Autism Spectrum Disorder
Conditions
Keywords
Autism Spectrum Disorder, ASD, Folinic Acid, Leucovorin, Children, Pediatric, Randomized Controlled Trial, Placebo-Controlled, Open-Label Extension
Brief summary
Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects communication, behavior, and social interaction in children. Current treatments are limited and mainly focus on managing symptoms. This study aims to evaluate whether folinic acid is safe and effective in improving symptoms of autism spectrum disorder in children. Participants will be randomly assigned to receive either folinic acid or a placebo during the double-blind treatment phase. After this phase, all participants will have the option to receive folinic acid in an open-label extension. The results of this study may help determine whether folinic acid could be a potential treatment option for children with autism spectrum disorder.
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.
Interventions
DRUGFolinic Acid
Oral folinic acid administered during the double-blind randomised controlled trial (RCT) phase, followed by open-label folinic acid treatment.
DRUGPlacebo
Matching oral placebo administered during the double-blind randomised controlled trial (RCT) phase.
Sponsors
KK Women's and Children's Hospital
Singapore Health Services
Nanyang Technological University
National University of Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
3 Years to 10 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pervasive Developmental Disorder-Behavior Inventory (PDDBI) Autism Composite T-Score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in language function as measured by the Clinical Evaluation of Language Fundamentals (CELF) | 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. |
| Change from baseline in receptive vocabulary score as measured by the Receptive One-Word Picture Vocabulary Test (ROWPVT) | Baseline to Week 12 | Change from baseline 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. |
| Change from baseline in expressive vocabulary score as measured by the Expressive One-Word Picture Vocabulary Test (EOWPVT) | Baseline to Week 12 | Change from baseline 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. |
| Change from baseline in Clinical Global Impression-Severity and Improvement scores as measured by the Clinical Global Impression Scale (CGI-S and CGI-I) | Baseline to Week 12 | Change from baseline 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. |
| Change from baseline in Aberrant Behavior Checklist total score as measured by the Aberrant Behavior Checklist (ABC) | 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. |
| Change from baseline in total problem score as measured by the Child Behavior Checklist (CBCL) | 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. |
| Change from baseline in adaptive behavior composite score as measured by the Vineland Adaptive Behavior Scales (VABS) | 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. |
| Change from baseline in proportion of gaze duration to social stimuli as measured by eye-tracking assessment | 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. |
| Incidence of adverse events and serious adverse events as measures of safety and tolerability of folinic acid | 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. |
Countries
Singapore
Contacts
CONTACTStudy Coordinator
Outcome results
None listed