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

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.

Study Overview

• Status: Recruiting
• Conditions: Treatment Adherence; Autism; Dup15Q Syndrome; Retinoic Acid
• Intervention / Treatment: Drug: Retinoic acid

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jianhua Feng, Master; Phone Number: +8613588172577; Email: hzhz87083886@zju.edu.cn

Study Locations

• China
  • Hangzhou, China, 310009
    • Recruiting
    • Miao pu
    • Contact: pu Miao; Phone Number: +8618267179356; Email: 2517105@zju.edu.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Zhejiang University
      • Contact: Jianhua Feng; Phone Number: 0571 89713749; Email: 380028654@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group	Drug: Retinoic acid; Retinoic acid oral
Experimental: Experimental group	Drug: Retinoic acid; Retinoic acid oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADORS-2	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.	3 months，6 months，9 months，12 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2024

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: 2021-0438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No