Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wen-Hann Tan, Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT00829439
First received: January 26, 2009
Last updated: October 10, 2012
Last verified: October 2012
  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 Phase
Angelman Syndrome
Drug: Levodopa/Carbidopa (4:1)
Phase 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:


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)
Arms Assigned Interventions
Experimental: Levodopa/Carbidopa

Other Names:

Sinemet L-dopa

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.

Drug: Levodopa/Carbidopa (4:1)

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, 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: October 10, 2012
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 August 18, 2014