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

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

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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

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


Condition

Angelman Syndrome

Intervention

Levodopa/Carbidopa (4:1)

Study Arms / Comparison Groups

 Levodopa/Carbidopa
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

16

Start Date

January 2009

Completion Date

June 2010

Primary Completion Date

June 2010

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
      

Gender

All

Ages

4 Years - 12 Years

Accepts Healthy Volunteers

No

Contacts

Wen-Hann Tan, BMBS, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00829439

Organization ID

08-10-0490


Responsible Party

Principal Investigator

Study Sponsor

Boston Children's Hospital


Study Sponsor

Wen-Hann Tan, BMBS, Principal Investigator, Boston Children's Hospital


Verification Date

September 2016