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

Primary Purpose

Angelman Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Levodopa/Carbidopa (4:1)
Sponsored by
Boston Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  • 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

Sites / Locations

  • Children's Hospital Boston

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Levodopa/Carbidopa

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects.

Secondary Outcome Measures

Full Information

First Posted
January 26, 2009
Last Updated
September 29, 2016
Sponsor
Boston Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00829439
Brief Title
Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
Official Title
A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Boston Children's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

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 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levodopa/Carbidopa
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Levodopa/Carbidopa (4:1)
Other Intervention Name(s)
Sinemet, L-dopa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects.
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Hann Tan, BMBS
Organizational Affiliation
Boston Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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