A Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia in 8 to 17 Year Olds

Purpose:

This pilot study is being conducted as a prelude to a randomized trial to compare levodopa/carbidopa plus patching versus patching alone. The purpose of the pilot study is to demonstrate recruitment potential, to provide prospective data on the tolerability of levodopa as a treatment for amblyopia, and to provide limited data on its safety, to provide limited data on it's efficiency, and to provide data to assist in selecting a dose to use in a subsequent phase 3 randomized trial. In addition, this study will provide the opportunity for investigators to gain experience in using levodopa prior to a randomized trial.

The objectives of the pilot study are to:

Demonstrate recruitment potential, including the willingness of parents and subjects to participate in a levodopa study

Collect prospective data on the tolerability of levodopa as a treatment for amblyopia and to provide limited data on its safety

Collect prospective data on the visual acuity response to treatment to estimate the magnitude of effect that might be seen in a randomized trial (if no improvement in acuity was seen, this might be sufficient evidence to decide not to conduct a randomized trial)

Provide the opportunity for investigators to gain experience in using levodopa prior to a randomized trial

In the future, we propose to perform a randomized clinical trial in this subject population comparing patching treatment (2 hours of daily patching) plus oral administration of levodopa-carbidopa with a control group that will be treated with patching (2 hours daily) and oral placebo. The information from this study will be evaluated to determine the feasibility of a trial as well as which dosage of levodopa to use in the future randomized trial.

Background:

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children. Despite best efforts with conventional amblyopia treatment, many older children and teenagers with amblyopia fail to achieve normal visual acuity in the amblyopic eye. In a previous PEDIG study where children 7 to 13 years were treated with atropine and patching, only 36% of the children with moderate amblyopia and only 23% of the children with severe amblyopia achieved 20/40 or better acuity.

Description:

All subjects will have two hours of daily patching prescribed plus be randomized to one of two levodopa doses for about 8 weeks with a rapid taper prior to the primary outcome exam:

Oral levodopa 0.51 mg/kg/tid with carbidopa 0.17 mg/kg/tid (3 to 1 formulation).

Oral levodopa 0.76 mg/kg/tid with carbidopa 0.17 mg/kg/tid (approximately 4.5 to 1 formulation).

All subjects will build up to this daily dose over one week with a rapid taper of medication before a primary outcome visit 8 to 10 weeks after starting levodopa/carbidopa treatment. Subjects will continue with the prescribed 2 hours daily patching between the primary outcome visit #2 and the off-treatment visit #3, 8 to 12 weeks after stopping levodopa/carbidopa treatment.

The subject, parents, and the site staff will be masked to treatment assignment.

The patient will have the following study visits / interactions:

Phone calls at 1 and 2 weeks post-enrollment

Office visit at 4 weeks post-enrollment (Visit 1)

Phone call at 6 weeks after starting levodopa treatment

Office visit at 8 to 10 weeks after starting levodopa treatment (Visit 2)

Office visit at 8 to 12 weeks after stopping levodopa treatment (Visit 3)

Patient Eligibility:

Major Eligibility Criteria

Age 8 to < 18 years

Amblyopia associated with strabismus, anisometropia, or both

Visual acuity in the amblyopic eye 18 to 67 letters inclusive (20/50 to 20/400)

Visual acuity in the sound eye > 78 letters (20/25 or better)

Current amblyopia treatment of at least 2 hours patching per day

No improvement in best-corrected amblyopic eye visual acuity between two consecutive visits at least 4 weeks apart using the same testing method and optimal spectacle correction (if needed), with no improvement of more than 4 letters or one logMAR line.

Exclusions

Females who are pregnant, lactating, or intending to become pregnant within the next 16 weeks.

A negative urine pregnancy test will be required for all females who have experienced menarche.

Patient Recruitment Status:

No longer recruiting. Comments: Recruitment ended in May 2009 with 33 subjects enrolled.

Current Status of Study:

Ongoing. Comments: Follow up will continue through September 2009.

Results:

None

Publications

None

NEI Representative

Donald F. Everett, M.A.
National Eye Institute
National Institutes of Health
Suite 1300
5635 Fishers Lane MSC 9300
Bethesda, MD 20892-9300
USA
Telephone: (301) 451-2020
Fax: (301) 402-0528
Email: deverett@nei.nih.gov

Resource Centers

Study Chair
Michael X. Repka, M.D.
Wilmer Eye Institute
Johns Hopkins University School of Medicine
600 N. Wolfe Street
Baltimore, MD 21287-9028
USA
Telephone: (410) 955-8314
Fax: (410) 955-0809
Email: mrepka@jhmi.edu

Last Updated: 11/20/2009

U. S. Department of Health and Human Services

National Institutes of Health