Dietary Supplements for the Treatment of Angelman Syndrome
Condition: Angelman Syndrome; Nervous System Diseases
MeSH terms: Nervous System Diseases; Angelman Syndrome; Syndrome
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Betaine; Creatine; Metafolin; Vitamin B12
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses; 200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses; 0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses; 1 mg by mouth per day for all weights and ages
Intervention MeSH terms: Vitamin B 12; Hydroxocobalamin; Betaine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Developmental Delay; Mental Retardation; Ataxia; Microcephaly; Seizures