Understanding the Mechanisms of Autism : an MRI and Social Cognition Study (ECLAT)

The main goal of this study is to investigate anatomo-functional brain abnormalities associated with autism spectrum disorders using a multimodal brain imaging approach, as well as its links to social cognition difficulties measured using eye-tracking

Study Overview

• Status: Not yet recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Device: Eye-tracking; Diagnostic test: MRI; Other: Clinical Scales; Genetic: Research of genetic anomalies

Detailed Description

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose first manifestations appear early in childhood. Even if ASDs present a wide heterogeneity in clinical manifestations, abnormalities in social behavior, characterized in particular by a lack of preference for social information, remain the core of difficulties characteristic of autism.

Brain imaging investigations have revealed anatomo-functional abnormalities in autism, particularly in social brain regions. In parallel, eye-tracking studies have provided objective measures of social perception abnormalities in autism. These results illustrate the relevance of these research strategies in the context of ASD. Acquiring objective data on social behavior and linking them with brain imaging data opens up new avenues for research into the evolution of social skills during child development, and the brain changes underlying this process.

In this context, the main hypothesis of this study is that the investigation of the neural bases of autism spectrum disorders, using an approach combining multimodal brain imaging and the investigation of social behavior using eye-tracking, would make it possible not only to better describe abnormalities, but also to identify individual patterns at brain and behavioral level. This could help to better characterize ASDs with and without genetic abnormalities, an area which to date has received very little investigation. In addition, the objective measurements obtained with this approach would also enable the proposal of biomarkers, which would contribute not only to better monitoring of the disorder's evolution, but also to the evaluation of the effectiveness of new therapeutic interventions

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nathalie BODDAERT, MD, PhD; Phone Number: +33 1.71.39.65.30; Email: nathalie.boddaert@aphp.fr
• Study Contact Backup: Name: Laure CHOUPEAUX, Master; Phone Number: + 33 1 44 38 17 11; Email: laure.choupeaux@aphp.fr

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker Enfants Malades
    • Contact: Nathalie BODDAERT, MD, PhD; Phone Number: +33 1.71.39.65.30; Email: nathalie.boddaert@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For subjects diagnosed with ASD or suspected of ASD :

• 3 months ≤ age < 25 years ;
• an MRI required as part of the clinical procedures
• written consent obtained from parents or legal guardians.
• Affiliated to social security

For Healthy control subjects over 3 years of age:

• between 3 and 18 years of age
• no known neurological or psychiatric pathology
• written consent obtained from parents or legal guardian.
• Affiliated to social security

For Healthy control subjects under 5 years of age:

• age between 3 months and 5 years
• who have had an MRI scan in the pediatric radiology department at Necker Hospital, which was found to be normal.
• with no known neurological or psychiatric pathology
• no opposition from legal representative

Exclusion Criteria:

• Contraindication to MRI (pacemaker, intracorporeal metallic body, claustrophobia).
• Impossibility for healthy volunteers to remain still during MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Suspected or confirmed Autism Spectrum Disorders (ASD); Patient with ASD or suspected ASD for whom an MRI is requested by the clinician as part of care	Device: Eye-tracking; Eye movements and follow a person's gaze will be recorded during visualization of stimuli presented in the screen by analyzing images of the eye captured by an infrared camera; Diagnostic test: MRI; Anatomical and functional images will be acquired and review by an experienced neuro-radiologist; Other: Clinical Scales; CGI, E-CAR and ABC will be used for behavior and clinical evaluation; Genetic: Research of genetic anomalies; For the diagnosis of autism, patients benefit from a a genetic assessment. This is carried out as part of their care
Experimental: Healthy volunteers over 3 years of age; Healthy Control Children will be recruited specifically for the research	Device: Eye-tracking; Eye movements and follow a person's gaze will be recorded during visualization of stimuli presented in the screen by analyzing images of the eye captured by an infrared camera; Diagnostic test: MRI; Anatomical and functional images will be acquired and review by an experienced neuro-radiologist; Other: Clinical Scales; CGI, E-CAR and ABC will be used for behavior and clinical evaluation
No Intervention: Healthy volunteers under 5 years of age; Children who have already undergone an MRI for various medical reasons and whose MRI was normal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rest cerebral blood flow (CBF)	Whole brain rest CBF measured with Arterial spin labelling MRI	at inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurements of white matter microstructure - fractional anisotropy	Measurements of white matter microstructure integrity by diffusion tensor imaging MRI, measured by fractional anisotropy (indicates the orientation of diffusion)	at inclusion
Measurements of white matter microstructure - mean diffusivity	Measurements of white matter microstructure integrity by diffusion tensor imaging MRI, measured by mean diffusivity (the mean amount of diffusion in each of the principal directions calculated in the tensor	at inclusion
Measurements of white matter microstructure - radial diffusivity	Measurements of white matter microstructure integrity by diffusion tensor imaging MRI, measured by radial diffusivity (the apparent water diffusion coefficient in the direction perpendicular to the axonal fibers)	at inclusion
Measurements of white matter microstructure - axial diffusivity	Measurements of white matter microstructure integrity by diffusion tensor imaging MRI, measured by axial diffusivity (the magnitude of diffusion parallel to fiber tracts)	at inclusion
Measurements of resting state functional connectivity	MRI-resting state measurements of correlation coefficients between different regions within different brain networks, in particular the social brain network.	at inclusion
Correlation between social perception and multimodal brain imaging	Correlation measurements between social perception parameters measured by eye-tracking (number of fixations in social and non-social regions) and various multimodal brain imaging parameters obtained with MRI.	at inclusion
Correlation between clinical severity and multimodal brain imaging	Measures of correlation between autism severity scores measured by the ADI-R and various multimodal brain imaging parameters obtained in MRI	at inclusion
Imaging abnormalities associated with known genetic mutations	Multimodal brain imaging in patients with a known genetic abnormality compared with the same measures obtained in patients without known genetic abnormalities or in healthy controls.	at inclusion
Social perception abnormalities associated with known genetic mutations	Social perception measures (number of fixations in social and non-social regions) in patients with a known genetic abnormality compared with the same measures obtained in patients without known genetic abnormalities or in healthy controls.	at inclusion
Anatomic changes over time - study of developmental trajectory	Measures of change over time (between inclusion and 2 years) in brain anatomy and function in a subgroup of ASD patients and healthy volunteers.	2 years
Social perception changes over time - study of developmental trajectory	Measures of change over time (between inclusion and 2 years) in social perception parameters in a subgroup of ASD patients and healthy volunteers.	2 years
Brain imaging in young children associated with ASD	Multimodal brain imaging measures in young patients (<5 years) with a ASD compared with the same measures obtained in young children (<5 years) without ASD (control children)	at inclusion
Early data on social perception	Social perception measures (number of fixations in social and non-social regions) in very young patients with ASD (3 months to 5 years) compared with a subgroup of control children aged under 5 years	at inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Study Director: Monica ZILBOVICIUS, INSERM INSERM ERL "Trajectoires Développementales en Psychiatrie"

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2031

Study Registration Dates

• First Submitted: February 22, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Genetics; Autism spectrum disorders; Social perception; Eye-tracking; Multimodal brain imaging; Developmental trajectory
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder
• Other Study ID Numbers: APHP240105; 2023-A02668-37 (Registry Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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