Treatment of Residual Amblyopia With Donepezil

• ClinicalTrials.gov Identifier: NCT01584076
• Recruitment Status: Completed
• First Posted: April 24, 2012
• Last Update Posted: June 18, 2021
• Sponsor: Boston Children's Hospital
• Information provided by (Responsible Party): Carolyn Wu, Boston Children's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Amblyopia	Drug: Donepezil; Other: Patching	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Recovery From Amblyopia With Cholinesterase Inhibitors
• Actual Study Start Date: August 2012
• Actual Primary Completion Date: January 2021
• Actual Study Completion Date: January 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Amblyopia Eye Visual Acuity Improvement [ Time Frame: 22 weeks after enrollment ]
   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.

Secondary Outcome Measures :

1. Amblyopic Eye Visual Acuity [ Time Frame: 4, 8, 12, and 22 weeks after enrollment ]
   Analysis of amblyopia eye visual acuity measured at each visit.
2. Recurrence of Amblyopia after 10 Weeks Off Study Treatment [ Time Frame: 22 weeks after enrollment ]
   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.
3. Adverse Events [ Time Frame: 4, 8, 12, and 22 weeks after enrollment ]
   Analysis of the proportion of subjects reporting adverse events.
4. Adverse Events Requiring Discontinuation of Study Treatment [ Time Frame: 4, 8, and 12 weeks after enrollment ]
   Analysis of the proportion of subjects requiring discontinuation of study treatment secondary to adverse events.
5. Completion of Study Treatment [ Time Frame: 12 weeks after enrollment ]
   Analysis of the proportion of subjects completing study treatment.
6. Sound Eye Visual Acuity [ Time Frame: 22 weeks after enrollment ]
   Analysis of sound eye visual acuity at 22 weeks to assess any adverse effect on the occluded eye.

Eligibility Criteria

• Ages Eligible for Study: 8 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

Boston Children's Hospital at Waltham

Waltham, Massachusetts, United States, 02453

Boston Children's Physicians South

Weymouth, Massachusetts, United States, 02190

Sponsors and Collaborators

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

More Information

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.

• Responsible Party: Carolyn Wu, Assistant Professor of Ophthalmology, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT01584076
• Other Study ID Numbers: IRB-P00002887
• First Posted: April 24, 2012
• Last Update Posted: June 18, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Carolyn Wu, Boston Children's Hospital:

Amblyopia; Donepezil

Additional relevant MeSH terms:

Amblyopia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Donepezil; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Nootropic Agents