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Folinic Acid as a Treatment for Autism Spectrum Disorder in Children (FOLIN-A)

1 de junho de 2026 atualizado por: Wong Chui Mae, KK Women's and Children's Hospital

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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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.

Tipo de estudo

Intervencional

Inscrição (Estimado)

184

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Cingapura
    • Singapore
      • Singapore, Singapore, Cingapura
        • Recrutamento
        • KK Women's and Children's Hospital

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Filho

Aceita Voluntários Saudáveis

Não

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Folinic Acid
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.
Medicamento: Folinic Acid
Oral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment.
Comparador de Placebo: Placebo
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.
Medicamento: Placebo
Matching oral placebo administered during the double-blind randomised controlled trial (RCT) phase.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score
Prazo: Baseline to Week 12
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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in standardized language function scores as assessed using the Clinical Evaluation of Language Fundamentals (CELF), a standardized individually administered assessment of receptive and expressive language skills in children. CELF standardized scores have a mean of 100 and a standard deviation of 15, with higher scores indicating better language performance. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in standardized receptive vocabulary scores as assessed using the Receptive One-Word Picture Vocabulary Test (ROWPVT), a standardized individually administered assessment of a child's ability to understand spoken words. Scores are standardized with a mean of 100 and a standard deviation of 15, where higher scores indicate better receptive vocabulary ability. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in standardized expressive vocabulary scores as assessed using the Expressive One-Word Picture Vocabulary Test (EOWPVT), a standardized individually administered assessment of a child's ability to produce spoken words. Scores are standardized with a mean of 100 and a standard deviation of 15, where higher scores indicate better expressive vocabulary ability. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
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)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores, assessed using the Clinical Global Impression Scale, a standardized assessor-rated measure of illness severity and overall clinical improvement. CGI-S scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill), where lower scores indicate better outcomes, and CGI-I scores range from 1 (very much improved) to 7 (very much worse), where lower scores indicate greater improvement. Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in total scores on the Aberrant Behavior Checklist (ABC), a standardized caregiver-completed questionnaire that assesses behavioural symptoms in children across domains such as irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech. Total scores range from 0 to 174, with higher scores indicating greater severity of behavioural problems (worse outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in total problem scores on the Child Behavior Checklist (CBCL), a standardized caregiver-reported questionnaire that assesses a broad range of emotional and behavioural problems in children. Total scores are standardised T-scores (typically ranging from approximately 30 to 100, with a mean of 50 and standard deviation of 10), where higher scores indicate greater behavioural and emotional problems (worse outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in standardised adaptive behavior scores as assessed using the Vineland Adaptive Behavior Scales (VABS), a standardized caregiver-reported assessment of a child's adaptive functioning across domains such as communication, daily living skills, socialization, and motor skills. Adaptive behavior composite scores are standardised (typically ranging from approximately 20 to 160, with a mean of 100 and standard deviation of 15), where higher scores indicate better adaptive functioning (better outcomes). Changes in scores will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment
Prazo: Baseline to Week 12
Change from baseline to Week 12 in eye-tracking measures of visual attention, specifically the proportion of total gaze duration directed toward social stimuli (e.g., faces or biological motion) compared with non-social stimuli, assessed using a standardized eye-tracking paradigm. Higher proportions indicate greater relative attention to social stimuli. Changes in proportions will be compared between participants receiving folinic acid and those receiving placebo.
Baseline to Week 12
Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid
Prazo: Baseline to Week 24
Change from baseline to Week 24 in the incidence of adverse events (AEs) and serious adverse events (SAEs), monitored throughout the study period to assess the safety and tolerability of folinic acid treatment.
Baseline to Week 24

Outras medidas de resultado

Medida de resultado
Descrição da medida
Prazo
Change from baseline in plasma glutathione redox ratio (GSH:GSSG)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in plasma glutathione redox ratio (reduced glutathione:oxidized glutathione; GSH:GSSG), a biomarker of oxidative stress balance. Higher ratios indicate a more reduced (favorable) redox state. Plasma reduced glutathione (GSH, µM) and oxidized glutathione (GSSG, µM) will be measured at baseline (T1) and Week 12 (T2).
Baseline to Week 12
Change from baseline in plasma methylation ratio (S-adenosylmethionine:S-adenosylhomocysteine; SAM:SAH)
Prazo: Baseline to Week 12
Change from baseline to Week 12 in plasma methylation ratio (S-adenosylmethionine:S-adenosylhomocysteine; SAM:SAH), a biomarker of methylation capacity. Higher ratios indicate greater methylation potential (better outcomes). Additional biomarkers related to one-carbon metabolism, including plasma homocysteine (µmol/L), will measured where available.
Baseline to Week 12
Change in Plasma Ergothioneine Levels
Prazo: Baseline to Week 12
Change from baseline to Week 12 in plasma ergothioneine concentration (ET, nM). Plasma ergothioneine (ET, nM), hercynine (nM), and ophthalmic acid will be measured at baseline (T1) and Week 12 (T2).
Baseline to Week 12
Change in Folate Status Biomarkers
Prazo: Baseline to Week 12
Change from baseline in serum and plasma folate status biomarkers. Folate status biomarkers include measures related to one-carbon metabolism and amino acid pathways. Plasma amino acid concentrations (µmol/L) will be interpreted with reference to established age-specific clinical ranges.
Baseline to Week 12
Association of FRAA Status With Treatment Response
Prazo: Baseline to Week 12
Association between folate receptor autoantibody (FRAA) status and change in autism outcome measures. FRAA status will be classified as positive or negative based on the assay-specific cutoff defined by the testing laboratory: Blocking FRAA (pmol blocked per mL) and binding FRAA (optical density [OD] units per µL).
Baseline to Week 12
Sustained Effects of Folinic Acid on Autism Symptoms
Prazo: Baseline to Week 24
Change from baseline in autism outcome measures following 24 weeks of folinic acid treatment.
Baseline to Week 24

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

KK Women's and Children's Hospital

Colaboradores

Nanyang Technological University
Singapore Health Services
National University of Singapore

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

19 de maio de 2025

Conclusão Primária (Estimado)

30 de junho de 2027

Conclusão do estudo (Estimado)

30 de junho de 2027

Datas de inscrição no estudo

Enviado pela primeira vez

8 de maio de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

1 de junho de 2026

Primeira postagem (Real)

5 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

5 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

1 de junho de 2026

Última verificação

1 de maio de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • FOLIN-A-01
  • MOH-CIRG24jan-0004 (Número de outro subsídio/financiamento: National Medical Research Council (NMRC), Singapore)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

INDECISO

Descrição do plano IPD

At this time, there is no confirmed plan to share individual participant data (IPD) collected in this study. The study team will consider requests for access to de-identified individual participant data, including the analyzable dataset and relevant supporting documentation, on a case-by-case basis following completion of the study. Any data sharing will be subject to applicable institutional review board (IRB) requirements, data protection regulations, and data sharing agreements to ensure participant confidentiality and appropriate use.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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