Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia (ATS14)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ray Kraker, Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT00789672
First received: October 27, 2008
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Amblyopia
Drug: levodopa/carbidopa
Device: patching
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate Levodopa as Treatment for Residual Amblyopia in 8 to 17 Year Olds

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Distribution of Amblyopic Eye Visual Acuity Letter Scores at 9 Weeks After Starting Levodopa [ Time Frame: 9 weeks after starting levodopa ] [ Designated as safety issue: No ]
    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 [ Time Frame: 9 weeks after starting levodopa ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline to 9 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline to 9 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Number of adverse events reported throughout entire study.


Secondary Outcome Measures:
  • Distribution of Amblyopic Eye Visual Acuity Letter Scores at 4 Weeks After Enrollment [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 4 weeks after enrollment ] [ Designated as safety issue: No ]
    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 [ Time Frame: 10 weeks after stopping levodopa ] [ Designated as safety issue: No ]
    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 [ Time Frame: 10 weeks after stopping levodopa ] [ Designated as safety issue: No ]
    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 Change in Amblyopic Eye Visual Acuity Scores at 4 Weeks Post Enrollment [ Time Frame: enrollment to 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: enrollment to 4 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline to 10 weeks after stopping levodopa ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline to 10 weeks after stopping levodopa ] [ Designated as safety issue: No ]
    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: 33
Study Start Date: January 2009
Study Completion Date: December 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Device: patching
2 hours daily patching
Other Name: Coverlet, 3M Opticlude, Ortopad®
Drug: levodopa/carbidopa
Oral levodopa 0.51mg/kg tid with carbidopa 0.17 mg/kg tid (3 to 1 formulation)
Other Name: levodopa/carbidopa
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.
Drug: levodopa/carbidopa
Oral levodopa 0.76 mg/kg tid with carbidopa 0.17 mg/kg tid (approximately 4.5 to 1 formulation)
Other Name: levodopa/carbidopa
Device: patching
2 hours daily patching
Other Name: Coverlet, 3M Opticlude, Ortopad®

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.

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00789672

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, M.D. Wilmer Eye Institute
  More Information

No publications provided

Responsible Party: Ray Kraker, Director, PEDIG Coordinating Center, Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT00789672     History of Changes
Other Study ID Numbers: NEI-141, 2U10EY011751
Study First Received: October 27, 2008
Results First Received: September 14, 2010
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jaeb Center for Health Research:
Amblyopia
Patching
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
Carbidopa
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014