Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder

• Status: Recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the effectiveness of folinic acid in the treatment of language problems in children with autism spectrum disorder. Folinic acid, also known as leucovorin, is approved by the U.S. Food and Drug Administration (FDA) to decrease side effects during cancer chemotherapy. Folinic acid may be helpful in treating language problems in children with autism spectrum disorder, but this is not known. Therefore, folinic acid is an investigational new drug for this study. Investigators will enroll a total of 134 participants across all three centers, over a 5 year period and participation will last between 12 and 24 weeks.

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

Details

• Lead Sponsor: Emory University; Phoenix Children's Hospital
• Collaborators: Aprofol; Arkansas Children's Hospital Research Institute; Emory University; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Harvard University
• Treatments: Folic Acid; Leucovorin; Levoleucovorin

Criteria

Inclusion Criteria:

• Boys and girls ≥ 5 years and < 12 years 5 months of age;

• Weight ≥ 15 kg;

• DSM-5 diagnosis of Autism Spectrum Disorder as established by clinical assessment, corroborated by the Social Communication Questionnaire and the Autism Diagnostic Observational Schedule.

• A score < 80 on the Core Language score of the Clinical Evaluation of Language Fundamentals -4 (CELF)- 4 or the Second Edition of the CELF-Preschool test (CELF-P).

• Current Clinical Global Impression Severity score ≥ 4 on ASD + communication delay.

• IQ at least 40 as measured by the Leiter-3 or mental age at least 18 months as measured on the Receptive Language Scale of the Mullen.

• Stable educational plan (one month) with no planned changes in the intensity of treatment for 12 weeks. (Otherwise eligible subjects with anticipated changes in their school program in the near term will be invited to return when the transition has been accomplished.

• Stable speech therapy program in the community (one month) with no planned changes for 12 weeks.

• English is spoken in the home and at least one parent is able to read, write and speak English.

• Stable medication (no changes in past 6 weeks and no planned changes for the next 6 months (duration of the study).

Exclusion Criteria:

• IQ below 40 as measured by the Leiter-3 or below a mental age of 18 months on the Receptive Language Scale of Mullen. (N.B. subjects who test below 18 months of age, but are otherwise eligible, may be enrolled following a case review by the Steering Committee - e.g., child's uncooperative behavior resulted in a likely underestimate of intellectual ability);

• Score of 40 on the Core-CELF -4 or 45 on the CELF-P (indicates more severe language);

• Current DSM-IV diagnosis requiring alternative pharmacotherapy, e.g., Major Depression, Bipolar Disorder, a psychotic disorder (based on clinical assessment assisted by the Child and Adolescent Symptom Inventory);

• Presence of serious behavioral problems (tantrums, aggression, self-injury) for which another treatment is warranted.

• Significant medical condition by history or by physical examination or lab tests that would be incompatible with the study drug.

• Children taking anticonvulsant medication for seizures.

• Children taking Bactrim (trimethoprim + sulfamethoxazole) because Bactrim can interfere with folate metabolism. Children who discontinue use of Bactrim for 2 months may be re-evaluated for the study. Caregivers will be advised not to use any of these medications during the trial.

• Children taking valproic acid or derivatives or lamotrigine for any purpose will be excluded because these drugs can interfere with folate metabolism. Caregivers will be advised not to use any of these medications during the trial.

• Children on mineral or vitamin supplements that exceed the Recommended Daily Allowance set by the IOM.