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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00829439
Recruitment Status : Completed
First Posted : January 27, 2009
Results First Posted : November 21, 2016
Last Update Posted : November 21, 2016
Sponsor:
Information provided by (Responsible Party):
Wen-Hann Tan, Boston Children's Hospital

Tracking Information
First Submitted Date  ICMJE January 26, 2009
First Posted Date  ICMJE January 27, 2009
Results First Submitted Date  ICMJE August 5, 2016
Results First Posted Date  ICMJE November 21, 2016
Last Update Posted Date November 21, 2016
Study Start Date  ICMJE January 2009
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2016)
Maximum Dose of Levodopa/Carbidopa That Can be Tolerated (Without Any Dose Limiting Toxicity) by at Least 3 Subjects. [ Time Frame: 1 week ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on Tolerability of Levodopa/Carbidopa in Children With Angelman Syndrome
Official Title  ICMJE A Dose-escalation Tolerability Study of Levodopa/Carbidopa in Angelman Syndrome
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Angelman Syndrome
Intervention  ICMJE 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
Study Arms  ICMJE 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.

Intervention: Drug: Levodopa/Carbidopa (4:1)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 29, 2016)
16
Original Estimated Enrollment  ICMJE
 (submitted: January 26, 2009)
15
Actual Study Completion Date  ICMJE June 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 12 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00829439
Other Study ID Numbers  ICMJE 08-10-0490
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Wen-Hann Tan, Boston Children's Hospital
Study Sponsor  ICMJE Boston Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wen-Hann Tan, BMBS Boston Children's Hospital
PRS Account Boston Children's Hospital
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP