MedTrace Logo

Investigating the Therapeutic Efficacy of All-trans Retinoic Acid in Autism Spectrum Disorder Patients With 15q11-13 Duplication Syndrome

NCT07079696 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 90

Last updated 2025-07-23

No results posted yet for this study

Summary

Autism spectrum disorder (ASD) , hereafter referred to as autism, is a group of neurodevelopmental disorders caused by genetic and environmental factors. Its core symptoms are social impairment, repetitive stereotyped behaviors, and restricted interests.

The 15q11-13 region of the human chromosome is a locus prone to structural abnormalities leading to neurological disorders. Maternal duplications within this region lead to Dup15q syndrome , which accounts for approximately 1% of ASD cases .

This region harbors multiple alleles, and current research indicates that the pathophysiological alterations in this syndrome primarily involve UBE3A . Among all genes in the 15q11-13 region, only UBE3A exhibits cell-type-specific maternal monoallelic expression . Consequently, duplication of the UBE3A gene is considered the primary pathogenic factor in the pathology of Dup15q syndrome.

Studies show that the metabolic conversion of retinol to retinoic acid is impaired in ASD patients with UBE3A overexpression and corresponding animal models . Notably, dietary supplementation with all-trans retinoic acid (ATRA) has been shown to significantly ameliorate autism-like behaviors caused by UBE3A overexpression in male mice .

This study aims to evaluate ATRA treatment in children with Dup15q syndrome-related autism , assessing changes in their ADOS-2 scores , to potentially provide a novel therapeutic approach for autism treatment.

Conditions

Interventions

DRUG

ATRA

Treatment Phase (Duration: 18 months) Intervention: ATRA oral administration using a stepwise titration protocol (detailed below). Patients may discontinue treatment if intolerable adverse events occur; post-withdrawal symptom exacerbation is monitored. \*Titration Protocol\* Treatment Cycle (C): 3 weeks per cycle. Dose escalation follows: Cycle Dosage Duration C1.1 15 mg/m²/day 2 weeks on / 1 week off C1.2 20 mg/m²/day 2 weeks on / 1 week off C1.3 25 mg/m²/day 2 weeks on / 1 week off Blinded Assessments: primary endpoints: ADOS-2 SA score, CARS, SRS, ATEC, Gesell, and Sensory Motor (SM) scales. Biomarker/Diagnostic tests: blood tests (CBC, liver/kidney function, vitamin panels, ATRA levels, hepatitis markers), neuroimaging (cranial fMRI), neurophysiology (EEG, audiometry), skeletal imaging (limb long-bone radiographs, growth monitoring), and biobanking: 1 blood tube for proteomics (baseline, 6/12/18 months). Repeat all assessments at 6, 12, and 18 months after ATRA treatment.

Sponsors & Collaborators

  • Second Affiliated Hospital, School of Medicine, Zhejiang University

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
3 Years
Max Age
7 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-09-01
Primary Completion
2027-01-31
Completion
2027-01-31

Countries

  • China

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07079696 on ClinicalTrials.gov