NCT04060030 · Southwest Autism Research & Resource Center
Treatment of Social and Language Deficits With Leucovorin for Young Children With Autism
What this study is about
The primary objective of this study is to evaluate the cognitive and behavioral effects of liquid leucovorin calcium on young children with autism spectrum disorder (ASD) and determine whether it improves social communication as well as the core and associated symptoms of ASD. The investigators will enroll 80 children across two sites, between the ages of 2.
View original scientific description
The primary objective of this study is to evaluate the cognitive and behavioral effects of liquid leucovorin calcium on young children with autism spectrum disorder (ASD) and determine whether it improves social communication as well as the core and associated symptoms of ASD. The investigators will enroll 80 children across two sites, between the ages of 2.5 and 5 years, with confirmed ASD and known social and communication delays.
Interventions
DRUG
Levoleucovorin Calcium
Liquid leucovorin calcium dosed by weight
OTHER
Placebo
Placebo
Primary outcome measures
Evaluate the change in social communication symptoms
Time frame: Baseline, Week 6, Week 12, Week 24
Aberrant Behavior Checklist-2, Social Withdrawal Subscale. The ABC is a 58-item parent-reported measure with ratings in the following domains: irritability, social withdrawal, stereotypic behavior, hyperactivity, and inappropriate speech. Each item is rated from 0 (Not a Problem) to 3 (Severe Problem). The raw score will be reported. The total raw score is the sum of the domain raw scores. A higher raw score in any of the domains indicates more severe problems in that domain; a higher total raw score indicates more severity of stereotypical autism symptoms overall.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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
- Current or history of liver or kidney disease as determined by medical history and safety labs
- Genetic syndromes
- Congenital brain malformations
- Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data
- Significant negative reaction (i.e. fainting, vomiting, etc.) as a result of a previous blood draw.
- 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.
- 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
- Evaluation with the MSEL or BOSCC within 3 months of entering the study
- Planned evaluation with the MSEL or BOSCC during the study
- 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)
Where
- Phoenix, Arizona
- Brooklyn, New York
Collaborators
Autism Speaks, State University of New York - Downstate Medical Center
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 27, 2026 · Source of record for eligibility and locations