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 : July 15, 2020
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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 |
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Angelman Syndrome | Drug: Levodopa Drug: Placebo Oral Capsule | Phase 2 Phase 3 |
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 (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 |
Actual Primary Completion Date : | July 2015 |
Actual Study Completion Date : | July 2015 |

Arm | Intervention/treatment |
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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.
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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:
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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.
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Drug: Placebo Oral Capsule
The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa. |
- Bayley Cognitive Age Equivalent at 1 Year [ Time Frame: 12 months ]
- Presence of Tremors [ Time Frame: 1 year ]

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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:
- 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

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 |
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 |
Responsible Party: | Wen-Hann Tan, Attending Physician in Genetics, Boston Children's Hospital |
ClinicalTrials.gov Identifier: | NCT01281475 |
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: | July 15, 2020 |
Last Verified: | July 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Angelman syndrome Levodopa Carbidopa L-dopa |
Angelman Syndrome Syndrome Disease Pathologic Processes Movement Disorders Central Nervous System Diseases Nervous System Diseases Abnormalities, Multiple Congenital Abnormalities |
Chromosome Disorders Genetic Diseases, Inborn Levodopa Antiparkinson Agents Anti-Dyskinesia Agents Dopamine Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |