Interventional rTMS for Improving Social Perception in Autism (IRIS-gaze)

September 17, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by difficulties in social interaction and social communication. Over the last 30 years, neuroimaging studies have identified anatomical and functional abnormalities localized in the superior temporal sulcus (STS) in individuals with ASD. The STS is a brain region that plays a central role in the perception and interpretation of social information. These findings make the STS a particularly relevant target for developing new therapeutic approaches aimed at improving social difficulties associated with ASD.

The IRIS study aims to evaluate the effects of a non-invasive neuromodulation technique, transcranial magnetic stimulation (TMS), on social perception and social behavior in pre-adolescents and adolescents with ASD aged 10 to 17 years. The stimulation protocol, called intermittent theta-burst stimulation (iTBS), will target the right posterior STS. Previous studies conducted by the research team have established the feasibility and good tolerability of this approach in young adults with ASD.

This is a randomized, double-blind, placebo-controlled clinical trial involving 16 participants and using a crossover design. Each participant will receive both active and placebo stimulation, in a randomized order, with an interval of approximately three months between the two periods. Each treatment period will consist of five sessions per day for four consecutive days, for a total of 20 sessions.

The effects of the intervention on social perception and behavior will be objectively assessed using eye-tracking during the viewing of social scenes. Brain MRI will also be used to investigate potential changes in brain function, connectivity, and structure. In addition, clinical scales completed with the parents will be used to assess social behavior and overall functioning.

The study will therefore determine whether an accelerated TMS protocol targeting a brain region involved in social cognition can improve social perception and behavior in young people with ASD, while also assessing its safety, tolerability, and effects on brain function.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by persistent difficulties in social communication and interaction, together with restricted and repetitive patterns of behavior. Despite substantial progress in understanding the neurobiological mechanisms underlying ASD, therapeutic options specifically targeting core social difficulties remain limited. Non-invasive brain stimulation techniques, including transcranial magnetic stimulation (TMS), therefore represent a promising approach for investigating and potentially modulating neural networks involved in social functioning.

Neuroimaging studies have consistently identified structural and functional abnormalities localized in the superior temporal sulcus (STS) in individuals with ASD. The STS is a key component of the social brain network and is involved in the processing and integration of socially relevant information, including faces, gaze, voices, biological motion, and other dynamic social cues. Functional and structural abnormalities of this region, as well as altered connectivity between the STS and other components of the social brain network, have been reported in ASD. These findings provide the neurobiological rationale for targeting the STS in the present study.

Previous work by our research team has investigated whether modulation of the right posterior STS (pSTS) using TMS can influence social perception. A first study in typically developing adults established a causal relationship between modulation of pSTS activity and changes in visual exploration of socially relevant information. Subsequent studies in young adults with ASD demonstrated the feasibility and good tolerability of excitatory intermittent theta-burst stimulation (iTBS) targeting the right pSTS. More recently, a pilot randomized, double-blind, sham-controlled clinical trial in young adults with ASD evaluated repeated iTBS sessions targeting this region. The intervention was feasible and well tolerated, and preliminary findings suggested differential changes in social behavior following active compared with sham stimulation. These findings support further investigation of this approach using a more intensive stimulation protocol.

The IRIS-gaze study investigates an accelerated iTBS protocol targeting the right pSTS in pre-adolescents and adolescents with ASD. Adolescence represents a developmental period characterized by substantial brain plasticity and may therefore constitute a particularly relevant period for neuromodulatory interventions. Accelerated TMS protocols, in which several stimulation sessions are administered each day over a limited number of days, are designed to induce cumulative neuroplastic effects while substantially reducing the overall duration of treatment compared with conventional repeated TMS schedules.

IRIS-gaze is an interventional, randomized, double-blind, sham-controlled crossover clinical trial. Sixteen participants will receive both active and sham stimulation in a randomized order. Each treatment period consists of five iTBS sessions per day for four consecutive days, for a total of 20 sessions per treatment period. The two treatment periods are separated by a washout period of approximately three months (3 months ± 2 weeks), selected to minimize potential carry-over effects between active and sham stimulation. The crossover design allows each participant to serve as his or her own control, thereby reducing the influence of inter-individual variability, and insures that all participants receive the active condition.

Stimulation will be performed using a MAGSTIM RAPID2® stimulator and a cooled figure-of-eight coil. The right pSTS target will be individually identified from each participant's structural MRI and localized during stimulation using MRI-guided neuronavigation. Before stimulation, the individual motor threshold will be determined using single-pulse TMS. Each iTBS session will deliver 1,800 pulses, consisting of bursts of three pulses at 50 Hz repeated at 5 Hz, delivered in 2-second trains separated by 8-second intervals. Five sessions will be administered each day, separated by 50-minute intervals.

The sham condition will follow the same schedule and procedures as active stimulation. A dedicated sham coil will reproduce the appearance, acoustic characteristics, and sensory experience of active stimulation without inducing cortical stimulation. Investigators conducting MRI, eye-tracking, and clinical assessments will remain blinded to stimulation condition.

A multimodal evaluation strategy will be used to characterize potential effects of the intervention. Social visual behavior will be objectively assessed using infrared eye-tracking during the presentation of dynamic social stimuli. Brain MRI will complement the behavioral assessment by investigating potential changes in cerebral perfusion, resting-state functional connectivity, and white-matter microstructure. Clinical assessments completed with parents will provide complementary information regarding social behavior and overall functioning. Assessments will be performed at predefined time points throughout the crossover protocol, allowing comparison of changes associated with active and sham stimulation.

The study combines targeted non-invasive neuromodulation with objective behavioral measurements and multimodal neuroimaging to investigate the effects of accelerated iTBS on neural systems involved in social functioning in young people with ASD. Beyond evaluating the potential clinical relevance of this approach, IRIS-gaze aims to improve understanding of the relationship between modulation of the right pSTS, brain network plasticity, and social behavior in ASD. Ultimately, this study could pave the way for a novel non-invasive therapeutic approach aimed at improving social functioning in children and adolescents with ASD.

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75013
        • Plateforme CENIR_PANAM au centre de Neuro Imagerie de recherche à l' " Institut du Cerveau " (ICM)
        • Contact:
      • Paris, France, 75015
        • Hôpital Necker - Enfants Malades - Service de radiologie pédiatrique
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of Autism Spectrum Disorder (ASD) according to DSM-5 criteria and confirmed by the Autism Diagnostic Interview-Revised (ADI-R).
  • Aged 10 to 17 years, inclusive.
  • Able to undergo an MRI examination.
  • Affiliated with or beneficiary of a social
  • Affiliated with or beneficiary of a social security system.
  • Written informed consent provided by the participant and/or their legal representative

Exclusion Criteria:

  • Presence of epilepsy or a history of seizures.
  • Contraindication to TMS, including personal or family history of epilepsy, history of craniotomy, cardiac pacemaker, intraocular or intracerebral metallic foreign body, cochlear implant, cardiac valve or metallic surgical material, or any material likely to concentrate radiofrequency pulses, and open wounds on the head or irritated scalp.
  • Contraindication to MRI, including cardiac pacemaker, intracorporeal metallic foreign body, or occupational exposure to metallic particles.
  • Presence of a neurological condition (epilepsy, cerebral palsy, neuromuscular disease, neurological sequelae of brain injury, or central nervous system malformation)
  • Initiation, discontinuation, or modification of treatment with neuroleptics or benzodiazepines during the previous month (unstable treatment)
  • Pregnancy or breastfeeding (based on patient/parental interview).
  • Current participation in another clinical trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TMS / sham
The active TMS session takes place during the first series. The second series is a sham series
Device: Neuromodulation by transcranial magnetic stimulation (TMS)
2 series of 5 TMS applied each day, during 4 consecutive days : active or sham according randomization
Radiation: Anatomo-functional MRI

For all patients, each MRI scan will include:

  • an ASL MRI to measure cerebral blood flow (CBF) at rest,
  • a resting-state functional MRI (rs-fMRI) to measure functional connectivity,
  • a diffusion-weighted MRI (DWI-MRI) to assess the microstructural integrity of the white matter.

The total duration of each MRI scan will be approximately 30 minutes, and no injections or premedication will be used.

Device: Eye-tracking
Eye-tracking technology records eye movements and tracks a participant's gaze while they view stimuli presented on a screen, by analyzing images of the eye captured by an infrared camera.
Other: Social Responsiveness Scale, Second Edition (SRS-2)
A Social Responsiveness Scale, Second Edition (SRS-2), Autism Behavior Checklist (ABC) and Clinical Global Impressions (CGI) will be used for assessment of Changes Induced by TMS on Social Behavior and Autistic Symptoms before the start of TMS sessions and during the 24 hours following the last stimulation session.
Experimental: Sham / TMS
The active TMS session takes place during the second series. The first series is a sham series
Device: Neuromodulation by transcranial magnetic stimulation (TMS)
2 series of 5 TMS applied each day, during 4 consecutive days : active or sham according randomization
Radiation: Anatomo-functional MRI

For all patients, each MRI scan will include:

  • an ASL MRI to measure cerebral blood flow (CBF) at rest,
  • a resting-state functional MRI (rs-fMRI) to measure functional connectivity,
  • a diffusion-weighted MRI (DWI-MRI) to assess the microstructural integrity of the white matter.

The total duration of each MRI scan will be approximately 30 minutes, and no injections or premedication will be used.

Device: Eye-tracking
Eye-tracking technology records eye movements and tracks a participant's gaze while they view stimuli presented on a screen, by analyzing images of the eye captured by an infrared camera.
Other: Social Responsiveness Scale, Second Edition (SRS-2)
A Social Responsiveness Scale, Second Edition (SRS-2), Autism Behavior Checklist (ABC) and Clinical Global Impressions (CGI) will be used for assessment of Changes Induced by TMS on Social Behavior and Autistic Symptoms before the start of TMS sessions and during the 24 hours following the last stimulation session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in eye-gaze pattern during social visual exploration
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in visual exploration of socially relevant information following active versus sham iTBS targeting the right posterior superior temporal sulcus (pSTS), assessed using eye-tracking during the presentation of social scenes. Eye-gaze patterns will be quantified using predefined areas of interest (AOIs), with fixation data extracted using Tobii eye-tracking technology and normalized for statistical analysis.
24 hours after each 4-day iTBS treatment block (active and sham)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in resting cerebral blood flow
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in rest cerebral blood flow (CBF) following active versus sham iTBS targeting the right posterior superior temporal sulcus, assessed using arterial spin labeling magnetic resonance imaging (ASL-MRI).
24 hours after each 4-day iTBS treatment block (active and sham)
Change in resting-state functional connectivity
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in resting-state functional brain connectivity following active versus sham iTBS targeting the right posterior superior temporal sulcus, assessed using resting-state functional magnetic resonance imaging (rs-fMRI).
24 hours after each 4-day iTBS treatment block (active and sham)
Change in white matter microstructure
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in white matter microstructural integrity following active versus sham iTBS targeting the right posterior superior temporal sulcus, assessed using diffusion-weighted magnetic resonance imaging (DWI-MRI)
24 hours after each 4-day iTBS treatment block (active and sham)
Change in social responsiveness assessed by the SRS-2
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in social functioning following active versus sham iTBS, assessed using the Social Responsiveness Scale, Second Edition (SRS-2), completed with the participant's parents.
24 hours after each 4-day iTBS treatment block (active and sham)
Change in autism-related behaviors assessed by the ABC
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in autism-related behaviors following active versus sham iTBS, assessed using the Autism Behavior Checklist (ABC), completed with the participant's parents.
24 hours after each 4-day iTBS treatment block (active and sham)
Change in global clinical functioning assessed by the CGI
Time Frame: 24 hours after each 4-day iTBS treatment block (active and sham)
Change in overall clinical functioning following active versus sham iTBS, assessed using the Clinical Global Impressions (CGI).
24 hours after each 4-day iTBS treatment block (active and sham)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Principal Investigator: Nathalie BODDAERT, MD, PhD, Assistance Publique - Hôpitaux de Paris
  • Study Chair: Monica ZILBOVICIUS, PhD, INSERM INSERM ERL "Trajectoires Développementales en Psychiatrie" Service de Radiologie Pédiatrique Hospital Necker Enfants Malades

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

January 1, 2029

Study Registration Dates

First Submitted

September 11, 2026

First Submitted That Met QC Criteria

September 17, 2026

First Posted (Actual)

September 18, 2026

Study Record Updates

Last Update Posted (Actual)

September 18, 2026

Last Update Submitted That Met QC Criteria

September 17, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP260108
  • 2026-A00951-50 (Registry Identifier: ID-RCB)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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