Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Amblyopia

Intervention / Treatment
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* Drug: levodopa/carbidopa
* Device: patching
* Drug: levodopa/carbidopa


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lower Dose (3-1) levodopa/carbidopa<br>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. | Device: patching<br>* 2 hours daily patching<br>* Other names: Coverlet, 3M Opticlude, Ortopad®;Drug: levodopa/carbidopa<br>* Oral levodopa 0.51mg/kg tid with carbidopa 0.17 mg/kg tid (3 to 1 formulation)<br>|
| Active Comparator: Higher Dose (4.5-1) levodopa/carbidopa<br>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. | Drug: levodopa/carbidopa<br>* Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid (approximately 4.5 to 1 formulation)<br>Device: patching<br>* 2 hours daily patching<br>* Other names: Coverlet, 3M Opticlude, Ortopad®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. Letter scores are presented as Snellen Equivalents for presentation (i.e. 20/20 includes those with letter scores between 83 and 87 letters, 20/25 includes those with letter scores between 78 to 82 letters, etc.). | 9 weeks after starting levodopa | 
| Mean Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 being the best. | 9 weeks after starting levodopa | 
| Distribution of Change in Amblyopic Eye Visual Acuity Scores at 9 Weeks After Starting Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | baseline to 9 weeks | 
| Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | baseline to 9 weeks | 
| Tolerability of Study Medication-Adverse Event Reporting | Number of adverse events reported throughout entire study. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distribution of Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks After Enrollment | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. Letter scores are presented as Snellen Equivalents for presentation (i.e. 20/20 includes those with letter scores between 83 and 87 letters, 20/25 includes those with letter scores between 78 to 82 letters, etc.). | 4 weeks after enrollment | 
| Mean Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. | 4 weeks after enrollment | 
| Distribution of Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. Letter scores are presented as Snellen Equivalents for presentation (i.e. 20/20 includes those with letter scores between 83 and 87 letters, 20/25 includes those with letter scores between 78 to 82 letters, etc.). | 10 weeks after stopping levodopa | 
| Mean Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. | 10 weeks after stopping levodopa | 
| Distribution of Change in Amblyopic Eye Visual Acuity Scores at 4 Weeks Post Enrollment | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | enrollment to 4 weeks | 
| Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | enrollment to 4 weeks | 
| Distribution of Change in Amblyopic Eye Visual Acuity Scores at 10 Weeks After Stopping Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | baseline to 10 weeks after stopping levodopa | 
| Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa | Visual acuity was measured with the electronic early treatment diabetic retinopathy study (E-ETDRS) method and resulted in a letter score that could range from 0 to 97 letters, with 0 being the worst and 97 the best. A difference was calculated as the difference in letters between baseline and outcome with positive difference indicating improvement in acuity. | baseline to 10 weeks after stopping levodopa | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amblyopia, Patching, Levodopa