Efficacy Study of Subcutaneous Methyl-B12 in Children With Autism

NCT ID: NCT00273650

Last Updated: 2019-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2009-08-31

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.

Conditions

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Autistic Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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A

Methyl-B12

Group Type ACTIVE_COMPARATOR

methylcobalamin

Intervention Type DRUG

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.

B

Saline placebo

Group Type PLACEBO_COMPARATOR

saline placebo

Intervention Type OTHER

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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Vitamin B-12 Methyl-B12 saline

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
Minimum Eligible Age

3 Years

Maximum Eligible Age

8 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert L Hendren, D.O.

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

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UC Davis MIND Institute

Sacramento, California, United States

Site Status

Countries

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United States

References

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Beaudet AL. Is medical genetics neglecting epigenetics? Genet Med. 2002 Sep-Oct;4(5):399-402. doi: 10.1097/00125817-200209000-00013. No abstract available.

Reference Type BACKGROUND
PMID: 12394355 (View on PubMed)

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. doi: 10.1542/peds.108.5.1155.

Reference Type BACKGROUND
PMID: 11694696 (View on PubMed)

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. doi: 10.1542/peds.113.2.259.

Reference Type BACKGROUND
PMID: 14754936 (View on PubMed)

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. doi: 10.1007/s10803-004-2549-6.

Reference Type BACKGROUND
PMID: 15628608 (View on PubMed)

Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 2000;26(3):219-25. doi: 10.1055/s-2000-8466.

Reference Type BACKGROUND
PMID: 11011839 (View on PubMed)

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. doi: 10.1006/bbrc.1999.0696.

Reference Type BACKGROUND
PMID: 10362526 (View on PubMed)

Keller F, Persico AM. The neurobiological context of autism. Mol Neurobiol. 2003 Aug;28(1):1-22. doi: 10.1385/MN:28:1:1.

Reference Type BACKGROUND
PMID: 14514983 (View on PubMed)

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. doi: 10.1097/00004703-200312000-00003.

Reference Type BACKGROUND
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London EA. The environment as an etiologic factor in autism: a new direction for research. Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):401-4. doi: 10.1289/ehp.00108s3401.

Reference Type BACKGROUND
PMID: 10852835 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 12611557 (View on PubMed)

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. doi: 10.1016/s0165-1781(03)00200-2.

Reference Type BACKGROUND
PMID: 14572619 (View on PubMed)

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. doi: 10.1086/321262. Epub 2001 Jun 5.

Reference Type BACKGROUND
PMID: 11391481 (View on PubMed)

Schulz JB, Lindenau J, Seyfried J, Dichgans J. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem. 2000 Aug;267(16):4904-11. doi: 10.1046/j.1432-1327.2000.01595.x.

Reference Type BACKGROUND
PMID: 10931172 (View on PubMed)

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. doi: 10.1016/s0009-8981(03)00119-0.

Reference Type BACKGROUND
PMID: 12691871 (View on PubMed)

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. doi: 10.1016/s0002-7138(09)60225-9. No abstract available.

Reference Type BACKGROUND
PMID: 3486202 (View on PubMed)

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. doi: 10.1016/j.ridd.2004.09.002.

Reference Type BACKGROUND
PMID: 15590241 (View on PubMed)

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. doi: 10.1001/jama.289.1.49.

Reference Type BACKGROUND
PMID: 12503976 (View on PubMed)

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. doi: 10.1054/plef.2002.0439.

Reference Type BACKGROUND
PMID: 12445495 (View on PubMed)

Other Identifiers

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MB12-AUT

Identifier Type: -

Identifier Source: org_study_id

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