Study of the Genetic Factors Involved in Autism and Related Disorders

Autism Spectrum Disorder Clinical Trial

— Gene&autism  

Official title:

Study of the Genetic Factors Involved in Autism and Related Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04727489
• Other study ID #: C16-89
• Status: Recruiting
• Start date: March 30, 2021
• Est. completion date: December 31, 2037

Study information

• Verified date: April 2021
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Richard Delorme, M.D, Ph.D
• Phone: +0033662725334
• Email: richard.delorme[@]aphp.fr
• Is FDA regulated: No
• 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.

Description:

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 identify the neuronal phenotypes caused by deleterious synaptic mutations for further translational studies

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3800
• Est. completion date: December 31, 2037
• Est. primary completion date: December 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 24 Months to 70 Years

Eligibility

Inclusion Criteria----------------------------------------------------------------------------------- ----------------

Probands with Autism Spectrum Disorder

• Meet the diagnostic criteria for ASD of the DSM-5 [American Psychiatric Association, 2013] based on a consensus between the clinical expertise of expert clinicians, the scores of the Autism Diagnostic Interview-Revised (ADI-R) (Rutter et al, 2003) and those of the Autism Diagnosis Observation Schedule (ADOS-2) (Lord et al, 2012)

• Be at least 24 months (no upper age limit)

• Somatic and Intellectual state compatible with a blood test

• Affiliation to the social insurance

• Signature of informed consent by the applicant or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Controls without ASD

• At least 24 months old

• Somatic and Intellectual state compatible with a blood test

• Affiliation to the social insurance

• Signature of informed consent by the subject or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Relatives of the probands with ASD or of controls without ASD

• At least 24 months old

• Somatic and Intellectual state compatible with a blood test

• Affiliation to the social insurance

• Signature of informed consent by the subject or by holders of parental authority if the subject is a minor or by the guardian if the subject is under guardianship

Exclusion Criteria ------------------------------------------------------------------------------------------- -------

Probands with Autism Spectrum Disorder

• Severe Intelectual Deficiency (IQ,35 or developmental age <18 months)

?. Personal psychiatric history (schizophrenia, bipolar disorder, substance use disorder (except tobacco), recurrent depression disorder, severe instable anxiety disorder)

• Personal neurologic history (epilepsy, or severe neurological disease)

Relatives of the probands with ASD, of the controls or the controls:

? Medical condition (psychiatric or somatic) not compatible with the inclusion

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Disease

Intervention

Genetic:
• DNA from subjects will be stored in the biobank of our study.
Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders.

Locations

Country	Name	City	State
France	CIC, CHU Bordeaux	Bordeaux
France	CRA, Hopital Charles Perrens, Bordeaux	Bordeaux
France	Albert Chenevier Hospital	Creteil	Ile De France
France	CIC, H. Mondor, Creteil	Créteil
France	Centre de rehabilitation psychosociale, Hopital Saint Egreve	Grenoble
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	Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder	up to 12 months after completion of the inclusion and molecular explorations
Secondary	Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorder	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

External Links

•   Description website of the sponsor