Levodopa for the Treatment of Residual Amblyopia

NCT ID: NCT01190813

Last Updated: 2016-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 139 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2014-04-30

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of oral levodopa and patching versus oral placebo and patching as treatment for residual amblyopia in children 7 to <13 years old with visual acuity of 20/50 to 20/400 in the amblyopic eye.

Detailed Description

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 12 years old 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.

Many clinicians have recognized that conventional therapies with patching and atropine have not been universally successful and have sought alternatives. PEDIG has discussed for several years the problem of residual amblyopia and how the remaining visual acuity deficit could be reduced. A number of research groups have evaluated the short term use of oral levodopa-carbidopa as an adjunct to patching therapy for older children.

Conditions

Amblyopia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levodopa/Carbidopa

Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid

Group Type: ACTIVE_COMPARATOR

Levodopa/Carbidopa

Intervention Type: DRUG

Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid

Patching

Intervention Type: OTHER

Two hours of daily patching

Placebo

Oral placebo tid

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral placebo tid

Patching

Intervention Type: OTHER

Two hours of daily patching

Interventions

Levodopa/Carbidopa

Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid

Intervention Type: DRUG

Placebo

Oral placebo tid

Intervention Type: DRUG

Patching

Two hours of daily patching

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age 7 to 12

2. Amblyopia associated with strabismus, anisometropia, or both

• Criteria for strabismus: One of the following criteria must be met: Heterotropia at distance and/or near fixation on examination (with or without spectacles); History of strabismus surgery; Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)
• Criteria for anisometropia: One of the following criteria must be met: ≥0.50 D difference between eyes in spherical equivalent; ≥1.50 D difference between eyes in astigmatism in any meridian

3. Visual acuity, measured in each eye (amblyopic eye without cycloplegia) within 7 days prior to enrollment using the E-ETDRS protocol by a study certified visual acuity tester as follows:

• Visual acuity in the amblyopic eye 18 to 67 letters inclusive (20/50 to 20/400)
• Visual acuity in the fellow eye ≥78 letters (20/25 or better)

4. Current amblyopia treatment (other than spectacles)

• 12 weeks of at least 2 hours of occlusion per day prescribed for the fellow eye during the immediate pre-enrollment period.
• While on current treatment, visual acuity has not improved one line (5 letters) or more since a non-study visit at least 6 weeks ago. Both acuity measurements to define no improvement must have been done using the same testing method.
• Treatment with atropine at any time during this pre-enrollment period is not allowed.
• Any treatment prior to the current patching episode with stable acuity is acceptable.

5. Spectacle correction (if applicable) for measurement of enrollment visual acuity must meet the following criteria and be based on a cycloplegic refraction that is no more than 6 months old:

1. Requirements for spectacle correction:

• Spherical equivalent must be within 0.50 D of fully correcting the anisometropia.
• Hypermetropia of 3.00D or more must be corrected.
• Hypermetropia must not be under corrected by more than 1.50 D spherical equivalent, and reduction in plus sphere must be symmetric in the two eyes.
• Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism.
• Cylinder axis in both eyes is within 6 degrees of the axis in the spectacles when cylinder power is ≥1.00 D.
• Myopia of amblyopic eye greater than 0.50 D by spherical equivalent must be corrected, and the glasses must not under correct the myopia by more than 0.25 D or overcorrect it by more than 0.50 D.

2. Spectacles meeting above criteria must be worn :until visual acuity in amblyopic eye is stable (defined as 2 consecutive visual acuity measurements by the same testing method at least 4 weeks apart with no improvement of one line (5 letters) or more.

6. Eye examination within 6 months prior to enrollment

7. Parent available for at least one year of follow-up, has access to phone), and willing to be contacted by clinical site and Jaeb Center staff

8. In the investigator's judgment, the subject is likely to comply with prescribed treatment (e.g., no history of poor compliance with patching treatment) and unlikely to continue to improve by using 2 hours of patching per day alone.

Exclusion Criteria

1. Myopia more than -6.00 D (spherical equivalent) in either eye.

2. Current vision therapy or orthoptics

3. Ocular cause for reduced visual acuity

• nystagmus per se does not exclude the subject if the above visual acuity criteria are met

4. Prior intraocular or refractive surgery

5. History of narrow-angle glaucoma

6. Bronchial asthma or severe pulmonary disease

7. Strabismus surgery planned within 26 weeks

8. Known allergy to levodopa or carbidopa

9. History of dystonic reactions

10. Current use of oral iron supplements including multivitamins containing iron during treatment with levodopa-carbidopa

11. Current use of antihypertensive, anti-depressant medications, phenothiazines, butyrophenones, risperidone and isoniazid, non-specific monoamine oxidase inhibitors, or medication for the treatment of attention deficit hyperactivity disorder

12. Known liver disease

13. History of melanoma

14. Known psychological problems

15. Known skin reactions to patch or bandage adhesives

16. Prior levodopa treatment

17. Treatment with topical ophthalmic atropine within the past 12 weeks

18. A physician-prescribed diet high in protein

19. Females who are pregnant, lactating, or intend to become pregnant within the next 34 weeks.

• A negative urine pregnancy test will be required for all females who have experienced menarche.
• Requirements regarding pregnancy testing prior to enrollment may be further defined by each individual Institutional Review Board.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael X Repka, MD

Role: STUDY_CHAIR

Jaeb Center for Health Research

Locations

Wilmer Eye Institute

Baltimore, Maryland, United States

Countries

United States

References

Pediatric Eye Disease Investigator Group; Repka MX, Kraker RT, Dean TW, Beck RW, Siatkowski RM, Holmes JM, Beauchamp CL, Golden RP, Miller AM, Verderber LC, Wallace DK. A randomized trial of levodopa as treatment for residual amblyopia in older children. Ophthalmology. 2015 May;122(5):874-81. doi: 10.1016/j.ophtha.2015.01.002. Epub 2015 Feb 9.

Reference Type: RESULT

PMID: 25676904 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/25676904

PubMed abstract

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414716/

PubMed Central HHS Public Access - Full Text

Other Identifiers

2U10EY011751

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ATS 17

Identifier Type: -

Identifier Source: org_study_id