Autistic Disorder
Conditions
Keywords
Autism, Pervasive Developmental Disorders
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.
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.
Interventions
DRUGMethyl B12
75 µg/Kg subcutaneously injected once every 3 days
DIETARY_SUPPLEMENTPlacebo
placebo
Sponsors
University of California, Davis
Arkansas Children's Hospital Research Institute
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Years to 7 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
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 details
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
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo
Placebo: Syringes were tightly taped with opaque material to hide the color of the liquid | 23 |
| Active Active Methyl B12
Methyl B12: 75 µg/Kg subcutaneously injected once every 3 days | 27 |
| Total | 50 |
Baseline characteristics
| Characteristic | Active | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 27 Participants | 23 Participants | 50 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 67 months STANDARD_DEVIATION 16 | 58 months STANDARD_DEVIATION 14 | 63 months STANDARD_DEVIATION 16 |
| Gender Female | 6 Participants | 4 Participants | 10 Participants |
| Gender Male | 21 Participants | 19 Participants | 40 Participants |
| Region of Enrollment United States | 27 Participants | 23 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 23 | 13 / 27 |
| serious Total, serious adverse events | 0 / 24 | 0 / 27 |
Outcome results
Primary
Clinical Global Impression-Improvement (CGI-I)
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
Population: comparing placebo vs active B12 subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression-Improvement (CGI-I) | 3.1 CGI- Improvement | Standard Deviation 0.8 |
| Active | Clinical Global Impression-Improvement (CGI-I) | 2.4 CGI- Improvement | Standard Deviation 0.8 |