A 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
Drug: Placebo Oral Capsule
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome|
- Bayley Cognitive Age Equivalent at 1 Year [ Time Frame: 12 months ]
- Presence of Tremors [ Time Frame: 1 year ]
|Study Start Date:||January 2011|
|Study Completion Date:||July 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
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.
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.
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.
Drug: Placebo Oral Capsule
The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01281475
|United States, California|
|Rady Children's Hospital, San Diego|
|San Diego, California, United States, 92123|
|University of California, San Francisco|
|San Francisco, California, United States, 94121|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Ohio|
|Cincinnati Children's Hospital|
|Cincinnati, Ohio, United States, 45229|
|United States, South Carolina|
|Greenwood Genetic Center|
|Greenwood, South Carolina, United States, 29646|
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37212|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|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|