Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia

Official Title: “A Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia in 8 to 17 Year Olds”

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, 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.

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 (ATS3) where children 7 to 13 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.

Intervention(s) in this Clinical Trial

• Drug: levodopa/carbidopa
  • Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid (approximately 4.5 to 1 formulation)
• Device: patching
  • 2 hours daily patching
• Drug: levodopa/carbidopa
  • Oral levodopa 0.51mg/kg tid with carbidopa 0.17 mg/kg tid (3 to 1 formulation)

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Lower Dose (3-1) levodopa/carbidopa
  • Oral levodopa 0.51 mg/kg tid with carbidopa 0.17 mg/kg tid (3 to 1 formulation) combined with 2 hours of daily patching, with a rapid taper of medication before a primary outcome exam 9 weeks after starting medication.
• Active Comparator: Higher Dose (4.5-1) levodopa/carbidopa
  • Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid (approximately 4.5 to 1 formulation) combined with 2 hours of daily patching, with a rapid taper of medication before a primary outcome exam 9 weeks after starting medication.

Primary Measures

• Distribution of Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa
  • Time Frame: 9 weeks after starting levodopa
    Safety Issue?: No
• Mean Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa
  • Time Frame: 9 weeks after starting levodopa
    Safety Issue?: No
• Distribution of Change in Amblyopic Eye Visual Acuity Scores at 9 Weeks After Starting Levodopa
  • Time Frame: baseline to 9 weeks
    Safety Issue?: No
• Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa
  • Time Frame: baseline to 9 weeks
    Safety Issue?: No
• Tolerability of Study Medication-Adverse Event Reporting
  • Time Frame: 24 weeks
    Safety Issue?: Yes

Secondary Measures

• Distribution of Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks After Enrollment
  • Time Frame: 4 weeks after enrollment
    Safety Issue?: No
• Mean Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment
  • Time Frame: 4 weeks after enrollment
    Safety Issue?: No
• Distribution of Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa
  • Time Frame: 10 weeks after stopping levodopa
    Safety Issue?: No
• Mean Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa
  • Time Frame: 10 weeks after stopping levodopa
    Safety Issue?: No
• Distribution of Change in Amblyopic Eye Visual Acuity Scores at 4 Weeks Post Enrollment
  • Time Frame: enrollment to 4 weeks
    Safety Issue?: No
• Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment
  • Time Frame: enrollment to 4 weeks
    Safety Issue?: No
• Distribution of Change in Amblyopic Eye Visual Acuity Scores at 10 Weeks After Stopping Levodopa
  • Time Frame: baseline to 10 weeks after stopping levodopa
    Safety Issue?: No
• Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa
  • Time Frame: baseline to 10 weeks after stopping levodopa
    Safety Issue?: No

Inclusion Criteria:

• Age 8 to < 18 years old
• 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.

Exclusion Criteria:

• Myopia more than -6.00 D (spherical equivalent) in either eye.
• Current vision therapy or orthoptics
• Ocular cause for reduced visual acuity
• • nystagmus per se does not exclude the subject if the above visual acuity criteria are met
• Prior intraocular or refractive surgery
• History of narrow-angle glaucoma
• Strabismus surgery planned within 16 weeks
• Known allergy to levodopa-carbidopa
• History of dystonic reactions
• Current requirement to take oral iron supplements including multivitamins containing iron during the 8 weeks of treatment with levodopa-carbidopa
• Current use of antihypertensive, anti-depressant medications, phenothiazines, butyrophenones, risperidone and isoniazid, non-specific monoamine oxidase inhibitors
• Current use of medication for the treatment of attention deficit hyperactivity disorder
• Known gastrointestinal or liver disease
• History of melanoma
• Known psychological problems
• Known skin reactions to patch or bandage adhesives
• Prior levodopa treatment
• Current treatment with topical atropine
• 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.
• Requirements regarding the establishment of pregnancy and monitoring of pregnancy over the course of the study as defined by each individual
• Institutional Review Board may supersede these criteria.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 8 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Jaeb Center for Health Research Other

Overall Clinical Trial Officials and Contacts

Michael X. Repka, M.D. Study Chair Wilmer Eye Institute  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00789672

Study ID Number: NEI-141

ClinicalTrials.gov Identifier: NCT00789672

Health Authority: United States: Food and Drug Administration

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