- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00829439
Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Children's Hospital Boston
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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. |
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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects.
Time Frame: 1 week
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1 week
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Central Nervous System Diseases
- Nervous System Diseases
- Disease
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Movement Disorders
- Abnormalities, Multiple
- Chromosome Disorders
- Syndrome
- Angelman Syndrome
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Dopamine Agents
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Aromatic Amino Acid Decarboxylase Inhibitors
- Levodopa
- Carbidopa
Other Study ID Numbers
- 08-10-0490
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Angelman Syndrome
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Ovid Therapeutics Inc.CompletedPrimary Disease or Condition Being Studied: Angelman Syndrome (AS)United States, Australia, Germany, Israel, Netherlands
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Fondazione per la Ricerca Ospedale MaggioreCompleted
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Puerta de Hierro University HospitalParc Taulí Hospital UniversitariRecruiting
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Foundation for Angelman Syndrome Therapeutics,...Queensland University of TechnologyRecruiting
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University of Colorado, DenverCompleted
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Clinical Trials on Levodopa/Carbidopa (4:1)
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AbbVie (prior sponsor, Abbott)Completed
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NeuroDerm Ltd.Quotient ClinicalCompletedParkinson's DiseaseUnited Kingdom
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Centre for Addiction and Mental HealthCompleted
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Novartis PharmaceuticalsWithdrawn
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Academisch Medisch Centrum - Universiteit van Amsterdam...ZonMw: The Netherlands Organisation for Health Research and DevelopmentCompleted
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Novartis PharmaceuticalsOrion Corporation, Orion PharmaCompletedParkinson's DiseaseUnited States, Switzerland, Germany, Finland, Greece, Italy, Spain, United Kingdom, Canada, France, Turkey, Belgium, Sweden, Austria