A Trial of Levodopa in Angelman Syndrome

NCT01281475 | Completed Phase 2 Results DMC

• 2 other identifiers: 09-12-06103523
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 7

Brief Summary

This study is designed to determine whether levodopa will lead to an improvement in the development and tremor in children with Angelman syndrome (AS). It has been suggested that levodopa, a medication that is usually used to treat Parkinson disease in adults, may help children with AS in their overall development and reduce the tremor that some of them have. If levodopa is found to be beneficial for children with AS, this could lead to a new treatment for AS. Funding Source - FDA-OOPD

Conditions

Angelman Syndrome

Keywords

Angelman syndrome; Levodopa; Carbidopa; L-dopa

Outcome Measures

Primary Outcomes (1)

• Bayley Cognitive Age Equivalent at 1 Year

  12 months

Secondary Outcomes (1)

• Presence of Tremors

  1 year

Study Arms (2)

Levodopa

EXPERIMENTAL

Levodopa is prescribed as a combination of levodopa/carbidopa (4:1) to reduce the peripheral side effects. The dosage used was 15 mg/kg/day in 3 divided doses.

Drug: Levodopa

Placebo

PLACEBO COMPARATOR

The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa, so it is not expected to have any effect.

Drug: Placebo Oral Capsule

Interventions

Levodopa DRUG

Levodopa/Carbidopa (4:1) Dosages are based on levodopa. Subjects randomized to the levodopa arm will receive a levodopa dose of 5 mg/kg/day in the first 2 weeks of the study, a levodopa dose of 10 mg/kg/day in the second 2 weeks of the study, and a levodopa dose of 15 mg/kg/day (up to a maximum of 800 mg per day) for the remaining duration of the study. Levodopa/Carbidopa is a combined formulation that will be dispensed as capsules. It should be taken 3 times a day.

Also known as: Sinemet, L-dopa

Levodopa

Placebo Oral Capsule DRUG

The placebo contains excipients similar to those in the active drug, but it does not contain levodopa or carbidopa.

Placebo

Eligibility Criteria

• Age: 4 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 4 years and 12 years (i.e., before the 13th birthday)
• Molecular confirmation of the diagnosis of AS, which may include abnormal methylation studies or UBE3A mutation analyses - only subjects with a molecular diagnosis will be allowed to enroll
• Not on LD, CD, or any dopamine agonists in the 2 weeks prior to participation

You may not qualify if:

• Co-morbid disorders that may be associated with developmental or cognitive delays
• Poorly controlled seizures - An average of more than 2 clinical seizures per month in the 12 months prior to enrollment.
• Use of medications that may interact with LD/CD including atypical antipsychotics (aripiprazole, asenapine, iloperidone, olanzapine, paliperidone, risperidone, ziprasidone), monoamine oxidase inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine), or phenytoin within the last 14 days, or other investigational interventions within the past 3 months
• Presence of cardiovascular disease or instability, respiratory disease, liver disease, peptic ulcer disease, renal impairment, or hematological disorders
• Pregnancy

Sponsors & Collaborators

• Wen-Hann Tan: lead
• Rady Children's Hospital, San Diego: collaborator
• University of California, San Francisco: collaborator
• Baylor College of Medicine: collaborator
• Vanderbilt University Medical Center: collaborator
• Greenwood Genetic Center: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• Angelman Syndrome Foundation, Inc.: collaborator

Study Sites (7)

Rady Children's Hospital, San Diego

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94121, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Angelman Syndrome

Interventions

Levodopa; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Results Point of Contact

• Title: Wen-Hann Tan
• Organization: Boston Children's Hospital

wen-hann.tan@childrens.harvard.edu

617-355 6394

Study Officials

• Wen-Hann Tan, BMBS

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Lynne M. Bird, MD

  Rady Children's Hospital, San Diego

  PRINCIPAL INVESTIGATOR

• Steven A. Skinner, MD

  Greenwood Genetic Center

  PRINCIPAL INVESTIGATOR

• Carlos A. Bacino, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Anne Slavotinek, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Cary Fu, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Logan Wink, M.D

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician in Genetics

Study Record Dates

• First Submitted: January 20, 2011
• First Posted: January 24, 2011
• Study Start: January 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 15, 2020
• Results First Posted: January 13, 2017

Record last verified: 2020-07

Locations

US (7)