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

NCT07079696 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2025-0465
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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

Dup15q Syndrome; Autism Spectrum Disorder; Therapy; All-trans Retinoic Acid

Outcome Measures

Primary Outcomes (1)

• ADOS-2 SA score

  6、12、18months after ATRA administration

Secondary Outcomes (1)

• development scale score

  6、12、18months after ATRA administration

Study Arms (1)

Group experimental

EXPERIMENTAL

Age: 3-7 years old (stratified into Group 1: 3-5 years; Group 2: 5-7 years).

Drug: ATRA

Interventions

ATRA DRUG

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.

Group experimental

Eligibility Criteria

• Age: 3 Years - 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Clinical Diagnosis Conducted by two experienced physicians based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition （DSM-V）
• Diagnostic Scale Assessment Performed by professionally certified examiners using ADOS-2
• Genetic Testing Diagnostic criteria via genomic analysis : detection of 15q11-13 duplication containing UBE3A

You may not qualify if:

• History of acute or chronic infection within the past 3 months
• Active epileptic seizures within the past 6 months
• Intake of nutritional supplements (e.g., vitamin A and/or minerals) within the past 1 month
• History of chronic diseases, including abnormal liver function, abnormal renal function, or thyroid dysfunction

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Department of Pediatrics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Central Study Contacts

Jianhua Feng

CONTACT

86+13588172577; hzhz87083886@zju.edu.cn

Xueting Lin

CONTACT

86+19858126052; lin_xt@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 23, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 23, 2025

Record last verified: 2025-06

Locations

CN (1)