Autism Spectrum DisorderPhase 2AFATNCT07642661
A Placebo-controlled Trial of Folinic Acid in Children With ASD
A Phase 2 study testing Folinic Acid in people with Autism Spectrum Disorder, run by Prof. Adi Aran at 1 site in Israel.
Trial summary
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and the presence of restricted or repetitive behaviors. Although behavioral and educational interventions can be helpful, there is currently no established medication for the core symptoms of ASD. Read more about this study
- Who is it for?
- Ages 3 to 6 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
- 150 participants
- Where
- 1 siteIsrael
- Study dates
- 23 Jun 2026to 31 Dec 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 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged 3 to 6 years.
- Diagnosis of autism spectrum disorder (ASD) according to DSM-5 criteria.
- ASD diagnosis confirmed by Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).
- ASD diagnosis made at least 6 months before screening.
- Non-syndromic ASD, defined as ASD occurring in the absence of a known genetic syndrome, chromosomal abnormality, major congenital anomaly, or identifiable metabolic or neurological disorder.
- CGI-S score ≥ 4.
Show all 9Show fewer
- ABC-I score ≥ 12.
- SRS-2 total T-score ≥ 66.
- Body weight between 11.45 kg and <27 kg.
Who cannot join
- A seizure or a change in antiepileptic medication within 8 weeks prior to randomization.
- Clinically significant abnormalities on physical examination or laboratory testing, including significant impairment of cardiac, hepatic, or renal function.
- Treatment with folinic acid within 3 months prior to randomization.
- Any change in pharmacological treatment, behavioral treatment, home environment, or school setting (other than school holidays) within 4 weeks prior to randomization, or planned changes during study participation.
- Predicted inability or unwillingness to comply with study procedures.
- Use of antifolate medications or other agents known to interfere with folate metabolism (e.g., methotrexate, trimethoprim).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Shaare Zedek Medical Center
Jerusalem, N/A = Not Applicable, 9103102
Shahar Feller, +97226555414, folinics@gmail.com
Adi Aran, MD
About this study
Official title: A Placebo-Controlled, Randomized, Double-Blind Study to Assess the Safety, Tolerability and Efficacy of Folinic Acid Administered to Pediatric Subjects With Autism Spectrum Disorder (ASD)
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication and the presence of restricted or repetitive behaviors. Although behavioral and educational interventions can be helpful, there is currently no established medication for the core symptoms of ASD. Medications approved for associated irritability may be effective in some children but are often associated with significant adverse effects.
Folinic acid (also known as leucovorin) is a reduced form of folate that plays an important role in brain development, neurotransmitter production, DNA methylation, and cellular metabolism. Previous clinical studies have suggested that folinic acid may improve communication, social functioning, and behavioral symptoms in some children with ASD. However, existing studies have generally been small and have used different outcome measures, and the current evidence is insufficient to establish the efficacy and optimal dosing of folinic acid in ASD.
Read more
This multicenter, randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the safety, tolerability, and efficacy of folinic acid in children with ASD. A total of 150 children aged 3 to 6 years with ASD and clinically significant behavioral symptoms will be enrolled at multiple sites in Israel. Participants will be randomly assigned in a 1:1 ratio to receive either folinic acid or matching placebo for 9 weeks in addition to their existing treatments.
The primary objective of the study is to determine whether folinic acid improves behavioral symptoms compared with placebo, as measured by the Aberrant Behavior Checklist Irritability Subscale (ABC-I). Secondary objectives include evaluating the effects of folinic acid on communication, socialization, adaptive functioning, autism symptoms, emotional regulation, disruptive behavior, sleep, gastrointestinal symptoms, caregiver quality of life, and overall clinical improvement.
Following completion of the initial 9-week placebo-controlled phase, participants will enter a second 8-week double-blind treatment phase in which they will be randomly assigned to receive one of two folinic acid dose regimens. This phase is intended to explore whether different maintenance doses are associated with differences in clinical outcomes.
The study will also investigate potential biological markers associated with treatment response. Blood and stool samples will be collected to assess folate-related biomarkers, folate receptor alpha autoantibodies, oxidative stress markers, transcriptomic profiles, proteomic signatures, and gut microbiota composition. The study will also examine whether these biological measures are associated with symptom severity or response to treatment.
The results of this study are expected to provide important information regarding the efficacy, safety, and optimal use of folinic acid in children with ASD and may help identify biological factors associated with treatment response.
Read the detailed description
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent deficits in social communication and social interaction, together with restricted, repetitive patterns of behavior, interests, or activities. In addition to these core features, many children with ASD experience associated behavioral difficulties including irritability, emotional dysregulation, hyperactivity, sleep disturbances, and gastrointestinal symptoms. ASD affects approximately 1-3% of children worldwide and is associated with substantial long-term impact on affected individuals, families, educational systems, and healthcare resources.
At present, there is no established pharmacological treatment for the core symptoms of ASD. While behavioral and educational interventions remain the foundation of treatment, access, intensity, and effectiveness vary considerably among individuals. Pharmacological treatments currently approved for ASD-related irritability may reduce disruptive behaviors in some children but are often associated with adverse effects including weight gain, metabolic abnormalities, sedation, and extrapyramidal symptoms. Consequently, there remains a significant unmet need for safe and effective interventions that address both core and associated symptoms of ASD.
Folate plays a central role in neurodevelopment and brain function. Folate-dependent pathways are involved in DNA synthesis and repair, epigenetic regulation through methylation, neurotransmitter synthesis, mitochondrial function, and cellular redox balance. Disturbances in folate transport and metabolism have been implicated in a subset of individuals with ASD.
One mechanism that has received increasing attention is dysfunction of folate transport into the central nervous system. The folate receptor alpha (FRα) is responsible for transporting 5-methyltetrahydrofolate into the brain. Autoantibodies directed against this receptor may interfere with folate transport and contribute to cerebral folate deficiency. Multiple studies have reported an increased prevalence of folate receptor alpha autoantibodies in children with ASD compared with the general population. In addition, genetic variants affecting folate metabolism and transport pathways may influence neurodevelopment and treatment response.
Folinic acid (leucovorin calcium) is a reduced form of folate that bypasses several metabolic steps required for folic acid utilization and can utilize transport mechanisms that are less dependent on folate receptor alpha function. Folinic acid has been used safely for many years in pediatric and adult medicine for a variety of indications and has a well-characterized safety profile.
Over the past decade, several randomized placebo-controlled studies have suggested that high-dose folinic acid may improve language abilities, social communication, adaptive functioning, and behavioral symptoms in some children with ASD. These findings have generated considerable interest among clinicians and families and have led to increasing off-label use of folinic acid in clinical practice. However, the currently available evidence remains limited. Previous studies were generally small, used different outcome measures, enrolled relatively heterogeneous populations, and were not designed to determine the optimal duration or dose of treatment. Furthermore, uncertainty remains regarding which biological characteristics may predict treatment response.
As a result, major clinical guidelines do not currently recommend routine treatment with folinic acid for children with ASD, and there is a need for adequately powered confirmatory trials using standardized outcome measures and rigorous methodology.
The current study was designed to address these knowledge gaps. The trial will evaluate whether folinic acid is superior to placebo in improving behavioral symptoms and adaptive functioning in young children with ASD. The study will use a randomized, double-blind, placebo-controlled design to minimize bias and provide high-quality evidence regarding efficacy, safety, and tolerability.
In addition to evaluating clinical outcomes, the study incorporates an extensive translational research program intended to improve understanding of the biological mechanisms associated with treatment response. Biological samples will be collected to assess folate-related biomarkers, folate receptor alpha autoantibodies, markers of oxidative stress, transcriptomic signatures, proteomic profiles, and gut microbiota composition. These analyses may help identify biological subgroups that are more likely to benefit from treatment and may contribute to future precision medicine approaches in ASD.
Maternal folate receptor alpha autoantibody status will also be evaluated because emerging evidence suggests that maternal folate-related factors may influence neurodevelopmental outcomes. Exploratory analyses will investigate associations among biological markers, clinical characteristics, and treatment outcomes.
The study includes an initial placebo-controlled phase followed by an active-treatment dose-comparison phase. This design allows rigorous evaluation of efficacy against placebo while also generating information regarding potential dose-related differences in response and tolerability. The study therefore aims not only to determine whether folinic acid is effective, but also to provide data that may guide future treatment strategies and trial design.
By combining a large multicenter randomized clinical trial with detailed biological characterization, this study seeks to provide definitive evidence regarding the role of folinic acid in ASD and to advance understanding of folate-related mechanisms in neurodevelopmental disorders. The findings may help identify children most likely to benefit from treatment, improve evidence-based clinical decision-making, and support the development of more individualized therapeutic approaches for ASD.
- Conditions
- Autism Spectrum Disorder
- Being tested
- Folinic Acid, Placebo
- Keywords
- ASD, Autism, Folinic Acid, Leucovorin, Calcium Folinate, placebo, Folate Receptor Alpha Autoantibodies
- Medical subject headings
- Autism Spectrum Disorder, Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folinic AcidDrug
Also called Leucovorin, Calcium Folinate, Leucovorin Calcium
Calcium folinate hydrate oral solution administered at a target dose of 2 mg/kg/day (maximum 50 mg/day) in two divided doses.
PlaceboDrug
Matching oral placebo solution containing inactive aqueous excipients and matched in appearance, taste, and smell to the folinic acid formulation
| Study group | Role | What they receive |
|---|---|---|
| Folinic Acid | Active comparator | Participants receive oral folinic acid (calcium folinate hydrate) oral solution as an add-on to their existing treatments. During the initial 9-week double-blind phase, participants receive folinic acid at a target dose of 2 mg/kg/day (maximum 50 mg/day) administered in two divided doses following a brief dose-titration period. After completion of the first phase, participants are independently randomized to receive folinic acid at either 1 mg/kg/day or 2 mg/kg/day for an additional 8 weeks while remaining blinded to dose assignment. Receives: Drug: Folinic Acid |
| Placebo | Placebo comparator | Participants receive a matching placebo oral solution as an add-on to their existing treatments during the initial 9-week double-blind phase. After completion of the placebo-controlled phase, participants are independently randomized to receive folinic acid at either 1 mg/kg/day or 2 mg/kg/day for an additional 8 weeks while remaining blinded to dose assignment. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 9 in Aberrant Behavior Checklist-Irritability Subscale (ABC-I) Score. Scores range from 0 to 45, with higher scores indicating greater irritability and behavioral problems
The ABC-I is a caregiver-completed measure of irritability and behavioral symptoms in children with autism spectrum disorder. The ABC-I consists of 15 items assessing behaviors such as aggression, self-injury, temper tantrums, depressed mood, and rapidly changing mood. Individual items are scored from 0 (not a problem) to 3 (severe problem).
Measured: Baseline to Week 9
Secondary outcomes (4)
Change From Baseline to Week 9 in Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Communication Domain Standard Score
The VABS-3 Communication Domain assesses receptive, expressive, and written communication skills through a structured caregiver interview. Standard scores have a mean of 100 and a standard deviation of 15, with higher scores indicating better adaptive functioning.
Measured: Baseline to Week 9
Change From Baseline to Week 9 in VABS-3 Socialization Domain Standard Score
The VABS-3 Socialization Domain assesses interpersonal relationships, play and leisure skills, and coping skills through a structured caregiver interview. Standard scores have a mean of 100 and a standard deviation of 15, with higher scores indicating better adaptive functioning.
Measured: Baseline to Week 9
Change From Baseline to Week 9 in Clinical Global Impression-Improvement (CGI-I)
Clinician-rated global improvement since baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse)
Measured: Week 9
Change From Baseline to Week 9 in MacArthur-Bates Communicative Development Inventories (MB-CDI)
Parent-reported measure of expressive vocabulary and communication skills. Higher scores indicate better communication abilities
Measured: Baseline to Week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2026
- Study start23 Jun 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 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.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Adi Aran
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Adi Aran, Shaare Zedek Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07642661
- Sponsor's protocol ID
- 0038-26-SZMC
- Acronym
- AFAT
- Status last verified
- Jun 2026
- First submitted
- 7 Jun 2026
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data that underlie the results reported in publications arising from this study, including demographic and baseline characteristics, clinical outcome measures (ABC-I, VABS-3, CGI-I, MB-CDI, SRS-2 and other study assessments), adverse event data, laboratory safety data, and selected biomarker datasets generated during the study
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled, Randomized, Double-Blind Study to Assess the Safety, Tolerability and Efficacy of Folinic Acid Administered to Pediatric Subjects With Autism Spectrum Disorder (ASD)
- ClinicalTrials.gov ID
- NCT07642661
- Acronym / sponsor ID
- AFAT / 0038-26-SZMC
- Conditions
- Autism Spectrum Disorder
- Keywords
- ASD, Autism, Folinic Acid, Leucovorin, Calcium Folinate, placebo, Folate Receptor Alpha Autoantibodies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Prof. Adi AranUniversity, hospital or other
- Study start
- 23 Jun 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 11 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 characterized by difficulties in social communication and the presence of restricted or repetitive behaviors. Although behavioral and educational interventions can be helpful, there is currently no established medication for the core symptoms of ASD. Medications approved for associated irritability may be effective in some children but are often associated with significant adverse effects.
Folinic acid (also known as leucovorin) is a reduced form of folate that plays an important role in brain development, neurotransmitter production, DNA methylation, and cellular metabolism. Previous clinical studies have suggested that folinic acid may improve communication, social functioning, and behavioral symptoms in some children with ASD. However, existing studies have generally been small and have used different outcome measures, and the current evidence is insufficient to establish the efficacy and optimal dosing of folinic acid in ASD.
This multicenter, randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the safety, tolerability, and efficacy of folinic acid in children with ASD. A total of 150 children aged 3 to 6 years with ASD and clinically significant behavioral symptoms will be enrolled at multiple sites in Israel. Participants will be randomly assigned in a 1:1 ratio to receive either folinic acid or matching placebo for 9 weeks in addition to their existing treatments.
The primary objective of the study is to determine whether folinic acid improves behavioral symptoms compared with placebo, as measured by the Aberrant Behavior Checklist Irritability Subscale (ABC-I). Secondary objectives include evaluating the effects of folinic acid on communication, socialization, adaptive functioning, autism symptoms, emotional regulation, disruptive behavior, sleep, gastrointestinal symptoms, caregiver quality of life, and overall clinical improvement.
Following completion of the initial 9-week placebo-controlled phase, participants will enter a second 8-week double-blind treatment phase in which they will be randomly assigned to receive one of two folinic acid dose regimens. This phase is intended to explore whether different maintenance doses are associated with differences in clinical outcomes.
The study will also investigate potential biological markers associated with treatment response. Blood and stool samples will be collected to assess folate-related biomarkers, folate receptor alpha autoantibodies, oxidative stress markers, transcriptomic profiles, proteomic signatures, and gut microbiota composition. The study will also examine whether these biological measures are associated with symptom severity or response to treatment.
The results of this study are expected to provide important information regarding the efficacy, safety, and optimal use of folinic acid in children with ASD and may help identify biological factors associated with treatment response.
Detailed description
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent deficits in social communication and social interaction, together with restricted, repetitive patterns of behavior, interests, or activities. In addition to these core features, many children with ASD experience associated behavioral difficulties including irritability, emotional dysregulation, hyperactivity, sleep disturbances, and gastrointestinal symptoms. ASD affects approximately 1-3% of children worldwide and is associated with substantial long-term impact on affected individuals, families, educational systems, and healthcare resources.
At present, there is no established pharmacological treatment for the core symptoms of ASD. While behavioral and educational interventions remain the foundation of treatment, access, intensity, and effectiveness vary considerably among individuals. Pharmacological treatments currently approved for ASD-related irritability may reduce disruptive behaviors in some children but are often associated with adverse effects including weight gain, metabolic abnormalities, sedation, and extrapyramidal symptoms. Consequently, there remains a significant unmet need for safe and effective interventions that address both core and associated symptoms of ASD.
Folate plays a central role in neurodevelopment and brain function. Folate-dependent pathways are involved in DNA synthesis and repair, epigenetic regulation through methylation, neurotransmitter synthesis, mitochondrial function, and cellular redox balance. Disturbances in folate transport and metabolism have been implicated in a subset of individuals with ASD.
One mechanism that has received increasing attention is dysfunction of folate transport into the central nervous system. The folate receptor alpha (FRα) is responsible for transporting 5-methyltetrahydrofolate into the brain. Autoantibodies directed against this receptor may interfere with folate transport and contribute to cerebral folate deficiency. Multiple studies have reported an increased prevalence of folate receptor alpha autoantibodies in children with ASD compared with the general population. In addition, genetic variants affecting folate metabolism and transport pathways may influence neurodevelopment and treatment response.
Folinic acid (leucovorin calcium) is a reduced form of folate that bypasses several metabolic steps required for folic acid utilization and can utilize transport mechanisms that are less dependent on folate receptor alpha function. Folinic acid has been used safely for many years in pediatric and adult medicine for a variety of indications and has a well-characterized safety profile.
Over the past decade, several randomized placebo-controlled studies have suggested that high-dose folinic acid may improve language abilities, social communication, adaptive functioning, and behavioral symptoms in some children with ASD. These findings have generated considerable interest among clinicians and families and have led to increasing off-label use of folinic acid in clinical practice. However, the currently available evidence remains limited. Previous studies were generally small, used different outcome measures, enrolled relatively heterogeneous populations, and were not designed to determine the optimal duration or dose of treatment. Furthermore, uncertainty remains regarding which biological characteristics may predict treatment response.
As a result, major clinical guidelines do not currently recommend routine treatment with folinic acid for children with ASD, and there is a need for adequately powered confirmatory trials using standardized outcome measures and rigorous methodology.
The current study was designed to address these knowledge gaps. The trial will evaluate whether folinic acid is superior to placebo in improving behavioral symptoms and adaptive functioning in young children with ASD. The study will use a randomized, double-blind, placebo-controlled design to minimize bias and provide high-quality evidence regarding efficacy, safety, and tolerability.
In addition to evaluating clinical outcomes, the study incorporates an extensive translational research program intended to improve understanding of the biological mechanisms associated with treatment response. Biological samples will be collected to assess folate-related biomarkers, folate receptor alpha autoantibodies, markers of oxidative stress, transcriptomic signatures, proteomic profiles, and gut microbiota composition. These analyses may help identify biological subgroups that are more likely to benefit from treatment and may contribute to future precision medicine approaches in ASD.
Maternal folate receptor alpha autoantibody status will also be evaluated because emerging evidence suggests that maternal folate-related factors may influence neurodevelopmental outcomes. Exploratory analyses will investigate associations among biological markers, clinical characteristics, and treatment outcomes.
The study includes an initial placebo-controlled phase followed by an active-treatment dose-comparison phase. This design allows rigorous evaluation of efficacy against placebo while also generating information regarding potential dose-related differences in response and tolerability. The study therefore aims not only to determine whether folinic acid is effective, but also to provide data that may guide future treatment strategies and trial design.
By combining a large multicenter randomized clinical trial with detailed biological characterization, this study seeks to provide definitive evidence regarding the role of folinic acid in ASD and to advance understanding of folate-related mechanisms in neurodevelopmental disorders. The findings may help identify children most likely to benefit from treatment, improve evidence-based clinical decision-making, and support the development of more individualized therapeutic approaches for ASD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folinic Acid | Active comparator | Drug: Folinic AcidParticipants receive oral folinic acid (calcium folinate hydrate) oral solution as an add-on to their existing treatments. During the initial 9-week double-blind phase, participants receive folinic acid at a target dose of 2 mg/kg/day (maximum 50 mg/day) administered in two divided doses following a brief dose-titration period. After completion of the first phase, participants are independently randomized to receive folinic acid at either 1 mg/kg/day or 2 mg/kg/day for an additional 8 weeks while remaining blinded to dose assignment. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receive a matching placebo oral solution as an add-on to their existing treatments during the initial 9-week double-blind phase. After completion of the placebo-controlled phase, participants are independently randomized to receive folinic acid at either 1 mg/kg/day or 2 mg/kg/day for an additional 8 weeks while remaining blinded to dose assignment. |
Who may qualify
- Ages
- 3 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Children aged 3 to 6 years.
- Diagnosis of autism spectrum disorder (ASD) according to DSM-5 criteria.
- ASD diagnosis confirmed by Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).
- ASD diagnosis made at least 6 months before screening.
- Non-syndromic ASD, defined as ASD occurring in the absence of a known genetic syndrome, chromosomal abnormality, major congenital anomaly, or identifiable metabolic or neurological disorder.
Key exclusion criteria (6 listed)
- A seizure or a change in antiepileptic medication within 8 weeks prior to randomization.
- Clinically significant abnormalities on physical examination or laboratory testing, including significant impairment of cardiac, hepatic, or renal function.
- Treatment with folinic acid within 3 months prior to randomization.
- Any change in pharmacological treatment, behavioral treatment, home environment, or school setting (other than school holidays) within 4 weeks prior to randomization, or planned changes during study participation.
- Predicted inability or unwillingness to comply with study procedures.
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 AcidAlso: Leucovorin, Calcium Folinate, Leucovorin CalciumCalcium folinate hydrate oral solution administered at a target dose of 2 mg/kg/day (maximum 50 mg/day) in two divided doses. | Drug | Folinic Acid |
| PlaceboMatching oral placebo solution containing inactive aqueous excipients and matched in appearance, taste, and smell to the folinic acid formulation | Drug | Placebo |
Primary outcome
Change From Baseline to Week 9 in Aberrant Behavior Checklist-Irritability Subscale (ABC-I) Score. Scores range from 0 to 45, with higher scores indicating greater irritability and behavioral problems
Time frame: Baseline to Week 9
The ABC-I is a caregiver-completed measure of irritability and behavioral symptoms in children with autism spectrum disorder. The ABC-I consists of 15 items assessing behaviors such as aggression, self-injury, temper tantrums, depressed mood, and rapidly changing mood. Individual items are scored from 0 (not a problem) to 3 (severe problem).
4 secondary outcomes
Change From Baseline to Week 9 in Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Communication Domain Standard Score
Time frame: Baseline to Week 9
Change From Baseline to Week 9 in VABS-3 Socialization Domain Standard Score
Time frame: Baseline to Week 9
Change From Baseline to Week 9 in Clinical Global Impression-Improvement (CGI-I)
Time frame: Week 9
Change From Baseline to Week 9 in MacArthur-Bates Communicative Development Inventories (MB-CDI)
Time frame: Baseline to Week 9
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 22 Jun 2026.
- The study protocol, Statistical Analysis Plan (SAP), and informed consent form are available through the Open Science Framework (OSF). The link provides view-only access to these study documentsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data that underlie the results reported in publications arising from this study, including demographic and baseline characteristics, clinical outcome measures (ABC-I, VABS-3, CGI-I, MB-CDI, SRS-2 and other study assessments), adverse event data, laboratory safety data, and selected biomarker datasets generated during the study
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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 Prof. Adi Aran at 1 site in Israel.
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 9 inclusion and 6 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 22 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 Israel. 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 Adi Aran, MD (+97226555414, aaran@szmc.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Week 9 in Aberrant Behavior Checklist-Irritability Subscale (ABC-I) Score. Scores range from 0 to 45, with higher scores indicating greater irritability and behavioral problems (time frame: Baseline to Week 9). 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 22 Jun 2026.