Treatment of Residual Amblyopia With Donepezil

Recovery From Amblyopia With Cholinesterase Inhibitors

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.

Study Overview

• Status: Completed
• Conditions: Amblyopia
• Intervention / Treatment: Drug: Donepezil; Other: Patching

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Waltham, Massachusetts, United States, 02453
      • Boston Children's Hospital at Waltham
    • Weymouth, Massachusetts, United States, 02190
      • Boston Children's Physicians South

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥8 years
2. Amblyopia associated with strabismus and/or anisometropia
3. Amblyopic eye visual acuity of 20/50 - 20/400
4. Sound eye visual acuity of ≥20/25
5. 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)
6. For ≥18 year olds, history of prior amblyopia treatment with patching
7. 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)
8. Complete eye examination within 6 months prior to enrollment
9. Available for at least 6 months of follow-up, have access to a phone, and willing to be contacted by clinical staff
10. Likely to comply with prescribed treatment and unlikely, if applicable, to continue to improve with 2 hours of daily patching alone

Exclusion Criteria:

1. Myopia more than -6.00 D spherical equivalent
2. Presence of associated findings that could cause reduced visual acuity
3. Previous intraocular or refractive surgery
4. Strabismus surgery planned within 22 weeks
5. Current vision therapy or orthoptics
6. Treatment with topical atropine within the past 4 weeks
7. Presence of cardiac condition, asthma, obstructive pulmonary disease, seizure disorder, urinary incontinence, and/or peptic ulcer disease receiving concurrent NSAIDs
8. History of gastrointestinal bleeding from peptic ulcer disease
9. Known psychological problems
10. Known skin reaction to patch or bandage adhesives for 8 to 17 year olds
11. Known allergies or contraindications to the use of acetylcholinesterase inhibitors
12. Prior acetylcholinesterase inhibitor treatment
13. Current use of medication for the treatment of ADHD or psychological disorders
14. Inability to swallow pills equivalent in size to the 5 mg donepezil tablet
15. Females who are pregnant, lactating, or intending to become pregnant within the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Donepezil

Drug: Donepezil; 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.; Other Names: Aricept; Other: Patching; Patching: 2 hours of daily patching will also be prescribed for 8 to 17 year olds only.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Investigators: Principal Investigator: Carolyn Wu, MD, Boston Children's Hospital; Principal Investigator: David G. Hunter, MD, PhD, Boston Children's Hospital; Principal Investigator: Bharti Gangwani, MD, Boston Children's Hospital

Publications and helpful links

General Publications

• Morishita H, Miwa JM, Heintz N, Hensch TK. Lynx1, a cholinergic brake, limits plasticity in adult visual cortex. Science. 2010 Nov 26;330(6008):1238-40. doi: 10.1126/science.1195320. Epub 2010 Nov 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2012
• Primary Completion (ACTUAL): January 1, 2021
• Study Completion (ACTUAL): January 1, 2021

Study Registration Dates

• First Submitted: April 23, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (ESTIMATE): April 24, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Amblyopia; Donepezil
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; Amblyopia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: IRB-P00002887

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO