Atropine 0.01% Eye Drops in Myopia Study (AIMS)

August 5, 2020 updated by: Anuradha Ganesh, Sultan Qaboos University

Randomized Clinical Trial on Atropine 0.01% for the Control of Myopia in Omani Children

Control of myopia progression has become an important goal because of concerns regarding significantly increased risks of retinal degeneration, retinal detachment, glaucoma and cataract associated with high myopia. It is also clear there prevalence of myopia in children and young adults is increasing all over the world. Several methods including use of progressive addition lenses, rigid gas-permeable contact lenses, and life-style modifications (increased outdoor activity) have reported to alter myopia progression with varying efficacy. In general they have yielded clinical results of marginal significance. Atropine sulphate eye drops has consistently been demonstrated to inhibit axial myopia progression in both humans and animal models. Yet it has not found widespread clinical application for myopia control due to ocular side-effects of cycloplegia and pupil dilation. Recently 0.01% atropine has been shown to be effective in arresting myopia progression without side-effects of cycloplegia and near vision impairment and pupil dilatation and increased light sensitivity. Almost all studies on atropine have been carried out on children of Chinese origin. Efficacy (concentration and dosing) and safety need to be established in the population of interest, before routine use can be recommended. We plan to evaluate the efficacy and safety of topical 0.01% atropine eye drops in slowing the progression of myopia and ocular axial elongation in Omani children. A total of 150 children of ages 6-16 years will be randomized to two groups. Intervention group will receive atropine 0.01% once daily in each eye for two years (Phase 1). Control group will not receive any medications. Follow up visits will be scheduled every three months in Phase 1. Subsequently, medication will be stopped and the study patients will be followed up every six months for one year (Phase 2). The progression of myopia (change in refractive error and axial length) will be compared in the two groups by objective methods.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To assess the efficacy and safety of using 0.01% atropine eye drops in reducing the progression of myopia in Omani population.

Objectives:

  • To compare the effect of 0.01% atropine eye drops on progression of myopic refractive error and axial length with that in the control group.
  • To study the effect of 0.01% atropine eye drops on pupil dilatation
  • To study the effect of 0.01% atropine eye drops on amplitude of accommodation
  • To study the effect of 0.01% atropine eye drops on near visual acuity
  • To study the effect of 0.01% atropine eye drops on glare, photophobia and contrast senstivity

Research Methodology

Study design: Randomized, interventional, clinical trial.

Study population: Omani population (6 to 15 years of age) with myopia ≥ 2.00 < 8.00 Diopters (D).

Recruitment of participants: (1) Patients attending the pediatric ophthalmology out-patient department in Sultan Qaboos University Hospital (SQUH). (2) Children from primary schools.

Material:

WAM-5500 (Grand Seiko auto refractor/keratometer) Advanced binocular kerato-refractometer: The machine measures refraction, corneal curvature, pupil size and accommodation IOL master: 500 (Carl Zeiss; Meditec Inc, Dublin, CA) - Anterior chamber depth, axial length Standard Ophthalmic examination equipment

Study groups:

Intervention group: Optimal myopia correction with single vision glasses and topical atropine 0.01%, one drop at night time.

Control group: Optimal myopia correction with single vision glasses

Procedure:

  1. Examination at enrollment (Eligibility Assessment): All eligible and willing subjects will undergo standard orthoptic and ophthalmic examination by one of the study investigators including measurement of best corrected visual acuity (both distant and near), accommodation, intraocular pressure, keratometry, cycloplegic refraction (autorefractor), slit lamp examination, and dilated fundus examination. Axial length, pupil size, anterior chamber depth will be measured. Cycloplegic refraction will be done 45min after instillation of cyclopentolate 1.0% eye drop (one drop every three times in 5min intervals)
  2. Written informed consent will be obtained from the parents or legal guardians after thorough explanation of the nature and risks of the study (with use of patient information leaflet) before enrollment.
  3. Randomization: Subjects will be allocated to intervention or control group in a randomized manner. Block randomization will be done with the blocks of 6, 4 and 2 with 30%, 40% and 30% respectively. The randomization will be done using SAS 9.1 version software.
  4. Allocation Concealment: The allocation of treatment based on the randomization will be done using opaque envelops. These envelops will be sealed. These envelopes will be organized in an ascending order and will be kept in a binder folder and the binder clips will be sealed. This folder will be handed over to the Pharmacy department at the SQUH. These will be prepared at the Statistics and Health Information Department at the SQUH.
  5. Phase 1: Intervention: Intervention group will receive atropine sulphate 0.01% once nightly for 2 years. Control group will not receive any medication. Atropine 0.01% minims will be made available by Pharmacy at SQUH. To aid and monitor compliance with the treatment regimen, each child / care-giver will be given a small calendar to tick off the days when the eye drop is instilled.
  6. Phase 2: 1 year follow up after cessation of atropine 0.01% eye drops
  7. Examination at follow up:

Follow up visits will be scheduled at 2 weeks following enrollment - base line measurements. Phase 1: 3 monthly intervals. Phase 2: 6 monthly intervals thereafter.

All assessments will be performed by investigators. A study coordinator will assess i) compliance with medication by checking the calendar, and ii) presence of any drug related discomfort using a questionnaire. Subsequently measurement of best corrected visual acuity, accommodation, pupil size, intraocular pressure, cycloplegic refraction, accommodation, axial length, anterior chamber depth slitlamp examination and dilated fundus examination (6 monthly intervals) will be carried out.

Outcome measures:

Efficacy. The primary outcome was progression of myopia, defined as the change in spherical equivalent refractive error (SER) relative to baseline. The assessment at 2 weeks after commencement of treatment will be considered at baseline value. This is necessary because atropine induces an additional cycloplegic effect that could lower further the SER. As such, a run-in period allows stabilization of the cycloplegic effect, thus making comparison of SER between the baseline and subsequent visits more meaningful. The SER is computed at each follow up visit. The secondary outcome is change in axial length during follow-up relative to baseline measured by A-scan ultrasonography.

Safety. The primary safety outcome monitored will be the occurrence of adverse events. The adverse effects description from previous studies include pupil dilation, photophobia, loss of accommodation, near visual impairment, and allergic response. Patients / parents will be questioned regarding glare, photophobia, contrast sensitivity, or any other adverse effects (questionnaire). Response to adverse events - The relationship of the event to the study medication will be assessed by the investigators as none, unlikely, possible, or definite. If patients experience glare / photophobia due to pupillary dilatation, they will be advised photochromic spectacles. Near adds will be advised in case of problem with near vision. Atropine will be discontinued in case of allergic response to medication.

Placebo effect:

The control group in our study will not receive any medication. Myopia progression will be assessed by objective (automated) methods - i.e. use of autorefractor for measuring change in refractive error and use of IOL-Master for measuring axial length. Side effects from use of atropine will also be measured objectively by quantifying pupil size and accommodation. Since there is no scope for bias from either the patient or the examiner in the above assessments, we believe that administering placebo drops as tear substitute would add to the cost and study protocol without added benefit.

Study duration: 3years

Statistical methods:

  1. Sample size calculation:- The mean (SD) of progression myopia in the control is 0.75D (0.25D). In order to expect 20% reduction in the progression in the atropine arm with 90% power and 5% alpha error with two sided test, we need to study 58 subjects in each arm. However, incorporating 30% drop out we need to study about 75 subjects in each arm.
  2. Data management: The data will be entered and managed in EPIDATA software enables with quality control checks. Double data entry will be done by the research assistant who is blinded. Queries will be generated and sent to the investigator and the corrections received will be updated in the database with the approval of the Research Officer or PI of the project. The data will be imported to SPSS for further analyses.

4. Analysis of results:

  1. Pre-analysis Statistical Review Basic frequencies and distribution tables and/or plots will be performed for each variable. For example, histograms will be made for continuous variables and bar graphs will be generated for categorical variables.

  2. Analyses of the Primary Outcome:

    The primary outcome (change in myopia) will be analysed using Intention To Treat (ITT) principles. The mean difference of myopia progression between the two groups will be computed with 95% CI, if the outcome is continuous variable and follows Normal distribution. Otherwise, bootstrapping will be done to establish 95%CI for the difference between two groups in the outcome and Mann Whitney U test will be done to test the hypothesis.However, the primary outcome will be further evaluated using Per Protocol (PP) principle, by excluding the cases who have had Protocol deviations. Secondary outcome (change in axial length) will be analysed and reported appropriately.

  3. Safety Analysis set (As Treated Analyses set):

A separate dataset will be established for Adverse Events (AE) . These AE will be analysed using non parametric tests.. The analysis for safety includes all subjects, according to the route of intervention that they received and with at least one safety assessment. In addition, we will summarize explicitly any severe reactions or serious adverse events (SAE) in subjects received the wrong allocation.

Timing of Analyses and Stopping rule:

Two interim analyses will be done. One at the end of 1 year and another at the end 2 years. The stopping rule will be based Pocock method for 2 interim analyses. That is p<0.01 level will be considered as significant during the interim analyses.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Oman
      • Muscat, Oman, 123
        • Sultan Qaboos University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age: 6 to 15 years
  • Myopia ≥ 2.00 D (cycloplegic refraction; spherical equivalent)
  • No prior or current treatment for preventing myopia progression (bifocals / progressive addition lenses / orthokeratology)

Exclusion Criteria:

  • Best corrected visual acuity < 0.5 (6/12)
  • Refractive Myopia
  • Astigmatism ≥ 1.5 D
  • Amblyopia
  • Ocular hypertension / Glaucoma
  • Prior intraocular surgery
  • Allergy to atropine eye drops
  • Systemic diseases associated with myopia such as Marfan syndrome, Stickler syndrome
  • History of cardiac or significant respiratory diseases
  • Lack of consent for participating in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Atropine Sulfate 0.01% Eye Drops Group
Intervention group will receive atropine sulphate eye drops 0.01% once nightly for 2 years.
Drug: Atropine Sulfate 0.01% Eye Drops
atropine eye drop in study eye once nightly for two years.
Other Names:
  • Atropine
No Intervention: Control group
Control group will not receive any medication.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The primary outcome is progression of myopia
Time Frame: 2 years
defined as the change in spherical equivalent refractive error (SER) relative to baseline
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
change in axial length
Time Frame: 2 years
change in axial length during follow-up relative to baseline measured by A-scan ultrasonography
2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
monitor of adverse events
Time Frame: 3 years
The adverse effects description from previous studies include pupil dilation, photophobia, loss of accommodation, near visual impairment, and allergic response.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sultan Qaboos University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Christian Medical College, Vellore, India

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anuradha Ganesh, MD, Sultan Qaboos University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 20, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MREC 1473

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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