Treatment of Residual Amblyopia With Donepezil

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Children's Hospital Boston
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT01584076
First received: April 23, 2012
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

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 acetylcholine, a neurotransmitter, 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 Intervention Phase
Amblyopia
Drug: Donepezil
Other: Patching
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Recovery From Amblyopia With Cholinesterase Inhibitors

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • Amblyopia Eye Visual Acuity Improvement [ Time Frame: 22 weeks after enrollment ] [ Designated as safety issue: No ]
    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:
  • Amblyopic Eye Visual Acuity [ Time Frame: 4, 8, 12, and 22 weeks after enrollment ] [ Designated as safety issue: No ]
    Analysis of amblyopia eye visual acuity measured at each visit.

  • Recurrence of Amblyopia after 10 Weeks Off Study Treatment [ Time Frame: 22 weeks after enrollment ] [ Designated as safety issue: No ]
    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.

  • Adverse Events [ Time Frame: 4, 8, 12, and 22 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Analysis of the proportion of subjects reporting adverse events.

  • Adverse Events Requiring Discontinuation of Study Treatment [ Time Frame: 4, 8, and 12 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Analysis of the proportion of subjects requiring discontinuation of study treatment secondary to adverse events.

  • Completion of Study Treatment [ Time Frame: 12 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Analysis of the proportion of subjects completing study treatment.

  • Sound Eye Visual Acuity [ Time Frame: 22 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Analysis of sound eye visual acuity at 22 weeks to assess any adverse effect on the occluded eye.


Estimated Enrollment: 20
Study Start Date: August 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01584076

Contacts
Contact: Caitlin Rook, OC(C) 781-216-1463 caitlin.rook@childrens.harvard.edu
Contact: Carolyn Wu, MD 617-355-8761 carolyn.wu@childrens.harvard.edu

Locations
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Caitlin Rook, OC(C)    781-216-1463    caitlin.rook@childrens.harvard.edu   
Contact: Carolyn Wu, MD    617-355-8761    carolyn.wu@childrens.harvard.edu   
Boston Children's Hospital at Waltham Recruiting
Waltham, Massachusetts, United States, 02453
Contact: Caitlin Rook, OC(C)    781-216-1463    caitlin.rook@childrens.harvard.edu   
Contact: Carolyn Wu, MD    617-355-8761    carolyn.wu@childrens.harvard.edu   
Boston Children's Physicians South Recruiting
Weymouth, Massachusetts, United States, 02190
Contact: Caitlin Rook, OC(C)    781-216-1463    caitlin.rook@childrens.harvard.edu   
Contact: Carolyn Wu, MD    617-355-8761    carolyn.wu@childrens.harvard.edu   
Sponsors and Collaborators
Children's Hospital Boston
Investigators
Principal Investigator: Carolyn Wu, MD Children's Hospital Boston
Principal Investigator: David G. Hunter, MD, PhD Children's Hospital Boston
  More Information

Publications:
Responsible Party: Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT01584076     History of Changes
Other Study ID Numbers: IRB-P00002887
Study First Received: April 23, 2012
Last Updated: December 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:
Amblyopia
Donepezil

Additional relevant MeSH terms:
Amblyopia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Eye Diseases
Signs and Symptoms
Cholinesterase Inhibitors
Donepezil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014