Autistic DisorderPhase 2/3NCT00273650
Efficacy Study of Subcutaneous Methyl-B12 in Children With Autism
A Phase 2/3 study testing methylcobalamin in people with Autistic Disorder, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 8 years
- Conditions the study is for
- Autistic Disorder
- What is being tested?
- methylcobalamin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Aug 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 8 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- Clinical evidence of seizure disorder
- Cancer
- Recent surgery
- Active infection with fever
- Fragile X or other known genetic cause of autism
- Bleeding disorder
Show all 9Show fewer
- Perinatal brain injury (e.g. cerebral palsy)
- Current use of any methyl B12 product
- Evidence for malnutrition seen in abnormal albumin level
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis MIND Institute
Sacramento, California, 95817
About this study
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.
Read the 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.
- Conditions
- Autistic Disorder
- Being tested
- methylcobalamin, saline placebo
- Keywords
- Autism, Placebo, B12, Controlled, Complementary Alternative Medicine, Vitamin Supplement
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylcobalaminDrug
Also called Vitamin B-12, Methyl-B12
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.
saline placeboOther
Also called saline
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.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Methyl-B12 Receives: Drug: methylcobalamin |
| B | Placebo comparator | Saline placebo Receives: Other: saline placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 Weeks to 6 Months
Secondary outcomes (1)
Secondary measures:NEPSY, ABC, PPVT, SB:V, PDRF, MCDI, PIA-CV, and CARS.
Measured: 12 Weeks to 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2006 (estimated)
- Study startJul 2005
- Primary completionJun 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Autistic DisorderStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert L Hendren, D.O., Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00273650
- Sponsor's protocol ID
- MB12-AUT
- Status last verified
- Sep 2019
- First submitted
- 6 Jan 2006
- Last updated
- 9 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 12394355Bertrand 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.
PubMed 11694696DeStefano 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.
PubMed 14754936Esch 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.
PubMed 15628608Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 2000;26(3):219-25. doi: 10.1055/s-2000-8466.
PubMed 11011839Gulati 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.
PubMed 10362526Keller F, Persico AM. The neurobiological context of autism. Mol Neurobiol. 2003 Aug;28(1):1-22. doi: 10.1385/MN:28:1:1.
PubMed 14514983Levy 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.
PubMed 14671475London 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.
PubMed 10852835Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev. 2003 Feb;8(1):7-19.
PubMed 12611557Muntjewerff 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.
PubMed 14572619Pogribna 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.
PubMed 11391481Schulz 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.
PubMed 10931172Sogut 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.
PubMed 12691871Steinhausen 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.
PubMed 3486202
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Placebo Controlled, Cross-over Trial of Subcutaneous B12 on Behavioral and Metabolic Measures in Children With Autism.
- ClinicalTrials.gov ID
- NCT00273650
- Acronym / sponsor ID
- MB12-AUT
- Conditions
- Autistic Disorder
- Keywords
- Autism, Placebo, B12, Controlled, Complementary Alternative Medicine, Vitamin Supplement
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Jul 2005
- Primary completion
- Jun 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 9 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: methylcobalaminMethyl-B12 |
| B | Placebo comparator | Other: saline placeboSaline placebo |
Who may qualify
- Ages
- 3 to 8 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- Clinical evidence of seizure disorder
- Cancer
- Recent surgery
- Active infection with fever
- Fragile X or other known genetic cause of autism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methylcobalaminAlso: Vitamin B-12, Methyl-B12Methylcobalamin (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. | Drug | A |
| saline placeboAlso: salineMethylcobalamin (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 | B |
Primary outcome
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
1 secondary outcome
Secondary measures:NEPSY, ABC, PPVT, SB:V, PDRF, MCDI, PIA-CV, and CARS.
Time frame: 12 Weeks to 6 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2019.
- Background: PubMed 12394355Beaudet AL. Is medical genetics neglecting epigenetics? Genet Med. 2002 Sep-Oct;4(5):399-402. doi: 10.1097/00125817-200209000-00013. No abstract available.
- Background: PubMed 11694696Bertrand 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.
- Background: PubMed 14754936DeStefano 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.
- Background: PubMed 15628608Esch 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.
- Background: PubMed 11011839Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 2000;26(3):219-25. doi: 10.1055/s-2000-8466.
- Background: PubMed 10362526Gulati 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.
- Background: PubMed 14514983Keller F, Persico AM. The neurobiological context of autism. Mol Neurobiol. 2003 Aug;28(1):1-22. doi: 10.1385/MN:28:1:1.
- Background: PubMed 14671475Levy 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.
- Background: PubMed 10852835London 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.
- Background: PubMed 12611557Miller AL. The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev. 2003 Feb;8(1):7-19.
- Background: PubMed 14572619Muntjewerff 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.
- Background: PubMed 11391481Pogribna 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert L Hendren, D.O. principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing methylcobalamin in people with Autistic Disorder, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00273650, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2019.