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

Prior treatment

• Significant negative reaction (i.e. fainting, vomiting, etc.) as a result of a previous blood draw.
• 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).
• Allergy or Sensitivity to ingredients in the investigational product or placebo
• Exclusion Criteria for the MEG recording include:
  • Ferromagnetic implants, artificial joints, fixation hardware, dental work or shrapnel (additional screening will be completed to determine MRI eligibility)
  • Ferromagnetic products attached to the body (including hair extensions)
  • Head circumference greater than 60 cm
  • A weight greater than 407 lbs. (185 kg)

Other illness

• Current or history of liver or kidney disease as determined by medical history and safety labs
• Genetic syndromes
• Epilepsy
• Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data
• 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.

Other

• Known FRAA status by clinically validated test performed outside of research studies.
• Mineral or vitamin supplementation that exceeds the Tolerable Upper Daily Intake Levels set by the Institute of Medicine (See Table 6 below)
• Significant self-abusive or violent behavior or evidence of suicidal ideation, plan or behavior
• Severely affected children as defined by CGI-Severity Standard Score = 7 (Extremely Ill)
• Severe prematurity (\<34 weeks gestation) as determined by medical history
• Current uncontrolled gastroesophageal reflux
• Congenital brain malformations
• Evaluation with the MSEL or BOSCC within 3 months of entering the study
• Planned evaluation with the MSEL or BOSCC during the study

• 1\. Autism Spectrum Disorder (diagnosed as Autistic Disorder on the ADOS-2 or the ADI-R).
• Between 2 years 6 months and 5 years 2 months of age at baseline
• Folate Receptor Alpha Autoantibody Positive status
• Language impairment (Ages and Stage Questionnaire between -1 and -3 SD for Language)
• English included in the languages in which the child is being raised
• 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.
• Ability to maintain all ongoing complementary, dietary, traditional, and behavioral treatments constant for the study period
• Unchanged complementary, dietary, traditional, and behavioral treatments for two months prior to study entry
• 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.
• Ability to attend to social stimulus and tolerate imaging procedures, as determined at the discretion of the investigator