Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome - Full Text View

Sponsor:	Children's Hospital Boston
Information provided by:	Children's Hospital Boston
ClinicalTrials.gov Identifier:	NCT00829439

Purpose

This study is designed to determine the highest dose of levodopa/carbidopa that can be tolerated without any serious side effects by children with Angelman syndrome.

It has been hypothesized that levodopa may lead to an improvement in the neurodevelopment and abnormal movements (e.g. tremors) in children with Angelman syndrome.

Data from this study will be used to design a phase II trial to determine the efficacy of levodopa in treating children with Angelman syndrome.

Condition	Intervention
Angelman Syndrome	Drug: Levodopa/Carbidopa (4:1)

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome

Resource links provided by NLM:

Genetics Home Reference related topics: 17q21.31 microdeletion syndrome Angelman syndrome familial paroxysmal nonkinesigenic dyskinesia tetrasomy 18p

Drug Information available for: Levodopa Carbidopa Sinemet

U.S. FDA Resources

Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:

Maximum dose of levodopa/carbidopa that can be tolerated (without any dose limiting toxicity) by at least 5 out of 6 different subjects. [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]

Enrollment:	17
Study Start Date:	January 2009
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Intervention Details:

Dosages are based on levodopa.

Each cohort of 3 subjects will be placed on an increasing dose of levodopa (2, 5, 10, and 15 mg/kg/day) for 1 week, provided subjects in the preceding cohort tolerated the lower dose.

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

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, so we do not know what dose of levodopa is most appropriate for children with Angelman syndrome.

Therefore, the purpose of this study is to find out the highest dose of levodopa that children with Angelman syndrome can tolerate without any serious side effects.

Once we know the dose of levodopa that can be tolerated by children with Angelman syndrome, we will conduct a larger follow-up study to find out whether levodopa will lead to an improvement in their development and tremor.

Eligibility

Ages Eligible for Study:	4 Years to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Angelman syndrome, confirmed by molecular testing
Must be willing to come for research visit on 2 days, exactly 1 week apart

Exclusion Criteria:

On levodopa, carbidopa, or any dopamine agonists in the 2 weeks prior to participation
Other medical conditions that may be associated with developmental or cognitive delays
More than 2 clinical seizures per month
Used monoamine oxidase (MAO) inhibitors within the last 2 weeks
Used phenytoin within the last 2 weeks
Used phenothiazines, butyrophenones, and thioxanthenes within last 2 weeks
Hypersensitive to levodopa or carbidopa
Cardiovascular disease or instability
Respiratory diseases, including asthma, emphysema, chronic cough, and shortness of breath
Liver disease
Stomach or intestinal ulcers
Kidney disease
Hematological problems, including anemia, leucopenia, and thrombocytopenia
Used investigational drugs/interventions within the past three months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829439

Locations

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Children's Hospital Boston

Investigators

Principal Investigator:

Wen-Hann Tan, BMBS

Children's Hospital Boston

More Information

No publications provided

Responsible Party:	Wen-Hann Tan, BMBS / Attending Physician in Genetics, Children's Hospital Boston
ClinicalTrials.gov Identifier:	NCT00829439 History of Changes
Other Study ID Numbers:	08-10-0490
Study First Received:	January 26, 2009
Last Updated:	December 27, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Hospital Boston:

Angelman syndrome
Levodopa
Carbidopa
L-dopa

Additional relevant MeSH terms:

Angelman Syndrome
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Carbidopa
Levodopa

Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012