Treatment of Residual Amblyopia With Donepezil

Study Overview
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Brief Summary
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Amblyopia is the leading cause of monocular visual impairment in children and adults. Despite conventional treatment with patching or eye drops, many older children and adults do not achieve normal vision in the amblyopic eye. Donepezil is an acetylcholinesterase inhibitor that increases levels of the neurotransmitter acetylcholine in the brain. Use of acetylcholinesterase inhibitors has been demonstrated by the Hensch lab (Department of Neurology, FM Kirby Neurobiology Center) at Boston Children's Hospital to improve vision and reverse amblyopia in animal models. The purpose of this study is to evaluate the efficacy of oral donepezil as treatment for residual amblyopia (20/50 - 20/400) in patients 8 years of age and older.

Official Title
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Recovery From Amblyopia With Cholinesterase Inhibitors

Conditions
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Amblyopia

Intervention / Treatment
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* Drug: Donepezil
* Other: Patching


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥8 years Amblyopia associated with strabismus and/or anisometropia Amblyopic eye visual acuity of 20/50 - 20/400 Sound eye visual acuity of ≥20/25 For 8 to 17 year olds, current amblyopia treatment of at least 2 hours of daily patching for at least 4 weeks during the pre-enrollment period with no improvement in best-corrected amblyopic eye visual acuity (<5 letters or 1 logMAR line between 2 consecutive visual acuity measurements at least 4 weeks apart while on current treatment) For ≥18 year olds, history of prior amblyopia treatment with patching Wearing optimal optical correction with stable amblyopic eye visual acuity (<5 letters or 1 logMAR line of improvement during 2 consecutive visual acuity measurements at least 4 weeks apart) Complete eye examination within 6 months prior to enrollment Available for at least 6 months of follow-up, have access to a phone, and willing to be contacted by clinical staff Likely to comply with prescribed treatment and unlikely, if applicable, to continue to improve with 2 hours of daily patching alone Exclusion Criteria: Myopia more than -6.00 D spherical equivalent Presence of associated findings that could cause reduced visual acuity Previous intraocular or refractive surgery Strabismus surgery planned within 22 weeks Current vision therapy or orthoptics Treatment with topical atropine within the past 4 weeks Presence of cardiac condition, asthma, obstructive pulmonary disease, seizure disorder, urinary incontinence, and/or peptic ulcer disease receiving concurrent NSAIDs History of gastrointestinal bleeding from peptic ulcer disease Known psychological problems Known skin reaction to patch or bandage adhesives for 8 to 17 year olds Known allergies or contraindications to the use of acetylcholinesterase inhibitors Prior acetylcholinesterase inhibitor treatment Current use of medication for the treatment of ADHD or psychological disorders Inability to swallow pills equivalent in size to the 5 mg donepezil tablet Females who are pregnant, lactating, or intending to become pregnant within the next 6 months

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br> | Drug: Donepezil<br>* Oral Donepezil Daily Initial Dosage: Donepezil 5 mg tablets will be used. 1/2 tablet (≈2.5 mg)/day for 8 to 17 year olds OR 1 tablet (5 mg)/day for ≥18 year olds. Dosage Escalation: Donepezil may be increased by 1/2 tablet (≈2.5 mg)/day every 4 weeks if the amblyopic eye visual acuity has not improved by ≥5 letters or 1 logMAR line to a maximum dosage of 1 1/2 tablets (≈7.5 mg)/day for 8 to 17 year olds OR 2 tablets (10 mg)/day for ≥18 year olds.<br>* Other names: Aricept;Other: Patching<br>* Patching: 2 hours of daily patching will also be prescribed for 8 to 17 year olds only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amblyopia Eye Visual Acuity Improvement | Study treatment will last for 12 weeks. Primary outcome measure is analysis of the proportion of subjects with improvement in amblyopic eye visual acuity of ≥ 15 letters or 3 logMAR lines at 22 weeks after 10 weeks off study treatment. | 22 weeks after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amblyopic Eye Visual Acuity | Analysis of amblyopia eye visual acuity measured at each visit. | 4, 8, 12, and 22 weeks after enrollment | 
| Recurrence of Amblyopia after 10 Weeks Off Study Treatment | Study treatment will be discontinued after 12 weeks. Amblyopic eye visual acuity at 12 weeks and 22 weeks will be compared. Analysis of the proportion of subjects with recurrence of amblyopia after 10 weeks off study treatment. | 22 weeks after enrollment | 
| Adverse Events | Analysis of the proportion of subjects reporting adverse events. | 4, 8, 12, and 22 weeks after enrollment | 
| Adverse Events Requiring Discontinuation of Study Treatment | Analysis of the proportion of subjects requiring discontinuation of study treatment secondary to adverse events. | 4, 8, and 12 weeks after enrollment | 
| Completion of Study Treatment | Analysis of the proportion of subjects completing study treatment. | 12 weeks after enrollment | 
| Sound Eye Visual Acuity | Analysis of sound eye visual acuity at 22 weeks to assess any adverse effect on the occluded eye. | 22 weeks after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amblyopia, Donepezil