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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2009

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.

Intervention(s) in this Clinical Trial

• Drug: methylcobalamin
  • 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.
• Other: saline placebo
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Methyl-B12
• Placebo Comparator: B
  • Saline placebo

Primary Measures

• 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.
  • Time Frame: 12 Weeks to 6 Months
    Safety Issue?: Yes

Secondary Measures

• Secondary measures:NEPSY, ABC, PPVT, SB:V, PDRF, MCDI, PIA-CV, and CARS.
  • Time Frame: 12 Weeks to 6 Months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 3 Years

Maximum Age for this Clinical Trial: 8 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, Davis

Overall Clinical Trial Officials and Contacts

Robert L Hendren, D.O. Principal Investigator University of California, Davis  

Overall Contact: Kiah Bertoglio, BS 9167030224 kiah.bertoglio@ucdmc.ucdavis.edu

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00273650

Study ID Number: MB12-AUT

ClinicalTrials.gov Identifier: NCT00273650

Health Authority: United States: Food and Drug Administration