A Clinical Study Evaluating the Efficacy and Safety of Retinoic Acid in Patients With 15q11-q13 Duplication Syndrome

Early Phase 1

• Conditions: Autism; Treatment Adherence; Dup15Q Syndrome; Retinoic Acid
• Interventions: Drug: Retinoic acid

• Registration Number: NCT05281965
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

Autism Spectrum Disorders (ASD), with its core symptoms of communication and repetitive behaviors, is a serious neurodevelopmental disorder common in childhood and affects about 1% of children. So far, autism remains a clinical dilemma with no effective therapy.

The most common chromsomal ability among ASD patients is 15q11-13q duplication syndrome(dup15q syndrome).Clinical phenotypes of dup15q syndrome include autism, mental retardation, epilepsy (usually refractory epilepsy, often manifested as infantile spasm), congenital heart disease, mild facial abnormalities, etc.

UBE3A is one of the most important genes in the 15q11-q13 region.Biochemistry and molecular biology of the Chinese Academy of Sciences Hu Ronggui group found a new kind of autism in mechanisms and potential therapeutic targets - describe the ubiquitin ligase UBE3A protein and retinoic acid.Previous studies have shown that the basis of the relevant treatment measures can effectively relieve the mouse model of autism characteristics. Therefore, retinoic acid supplementation in the treatment of dup15q syndrome is a potential therapeutic target.

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-03
• Study First Submitted: 2022-03-07
• Study First Submitted QC: 2022-03-07
• Last Update Submitted: 2022-03-07
• Study First Posted: 2022-03-16
• Last Update Posted: 2022-03-16
• Study Start: 2022-04-01
• Primary Completion: 2023-06-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Between 6 and 18 years old
2. Clinical diagnosis + scale diagnosis of autism (1) Clinical diagnosis: clinical diagnosis was made by 2 experienced doctors according to the medical history provided by the caregivers and the diagnostic criteria of ASD in DSM-V; (2) Scale diagnosis: The diagnostic assessment was conducted by highly qualified practitioners taking the ADOS-2 score, Restricted Behabior (RRB) and Social Affect (SA) scores. The scores were converted to standardized severity scores (CSS) for three diagnoses of non-spectrum disorders, autism and autism spectrum disorders.
3. Genetics: 15q11-13 duplicates diagnosed by SNP-Array or A-CGH microarray, including UBE3A gene

Exclusion Criteria

1. A history of acute or chronic infection within the last 3 months
2. There are still active seizures within the past 1 year
3. Have taken vitamin and/or mineral supplements within the last 6 months
4. A history of chronic diseases, including abnormal liver function, abnormal kidney function, and abnormal thyroid function;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Experimental group	Retinoic acid	-
Placebo group	Retinoic acid	-

Primary Outcome Measures

Name	Time	Method
ADORS-2	3 months，6 months，9 months，12 months	The primary outcome measure was changes in the social core symptom of ASD assessed using the social reciprocity score of Autism Diagnostic Observation Schedule (ADOS)39 module 4 (range: 0-14, higher values represent worse outcomes) between the baseline and end point of each administration period.

Trial Locations

Locations (2)

Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Miao pu; 🇨🇳 Hangzhou, China