Treatment of Residual Amblyopia With Donepezil

NCT01584076 | Completed Phase 1 DMC

• 1 other identifier: IRB-P00002887
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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.

Conditions

Amblyopia

Keywords

Amblyopia; Donepezil

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Amblyopic Eye Visual Acuity

  4, 8, 12, and 22 weeks after enrollment

• Recurrence of Amblyopia after 10 Weeks Off Study Treatment

  22 weeks after enrollment

• Adverse Events

  4, 8, 12, and 22 weeks after enrollment

• Adverse Events Requiring Discontinuation of Study Treatment

  4, 8, and 12 weeks after enrollment

• Completion of Study Treatment

  12 weeks after enrollment

Study Arms (1)

Donepezil

EXPERIMENTAL

Drug: Donepezil; Other: Patching

Interventions

Donepezil DRUG

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.

Also known as: Aricept

Donepezil

Patching OTHER

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

Donepezil

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (3)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston Children's Hospital at Waltham

Waltham, Massachusetts, 02453, United States

Location

Boston Children's Physicians South

Weymouth, Massachusetts, 02190, United States

Location

Related Publications (1)

• 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.

  PMID: 21071629 BACKGROUND

MeSH Terms

Conditions

Amblyopia

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Ophthalmology

Study Record Dates

• First Submitted: April 23, 2012
• First Posted: April 24, 2012
• Study Start: August 1, 2012
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: June 18, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)