Susceptibility Genes in Autism Spectrum Disorders

Autism Spectrum Disorders Clinical Trial

Official title:

Search of Susceptibility Genes in Autism Spectrum Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02628808
• Other study ID #: C07-33
• Secondary ID: 2008-A00019-46
• Status: Recruiting
• Phase: N/A
• First received: September 26, 2013
• Last updated: December 9, 2015
• Start date: August 2008
• Est. completion date: August 2018

Study information

• Verified date: November 2015
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Marion Leboyer, M.D, Ph.D
• Phone: +0033149813131
• Email: marion.leboyer[@]inserm.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéFrance: Committee for the Protection of PersonnesFrance: The Commission nationale de l’informatique et des libertés
• Study type: Observational

Clinical Trial Summary

The main objective of the study is to define, for Autism Spectrum Disorder, the extent of genetic variation in synaptic pathways that may be targeted for therapeutic development. For this purpose the investigators will take advantage of large, well-characterized cohorts of patients with Autism Spectrum Disorder for genetic screenings. Targeted sequencing of selected synaptic genes, previously associated with Autism Spectrum Disorder, will be carried out in these cohorts with deep coverage of coding regions and a strong focus on previously untested regulatory regions. Genomic data from Copy Number Variant, whole genome sequencing and exome sequencing, available for some of these patients, will be integrated in the overall analysis. The investigators will strongly emphasize the establishment of comprehensive genotype/phenotype correlations and set up an induced Pluripotent Stem Cells collection from selected patients with synaptic mutations for functional and expression analysis.

Description:

Specific aims are:

Aim 1: To identify genetic variants in selected synaptic genes, by targeted sequencing with deep coverage of coding regions and a strong focus on previously untested regulatory regions in Autism Spectrum Disorder

Aim 2: To define the range of clinical phenotypes caused by mutations in synaptic genes by establishing detailed genotype/phenotype correlations and analyzing segregation in families with multiple individuals affected by Autism Spectrum Disorder, Autism Spectrum Disorder traits or other neuropsychiatric disorders

Aim 3: To generate a repository of induced Pluripotent Stem Cells from Autism Spectrum Disorder subjects with synaptic mutations for translational studies, including expression and functional assays.

Aim 4: To identify the neuronal phenotypes caused by deleterious synaptic mutations for further translational studies

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: August 2018
• Est. primary completion date: August 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Months to 70 Years

Eligibility

Inclusion Criteria:

• Diagnosis for Autism Spectrum Disorders or Autism using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria

Exclusion Criteria:

• Patients with profound intellectual disability or with a known medical cause of autism, such as neurocutaneous syndromes, Fragile X, metabolic disorders, extreme prematurity, congenital rubella and other prenatal or postnatal neurological infections or gross dysmorphology, will be excluded

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Autism Spectrum Disorders
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease Susceptibility

Locations

Country	Name	City	State
France	Albert Chenevier Hospital	Creteil	Ile de France
France	Robert Debré Hospital	Paris	Ile de France

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (1)

Delorme R, Ey E, Toro R, Leboyer M, Gillberg C, Bourgeron T. Progress toward treatments for synaptic defects in autism. Nat Med. 2013 Jun;19(6):685-94. doi: 10.1038/nm.3193. Epub 2013 Jun 6. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder		up to 12 months after completion of the inclusion and molecular explorations	No
Secondary	Identification of biological pathways in Autism Spectrum Disorders	The deleterious mutations that the investigators will identify in genes related to Autism Spectrum Disorders will help to have a comprehensive framework of biological pathways involved in Autism Spectrum Disorder	up to 12 months after completion of the inclusion and molecular explorations)	No

External Links

•   website of the sponsor