Efficacy Study of Subcutaneous Methyl-B12 in Children With Autism

Study Overview
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Brief Summary
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We will be testing a specific dietary supplement, methylcobalamin (vitamin B12). Follow-up assessments with our clinical team will take place over the 12-week study period so that we can record any changes in development. The main goal of this study is to determine if subcutaneous injections of vitamin B12 given every three days can positively affect behavior and development in children with autism. Hypothesis: Methylcobalamin injections will improve measures of executive function, speech, and socialization in children with autism, and will be associated with metabolic improvement.

Detailed Description
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Autism is a complex neurodevelopmental disorder that is thought to involve an interaction between multiple and variable susceptibility genes (Keller & Persico, 2003), epigenetic effects (Beaudet, 2002), and environmental factors (London, 2000). The increase in the prevalence of autistic spectrum disorders from 4-5/10,000 in the 1980s to 30-60/10,000 in the last decade has raised great concern (Bertrand et al., 2001; DeStefano et al., 2004; Steinhausen et al., 1986; Yeargin-Allsopp et al., 2003). Research into potential therapeutic interventions designed to ameliorate the metabolic and clinical symptoms of autism is urgently needed to reduce the enormous public health burden of this disorder and to improve the quality of life for affected children and their families. Nutritional supplementation through subcutaneous injections of methyl B12 is a current treatment for children with autism that has anecdotal reports of remarkable clinical improvements and few side effects. However there are no published studies to support its clinical benefit. Comparison: Injections of methylcobalamin compared to injections of sterile saline over a six week period.

Official Title
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Double-Blind Placebo Controlled, Cross-over Trial of Subcutaneous B12 on Behavioral and Metabolic Measures in Children With Autism.

Conditions
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Autistic Disorder

Intervention / Treatment
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* Drug: methylcobalamin
* Other: saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of DSM IV defined autism and meets cut off on Autism Diagnostic Inventory-Revised (ADI-R) and the Autism Diagnostic Observation Scale (ADOS). Age 3 to 8 years IQ of 50 or above Willingness of parents to administer subcutaneous methyl B12. Parental agreement to continue present dietary, behavioral or psychotropic drug treatment but not change treatment during 12 week intervention or wait list. Exclusion Criteria: Clinical evidence of seizure disorder Cancer Recent surgery Active infection with fever Fragile X or other known genetic cause of autism Bleeding disorder Perinatal brain injury (e.g. cerebral palsy) Current use of any methyl B12 product Evidence for malnutrition seen in abnormal albumin level

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Methyl-B12 | Drug: methylcobalamin<br>* Methylcobalamin (25,000μg/ml), at a dosage of 64.5μg/kg, or saline placebo administered subcutaneously, once every three days for six weeks. At six weeks, subjects cross over to the other treatment given every three days for another six weeks. Post 12 weeks, treatment with open label methylcobalamin will continue once every three days, for six months.<br>* Other names: Methyl-B12;|
| Placebo Comparator: B<br>Saline placebo | Other: saline placebo<br>* Methylcobalamin (25,000μg/ml), at a dosage of 64.5μg/kg, or saline placebo administered subcutaneously, once every three days for six weeks. At six weeks, subjects cross over to the other treatment given every three days for another six weeks. Post 12 weeks, treatment with open label methylcobalamin will continue once every three days, for six months.<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary measure is the Clinical Global Impression Scale -Improvement supplemented by videos taken at all visits and rated blindly to measure executive function, speech, and language, and socio-economic development. |  | 12 Weeks to 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary measures:NEPSY, ABC, PPVT, SB:V, PDRF, MCDI, PIA-CV, and CARS. |  | 12 Weeks to 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B12, Autism, Placebo, Controlled, Complementary Alternative Medicine, Vitamin Supplement