MRI Study of Subjects With ASD, Their Relatives and TD

Magnetic Resonance Imaging Neuroanatomical Study of Patients With an Autism Spectrum Disorder, Their Relatives and Typically Developing Subjects.

This project is structured around a central study called "Study of genetic factors involved in autism and related conditions ("Genes and Autism" study, sponsor: INSERM). This study explores clinical and genetic aspects of ASD (autism spectrum disorders) and is complemented with several ancillary studies (such as this one) which will use the data of the main study and will allow an extensive review of phenotypes associated with ASD.

In this ancillary study, we will go on the acquisition of anatomical, diffusion and functional MRI in subjects with ASD, relatives and controls. Our group has already performed several neuroanatomical studies of ASD. IWe recruited since 2010 more than 600 subjects (proponents, relatives and controls) to better understand the implication of brain abnormalities in ASD.

This study involves specialized teams in neuroiamging based at INSERM, NeuroSpin (CEA), Robert Debré Hospital (APHP) and Pasteur Institute

Our main objective is to identify structural, connectivity and functional peculiarities in subjects with ASD

Secondary objectives include:

• the identification of familial heritability patterns of ASD
• correlate data obtained in brain imaging with genetic data
• assess specificity and statistical reproducibility of the obtained results

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Other: Neuroimaging (MRI)

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Richard Delorme, M.D, Ph.D; Phone Number: +33140032002; Email: richard.delorme@aphp.fr
• Study Contact Backup: Name: Josselin Houenou, M.D, Ph.D; Phone Number: +33149813051; Email: josselin.houenou@inserm.fr

Study Locations

• France
  • Gif-sur-Yvette, France, 91191
    • Not yet recruiting
    • NeuroSpin neuroimaging platforme
    • Contact: Josselin Houenou, MD, PhD; Email: josselin.houenou@inserm.fr
  • Paris, France, 75019
    • Recruiting
    • APHP, Hôpital Robert Debré
    • Contact: Richard Delorme, MD, PhD; Email: richard.delorme@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Three groups of subjects above 24 months (no upper limit of age):

• subjects with ASD
• relatives of subjects with ASD
• typically developing controls

Description

Inclusion Criteria:

• for patients:

  • being included in the main study "C16-89 - Study of genetic factors involved in ASD and related disorders"
  • having an ASD fulfilling DSM-5 diagnostic criteria (APA, 2012). Diagnosis will be done by a clinical expert, with the support of structured instruments (ADI-R, ADOS-2)
  • having at least 24 Months
  • being affiliated with the French health insurance
  • having signed the informed consent (by proposant or by legal tutors if the subject is <18 or under legal custody)

• for relatives

  • being included in the main study "C16-89 - Study of genetic factors involved in ASD and related disorders"
  • having at least 24 Months
  • being affiliated with the French health insurance
  • having signed the informed consent (by proposant or by legal tutors if the subject is <18 or under legal custody)

• for controls

  • being included in the main study "C16-89 - Study of genetic factors involved in ASD and related disorders"
  • having at least 24 Months
  • being affiliated with the French health insurance
  • having signed the informed consent (by proposant or by legal tutors if the subject is <18 or under legal custody)

Non-inclusion criteria:

• for all subjects

  • severe mental retardation (IQ<35 or developmental age<18 months)
  • medical condition (either psychiatric or physical) not compatible with an inclusion
  • MRI counter indication
  • Current pregnancy or breastfeeding, assessed by questionnaire
  • Not willing to be informed of a brain abnormality diagnosed with MRI

• for the relatives

  *discovery of non filiation during the genetic analyses

• for controls

  • Neurological history (except mental retardation)
  • Personal history of (checked with DIGS for Adults, Diagnostic Interview for Genetic Studies, Numberger et coll., 1994, or Kiddie SADS, Kiddie Schedule for Disorders and Schizophrenia for School Age Children, Orvaschel et coll., 1982): schizophrenia, addiction, bipolar disorder, recurrent depression (> 2 episodes lifetime), severe, not stabilized anxiety disorder, history of episodes of epilepsy, significant inflammatory disease of immunosuppressive medication

Exclusion Criteria:

• for patients: ASD diagnosis not confirmed by assessments after the inclusion
• for all subjects: discovery of a counter indication to MRI during the exam (e.g. claustrophobia)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Subjects with Autism Spectrum Disorders	Other: Neuroimaging (MRI); Multimodal magnetic resonance imaging
Relatives of subjects with Autism Spectrum Disorders	Other: Neuroimaging (MRI); Multimodal magnetic resonance imaging
Typically developing subjects	Other: Neuroimaging (MRI); Multimodal magnetic resonance imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3DT1 MRI derived variables	Cortical folding Cortical thickness Cortical surface Cortical, white matter and subcortical volumes	Day 0
Resting state fMRI derived variables	Whole-brain BOLD signal correlations	Day 0
Task based fMRI derived variables	BOLD activation signals BOLD signal correlations	Day 0
Diffusion MRI derived variables	Fractional anisotropy and mean diffusivity NODDI derived variables	Day 0
quantitative T1 and quantitative T2 MRI	Myelin Water Fraction	Day 0

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Institut Pasteur; APHP; Commissariat A L'energie Atomique
• Investigators: Principal Investigator: Richard Delorme, M.D, Ph.D, APHP, France; Study Chair: Josselin Houenou, M.D, Ph.D, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2022
• Primary Completion (Anticipated): September 13, 2023
• Study Completion (Anticipated): September 13, 2039

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: neuroimaging; phenotype; mri; genes; heritability
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: C16-90; 2017-A02356-47 (Registry Identifier: IDRCB)

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