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Study of the Genetic Factors Involved in Autism and Related Disorders (Gene&autism)

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ClinicalTrials.gov Identifier: NCT04727489
Recruitment Status : Recruiting
First Posted : January 27, 2021
Last Update Posted : May 5, 2021
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief 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.

Condition or disease Intervention/treatment
Autism Spectrum Disorder Genetic: DNA from subjects will be stored in the biobank of our study.

Detailed 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

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Study Type : Observational
Estimated Enrollment : 3800 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Study of the Genetic Factors Involved in Autism and Related Disorders
Actual Study Start Date : March 30, 2021
Estimated Primary Completion Date : December 21, 2022
Estimated Study Completion Date : December 31, 2037

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Autism Spectrum Disorder
Probands with Autism Spectrum Disorder, (N=700), Diagnosis of ASD according to DSM-V criteria For all patients included in the study, core assessment carried out by either collaborating partners consists of diagnosis using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders. 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.
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.
Other Name: diagnostic test

Control without Autism Spectrum Disorder
Controls without Austim Spectrum Disorder, aged 6 to 40, N=2100 (300 adultes, 300 children) Healthy individuals with or without idiopathic surgical or urological conditions (e.g. orthopaedic conditions, hernia repairs, renal malformations, pre- or post-circumcision, phimosis, balanitis, scoliosis, congenital hip dislocation, adenoid or tonsil removal, dental procedures such as wisdom tooth extraction, cosmetic procedures such as removal of skin tags or cleft lip repairs, non-head injuries such as fractures, drainage of subungual or perichondrial haematomata).
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.
Other Name: diagnostic test

Relatives of probands with Autism Spectrum Disorder

Relatives of probands with Autism Spectrum Disorder (N=1200 parents, N=600 siblings, N=300 other relatives)

  • Without Autism Spectrum Disorder diagnosis according to DSM-V,
  • With Autism Spectrum Disorder diagnosis according to DSM-V, and using the Autism Diagnostic Interview-Revised (ADI-R) criteria for autism and Autism Diagnostic Observation Schedule (ADOS-G) criteria for autism or Autism Spectrum Disorders
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.
Other Name: diagnostic test

Relatives of controls
Relatives of controls without Autism Spectrum Disorder, N=400 first degree relatives
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.
Other Name: diagnostic test




Primary Outcome Measures :
  1. Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder [ Time Frame: up to 12 months after completion of the inclusion and molecular explorations ]
    Prevalence of synaptic gene deleterious mutations in patients with Autism Spectrum Disorder


Secondary Outcome Measures :
  1. Prevalence of the deleterious mutations in the major biological pathways in Autism Spectrum Disorder [ Time Frame: up to 12 months after completion of the inclusion and molecular explorations ]
    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


Biospecimen Retention:   Samples With DNA
DNA from subjects will be stored in the biobank of our study. From some patients with deleterious mutations in synaptic genes,


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   24 Months to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
For all patients included in the study
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04727489


Contacts
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Contact: Richard Delorme, M.D, Ph.D +0033662725334 richard.delorme@aphp.fr

Locations
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France
Albert Chenevier Hospital Not yet recruiting
Creteil, Ile De France, France, 94000
Contact: Marion Leboyer, MD., PhD.    +33 (0)1 49 81 32 90    marion.leboyer@inserm.fr   
Robert Debré Hospital Not yet recruiting
Paris, Ile De France, France, 75019
Contact: richard delorme, MD., PhD.    +33 (0)6 62 72 53 34    richard.delorme@aphp.fr   
Principal Investigator: richard Delorme, M.D,Ph.D         
CIC, CHU Bordeaux Recruiting
Bordeaux, France
Contact: Michael Fayon, MD., PhD.    +33 (0)5 57 82 01 08    michael.fayon@chu-bordeaux.fr   
CRA, Hopital Charles Perrens, Bordeaux Recruiting
Bordeaux, France
Contact: Mauel Bouvard, MD., PhD.    +33 (0)5 56 56 17 19    bouvard.manuel@wanadoo.fr   
CIC, H. Mondor, Creteil Not yet recruiting
Créteil, France
Contact: Philippe Le Corvoisier, MD., PhD.    +33 (0)1 49 81 37 96    philippe.lecorvoisier@inserm.fr   
Centre de rehabilitation psychosociale, Hopital Saint Egreve Not yet recruiting
Grenoble, France
Contact: Julien Dubreucq, MD.    +33 (0)4 76 56 44 40    jdubreucq@ch-alpes-isere.fr   
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site

Publications of Results:
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Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT04727489    
Other Study ID Numbers: C16-89
First Posted: January 27, 2021    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
autism
developmental Disorder
gene
polymorphism
mutation
Additional relevant MeSH terms:
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Disease
Autistic Disorder
Autism Spectrum Disorder
Pathologic Processes
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders