Folinic Acid as a Treatment for Autism Spectrum Disorder in Children (FOLIN-A)
2026년 6월 1일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (추정된)
184
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
- 이름: Study Coordinator
- 전화번호: 6563947201
- 이메일: folin-a@kkh.com.sg
연구 장소
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Singapore
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Singapore, Singapore, 싱가포르
- 모병
- KK Women's and Children's Hospital
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 어린이
건강한 자원 봉사자를 받아들입니다
아니
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
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Oral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment.
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위약 비교기: 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.
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Matching oral placebo administered during the double-blind randomised controlled trial (RCT) phase.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in Clinical Global Impression-Severity and Improvement scores as measured by the Clinical Global Impression Scale (CGI-S and CGI-I)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid
기간: Baseline to Week 24
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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.
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Baseline to Week 24
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change from baseline in plasma glutathione redox ratio (GSH:GSSG)
기간: Baseline to Week 12
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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).
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Baseline to Week 12
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Change from baseline in plasma methylation ratio (S-adenosylmethionine:S-adenosylhomocysteine; SAM:SAH)
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Change in Plasma Ergothioneine Levels
기간: Baseline to Week 12
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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).
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Baseline to Week 12
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Change in Folate Status Biomarkers
기간: Baseline to Week 12
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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.
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Baseline to Week 12
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Association of FRAA Status With Treatment Response
기간: Baseline to Week 12
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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).
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Baseline to Week 12
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Sustained Effects of Folinic Acid on Autism Symptoms
기간: Baseline to Week 24
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Change from baseline in autism outcome measures following 24 weeks of folinic acid treatment.
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Baseline to Week 24
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2025년 5월 19일
기본 완료 (추정된)
2027년 6월 30일
연구 완료 (추정된)
2027년 6월 30일
연구 등록 날짜
최초 제출
2026년 5월 8일
QC 기준을 충족하는 최초 제출
2026년 6월 1일
처음 게시됨 (실제)
2026년 6월 5일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 6월 5일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 6월 1일
마지막으로 확인됨
2026년 5월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- FOLIN-A-01
- MOH-CIRG24jan-0004 (기타 보조금/기금 번호: National Medical Research Council (NMRC), Singapore)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
미정
IPD 계획 설명
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.
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .