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

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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. Participation will last approximately 26 weeks, from screening visit to end of treatment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Phoenix Children's Hospital
• Collaborators: Autism Speaks; New York State Institute for Basic Research; State University of New York - Downstate Medical Center; University of Arizona
• Treatments: Calcium; Calcium, Dietary; Leucovorin; Levoleucovorin

Criteria

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 and MSEL Expressive Language <=40)

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. A minimum of 10 hours of behavioral (ABA type) therapy per week

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)