Folinic Acid as a Treatment for Autism Spectrum Disorder in Children

Folinic Acid as a Treatment for Autism Spectrum Disorder in Children: A Double-blind Randomised Placebo-controlled Trial With Open Label Extension (FOLIN-A Trial)

Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects communication, behavior, and social interaction in children. Current treatments are limited and mainly focus on managing symptoms. This study aims to evaluate whether folinic acid is safe and effective in improving symptoms of autism spectrum disorder in children. Participants will be randomly assigned to receive either folinic acid or a placebo during the double-blind treatment phase. After this phase, all participants will have the option to receive folinic acid in an open-label extension. The results of this study may help determine whether folinic acid could be a potential treatment option for children with autism spectrum disorder.

This study is a double-blind, randomised, placebo-controlled clinical trial designed to evaluate the safety and effectiveness of folinic acid in children with autism spectrum disorder (ASD). Eligible participants will be randomly assigned to receive either 2 mg/kg/day of folinic acid or a matching placebo during a 12-week double-blind randomised controlled trial (RCT) treatment phase. Neither the participants, caregivers, nor study staff will know which treatment is assigned during this period. The primary aim is to assess whether folinic acid improves symptoms of autism spectrum disorder. Following completion of the double-blind phase, participants will enter a 12-week open-label extension, during which all participants will receive 2 mg/kg/day of folinic acid. This extension phase will allow for further evaluation of longer-term safety and potential benefits. The findings from this study may contribute to a better understanding of the role of folinic acid as a potential treatment option for children with autism spectrum disorder.

Inclusion Criteria:

• Children aged 3 years 0 months to 10 years 11 months at the time of enrolment
• Weight ≥ 10 kg and ≤ 30 kg at the time of enrolment
• Confirmed diagnosis of Autism Spectrum Disorder (ASD) based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) or Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, supported by standardized diagnostic assessments
• Stable on regular behavioral interventions and any medications for at least 6 months prior to enrolment
• At least one parent or legal guardian able to understand and complete study questionnaires in English
• Written informed consent obtained from a parent or legal guardian

Exclusion Criteria:

• Known allergy or intolerance to folinic acid
• Current or prior supplementation with folinic acid or other folate preparations (folic acid supplementation permitted)
• Vitamin B12 (cobalamin) deficiency or pernicious anemia
• Concurrent use of medications known to interfere with folate metabolism (e.g., methotrexate, trimethoprim, fluorouracil, capecitabine, glucarpidase)
• Known genetic, metabolic, or chromosomal disorder, or structural brain abnormalities
• History of epilepsy or seizures (except simple febrile seizures) or current use of antiepileptic or antipsychotic medication
• Significant sensory (hearing or visual) or motor impairment
• Participation in another interventional clinical trial for autism within the past 6 months
• Unable or unwilling to comply with study visits and procedures