Back to results

A Trial of Levodopa in Angelman Syndrome

Primary Purpose

Angelman Syndrome

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Levodopa

Placebo Oral Capsule

About this trial

This is an interventional treatment trial for Angelman Syndrome focused on measuring Angelman syndrome, Levodopa, Carbidopa, L-dopa

Eligibility Criteria

4 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Rady Children's Hospital, San Diego
University of California, San Francisco
Children's Hospital Boston
Cincinnati Children's Hospital
Greenwood Genetic Center
Vanderbilt University Medical Center
Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Levodopa

Placebo

Arm 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.

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.

Outcomes

Primary Outcome Measures

Bayley Cognitive Age Equivalent at 1 Year

Secondary Outcome Measures

Presence of Tremors

Full Information

NCT ID

NCT01281475

First Posted

January 20, 2011

Last Updated

July 4, 2020

Sponsor

Wen-Hann Tan

Collaborators

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.

1. Study Identification

Unique Protocol Identification Number

NCT01281475

Brief Title

A Trial of Levodopa in Angelman Syndrome

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

January 2011 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Wen-Hann Tan

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Angelman Syndrome

Keywords

Angelman syndrome, Levodopa, Carbidopa, L-dopa

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

67 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Levodopa

Arm Type

Experimental

Arm 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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Levodopa

Other Intervention Name(s)

Sinemet, L-dopa

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Capsule

Intervention Description

The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.

Primary Outcome Measure Information:

Title

Bayley Cognitive Age Equivalent at 1 Year

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Presence of Tremors

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Years

Maximum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials: