Clinical trial NCT01584076: Treatment of Residual Amblyopia With Donepezil
Official title: Recovery From Amblyopia With Cholinesterase Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amblyopia
Keywords: Amblyopia
Donepezil
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2012-04-24
Enrollment: 18
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Amblyopia Eye Visual Acuity Improvement
timeFrame: 22 weeks after enrollment
Secondary outcomes:
measure: Amblyopic Eye Visual Acuity
timeFrame: 4, 8, 12, and 22 weeks after enrollment
measure: Recurrence of Amblyopia after 10 Weeks Off Study Treatment
timeFrame: 22 weeks after enrollment
measure: Adverse Events
timeFrame: 4, 8, 12, and 22 weeks after enrollment
measure: Adverse Events Requiring Discontinuation of Study Treatment
timeFrame: 4, 8, and 12 weeks after enrollment
measure: Completion of Study Treatment
timeFrame: 12 weeks after enrollment
measure: Sound Eye Visual Acuity
timeFrame: 22 weeks after enrollment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Waltham
country: United States
facility: Boston Children's Hospital at Waltham
state: Massachusetts
city: Weymouth
country: United States
facility: Boston Children's Physicians South
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Carolyn Wu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: David G. Hunter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Bharti Gangwani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.