Efficacy Study of Subcutaneous Methyl-B12 in Children With Autism - Full Text View

Purpose

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.

Condition	Intervention	Phase
Autistic Disorder	Drug: methylcobalamin Other: saline placebo	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Double-Blind Placebo Controlled, Cross-over Trial of Subcutaneous B12 on Behavioral and Metabolic Measures in Children With Autism.

Resource links provided by NLM:

MedlinePlus related topics: Autism B Vitamins Dietary Supplements

Drug Information available for: Cyanocobalamin Vitamin B Complex Hydroxocobalamin Mecobalamin

U.S. FDA Resources

Further study details as provided by University of California, Davis:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Secondary measures:NEPSY, ABC, PPVT, SB:V, PDRF, MCDI, PIA-CV, and CARS. [ Time Frame: 12 Weeks to 6 Months ] [ Designated as safety issue: No ]

Enrollment:	35
Study Start Date:	July 2005
Study Completion Date:	August 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Methyl-B12	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 Names: Vitamin B-12 Methyl-B12
Placebo Comparator: B Saline placebo	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. Other Name: saline

Arms

Assigned Interventions

Active Comparator: A

Methyl-B12

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 Names:

Vitamin B-12
Methyl-B12

Placebo Comparator: B

Saline placebo

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.

Other Name: saline

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	3 Years to 8 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00273650

Locations

United States, California
UC Davis MIND Institute
Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

Principal Investigator:

Robert L Hendren, D.O.

University of California, Davis

More Information

Publications:

Beaudet AL. Is medical genetics neglecting epigenetics? Genet Med. 2002 Sep-Oct;4(5):399-402. No abstract available.

Bertrand J, Mars A, Boyle C, Bove F, Yeargin-Allsopp M, Decoufle P. Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation. Pediatrics. 2001 Nov;108(5):1155-61.

DeStefano F, Bhasin TK, Thompson WW, Yeargin-Allsopp M, Boyle C. Age at first measles-mumps-rubella vaccination in children with autism and school-matched control subjects: a population-based study in metropolitan atlanta. Pediatrics. 2004 Feb;113(2):259-66.

Esch BE, Carr JE. Secretin as a treatment for autism: a review of the evidence. J Autism Dev Disord. 2004 Oct;34(5):543-56. Review.

Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 2000;26(3):219-25. Review.

Gulati S, Brody LC, Banerjee R. Posttranscriptional regulation of mammalian methionine synthase by B12. Biochem Biophys Res Commun. 1999 Jun 7;259(2):436-42.

Keller F, Persico AM. The neurobiological context of autism. Mol Neurobiol. 2003 Aug;28(1):1-22. Review.

Levy SE, Mandell DS, Merhar S, Ittenbach RF, Pinto-Martin JA. Use of complementary and alternative medicine among children recently diagnosed with autistic spectrum disorder. J Dev Behav Pediatr. 2003 Dec;24(6):418-23.

London EA. The environment as an etiologic factor in autism: a new direction for research. Environ Health Perspect. 2000 Jun;108 Suppl 3:401-4. Review.

Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev. 2003 Feb;8(1):7-19. Review.

Muntjewerff JW, van der Put N, Eskes T, Ellenbroek B, Steegers E, Blom H, Zitman F. Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia. Psychiatry Res. 2003 Nov 1;121(1):1-9.

Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. Homocysteine metabolism in children with Down syndrome: in vitro modulation. Am J Hum Genet. 2001 Jul;69(1):88-95. Epub 2001 Jun 5.

Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 2000 Aug;267(16):4904-11. Review.

Sogut S, Zoroglu SS, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savas HA, Tarakcioglu M, Akyol O. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta. 2003 May;331(1-2):111-7.

Steinhausen HC, Gobel D, Breinlinger M, Wohlleben B. A community survey of infantile autism. J Am Acad Child Psychiatry. 1986 Mar;25(2):186-9. No abstract available.

Sturmey P. Secretin is an ineffective treatment for pervasive developmental disabilities: a review of 15 double-blind randomized controlled trials. Res Dev Disabil. 2005 Jan-Feb;26(1):87-97. Review.

Yeargin-Allsopp M, Rice C, Karapurkar T, Doernberg N, Boyle C, Murphy C. Prevalence of autism in a US metropolitan area. JAMA. 2003 Jan 1;289(1):49-55.

Yorbik O, Sayal A, Akay C, Akbiyik DI, Sohmen T. Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids. 2002 Nov;67(5):341-3.

Responsible Party:	University of California, Davis
ClinicalTrials.gov Identifier:	NCT00273650 History of Changes
Other Study ID Numbers:	MB12-AUT
Study First Received:	January 6, 2006
Last Updated:	October 30, 2012
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by University of California, Davis:

Autism
Placebo
B12

Controlled
Complementary Alternative Medicine
Vitamin Supplement

Additional relevant MeSH terms:

Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Vitamin B 12
Vitamins

Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013