A Trial of Levodopa in Angelman Syndrome

Brief Title

A Trial of Levodopa in Angelman Syndrome

Official Title

A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome

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.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Bayley Cognitive Age Equivalent at 1 Year

Secondary Outcome

 Presence of Tremors


Angelman Syndrome



Study Arms / Comparison Groups

Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

January 2011

Completion Date

July 2015

Primary Completion Date

July 2015

Eligibility Criteria

        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




4 Years - 12 Years

Accepts Healthy Volunteers



Wen-Hann Tan, BMBS, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Wen-Hann Tan


 Rady Children's Hospital, San Diego

Study Sponsor

Wen-Hann Tan, BMBS, Principal Investigator, Boston Children's Hospital

Verification Date

July 2020