessing the data must enter an email address.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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