Clinical trial NCT01281475: A Trial of Levodopa in Angelman Syndrome
Official title: A Phase 2 Randomized Placebo-Controlled Trial of Levodopa in Angelman Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Angelman Syndrome
Keywords: Angelman syndrome
Levodopa
Carbidopa
L-dopa
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Rady Children's Hospital, San Diego
name: University of California, San Francisco
name: Baylor College of Medicine
name: Vanderbilt University Medical Center
name: Greenwood Genetic Center
name: Children's Hospital Medical Center, Cincinnati
name: Angelman Syndrome Foundation, Inc.
First posted: 2011-01-24
Enrollment: 67
Sex: ALL
Minimum age (years): 4
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Bayley Cognitive Age Equivalent at 1 Year
timeFrame: 12 months
Secondary outcomes:
measure: Presence of Tremors
timeFrame: 1 year
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Greenwood
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Boston Children's Hospital
name: Wen-Hann Tan, BMBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Rady Children's Hospital, San Diego
name: Lynne M. Bird, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Greenwood Genetic Center
name: Steven A. Skinner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Carlos A. Bacino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Anne Slavotinek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Cary Fu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Logan Wink, M.D
role: PRINCIPAL_INVESTIGATOR
References: