Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder
Autism Spectrum Disorder
About this trial
This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Language Impairment
Eligibility Criteria
Inclusion Criteria:
- Boys and girls ≥ 5 years and < 17 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);
- Is within the scoreable range of the CELF-4 or CELF-P as detailed in the Language Algorithm;
- 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.
Sites / Locations
- Southwestern Research and Resource Center
- Children's Healtcare of Atlanta
- Harvard University
- State University of New York, DownstateRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Folinic Acid
Placebo Control
Subjects randomized to receive Folinic Acid will take Liquid levo-leucovorin via oral route. The target dose is 1 mg/kg/day with a maximum of 25 mg/day, divided in two daily doses. A two- to four-week supply of 15 ml vials will be dispensed in line with the visit schedule. With the exception of children in the lowest weight group (≥ 15 - < 20 kg) from days 1-14, parents will administer the prescribed dose twice a day at the same time each day.
Subjects randomized to receive placebo will take placebo twice a day (Exception: children in the lowest weight group ( ≥ 15 - < 20 kg) will start once a day for Days1-13). The pattern of dose escalation will be the same as the active compound. After 12 weeks, the blind will not be broken and subjects will be offered treatment for a 12-week open-label extension phase.