A Trial of Levodopa in Angelman Syndrome

Wen-Hann Tan

Status and phase: Completed; Phase 3; Phase 2

Conditions: Angelman Syndrome

Treatments: Drug: Placebo Oral Capsule; Drug: Levodopa

Study type: Interventional

Funder types: Other

Identifiers

NCT01281475

09-12-0610

3523 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 67 patients

Sex: All

Ages: 4 to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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67 participants in 2 patient groups, including a placebo group

Levodopa

Experimental group

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.

Treatment:

Drug: Levodopa

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo Oral Capsule