Treatment of Social and Language Deficits with Leucovorin for Young Children with Autism

Eligibility Criteria

• 1. 1. Autism Spectrum Disorder (diagnosed as Autistic Disorder on the ADOS-2 or the ADI-R).
• 2. Between 2 years 6 months and 5 years 2 months of age at baseline
• 3. Folate Receptor Alpha Autoantibody Positive status
• 4. Language impairment (Ages and Stage Questionnaire between -1 and -3 SD for Language)
• 5. English included in the languages in which the child is being raised
• 6. Autism severity of moderate or higher (≥4) under the 7-item clinical global impression-severity scale. Moderate level of autism severity (4) is defined by the diagnosis of ASD with language impairment, so fulfilling #1 and #4 fulfills this requirement.
• 7. Ability to maintain all ongoing complementary, dietary, traditional, and behavioral treatments constant for the study period
• 8. Unchanged complementary, dietary, traditional, and behavioral treatments for two months prior to study entry
• 9. Has at least 4 month old expressive language ability as assessed by the MSEL Expressive Language Scale (i.e., Parent answers "yes" to " Voluntary babbling (such as 'bu, bu, bu")" Question #7 on the MSEL Expressive Language Scale.
• 10. Ability to attend to social stimulus and tolerate imaging procedures, as determined at the discretion of the investigator
• 1. Known FRAA status by clinically validated test performed outside of research studies.
• 2. Mineral or vitamin supplementation that exceeds the Tolerable Upper Daily Intake Levels set by the Institute of Medicine (See Table 6 below)
• 3. Significant self-abusive or violent behavior or evidence of suicidal ideation, plan or behavior
• 4. Severely affected children as defined by CGI-Severity Standard Score = 7 (Extremely Ill)
• 5. Severe prematurity (\<34 weeks gestation) as determined by medical history
• 6. Current uncontrolled gastroesophageal reflux
• 7. Current or history of liver or kidney disease as determined by medical history and safety labs
• 8. Genetic syndromes
• 9. Congenital brain malformations
• 10. Epilepsy
• 11. Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data
• 12. Significant negative reaction (i.e. fainting, vomiting, etc.) as a result of a previous blood draw.
• 13. Failure to thrive or Body Mass Index \< 5%ile or \<5%ile for weight (male \<11.2kg; female \<10.8kg by CDC 2000 growth charts) at the time of the study.
• 14. Concurrent treatment with drug that would significantly interact with l-leucovorin such as specific chemotherapy agents, antimalarial and immune suppressive agents and select antibiotics (See Table 7 below).
• 15. Allergy or Sensitivity to ingredients in the investigational product or placebo
• 16. Evaluation with the MSEL or BOSCC within 3 months of entering the study
• 17. Planned evaluation with the MSEL or BOSCC during the study
• 18. Exclusion Criteria for the MEG recording include:
• 1. Ferromagnetic implants, artificial joints, fixation hardware, dental work or shrapnel (additional screening will be completed to determine MRI eligibility)
• 2. Ferromagnetic products attached to the body (including hair extensions)
• 3. Head circumference greater than 60 cm
• 4. A weight greater than 407 lbs. (185 kg)