Treatment of Residual Amblyopia With Donepezil

Amblyopia Clinical Trial

Official title:

Recovery From Amblyopia With Cholinesterase Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01584076
• Other study ID #: IRB-P00002887
• Status: Completed
• Phase: Phase 1
• Start date: August 2012
• Est. completion date: January 2021

Study information

• Verified date: June 2021
• Source: Boston Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: January 2021
• Est. primary completion date: January 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amblyopia

Intervention

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

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Boston Children's Hospital at Waltham	Waltham	Massachusetts
United States	Boston Children's Physicians South	Weymouth	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children's Hospital

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Amblyopic Eye Visual Acuity	Analysis of amblyopia eye visual acuity measured at each visit.	4, 8, 12, and 22 weeks after enrollment
Secondary	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
Secondary	Adverse Events	Analysis of the proportion of subjects reporting adverse events.	4, 8, 12, and 22 weeks after enrollment
Secondary	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
Secondary	Completion of Study Treatment	Analysis of the proportion of subjects completing study treatment.	12 weeks after enrollment
Secondary	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