Trial record 6 of 12 for:    Angelman Syndrome

Dietary Supplements for the Treatment of Angelman Syndrome

This study has been completed.
Sponsor:
Collaborators:
Baylor College of Medicine
Rady Children's Hospital, San Diego
Children's Hospital Boston
Greenwood Genetic Center
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Lynne M. Bird, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT00348933
First received: July 3, 2006
Last updated: September 21, 2012
Last verified: September 2012
  Purpose

Angelman syndrome (AS) is a complex genetic disorder that affects the nervous system. The purpose of this study is to determine the effectiveness of certain dietary supplements in treating the symptoms of AS.


Condition Intervention
Angelman Syndrome
Nervous System Diseases
Drug: Betaine
Drug: Creatine
Drug: Metafolin
Drug: Vitamin B12

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Average Change in Functioning in Specific Areas of Development, Including Speech and Communications Skills, Cognitive Abilities and Daily Living Skills [ Time Frame: Baseline, 1 year ] [ Designated as safety issue: No ]

    Primary:

    Bayley Scales of Infant Development measures Mental Developmental Index standard scores 0 (least skilled) - 100 (most skilled) Psychomotor Developmental Index standard scores 0 (least skilled - 10 (most skilled) Vineland Adaptive Behavior Scales (VABS), Communication standard scores 0 (least skilled) - 100 (most skilled) Daily Living Skills standard scores 0 (least skilled) - 100 (most skilled) Socialization standard scores 0 (least skilled) - 100 (most skilled) Motor Skills standard scores 0 (least skilled) - 100 (most skilled) Preschool Language Scale (PLS), Auditory Comprehension 0 (least skilled) - 100 (most skilled) Expressive Communication 0 (least skilled) - 100 (most skilled)



Secondary Outcome Measures:
  • Change in Levels of Betaine, Creatine, Dimethylglycine, Guanidinoacetate, Homocysteine, and Methionine. [ Time Frame: Baseline, 1 year ] [ Designated as safety issue: Yes ]
  • Change in RBC Folate [ Time Frame: Baseline, 1 year ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: July 2006
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.
Drug: Betaine
100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses
Drug: Creatine
200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses
Drug: Metafolin
0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses
Drug: Vitamin B12
1 mg by mouth per day for all weights and ages

Detailed Description:

AS is a neurologic disorder that may cause developmental delay, mental retardation, severe speech impairment, seizures, small head size, and problems with movement and balance in young children. AS is caused by a missing or incomplete chromosome 15 that is inherited from the mother. Diagnosis of AS is usually made between three and seven years of age, when the characteristic behaviors and features of the disease become most evident. Prior to AS diagnosis, the symptoms may be mistaken for cerebral palsy or autism. Physical, occupational, and speech therapy, communication skills development, and behavior modification help to improve the quality of life of these children, but other treatments are needed.

In a previous study, decreased DNA methylation, which is a type of chemical change in DNA, was observed in an individual with AS; this condition may be a primary cause of AS. It is hypothesized that promoting increased DNA methylation might reduce the severity of AS symptoms. Betaine, creatine, Metafolin, and vitamin B12 are compounds normally found in the body that are involved in the DNA methylation pathway. Increasing the concentrations of these compounds in the body may enhance DNA methylation. This study will evaluate the efficacy of four dietary supplements in treating the symptoms of AS.

This study will last 12 months. Study visits will occur at study entry and Month 12. A selected group of participants, those who meet the diagnostic criteria for autism, will also be evaluated at Month 6. At study visits, participants will undergo an electroencephalogram (EEG). Medical history, physical exam, neurological exams, and developmental assessments will also be performed. Urine and blood collection, including tests to determine the blood levels of the dietary supplements, will occur at study entry and Months 6 and 12. Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for the duration of the study. Parents will be asked to complete a questionnaire at each visit to report their child's behavior while taking the dietary supplements. Parents will also be contacted by phone periodically to assess changes and/or progress in their children.

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of AS
  • In stable condition with relatively good control of seizures
  • Willing to comply with treatment, study visit schedule, and study assessments
  • Willing to take oral or G-tube medication
  • Willing to be contacted monthly during the course of the study
  • Parent or guardian willing to provide informed consent

Exclusion Criteria:

  • History of liver or kidney disease
  • Currently being treated for a serious acute illness
  • Known hypersensitivity to any of the study drugs
  • Received high-dose folate drug treatment in the 12 months prior to study entry
  • Other significant medical problems, including those involving the liver, kidney, or heart
  • Other comorbidities, genetic disorders, or extreme prematurity; children with autism are not excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00348933

Locations
United States, California
Rady Children's Hospital San Diego
San Diego, California, United States, 92123
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States
United States, South Carolina
Greenwood Genetics Center
Greenwood, South Carolina, United States
United States, Texas
Baylor College of Medicine
Houston, Texas, United States
Sponsors and Collaborators
University of California, San Diego
Baylor College of Medicine
Rady Children's Hospital, San Diego
Children's Hospital Boston
Greenwood Genetic Center
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Arthur L. Beaudet, MD Department of Molecular and Human Genetics, Baylor College of Medicine
Principal Investigator: Carlos A. Bacino, MD Department of Molecular and Human Genetics, Baylor College of Medicine
Principal Investigator: Wen-Hann Tan, BMBS Harvard Medical School, Children's Hospital Boston
Principal Investigator: Lynne M. Bird, MD Division of Dysmorphology/Genetics, Children's Hospital San Diego, Department of Pediatrics, University of California, San Diego
Principal Investigator: Steven A. Skinner, MD Greenwood Genetic Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lynne M. Bird, Principal Investigator, University of California, San Diego
ClinicalTrials.gov Identifier: NCT00348933     History of Changes
Other Study ID Numbers: RDCRN 5204
Study First Received: July 3, 2006
Results First Received: June 16, 2011
Last Updated: September 21, 2012
Health Authority: United States: Federal Government

Keywords provided by University of California, San Diego:
Developmental Delay
Mental Retardation
Ataxia
Microcephaly
Seizures

Additional relevant MeSH terms:
Angelman Syndrome
Nervous System Diseases
Movement Disorders
Central Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Betaine
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex
Vitamins
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hematinics
Hematologic Agents

ClinicalTrials.gov processed this record on July 23, 2014