A Trial of Levodopa in Angelman Syndrome

Phase 2

Completed

Brief Summary: 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

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Age between 4 years and 12 years (i.e., before the 13th birthday)
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
Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation

Exclusion Criteria

Co-morbid disorders that may be associated with developmental or cognitive delays
Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
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
Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
Pregnancy

Arm && Interventions

Group	Intervention	Description
Levodopa	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.
Placebo	Placebo Oral Capsule	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.

Primary Outcome Measures

Name	Time	Method
Bayley Cognitive Age Equivalent at 1 Year	12 months

Secondary Outcome Measures

Name	Time	Method
Presence of Tremors	1 year

Locations (7): Cincinnati Children's Hospital
🇺🇸
Cincinnati, Ohio, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Rady Children's Hospital, San Diego
🇺🇸
San Diego, California, United States
Children's Hospital Boston
🇺🇸
Boston, Massachusetts, United States
Greenwood Genetic Center
🇺🇸
Greenwood, South Carolina, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States