Using leucovorin to improve social and language skills in young children with autism

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This study aims to evaluate the cognitive and behavioral effects of liquid leucovorin calcium on young children diagnosed with autism spectrum disorder (ASD) who exhibit social communication delays. The trial will enroll 80 children aged 2.5 to 5 years and will last approximately 26 weeks, during which participants will be randomly assigned to receive either leucovorin or a placebo. The primary objective is to determine if leucovorin can significantly improve social communication and core symptoms of ASD compared to placebo. The study will also assess the safety and tolerability of the treatment in this population.

Why it matters

Who can join: the full rules

Inclusion 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

Exclusion Criteria:

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)

Where it's running

• State University of New York, Downstate
  Brooklyn, New York, United States Recruiting
• Southwestern Research & Resource Center
  Phoenix, Arizona, United States Not yet recruiting

Study contacts

• Principal investigator: Richard E Frye, MD, PhD — Rossignol Medical Center, Phoenix AZ
• Study coordinator: Richard E Frye, MD, PhD
• Email: DrFrye@RossignolMedicalCenter.com
• Phone: (321) 259-7111

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.