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Low-dose Atropine for Myopia Control in Children (AIM)

Primary Purpose

Myopia, Progressive

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Atropine eye drops, 0.01%
Atropine eye drops, 0.02%
Placebo (NaCl 0.9%) eye drops
Sponsored by
University Eye Hospital, Freiburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myopia, Progressive focused on measuring Myopia, Children, Atropine, Low-dose, 0.01, 0.02

Eligibility Criteria

8 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female patients aged 8 to 12 years (up to the day before the 13th birthday)
  2. Myopia of -1 D to -6 D with reported or documented annual progression ≥ 0.5 D of myopia
  3. Written informed consent obtained from patient (if applicable) and parents or legal guardians according to international guidelines and local laws
  4. Ability to understand the nature of the trial and the trial related procedures and to comply with them

Exclusion Criteria:

  1. Asian or African origin
  2. Abnormal binocularity
  3. Strabismus
  4. Astigmatism >1.5 D
  5. Anisometropia >1.5 D
  6. History of amblyopia
  7. Corrected visual acuity in any eye <0.63
  8. Any acquired or developmental organic eye disease
  9. Premature birth
  10. Any known systemic metabolic disease or chromosomal anomaly
  11. Previous use of any kind of contact lenses
  12. Previous use of atropine eye drops
  13. Epilepsy
  14. Known hypersensitivity to the active substances or any of the excipients
  15. Participation in any other interventional clinical trial within the last 30 days before the start of this trial
  16. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registries and diagnostic trials is allowed
  17. Contraindications according to the Summary of Product Characteristics (SmPC): Increased intraocular pressure (primary forms of glaucoma or narrow angle glaucoma), chronic rhinitis sicca
  18. Caution and pediatric counselling shall be assured if any of the following conditions are present according to the Summary of Product Characteristics (SmPC): Cardiac insufficiency, arrhythmia, coronary stenosis, hyperthyroidism, stomach or bowel stenosis, bowel paralysis, megacolon, muscle weakness, lung edema, hypersensitivity to atropine, spastic paralysis
  19. Parents or children with poor understanding of the German language
  20. Person who is in a relationship of dependence/employment with the sponsor or the investigator

Sites / Locations

  • Augen-Zentrum-Nordwest, Augenpraxis AhausRecruiting
  • Universitäts-Augenklinik BonnRecruiting
  • Universitätsklinikum Erlangen, AugenklinikRecruiting
  • Universitätsklinikum Essen, Klinik für AugenheilkundeRecruiting
  • Medical Center - University of Freiburg, Eye HospitalRecruiting
  • Universitätsmedizin Göttingen, AugenklinikRecruiting
  • Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde
  • Medizinische Hochschule Hannover, Klinik für AugenheilkundeRecruiting
  • Universitätsklinikum Heidelberg, Augenklinik
  • Uniklinik Köln, Zentrum für AugenheilkundeRecruiting
  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Augenheilkunde
  • Universitätsklinikum Magdeburg A.ö.R., UniversitätsaugenklinikRecruiting
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik
  • Ludwig-Maximilians-Universität München, Augenklinik und PoliklinikRecruiting
  • Klinik für Augenheilkunde des UKM, Gebäude D15Recruiting
  • Pius-Hospital Oldenburg, Medizinischer Campus Universität Oldenburg, Universitätsklinik für AugenheilkundeRecruiting
  • AugenCentrum RosenheimRecruiting
  • Universitätsklinikum Ulm, Klinik für AugenheilkundeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A, Interventional group

Arm B, Control group

Arm Description

Treatment period 1: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 3: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months

Treatment period 1: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months Treatment period 3: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months

Outcomes

Primary Outcome Measures

Demonstration of superiority of low-dose atropine 0.02% eye drops compared to placebo for myopia control
Change in cycloplegic refraction [dioptre (D)/year] after one year will be performed using an analysis of covariance (ANCOVA) model with the annual change in refraction as the dependent variable. The mean value of both eyes is analysed.

Secondary Outcome Measures

Assessment of axial eye length growth under low-dose atropine 0.02% in comparison to placebo
Change in axial length [mm/year]. The mean value of both eyes is analysed. Analyses will be performed in a regression model.
Assessment of the categorized rate of change in refraction of low-dose atropine 0.02% compared to placebo
The primary endpoint change in cycloplegic refraction after one year will be categorized (patients progressing < 0.25D (dioptre), 0.25D - 0.75D and > 0.75D after one year of treatment) and will be analysed descriptively, giving absolute and relative frequencies of these categories as a supportive analysis.

Full Information

First Posted
March 3, 2019
Last Updated
October 4, 2022
Sponsor
University Eye Hospital, Freiburg
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1. Study Identification

Unique Protocol Identification Number
NCT03865160
Brief Title
Low-dose Atropine for Myopia Control in Children
Acronym
AIM
Official Title
Low-dose Atropine for Myopia Control in Children, a Prospective, Double-blind, Placebo-controlled, Multicentric, Randomized Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2021 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Eye Hospital, Freiburg

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Myopia (nearsightedness) is the most common eye disorder. Only second to age, it is the main risk factor for major degenerative eye diseases such as glaucoma, macular degeneration or retinal detachment. Their risk increases with the degree of myopia. Hence, prevention of myopia and slowing its progression is of high relevance. Almost all clinical studies, including two large randomised clinical trials (RCT) were performed in Asia with Asian study participants. The results indicate that atropine eye drops can attenuate myopic progression in children, even in low concentrations thus minimizing unwanted side effects. However, the cumulative evidence is yet not strong enough to recommend their unrestricted use, especially in a Non-Asian population. We therefore intend to set up an adequately powered RCT comparing atropine 0.02% eye drops with placebo to validate previous findings and to test whether this therapeutic concept holds its promise in a European population.
Detailed Description
Myopia (nearsightedness) is the most common developmental eye disorder in the first decades of life. It is the biggest risk factor for sight threatening degenerative eye diseases later in life, second only to age. Its prevalence is increasing worldwide in pandemic dimensions affecting now > 80% in Asian and > 40% in Caucasian populations. Myopia is one of the five eye diseases identified as immediate priorities by the WHO's global initiative for the elimination of avoidable blindness. It usually develops during primary school and its onset and progression are related to environmental factors such as near work and lack of day light exposure, to a lesser degree to genetic factors. Therefore, retardation of myopia progression is a major therapeutic goal. Clinical trials from Asia have shown that 0.01% atropine eye drops can attenuate progression of myopia while inducing only little side effects such as light sensitivity and reduced accommodation. Subsequent data also from Asia have suggested that a concentration of 0.05% atropine is slightly more effective with a still acceptable level of adverse effects. However, it is unclear whether this therapy is equally and sufficiently efficacious in a Caucasian population. It is also unclear which concentration of atropine represents the best compromise between efficacy and safety. Our own uncontrolled pilot data suggest that 0.01% delays progression by about 50% with negligible side effects, but that 0.05% induces a pupil dilation of > 3 mm, which is considered unacceptable. Due to the increasing prevalence also in Europe and an increasing demand from parents for means to retard myopia progression, the trial is the first European large scale randomized clinical trial investigating the safety and efficacy of 0.01% and 0.02% atropine eye drops in comparison to placebo drops. Such a trial is mandatory to substantiate the increasing off-label prescriptions of low-dose atropine in children and to develop clinical guidelines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myopia, Progressive
Keywords
Myopia, Children, Atropine, Low-dose, 0.01, 0.02

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Year one: arm A atropine 0.02% / arm B placebo Year two: arm A atropine 0.02% / arm B atropine 0.01% Year three: arm A placebo/ arm B atropine 0.01%
Masking
ParticipantInvestigator
Masking Description
Code labelled eye drop containers Blinded investigators
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A, Interventional group
Arm Type
Experimental
Arm Description
Treatment period 1: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 3: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months
Arm Title
Arm B, Control group
Arm Type
Experimental
Arm Description
Treatment period 1: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months Treatment period 3: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months
Intervention Type
Drug
Intervention Name(s)
Atropine eye drops, 0.01%
Intervention Description
One drop of the above mentioned drug will be installed into each eye daily at bedtime.
Intervention Type
Drug
Intervention Name(s)
Atropine eye drops, 0.02%
Intervention Description
One drop of the above mentioned drug will be installed into each eye daily at bedtime.
Intervention Type
Drug
Intervention Name(s)
Placebo (NaCl 0.9%) eye drops
Intervention Description
One drop of the above mentioned drug will be installed into each eye daily at bedtime.
Primary Outcome Measure Information:
Title
Demonstration of superiority of low-dose atropine 0.02% eye drops compared to placebo for myopia control
Description
Change in cycloplegic refraction [dioptre (D)/year] after one year will be performed using an analysis of covariance (ANCOVA) model with the annual change in refraction as the dependent variable. The mean value of both eyes is analysed.
Time Frame
Baseline - 12 months
Secondary Outcome Measure Information:
Title
Assessment of axial eye length growth under low-dose atropine 0.02% in comparison to placebo
Description
Change in axial length [mm/year]. The mean value of both eyes is analysed. Analyses will be performed in a regression model.
Time Frame
Baseline - 12 months
Title
Assessment of the categorized rate of change in refraction of low-dose atropine 0.02% compared to placebo
Description
The primary endpoint change in cycloplegic refraction after one year will be categorized (patients progressing < 0.25D (dioptre), 0.25D - 0.75D and > 0.75D after one year of treatment) and will be analysed descriptively, giving absolute and relative frequencies of these categories as a supportive analysis.
Time Frame
Baseline - 12 months
Other Pre-specified Outcome Measures:
Title
Assessment of rebound of myopia progression (refraction) after cessation of atropine 0.02% treatment
Description
Change in refraction [D/year] in year 3, to be determined only in the intervention group.
Time Frame
24-months - 36-months
Title
Assessment of rebound of myopia progression (axial length) after cessation of atropine 0.02% treatment
Description
Change in axial length [mm/year] in year 3, to be determined only in the intervention group.
Time Frame
24-months - 36-months
Title
Change in refraction [D/year]
Description
Change in refraction [D/year] after two years of treatment with low-dose atropine 0.02% eye drops (after year 2 in the interventional group) compared to low-dose atropine 0.01% eye drops (after year 3 in the control group).
Time Frame
intervention group: baseline - 24-months, control group: 12-months - 36-months
Title
Change in axial length [mm/year]
Description
Change in axial length [mm/year] after two years of treatment with low-dose atropine 0.02% eye drops (after year 2 in the interventional group) compared to low-dose atropine 0.01% eye drops (after year 3 in the control group).
Time Frame
intervention group: baseline - 24-months, control group: 12-months - 36-months
Title
Assessment of safety of topical preservative free atropine in comparison to placebo with regard to pupil size
Description
Pupil diameter in mm using the IOL Master 500 or 700 or a PlusoptiX device (preferred) at 200 - 300 lux room illumination. Parameter will be listed by site and patient and displayed in summary tables.
Time Frame
Baseline - 36-months
Title
Assessment of safety of topical preservative free atropine in comparison to placebo with regard to near vision
Description
Visual acuity at near (40 cm distance) using Landolt-C near vision charts (non-crowded version) as decimal acuity. Parameter will be listed by site and patient and displayed in summary tables.
Time Frame
Baseline - 36-months
Title
Assessment of safety of topical preservative free atropine in comparison to placebo with regard to accomodation
Description
Accommodation in D as the near point by the Royal air force near point rule (RAF) or by the Accommodation Convergence Rule (VISUS GmbH) (mean of three measurements of both eyes). Parameter will be listed by site and patient and displayed in summary tables.
Time Frame
Baseline - 36-months
Title
Assessment of safety of topical preservative free atropine in comparison to placebo with regard to pulse rate
Description
Pulse rate (per minute): parameter will be listed by site and patient and displayed in summary tables.
Time Frame
Baseline - 36-months
Title
Number of participants with treatment-related adverse events as assessed by the current CTCAE v4.0
Description
A questionnaire about potential side effects will be completed three times during the study course A patient diary of potential side effects will be provided for patients/parents or guardians to complete and bring to each study visit Adverse events will be documented in the eCRF The adverse events are displayed in summary tables by treatment.
Time Frame
Baseline - 36-months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients aged 8 to 12 years (up to the day before the 13th birthday) Myopia of -1 D to -6 D with reported or documented annual progression ≥ 0.5 D of myopia Written informed consent obtained from patient (if applicable) and parents or legal guardians according to international guidelines and local laws Ability to understand the nature of the trial and the trial related procedures and to comply with them Exclusion Criteria: Asian or African origin Abnormal binocularity Strabismus Astigmatism >1.5 D Anisometropia >1.5 D History of amblyopia Corrected visual acuity in any eye <0.63 Any acquired or developmental organic eye disease Premature birth Any known systemic metabolic disease or chromosomal anomaly Previous use of any kind of contact lenses Previous use of atropine eye drops Epilepsy Known hypersensitivity to the active substances or any of the excipients Participation in any other interventional clinical trial within the last 30 days before the start of this trial Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registries and diagnostic trials is allowed Contraindications according to the Summary of Product Characteristics (SmPC): Increased intraocular pressure (primary forms of glaucoma or narrow angle glaucoma), chronic rhinitis sicca Caution and pediatric counselling shall be assured if any of the following conditions are present according to the Summary of Product Characteristics (SmPC): Cardiac insufficiency, arrhythmia, coronary stenosis, hyperthyroidism, stomach or bowel stenosis, bowel paralysis, megacolon, muscle weakness, lung edema, hypersensitivity to atropine, spastic paralysis Parents or children with poor understanding of the German language Person who is in a relationship of dependence/employment with the sponsor or the investigator
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wolf Lagrèze, Prof.
Phone
+49 (0) 761 270
Ext
40110
Email
wolf.lagreze@uniklinik-freiburg.de
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Böhringer, Prof.
Phone
+49 (0) 761 270
Ext
40010
Email
daniel.boehringer@uniklinik-freiburg.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolf Lagrèze, Prof.
Organizational Affiliation
Eye Center, Medical Center, University Hospital Freiburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augen-Zentrum-Nordwest, Augenpraxis Ahaus
City
Ahaus
ZIP/Postal Code
48683
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefanie Schmickler, Dr.
Facility Name
Universitäts-Augenklinik Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bettina Wabbels, Prof. Dr.
Facility Name
Universitätsklinikum Erlangen, Augenklinik
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gabriele Gusek-Schneider, Prof. Dr.
Facility Name
Universitätsklinikum Essen, Klinik für Augenheilkunde
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anja Eckstein, Prof. Dr.
Facility Name
Medical Center - University of Freiburg, Eye Hospital
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolf A. Lagrèze, Prof.
Phone
+49 761 270
Ext
40110
Email
wolf.lagreze@uniklinik-freiburg.de
Facility Name
Universitätsmedizin Göttingen, Augenklinik
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Schittkowski, Prof. Dr.
Facility Name
Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Spitzer, Prof. Dr.
Facility Name
Medizinische Hochschule Hannover, Klinik für Augenheilkunde
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karsten Hufendiek, Dr.
Facility Name
Universitätsklinikum Heidelberg, Augenklinik
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina Beisse, Dr.
Facility Name
Uniklinik Köln, Zentrum für Augenheilkunde
City
Köln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Hedergott, Dr.
Facility Name
Universitätsklinikum Leipzig, Klinik und Poliklinik für Augenheilkunde
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ina Sterker, Prof. Dr.
Facility Name
Universitätsklinikum Magdeburg A.ö.R., Universitätsaugenklinik
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Schuart, Dr.
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karin Lorenz, PD Dr.
Facility Name
Ludwig-Maximilians-Universität München, Augenklinik und Poliklinik
City
München
ZIP/Postal Code
80336
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Theresia Ring-Mangold, Dr.
Facility Name
Klinik für Augenheilkunde des UKM, Gebäude D15
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Biermann, Prof. Dr.
Facility Name
Pius-Hospital Oldenburg, Medizinischer Campus Universität Oldenburg, Universitätsklinik für Augenheilkunde
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Lischka, Dr.
Facility Name
AugenCentrum Rosenheim
City
Rosenheim
ZIP/Postal Code
83022
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philipp Eberwein, Prof. Dr.
Facility Name
Universitätsklinikum Ulm, Klinik für Augenheilkunde
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Armin Wolf, Prof. Dr.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://aim-studie.de
Description
Homepage of AIM (German language)

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Low-dose Atropine for Myopia Control in Children

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