Trial of Methyl B12 on Behavioral and Metabolic Measures in Children With Autism

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01039792
• Collaborator: University of California, Davis (Other), Arkansas Children's Hospital Research Institute (Other)
• Enrollment: 57
• Location: 1
• Arms: 2
• Duration (Months): 46
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the supplement Methyl B12 is effective in treating some of the symptoms of Autism.

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Drug: Methyl B12; Dietary Supplement: Placebo	Phase 2/Phase 3

Detailed Description

Autism is a complex neurodevelopmental disorder with early childhood onset characterized by impairments in communication, social interaction, and repetitive behavior. Due to the lack of known treatments for autism, many parents seek complementary and alternative medical (CAM) therapies hoping to help their affected child. Methylcobalamin (methyl B12) is a commonly used CAM treatment that has anecdotal reports of remarkable clinical improvements with few side effects. Prior studies have found that children with autism have deficiencies in key metabolites and antioxidants which can be caused by methyl B12 deficiency; additional studies have shown that methyl B12 normalizes deficiencies in these metabolites and antioxidants. Based on these reports, a pilot study was conducted at UC Davis on the effect of methyl B12 on the behavioral and metabolic measures in children with autism. The preliminary results of 29 subjects revealed a subgroup of 9 responders to clinical behavior assessments. These responders also demonstrated significant improvement on the plasma measures of antioxidant capacity, suggesting methyl B12 improves symptoms in a subgroup of children with autism by increasing key antioxidants. The current study will have an 8 week double blind design with 50 subjects, designed to evaluate improvements from methyl B12 by using behavioral assessments and analysis of specific metabolites in the subjects' blood. This study will determine whether methyl B12 will lead to benefits in any of the core features of autism, and will examine metabolic changes with the hope of potentially identifying a biomarker for treatment response in a subgroup of subjects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Double Blind Placebo Controlled Trial of Methyl B12 on Behavioral and Metabolic Measures in Children With Autism
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo	Dietary Supplement: Placebo; placebo
Experimental: Active Active Methyl B12	Drug: Methyl B12; 75 µg/Kg subcutaneously injected once every 3 days; Other Names: Vitamin B12 methylcobalamin

Outcome Measures

Primary Outcome Measures

1. Clinical Global Impression-Improvement (CGI-I) [8 weeks]

   PI assesses subject's change using the CGI-I measure. This is a 7-point Likert scale that assesses improvement of the patient's condition. Scores range from the worst score of 7 (Very much worse) to the best score of 1 (Very much improved). Lower scores are better on this scale, and indicate greater improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 7 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of DSM IV defined autism and meets cut off on Autism Diagnostic Inventory-Revised (ADI-R) and/or the Autism Diagnostic Observation Scale (ADOS)

• Age 3 through 7 years

• IQ of 50 or above

• Parental agreement to continue present dietary, behavioral or psychotropic drug treatment but not change treatment during 8 week intervention

• Willingness to have blood drawn, without the use of a sedative prescription from the study doctor

Exclusion Criteria:

• Bleeding disorder

• Cancer

• Seizure disorder

• Fragile X or other known genetic cause of autism

• Perinatal brain injury (i.e.: cerebral palsy)

• Other serious medical illnesses

• Current use of any B12 supplement

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF	San Francisco	California	United States	94143

Sponsors and Collaborators

• University of California, San Francisco
• University of California, Davis
• Arkansas Children's Hospital Research Institute

Investigators

• Principal Investigator: Robert L. Hendren, DO, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Hendren, Professor of Psychiatry, Director of Child & Adolescent Psychiatry, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01039792
• Other Study ID Numbers: Autism Speaks 3031
• First Posted: Dec 25, 2009
• Last Update Posted: Feb 24, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Robert Hendren, Professor of Psychiatry, Director of Child & Adolescent Psychiatry, University of California, San Francisco: Autism; Pervasive Developmental Disorders
• Additional relevant MeSH terms: Autistic Disorder; Vitamin B 12

Study Results

Participant Flow

Recruitment Details	Children were recruited from the Autism clinic, an advertisement on Craigslist.org and letters to families of current and previous patients, between 12/8/10 to 10/22/13.
Pre-assignment Detail	Enrolled patients excluded from the trial prior to assignment phase were attributed to inattention/inability to focus, increased hyperactivity/stimming, lack of efficacy, challenging behavior- parent request to drop out

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo Placebo: placebo	Active Methyl B12 Methyl B12: 75 µg/Kg subcutaneously injected once every 3 days
Period Title: Overall Study
STARTED	29	28
COMPLETED	23	27
NOT COMPLETED	6	1

Baseline Characteristics

Arm/Group Title	Placebo	Active	Total
Arm/Group Description	Placebo Placebo: Syringes were tightly taped with opaque material to hide the color of the liquid	Active Methyl B12 Methyl B12: 75 µg/Kg subcutaneously injected once every 3 days	Total of all reporting groups
Overall Participants	23	27	50
Age (Count of Participants)
<=18 years	23 100%	27 100%	50 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	58 (14)	67 (16)	63 (16)
Gender (Count of Participants)
Female	4 17.4%	6 22.2%	10 20%
Male	19 82.6%	21 77.8%	40 80%
Region of Enrollment (Count of Participants)
United States	23 100%	27 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Global Impression-Improvement (CGI-I)
Description	PI assesses subject's change using the CGI-I measure. This is a 7-point Likert scale that assesses improvement of the patient's condition. Scores range from the worst score of 7 (Very much worse) to the best score of 1 (Very much improved). Lower scores are better on this scale, and indicate greater improvement.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

comparing placebo vs active B12 subjects

Arm/Group Title	Placebo	Active
Arm/Group Description	Placebo Placebo: Syringes were tightly taped with opaque material to hide the color of the liquid	Active Methyl B12 Methyl B12: 75 µg/Kg subcutaneously injected once every 3 days
Measure Participants	23	27
Mean (Standard Deviation) [CGI- Improvement]	3.1 (0.8)	2.4 (0.8)

Adverse Events

Arm/Group Title	Placebo		Active
Arm/Group Description	Placebo Placebo: placebo		Active Methyl B12 Methyl B12: 75 µg/Kg subcutaneously injected once every 3 days
All Cause Mortality
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Active
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/23 (60.9%)		13/27 (48.1%)
General disorders
fever	1/23 (4.3%)	1	2/27 (7.4%)	2
mouthing	1/23 (4.3%)	1	5/27 (18.5%)	5
trouble sleeping	3/23 (13%)	3	1/27 (3.7%)	1
Psychiatric disorders
increased hyperactivity	7/23 (30.4%)	7	2/27 (7.4%)	2
Respiratory, thoracic and mediastinal disorders
cold	2/23 (8.7%)	2	3/27 (11.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.