MTS1: Low-Dose Atropine for Treatment of Myopia

Sponsor

Jaeb Center for Health Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03334253

Collaborator

Pediatric Eye Disease Investigator Group (Other), National Eye Institute (NEI) (NIH)

187

Enrollment

Locations

Arms

Anticipated Duration (Months)

14.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study Objectives

The objectives for this randomized trial are:

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).
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.

Condition or Disease	Intervention/Treatment	Phase
Myopia	Drug: Atropine Other: Placebo Eyedrops	Phase 3

Detailed Description

Study Objectives

The objectives for this randomized trial are:

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).
To determine the efficacy of atropine treatment on myopia progression 6 months following cessation of low-dose atropine treatment (Secondary Outcome Off-Treatment).

Study Design

Study Type:

Interventional

Actual Enrollment :

187 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

Cycloplegic autorefraction, axial length, and additional biometry will be measured by a masked examiner at all follow-up visits using the same instrumentation on the participant throughout the study. Masking will be accomplished by having site personnel administer cyclopentolate to both eyes of each participant and wait 30 minutes before he/she sees the masked examiner. The masked examiner may be a technician or an investigator and must be certified to complete these measurements. Parents, patients, and investigators are also masked to treatment.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Sep 30, 2022

Anticipated Study Completion Date :

Nov 30, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Treatment group comparison of change in spherical equivalent refractive error. [At 24 months]
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.

Secondary Outcome Measures

Treatment group comparison of change from baseline to 30 months in spherical equivalent [At 30 months]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	The Emory Eye Center Dept of Ophthalmology	Atlanta	Georgia	United States	30322
3	St Luke's Hospital	Boise	Idaho	United States	83702
4	Ticho Eye Associates	Chicago Ridge	Illinois	United States	60415
5	Illinois College of Optometry	Chicago	Illinois	United States	60616
6	Boston Children's Hospital Waltham	Boston	Massachusetts	United States	02453
7	Pediatric Ophthalmology Associates, Inc.	Columbus	Ohio	United States	43205
8	Eye Care Associates, Inc.	Poland	Ohio	United States	44514
9	Dean A. McGee Eye Institute, University of Oklahoma	Oklahoma City	Oklahoma	United States	73104
10	Casey Eye Institute	Portland	Oregon	United States	97239
11	Vanderbilt University Medical Center - Vanderbilt Eye Institute	Nashville	Tennessee	United States	37232
12	University of Houston College of Optometry	Houston	Texas	United States	77204
13	Rocky Mountain Eye Care Associates	Salt Lake City	Utah	United States	84107

Sponsors and Collaborators

Jaeb Center for Health Research
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)

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