A Trial of Levodopa in Angelman Syndrome

Wen-Hann Tan67 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Angelman Syndrome

Interventions

LevodopaDRUG

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.

Placebo Oral CapsuleDRUG

The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.

Eligibility

Sex: ALLMin age: 4 YearsMax age: 12 Years

Medical Language ↔ Plain English

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

Locations (7)

Rady Children's Hospital, San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Children's Hospital Boston

Boston, Massachusetts, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Bayley Cognitive Age Equivalent at 1 Year

Time frame: 12 months

Secondary Outcomes

Presence of Tremors

Time frame: 1 year

Data from ClinicalTrials.gov

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