Conditions: Angelman Syndrome Nervous System Diseases
Keywords: Developmental Delay Mental Retardation Ataxia Microcephaly Seizures
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 90
Healthy volunteers: no

Brief 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.

Arms:
arm 1: Participants will receive two daily doses of Metafolin, betaine, and creatine, and one daily dose of vitamin B12 for 12 months.

Interventions: intervention 1: Betaine intervention 2: Creatine intervention 3: Metafolin intervention 4: Vitamin B12
Intervention descriptions: intervention 1: 100-200 mg per kg per day by mouth with a maximum of 6 grams divided in two daily doses intervention 2: 200 mg per kg per day with a daily maximum of 5 grams divided in two daily doses intervention 3: 0.5 mg per kg per day by mouth with a maximum of 8 milligrams divided in two daily doses intervention 4: 1 mg by mouth per day for all weights and ages

Protocol document: