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A Trial of Levodopa in Angelman Syndrome

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ClinicalTrials.gov Identifier: NCT01281475
Recruitment Status : Completed
First Posted : January 24, 2011
Results First Posted : January 13, 2017
Last Update Posted : January 9, 2018
Information provided by (Responsible Party):

Study Description
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

Condition or disease Intervention/treatment Phase
Angelman Syndrome Drug: Levodopa Drug: Placebo Oral Capsule Phase 2 Phase 3

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome
Study Start Date : January 2011
Primary Completion Date : July 2015
Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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.
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
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.

Outcome Measures

Primary Outcome Measures :
  1. Bayley Cognitive Age Equivalent at 1 Year [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Presence of Tremors [ Time Frame: 1 year ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Sponsors and Collaborators
Wen-Hann Tan
Rady Children's Hospital, San Diego
University of California, San Francisco
Baylor College of Medicine
Vanderbilt University Medical Center
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
More Information

Responsible Party: Wen-Hann Tan, Attending Physician in Genetics, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT01281475     History of Changes
Other Study ID Numbers: 09-12-0610
3523 ( Other Grant/Funding Number: OOPD )
First Posted: January 24, 2011    Key Record Dates
Results First Posted: January 13, 2017
Last Update Posted: January 9, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Wen-Hann Tan, Boston Children's Hospital:
Angelman syndrome

Additional relevant MeSH terms:
Angelman Syndrome
Pathologic Processes
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors