Clinical trial NCT03690089: Low-dose Atropine Eye Drops to Reduce Progression of Myopia in Children in the United Kingdom
Official title: Low-dose Atropine Eye Drops to Reduce Progression of Myopia in Children: a Multi-centre Placebo Controlled Randomised Trial in the United Kingdom
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myopia
Lead sponsor: Belfast Health and Social Care Trust
Sponsor class: OTHER
First posted: 2018-10-01
Enrollment: 289
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, randomised, double-masked, placebo-controlled superiority trial
Primary purpose: TREATMENT

Brief summary: Short-sightedness, also called myopia, makes objects in the distance, such as the television, look blurred. This is caused by the eye growing too long, something that usually happens while children are also getting taller. People with myopia can see better with glasses or contact lenses, but this doesn't stop their eyes continuing to become more short-sighted. The CHAMP UK study is investigating a type of eye drop called atropine that might help to stop myopia getting worse as children get older.

Detailed description: The study hypothesis is that low dose atropine eye drops will reduce the progression of short-sightedness in children compared with placebo eye drops. This is a randomised controlled trial which will be conducted across four Clinical Research Facilities associated with higher education institutions in the UK. It is a double masked trial, that is, neither the participant or the research team will know what treatment the participants are receiving. 289 children aged 6-12 years with short-sightedness will be recruited to the trial. They will be randomly chosen to receive either atropine eye drops or placebo eye drops on a 2:1 basis. Therefore, 193 participants will receive atropine eye drops, 96 participants will receive placebo eye drops.

Potential participants will be referred either by their high street optician or their parents will refer them directly. The study will be advertised on local radio. Potential participants will be invited to attend a baseline screening visit. Written informed consent and written informed assent will be obtained from the parent and child prior to undertaking any assessments. Potential participants will undergo a number of assessments similar to what is conducted by the high street optician or eye clinic to determine if they are eligible to participate. These include: assessment of near and distance vision, reading speed and different measurements of the eye using instruments. An eye drop will be put into each eye for some of these assessments. These drops cause a short-term increase in pupil size, which may last for 12-24 hours, and make close up vision (through their glasses) blurry for up to four hours, and may make them more sensitive to bright light. Participants will also be asked about their quality of life and their daily activities such as screen time, playing outside and reading.

Participants will be instructed in the use of the eye drops. They will put one drop in each eye daily for 24 months. The atropine eye drops contain 0.01% atropine sulphate. Placebo eye drops have been chosen as the comparator group as there is no alternative treatment for this condition. Participants will be given a six month supply of eye drops at each visit (except the last visit at 24 months). This will include seven bottles as each bottle can only be used for 28 days after opening.

Participants will have a further four visits to the research facility for the assessments to be repeated. This will be every six months, therefore five visits in total (baseline, 6 months, 12 months, 18 months and 24 months). It is anticipated that each visit will last approximately 1-2 hours. Children will be offered the opportunity to rest between assessments. At these follow up visits, in addition to the assessments, they will be asked about their tolerability of the eye drops. Also, five years after randomisation, the investigators will post a questionnaire to participants and ask details of any possible complications and adverse events. The investigators will also request information from their optometrist regarding their eye health, distance vision and refractive error data.

The primary outcome is the change in the severity of short-sightedness after 24 months. This will be measured using a machine called an autorefractor.

Eligibility criteria: Inclusion Criteria:

1. Age 6-12 years (at the time of consenting)
2. Myopia of -0.5D or greater (spherical equivalent refractive error) in both eyes
3. Best-corrected distance visual acuity (BCDVA) 0.20 logMAR or better in both eyes

Exclusion Criteria:

1. Children with other ocular morbidities
2. Myopia of -10D or greater in either eye
3. Astigmatism of 2D or higher in either eye
4. Amblyopia
5. Significant health problems that can compromise the ability to attend research visits or complete the trial
6. Other factors that may compromise the ability to attend the research appointments
7. Parents or children with poor understanding of the English language
8. Children enrolled in other interventional trials
9. Allergy or hypersensitivity to atropine or excipients

Primary outcomes:
measure: Spherical equivalent refractive error (i.e. myopia severity)
timeFrame: Baseline - 24-months
Secondary outcomes:
measure: Central axial length
timeFrame: Baseline - 24-months
measure: Best corrected distance visual acuity (BCdVA) (uniocular and binocular)
timeFrame: Baseline - 24-months
measure: Near visual acuity (uniocular and binocular)
timeFrame: Baseline - 24-months
measure: Reading speed
timeFrame: Baseline - 24-months
measure: Pupil diameter
timeFrame: Baseline - 24-months
measure: Accommodation
timeFrame: Baseline - 24-months
measure: Spectacle correction
timeFrame: Baseline - 24-months
measure: Eye drop tolerability
timeFrame: Baseline - 24-months
measure: Adverse event rates and allergic reactions rates
timeFrame: Baseline - 24-months
measure: Quality of Life: measured using the EQ-5D-Y
timeFrame: Baseline - 24-months
Other outcomes:
measure: Peripheral axial length
timeFrame: Baseline - 24-months
measure: Peripheral retinal defocus
timeFrame: Baseline - 24-months
measure: Anterior chamber depth
timeFrame: Baseline - 24-months
measure: Iris colour
timeFrame: Baseline - 24-months
measure: Height in cms
timeFrame: Baseline - 24-months
measure: Weight in kgs
timeFrame: Baseline - 24-months
measure: Hours of outdoor activity
timeFrame: Baseline - 24-months
measure: Ciliary body biometry
timeFrame: Baseline - 24-months
Locations:
city: Belfast
country: United Kingdom
facility: Northern Ireland Clinical Research
city: Birmingham
country: United Kingdom
facility: Aston University Eye Clinic
city: Cambridge
country: United Kingdom
facility: Anglia Ruskin University Eye Clinic
city: Glasgow
country: United Kingdom
facility: Centre for Living (Glasgow Caledonian University)
Study officials:
affiliation: Queen's University, Belfast
name: Augusto Azuara-Blanco, PhD FRCOphth
role: PRINCIPAL_INVESTIGATOR
References:
citation: Azuara-Blanco A, Logan N, Strang N, Saunders K, Allen PM, Weir R, Doherty P, Adams C, Gardner E, Hogg R, McFarland M, Preston J, Verghis R, Loughman JJ, Flitcroft I, Mackey DA, Lee SS, Hammond C, Congdon N, Clarke M. Low-dose (0.01%) atropine eye-drops to reduce progression of myopia in children: a multicentre placebo-controlled randomised trial in the UK (CHAMP-UK)-study protocol. Br J Ophthalmol. 2020 Jul;104(7):950-955. doi: 10.1136/bjophthalmol-2019-314819. Epub 2019 Oct 25.