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A Trial of Levodopa in Angelman Syndrome

This study has been completed.
Sponsor:
Collaborators:
Rady Children's Hospital, San Diego
University of California, San Francisco
Baylor College of Medicine
Vanderbilt University
Greenwood Genetic Center
Children's Hospital Medical Center, Cincinnati
Angelman Syndrome Foundation, Inc.
Information provided by (Responsible Party):
Wen-Hann Tan, Boston Children's Hospital
ClinicalTrials.gov Identifier:
NCT01281475
First received: January 20, 2011
Last updated: November 16, 2016
Last verified: November 2016

January 20, 2011
November 16, 2016
January 2011
July 2015   (Final data collection date for primary outcome measure)
Bayley Cognitive Age Equivalent at 1 Year [ Time Frame: 12 months ]
  • Developmental Outcome Measures [ Time Frame: 12 months ]

    Changes in raw or standard scores between baseline and after 12 months of treatment with either placebo or LD/CD of:

    I. Bayley Scales of Infant and Toddler Development, 3rd edition (or the Mullen Scales of Early Learning in the more developmentally advanced subjects) II. Vineland Adaptive Behavior Scales, 2nd edition (standard scores only) III. Preschool Language Scale, 4th edition IV. Aberrant Behavior Checklist - Community version

  • Tremor and Movement Disorder [ Time Frame: 12 months ]
    Changes in raw score of a modified Unified Parkinson's Disease Rating Scale (mUPDRS), a measure of tremor and movement disorder, from baseline after 12 months in the placebo or the LD/CD group.
Complete list of historical versions of study NCT01281475 on ClinicalTrials.gov Archive Site
Presence of Tremors [ Time Frame: 1 year ]
EEG [ Time Frame: 12 months, 24 months ]
Changes in electroencephalogram (EEG) scores at 12 months and 24 months.
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A Trial of Levodopa in Angelman Syndrome
A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome

This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS).

It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and reduce the tremor that some of them have.

If levodopa is found to be beneficial for children with AS, this could lead to a new treatment for AS.

Funding Source - FDA-OOPD

Levodopa is a prodrug that "delivers" dopamine to the brain. It is usually given with carbidopa, a peripheral decarboxylase inhibitor, to increase the bioavailability of levodopa. Animal studies have suggested that levodopa can reverse the excess phosphorylation of some enzymes involved in synaptic and neuronal function, including calcium/calmodulin-dependent kinase type 2 (CaMKII).

Recently, it was shown that excess phosphorylation of CaMKII may be responsible for some of the neurological deficits seen in Angelman syndrome. Therefore, it is hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.

Although many children have used levodopa for a variety of medical conditions over the last 30 years, it has not been approved by the Food and Drug Administration (FDA) for use in children, and it has not been formally studied in children with Angelman syndrome.

Therefore, the purpose of this study is to find out whether levodopa will lead to an improvement in the development and in the tremor in children with AS.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Angelman Syndrome
  • Drug: Levodopa

    Levodopa/Carbidopa (4:1)

    Dosages are based on levodopa.

    Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study.

    Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

    Other Names:
    • Sinemet
    • L-dopa
  • Drug: Placebo Oral Capsule
    The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.
  • Experimental: Levodopa
    Levodopa is prescribed as a combination of levodopa/carbidopa (4:1) to reduce the peripheral side effects. The dosage used was 15 mg/kg/day in 3 divided doses.
    Intervention: Drug: Levodopa
  • Placebo Comparator: Placebo
    The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa, so it is not expected to have any effect.
    Intervention: Drug: Placebo Oral Capsule
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
67
July 2015
July 2015   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age between 4 years and 12 years (i.e., before the 13th birthday)
  2. Molecular confirmation of the diagnosis of AS, which may include abnormal methylation studies or UBE3A mutation analyses - only subjects with a molecular diagnosis will be allowed to enroll
  3. Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation

Exclusion Criteria:

  1. Co-morbid disorders that may be associated with developmental or cognitive delays
  2. Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
  3. Use of medications that may interact with LD/CD including atypical antipsychotics (aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, risperidone, ziprasidone), monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine), or phenytoin within the last 14 days, or other investigational interventions within the past 3 months
  4. Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
  5. Pregnancy
Sexes Eligible for Study: All
4 Years to 12 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01281475
09-12-0610, 3523
Yes
Not Provided
Undecided
Not Provided
Wen-Hann Tan, Boston Children's Hospital
Wen-Hann Tan
  • Rady Children's Hospital, San Diego
  • University of California, San Francisco
  • Baylor College of Medicine
  • Vanderbilt University
  • Greenwood Genetic Center
  • Children's Hospital Medical Center, Cincinnati
  • Angelman Syndrome Foundation, Inc.
Principal Investigator: Wen-Hann Tan, BMBS Boston Children’s Hospital
Principal Investigator: Lynne M. Bird, MD Rady Children's Hospital, San Diego
Principal Investigator: Steven A. Skinner, MD Greenwood Genetic Center
Principal Investigator: Carlos A. Bacino, MD Baylor College of Medicine
Principal Investigator: Anne Slavotinek, MD University of California, San Francisco
Principal Investigator: Cary Fu, MD Vanderbilt University Medical Center
Principal Investigator: Logan Wink, M.D Children's Hospital Medical Center, Cincinnati
Boston Children’s Hospital
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP