Levodopa for the Treatment of Residual Amblyopia (ATS17)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT01190813
First received: August 17, 2010
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Amblyopia
Drug: Levodopa/Carbidopa
Drug: Placebo
Other: Patching
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Levodopa as Treatment for Residual Amblyopia (ATS 17)

Resource links provided by NLM:


Further study details as provided by Jaeb Center for Health Research:

Primary Outcome Measures:
  • Amblyopic Eye Visual Acuity [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: No ]
    The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity.


Secondary Outcome Measures:
  • Visual Acuity Improvement [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

  • Amblyopia Resolution [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

  • Visual Acuity Improvement [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

  • Visual Acuity Improvement [ Time Frame: 10 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

  • Visual Acuity Improvement [ Time Frame: 16 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

  • Visual Acuity Improvement [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects who have improved from baseline by 10 or more letters.

  • Amblyopia Resolution [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

  • Amblyopia Resolution [ Time Frame: 10 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

  • Amblyopia Resolution [ Time Frame: 16 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

  • Amblyopia Resolution [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: No ]
    Treatment group comparisons adjusted for baseline acuity scores using logistic regression of the proportion of subjects with 20/25 or better visual acuity.

  • Adverse Event [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: Yes ]
    The proportion of subjects reporting at least one adverse event will be compared between treatment groups using Fisher's Exact test.

  • Study Related Adverse Event [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: Yes ]
    The proportion of subjects reporting at least one adverse event thought by investigator to be related to study drug will be compared between treatment groups using Fisher's Exact test.

  • Adverse Event Requiring Drug Discontinuation [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: Yes ]
    The proportion of subjects who stopped study drug in response to an adverse event will be compared between treatment groups using Fisher's Exact test.

  • Amblyopic Eye Visual Acuity [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: No ]
    A treatment group comparison of the mean amblyopic eye visual acuity at 4 weeks after enrollment, adjusted for baseline acuity.

  • Amblyopic Eye Visual Acuity [ Time Frame: 10 weeks after enrollment ] [ Designated as safety issue: No ]
    A treatment group comparison of the mean amblyopic eye visual acuity at 10 weeks after enrollment, adjusted for baseline acuity.

  • Amblyopic Eye Visual Acuity [ Time Frame: 16 weeks after enrollment ] [ Designated as safety issue: No ]
    A treatment group comparison of the mean amblyopic eye visual acuity at 16 weeks after enrollment, adjusted for baseline acuity.

  • Amblyopic Eye Visual Acuity [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: No ]
    A treatment group comparison of the mean amblyopic eye visual acuity at 26 weeks after enrollment, adjusted for baseline acuity.

  • Fellow Eye Visual Acuity [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Similar to the analysis for the amblyopic eye, the fellow eye visual acuity will be evaluated to determine if study treatment had an adverse effect on the occluded eye. The analysis will be a treatment group comparison of the mean fellow eye visual acuity at 18 weeks after enrollment, adjusted for baseline acuity.

  • Stereoacuity [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: Yes ]
    Differences between treatment groups of change in stereoacuity from baseline at the primary outcome exam (18 weeks after enrollment) will be assessed using a comparison of the distributions using the Wilcoxon-Rank-Sum-Test.

  • Symptom Survey Score [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: Yes ]
    A treatment group comparison of symptom survey scores at the 4 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means.

  • Symptom Survey Score [ Time Frame: 10 weeks after enrollment ] [ Designated as safety issue: Yes ]
    A treatment group comparison of symptom survey scores at the 10 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means.

  • Symptom Survey Score [ Time Frame: 16 weeks after enrollment ] [ Designated as safety issue: Yes ]
    A treatment group comparison of symptom survey scores at the 16 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means.

  • Symptom Survey Score [ Time Frame: 18 weeks after enrollment ] [ Designated as safety issue: Yes ]
    A treatment group comparison of symptom survey scores at the primary outcome (18 week) visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means.

  • Symptom Survey Score [ Time Frame: 26 weeks after enrollment ] [ Designated as safety issue: Yes ]
    A treatment group comparison of symptom survey scores at the 26 week visit. The average of the overall item responses will be calculated and compared by treatment group with a t-test for difference in means.


Enrollment: 139
Study Start Date: September 2010
Estimated Study Completion Date: January 2015
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Levodopa/Carbidopa
Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid
Drug: Levodopa/Carbidopa
Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid
Other: Patching
Two hours of daily patching
Placebo Comparator: Placebo
Oral placebo tid
Drug: Placebo
Oral placebo tid
Other: Patching
Two hours of daily patching

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

Ages Eligible for Study:   7 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190813

Locations
United States, Maryland
Wilmer Eye Institute
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Jaeb Center for Health Research
Investigators
Study Chair: Michael X Repka, MD Jaeb Center for Health Research
  More Information

No publications provided

Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT01190813     History of Changes
Other Study ID Numbers: ATS 17, 2U10EY011751
Study First Received: August 17, 2010
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jaeb Center for Health Research:
amblyopia, levodopa

Additional relevant MeSH terms:
Amblyopia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Eye Diseases
Signs and Symptoms
Levodopa
Carbidopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014