Autism Spectrum DisorderPhase 2FOLIN-ANCT07630506
Folinic Acid as a Treatment for Autism Spectrum Disorder in Children
A Phase 2 study testing Folinic Acid in people with Autism Spectrum Disorder, run by KK Women's and Children's Hospital at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- Autism Spectrum Disorder
- What is being tested?
- Folinic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 184 participants
- Where
- 1 siteSingapore
- Study dates
- 19 May 2025to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Singapore1 site, 1 recruiting
- Recruiting
KK Women's and Children's Hospital
Singapore, Singapore
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Folinic Acid, Placebo
- Keywords
- Autism Spectrum Disorder, ASD, Folinic Acid, Leucovorin, Children, Pediatric, Randomized Controlled Trial, Placebo-Controlled, Open-Label Extension
- Medical subject headings
- Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folinic AcidDrug
Oral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment.
PlaceboDrug
Matching oral placebo administered during the double-blind randomised controlled trial (RCT) phase.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to Week 12
Secondary outcomes (9)
Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)
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.
Measured: Baseline to Week 12
Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)
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.
Measured: Baseline to Week 12
Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)
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.
Measured: 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)
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.
Measured: Baseline to Week 12
Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)
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.
Measured: Baseline to Week 12
Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL)
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.
Measured: Baseline to Week 12
Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS)
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.
Measured: Baseline to Week 12
Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment
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.
Measured: Baseline to Week 12
Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid
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.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start19 May 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- More trials run by KK Women's and Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomly assigned to receive either folinic acid or placebo in a parallel, double-blind design, followed by an open-label extension phase.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 184 participants (estimated)
Sponsor and investigators
- Lead sponsor
- KK Women's and Children's Hospital
- Sponsor type
- Other government
- Collaborators
- Singapore Health Services, Nanyang Technological University, National University of Singapore
- Responsible party
- Principal investigator, Wong Chui Mae, KK Women's and Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07630506
- Sponsor's protocol ID
- FOLIN-A-01
- Other IDs
- MOH-CIRG24jan-0004
- Acronym
- FOLIN-A
- Status last verified
- May 2026
- First submitted
- 8 May 2026
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT07630506
- Acronym / sponsor ID
- FOLIN-A / FOLIN-A-01
- Conditions
- Autism Spectrum Disorder
- Keywords
- Autism Spectrum Disorder, ASD, Folinic Acid, Leucovorin, Children, Pediatric, Randomized Controlled Trial, Placebo-Controlled
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 184 participants (estimated)
- Lead sponsor
- KK Women's and Children's HospitalOther government
- Collaborators
- Singapore Health Services, Nanyang Technological University, National University of Singapore
- Study start
- 19 May 2025 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 5 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomly assigned to receive either folinic acid or placebo in a parallel, double-blind design, followed by an open-label extension phase.
| Arm | Type | Receives |
|---|---|---|
| Folinic Acid | Experimental | Drug: Folinic AcidParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 3 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folinic AcidOral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment. | Drug | Folinic Acid |
| PlaceboMatching oral placebo administered during the double-blind randomised controlled trial (RCT) phase. | Drug | Placebo |
Primary outcome
Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score
Time frame: 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.
9 secondary outcomes
Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF)
Time frame: Baseline to Week 12
Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT)
Time frame: Baseline to Week 12
Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT)
Time frame: 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)
Time frame: Baseline to Week 12
Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC)
Time frame: Baseline to Week 12
Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL)
Time frame: Baseline to Week 12
Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS)
Time frame: Baseline to Week 12
Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment
Time frame: Baseline to Week 12
Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid
Time frame: Baseline to Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Individual participant dataSharing planned: Undecided. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Folinic Acid in people with Autism Spectrum Disorder, run by KK Women's and Children's Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Coordinator (6563947201, folin-a@kkh.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.