Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia

Phase 2

Completed

Conditions: Amblyopia

Interventions: Device: patching
Drug: levodopa/carbidopa

Registration Number: NCT00789672

Lead Sponsor: Jaeb Center for Health Research

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 33

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lower Dose (3-1) levodopa/carbidopa	patching	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.
Higher Dose (4.5-1) levodopa/carbidopa	patching	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.
Lower Dose (3-1) levodopa/carbidopa	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.
Higher Dose (4.5-1) levodopa/carbidopa	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 Outcome Measures

Name	Time	Method
Distribution of Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa	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.).
Mean Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa	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.
Distribution of Change in Amblyopic Eye Visual Acuity Scores at 9 Weeks After Starting Levodopa	baseline to 9 weeks	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.
Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa	baseline to 9 weeks	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.
Tolerability of Study Medication-Adverse Event Reporting	24 weeks	Number of adverse events reported throughout entire study.

Secondary Outcome Measures

Name	Time	Method
Distribution of Change in Amblyopic Eye Visual Acuity Scores at 4 Weeks Post Enrollment	enrollment to 4 weeks	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.
Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment	enrollment to 4 weeks	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.
Distribution of Change in Amblyopic Eye Visual Acuity Scores at 10 Weeks After Stopping Levodopa	baseline to 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.
Mean Change in Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa	baseline to 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.
Distribution of Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks After Enrollment	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.).
Mean Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks Post Enrollment	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.
Distribution of Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa	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.).
Mean Amblyopic Eye Visual Acuity Letter Scores at 10 Weeks After Stopping Levodopa	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.