Folinic Acid as a Treatment for Autism Spectrum Disorder in Children

NCT07630506 | Recruiting Phase 2

• 2 other identifiers: FOLIN-A-01MOH-CIRG24jan-0004
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autism Spectrum Disorder

Keywords

Autism Spectrum Disorder; ASD; Folinic Acid; Leucovorin; Children; Pediatric; Randomized Controlled Trial; Placebo-Controlled; Open-Label Extension

Outcome Measures

Primary Outcomes (1)

• Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score

  The Pervasive Developmental Disorder-Behavior Inventory (PDDBI) is a validated caregiver-completed instrument used to assess adaptive and maladaptive behaviors in individuals with autism spectrum disorder (ASD). The Autism Composite T-score is a standardized score (mean = 50, standard deviation = 10) that summarizes overall autism symptom severity, with higher scores indicating greater symptom severity. This outcome measure evaluates the change from baseline to Week 12 in PDDBI Autism Composite T-score. Lower T-scores indicate improvement in autism-related symptoms. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.

  Baseline to Week 12

Secondary Outcomes (9)

• Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)

  Baseline to Week 12

• Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)

  Baseline to Week 12

• Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)

  Baseline to Week 12

• Change from baseline in Clinical Global Impression-Severity and Improvement scores as measured by the Clinical Global Impression Scale (CGI-S and CGI-I)

  Baseline to Week 12

• Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)

  Baseline to Week 12

Other Outcomes (6)

• Change from baseline in plasma glutathione redox ratio (GSH:GSSG)

  Baseline to Week 12

• Change from baseline in plasma methylation ratio (S-adenosylmethionine:S-adenosylhomocysteine; SAM:SAH)

  Baseline to Week 12

• Change in Plasma Ergothioneine Levels

  Baseline to Week 12

Study Arms (2)

Folinic Acid

EXPERIMENTAL

Participants in this arm will receive folinic acid during the double-blind randomised controlled trial (RCT) phase of the study. After completion of the double-blind phase, participants will continue into an open-label extension in which folinic acid is provided.

Drug: Folinic Acid

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive a matching placebo during the double-blind randomised controlled trial (RCT) phase of the study. After completion of the double-blind phase, participants will continue into an open-label extension in which folinic acid is provided.

Drug: Placebo

Interventions

Folinic Acid DRUG

Oral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment.

Folinic Acid

Placebo DRUG

Matching oral placebo administered during the double-blind randomised controlled trial (RCT) phase.

Placebo

Eligibility Criteria

• Age: 3 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• KK Women's and Children's Hospital: lead
• Singapore Health Services: collaborator
• Nanyang Technological University: collaborator
• National University of Singapore: collaborator

Study Sites (1)

KK Women's and Children's Hospital

Singapore, Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Leucovorin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Central Study Contacts

Study Coordinator

CONTACT

6563947201; folin-a@kkh.com.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Model Details: Participants are randomly assigned to receive either folinic acid or placebo in a parallel, double-blind design, followed by an open-label extension phase.

Study Record Dates

• First Submitted: May 8, 2026
• First Posted: June 5, 2026
• Study Start: May 19, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-05

Locations

SG (1)