Clinical trial NCT01190813: Levodopa for the Treatment of Residual Amblyopia
Official title: A Randomized Trial of Levodopa as Treatment for Residual Amblyopia (ATS 17)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amblyopia
Keywords: amblyopia, levodopa
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2010-08-30
Enrollment: 139
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Distribution of Amblyopic Eye Visual Acuity Change From Baseline
timeFrame: 18 weeks after enrollment
measure: Mean Amblyopic Eye Visual Acuity Change From Baseline
timeFrame: 18 weeks after enrollment
Secondary outcomes:
measure: Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Distribution of Amblyopic Eye Visual Acuity at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Amblyopic Eye Visual Acuity at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Amblyopia Resolutionat 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Amblyopia Resolution at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Amblyopia Resolution at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Amblyopia Resolution at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Amblyopia Resolution at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Mean Change in Amblyopic Eye Visual Acuity From Baseline at 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Mean Change in Amblyopic Eye Visual Acuity From Baseline at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Mean Change in Amblyopic Eye Visual Acuity From Baseline at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Mean Change in Amblyopic Eye Visual Acuity From Baseline at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Distribution of Fellow Eye Visual Acuity at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Fellow Eye Visual Acuity at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Distribution of Fellow Eye Visual Acuity Change From Baseline at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Fellow Eye Visual Acuity Change From Baseline at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Child Symptom Survey Score at Enrollment
timeFrame: At enrollment
measure: Mean Child Symptom Survey Score at 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Mean Child Symptom Survey Score at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Mean Child Symptom Survey Score at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Mean Child Symptom Survey Score at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Child Symptom Survey Score at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Mean Parent Symptom Survey Score at Enrollment
timeFrame: At enrollment
measure: Mean Parent Symptom Survey Score at 4 Weeks
timeFrame: 4 weeks after enrollment
measure: Mean Parent Symptom Survey Score at 10 Weeks
timeFrame: 10 weeks after enrollment
measure: Mean Parent Symptom Survey Score at 16 Weeks
timeFrame: 16 weeks after enrollment
measure: Mean Parent Symptom Survey Score at 18 Weeks
timeFrame: 18 weeks after enrollment
measure: Mean Parent Symptom Survey Score at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Mean Systemic Adverse Events
timeFrame: Enrollment through 26 weeks
measure: Distribution of Fellow Eye Visual Acuity at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Mean Fellow Eye Visual Acuity at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Distribution of Fellow Eye Visual Acuity Change From Baseline at 26 Weeks
timeFrame: 26 weeks after enrollment
measure: Mean Fellow Eye Visual Acuity Change From Baseline at 26 Weeks
timeFrame: 26 weeks after enrollment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
Study officials:
affiliation: Jaeb Center for Health Research
name: Michael X Repka, MD
role: STUDY_CHAIR
References:
citation: 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.