<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04442061</url>
  </required_header>
  <id_info>
    <org_study_id>APHP191009</org_study_id>
    <nct_id>NCT04442061</nct_id>
  </id_info>
  <brief_title>Autism Spectrum Disorders: Double Blind Randomized Placebo-control Active Pilot Study of Transcranial Magnetic Stimulation Applied to the Superior Temporal Sulcus</brief_title>
  <acronym>STIMAUT</acronym>
  <official_title>Autism Spectrum Disorders: Double Blind Randomized Placebo-control Active Pilot Study of Transcranial Magnetic Stimulation Applied to the Superior Temporal Sulcus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondation de France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondation Malakoff Médéric</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Difficulties in social interactions are the core feature of autism spectrum disorder (ASD)&#xD;
      and are characterized by abnormal social perception, mainly concerning eye gaze.&#xD;
      Anatomo-functional abnormalities within the superior temporal sulcus (STS), a key region of&#xD;
      the social brain, have been described in ASD. The investigators had recently shown that it is&#xD;
      possible to modulate the neural activity of the STS with transcranial magnetic stimulation&#xD;
      (TMS) with an impact on social perception, measured by eye-tracking. In the context of ASD,&#xD;
      stimulation of the STS with excitatory TMS could lead to an improvement in social perception,&#xD;
      which would open up new therapeutic strategies. The purpose of this double-blind, randomized,&#xD;
      placebo-controlled study is to apply a therapeutic TMS protocol (10 daily sessions) at the&#xD;
      right STS in young adults with ASD to improve their social behavior, objectively measured&#xD;
      using eye-tracking.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autism Spectrum Disorders (ASD) are neuro-developmental disorders presumably related to&#xD;
      neural circuit alterations. The symptoms, that start very early in development and persist&#xD;
      through adulthood, can lead to severe handicap. Even though a wide variety of clinical&#xD;
      severity exists, difficulties in social interactions are a core feature of ASD. These&#xD;
      difficulties are characterized by social perception abnormalities, manifested mainly through&#xD;
      abnormal eye contact. Such abnormalities have been largely confirmed in the last decade by&#xD;
      eye-tracking studies, which allow objective and quantitative investigation of gaze behaviour.&#xD;
      Studies with adults and children with ASD during visualization of social scene have shown a&#xD;
      lack of preference for socially relevant information, mainly faces and eyes.&#xD;
&#xD;
      In the typically developing brain, socially relevant information is processed within a&#xD;
      specific network, called the social brain. Functional MRI (fMRI) activation studies have&#xD;
      shown the implication of a key region of the social brain, namely the superior temporal&#xD;
      sulcus (STS), is in processing social information, ranging from the perception of eyes, faces&#xD;
      and voices to the more complex processes of social cognition. Over the last decades, brain&#xD;
      imaging studies investigating the neuro basis of ASD have consistently described anatomical&#xD;
      and functional abnormalities within the social brain, particularly within the STS Currently&#xD;
      there are important limitations in the therapeutic interventions available for ASD.&#xD;
      Pharmacological treatments are only indicated for psychiatric comorbidity and has no impact&#xD;
      on ASD core manifestations. Behavioural interventions, on the other hand, are generally&#xD;
      expensive, time-consuming and have modest results. In more recent years non-invasive&#xD;
      neuromodulation techniques, such as Transcranial Magnetic Stimulation (TMS), have raised hope&#xD;
      as effective tool to address ASD core manifestations. Indeed, modulating the neural activity&#xD;
      of STS with an impact on social perception opens new therapeutic perspectives in ASD. The&#xD;
      effect of TMS on social behaviour has been recently showed by a study from our lab. Following&#xD;
      an inhibition of the right STS by inhibitory TMS, healthy volunteers look less at the eyes of&#xD;
      the characters during the visualization of social scenes.&#xD;
&#xD;
      In this context, the main objective of this study is to investigate the effect of repetitive&#xD;
      session of TMS applied to the STS on social perception in patients with ASD. In addition, the&#xD;
      investigators aim to research the impact of putative changes in social perception in broader&#xD;
      social behaviour using clinical scales. Finally, the investigators aim to research putative&#xD;
      changes in brain functioning at rest by measuring rest cerebral blood flow using Arterial&#xD;
      Spin Labeling (ASL)-MRI before and after TMS. This is a double-blind, randomized,&#xD;
      placebo-controlled therapeutic trial, ultimately aiming to improve broader social behaviour.&#xD;
&#xD;
      For that purpose, the investigators will include in the present study 20 participants with&#xD;
      non-syndromic ASD aged from 18 to 25 years old. Social perception will be measured using an&#xD;
      eye-tracking during passive visualization of social stimuli. All patients will undergo an MRI&#xD;
      for neuronavigation purposes and to obtain rest cerebral blood flow measures using arterial&#xD;
      spin labelling MRI sequence, as well as clinical scales to evaluate their global social&#xD;
      behavior: clinical global impressions (CGI), &quot;évaluation des comportements autistiques&#xD;
      revise&quot; (ECA-R) and autism behavior checklist (ABC). The 20 patients will be automatically&#xD;
      randomized in the active TMS arm (n = 10), or in the placebo arm (n = 10). Patients will&#xD;
      undergo 10 sessions of TMS applied to the posterior part of the right superior STS, from&#xD;
      Monday to Friday for two consecutive weeks. Following the 10 sessions, evaluations will be&#xD;
      performed: 5 days, 1 month and 3 months after the end of the treatment.&#xD;
&#xD;
      The investigators expect that stimulation of the posterior part of the STS, a region shown to&#xD;
      be strongly implicated in processing social information, mainly from the eyes, would lead to&#xD;
      an increase in eye-gaze perception and thus promote access to social cues necessary for&#xD;
      adapted broader social behavior. If so, TMS could be further considered as an alternative&#xD;
      therapeutical intervention in ASD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 2, 2022</start_date>
  <completion_date type="Anticipated">October 2025</completion_date>
  <primary_completion_date type="Anticipated">May 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes gaze pattern to the eyes</measure>
    <time_frame>Until 3 months after iTBS sessions</time_frame>
    <description>Changes number of fixations to the eyes measured by eye-tracking during passive visualization of social scenes following the 10 iTBS sessions applied to the right pSTS compared to baseline measures.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Autistic Behavior Checklist (ABC) scale at v1</measure>
    <time_frame>5 days before iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autistic Behavior Checklist (ABC) scale at v2</measure>
    <time_frame>5 days after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autistic Behavior Checklist (ABC) scale at v3</measure>
    <time_frame>1 month after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autistic Behavior Checklist (ABC) scale at v4</measure>
    <time_frame>3 months after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>&quot;Evaluation des comportements Autistiques révisée&quot; (ECA-R) scale at v1</measure>
    <time_frame>5 days before iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>&quot;Evaluation des comportements Autistiques révisée&quot;(ECA-R) scale at v2</measure>
    <time_frame>5 days after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>&quot;Evaluation des comportements Autistiques révisée&quot; (ECA-R) scale at v3</measure>
    <time_frame>1 month after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>&quot;Evaluation des comportements Autistiques révisée&quot; (ECA-R) scale at v4</measure>
    <time_frame>3 months after iTBS sessions</time_frame>
    <description>Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI) scale at v1</measure>
    <time_frame>5 days before iTBS sessions</time_frame>
    <description>global functioning (Lower score = 1 Higher score mean worse outcome=16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI) scale at v2</measure>
    <time_frame>5 days after iTBS sessions</time_frame>
    <description>global functioning (Lower score = 1 Higher score mean worse outcome=16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI) scale at v3</measure>
    <time_frame>1 month after iTBS sessions</time_frame>
    <description>global functioning (Lower score = 1 Higher score mean worse outcome=16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression (CGI) scale at v4</measure>
    <time_frame>3 months after iTBS sessions</time_frame>
    <description>global functioning (Lower score = 1 Higher score mean worse outcome=16)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in rest brain fonctionning at v1</measure>
    <time_frame>5 days before iTBS sessions</time_frame>
    <description>by measuring whole brain cerebral blood flow at rest using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in rest brain fonctioning at v2</measure>
    <time_frame>5 days after iTBS sessions</time_frame>
    <description>by measuring whole brain cerebral blood flow at rest using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in rest brain fonctioning at v4</measure>
    <time_frame>3 months after iTBS sessions</time_frame>
    <description>by measuring whole brain cerebral blood flow at rest using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Putative changes on brain functional connectivity at rest at V1</measure>
    <time_frame>5 days before iTBS sessions</time_frame>
    <description>by using the resting state sequence using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Putative changes on brain functional connectivity at rest at V2</measure>
    <time_frame>5 days after iTBS sessions</time_frame>
    <description>by using the resting state sequence using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Putative changes on brain functional connectivity at V4</measure>
    <time_frame>3 months after iTBS sessions</time_frame>
    <description>by using the resting state sequence using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anatomical connectivity abnormalities</measure>
    <time_frame>At V1 : 5 days before iTBS sessions</time_frame>
    <description>by using the diffusion tensor imaging sequence (DTI) using MRI-ASL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDNF/COMT polymorphisms</measure>
    <time_frame>5 days after baseline</time_frame>
    <description>Research of BDNF/COMT polymorphisms on salivary samples</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Autism Spectrum Disorders</condition>
  <arm_group>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>excitatory TMS will be applied to the right posterior STS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The sham TMS follows the same procedure of the active TMS without stimulating cortical tissue</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial magnetic stimulation</intervention_name>
    <description>Before the stimulation, identification of a motor &quot;hotspot&quot; and active motor threshold (AMT) will be performed. The TMS will be applied on the intermittent theta-burst modality (iTBS), i. e., 2 s of TBS trains (30 pulses) repeated every 10 s for 190 s, with a total number of 600 pulses (Huang et al, 2005). The whole TMS session, including preparation, will last up to 1h.&#xD;
The sham TMS follows the same procedure of the active TMS without stimulating cortical tissue</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>Anatomical and functional images will be acquired and review by an experienced neuro-radiologist.</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neuronavigation</intervention_name>
    <description>The neuronavigation system will allow to guide the stimulation using the individual anatomical MRI acquired with MRI, and to record the position and orientation of the coil during successive stimulations</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Eye-tracking</intervention_name>
    <description>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</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Salivary samples</intervention_name>
    <description>The DNA will be extracted from the salivary sample to genotyping analyses on the BDNF (Val66Met) and COMT (Val158Met) polymorphism</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical scales</intervention_name>
    <description>CGI, E-CAR and ABC will be used for behavior and clinical evaluation</description>
    <arm_group_label>Active transcranial magnetic stimulation</arm_group_label>
    <arm_group_label>Sham transcranial magnetic stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male patient diagnosed with ASD according to DSM-V and ADI-R&#xD;
&#xD;
          -  Patient aged 18 to 25&#xD;
&#xD;
          -  Patient apt to undergo an MRI&#xD;
&#xD;
          -  Patient affiliated with a social security system or beneficiary of such system&#xD;
&#xD;
          -  Informed consent signed by the patient or his legal guardian.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Presence of a somatic pathology&#xD;
&#xD;
          -  Presence of a neurological pathology&#xD;
&#xD;
          -  Presence of epilepsy, history of seizure.&#xD;
&#xD;
          -  Taking neuroleptics or benzodiazepines treatment in the previous month&#xD;
&#xD;
          -  Contraindication to MRI (pacemaker, intracorporeal metallic foreign body, metal&#xD;
             worker)&#xD;
&#xD;
          -  Contraindication to the use of TMS (epilepsy and family epilepsy, presence of&#xD;
             craniotomy scar, pacemaker or pacemaker, intraocular or intracerebral metallic foreign&#xD;
             body, cochlear implant, cardiac valve or metallic surgical arterial material, metallic&#xD;
             material capable of concentrating radio frequency pulses)&#xD;
&#xD;
          -  Participation in another pilot study or clinical trial that does not allow&#xD;
             participation in this protocol.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Monica ZILBOVICIUS</last_name>
    <role>Study Chair</role>
    <affiliation>INSERM ERL &quot;Trajectoires Developpementales en Psychiatrie&quot;</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nathalie BODDAERT, MD, PhD</last_name>
    <phone>+33171396530</phone>
    <email>nathalie.boddaert@aphp.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Laure CHOUPEAUX, Master</last_name>
    <phone>+33144381711</phone>
    <email>laure.choupeaux@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hôpital Necker Enfants Malades - Service de radiologie pédiatrique</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie BODDAERT, MD, PhD</last_name>
      <phone>01.71.39.65.30</phone>
      <email>nathalie.boddaert@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>April 20, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>transcranial magnetic stimulation</keyword>
  <keyword>superior temporal sulcus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04442061
org study id: APHP191009
nct id: NCT04442061
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Difficulties in social interactions are the core feature of autism spectrum disorder (ASD)
      and are characterized by abnormal social perception, mainly concerning eye gaze.
      Anatomo-functional abnormalities within the superior temporal sulcus (STS), a key region of
      the social brain, have been described in ASD. The investigators had recently shown that it is
      possible to modulate the neural activity of the STS with transcranial magnetic stimulation
      (TMS) with an impact on social perception, measured by eye-tracking. In the context of ASD,
      stimulation of the STS with excitatory TMS could lead to an improvement in social perception,
      which would open up new therapeutic strategies. The purpose of this double-blind, randomized,
      placebo-controlled study is to apply a therapeutic TMS protocol (10 daily sessions) at the
      right STS in young adults with ASD to improve their social behavior, objectively measured
      using eye-tracking.
Autism Spectrum Disorders (ASD) are neuro-developmental disorders presumably related to
      neural circuit alterations. The symptoms, that start very early in development and persist
      through adulthood, can lead to severe handicap. Even though a wide variety of clinical
      severity exists, difficulties in social interactions are a core feature of ASD. These
      difficulties are characterized by social perception abnormalities, manifested mainly through
      abnormal eye contact. Such abnormalities have been largely confirmed in the last decade by
      eye-tracking studies, which allow objective and quantitative investigation of gaze behaviour.
      Studies with adults and children with ASD during visualization of social scene have shown a
      lack of preference for socially relevant information, mainly faces and eyes.

      In the typically developing brain, socially relevant information is processed within a
      specific network, called the social brain. Functional MRI (fMRI) activation studies have
      shown the implication of a key region of the social brain, namely the superior temporal
      sulcus (STS), is in processing social information, ranging from the perception of eyes, faces
      and voices to the more complex processes of social cognition. Over the last decades, brain
      imaging studies investigating the neuro basis of ASD have consistently described anatomical
      and functional abnormalities within the social brain, particularly within the STS Currently
      there are important limitations in the therapeutic interventions available for ASD.
      Pharmacological treatments are only indicated for psychiatric comorbidity and has no impact
      on ASD core manifestations. Behavioural interventions, on the other hand, are generally
      expensive, time-consuming and have modest results. In more recent years non-invasive
      neuromodulation techniques, such as Transcranial Magnetic Stimulation (TMS), have raised hope
      as effective tool to address ASD core manifestations. Indeed, modulating the neural activity
      of STS with an impact on social perception opens new therapeutic perspectives in ASD. The
      effect of TMS on social behaviour has been recently showed by a study from our lab. Following
      an inhibition of the right STS by inhibitory TMS, healthy volunteers look less at the eyes of
      the characters during the visualization of social scenes.

      In this context, the main objective of this study is to investigate the effect of repetitive
      session of TMS applied to the STS on social perception in patients with ASD. In addition, the
      investigators aim to research the impact of putative changes in social perception in broader
      social behaviour using clinical scales. Finally, the investigators aim to research putative
      changes in brain functioning at rest by measuring rest cerebral blood flow using Arterial
      Spin Labeling (ASL)-MRI before and after TMS. This is a double-blind, randomized,
      placebo-controlled therapeutic trial, ultimately aiming to improve broader social behaviour.

      For that purpose, the investigators will include in the present study 20 participants with
      non-syndromic ASD aged from 18 to 25 years old. Social perception will be measured using an
      eye-tracking during passive visualization of social stimuli. All patients will undergo an MRI
      for neuronavigation purposes and to obtain rest cerebral blood flow measures using arterial
      spin labelling MRI sequence, as well as clinical scales to evaluate their global social
      behavior: clinical global impressions (CGI), "évaluation des comportements autistiques
      revise" (ECA-R) and autism behavior checklist (ABC). The 20 patients will be automatically
      randomized in the active TMS arm (n = 10), or in the placebo arm (n = 10). Patients will
      undergo 10 sessions of TMS applied to the posterior part of the right superior STS, from
      Monday to Friday for two consecutive weeks. Following the 10 sessions, evaluations will be
      performed: 5 days, 1 month and 3 months after the end of the treatment.

      The investigators expect that stimulation of the posterior part of the STS, a region shown to
      be strongly implicated in processing social information, mainly from the eyes, would lead to
      an increase in eye-gaze perception and thus promote access to social cues necessary for
      adapted broader social behavior. If so, TMS could be further considered as an alternative
      therapeutical intervention in ASD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Changes gaze pattern to the eyes
time frame: Until 3 months after iTBS sessions
description: Changes number of fixations to the eyes measured by eye-tracking during passive visualization of social scenes following the 10 iTBS sessions applied to the right pSTS compared to baseline measures.
measure: Autistic Behavior Checklist (ABC) scale at v1
time frame: 5 days before iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)
measure: Autistic Behavior Checklist (ABC) scale at v2
time frame: 5 days after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)
measure: Autistic Behavior Checklist (ABC) scale at v3
time frame: 1 month after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)
measure: Autistic Behavior Checklist (ABC) scale at v4
time frame: 3 months after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 174)
measure: "Evaluation des comportements Autistiques révisée" (ECA-R) scale at v1
time frame: 5 days before iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)
measure: "Evaluation des comportements Autistiques révisée"(ECA-R) scale at v2
time frame: 5 days after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)
measure: "Evaluation des comportements Autistiques révisée" (ECA-R) scale at v3
time frame: 1 month after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)
measure: "Evaluation des comportements Autistiques révisée" (ECA-R) scale at v4
time frame: 3 months after iTBS sessions
description: Evaluate social behavior and autistic symptoms (Lower score = 0 Higher score mean worse outcome = 116)
measure: Clinical Global Impression (CGI) scale at v1
time frame: 5 days before iTBS sessions
description: global functioning (Lower score = 1 Higher score mean worse outcome=16)
measure: Clinical Global Impression (CGI) scale at v2
time frame: 5 days after iTBS sessions
description: global functioning (Lower score = 1 Higher score mean worse outcome=16)
measure: Clinical Global Impression (CGI) scale at v3
time frame: 1 month after iTBS sessions
description: global functioning (Lower score = 1 Higher score mean worse outcome=16)
measure: Clinical Global Impression (CGI) scale at v4
time frame: 3 months after iTBS sessions
description: global functioning (Lower score = 1 Higher score mean worse outcome=16)
measure: Changes in rest brain fonctionning at v1
time frame: 5 days before iTBS sessions
description: by measuring whole brain cerebral blood flow at rest using MRI-ASL
measure: Changes in rest brain fonctioning at v2
time frame: 5 days after iTBS sessions
description: by measuring whole brain cerebral blood flow at rest using MRI-ASL
measure: Changes in rest brain fonctioning at v4
time frame: 3 months after iTBS sessions
description: by measuring whole brain cerebral blood flow at rest using MRI-ASL
measure: Putative changes on brain functional connectivity at rest at V1
time frame: 5 days before iTBS sessions
description: by using the resting state sequence using MRI-ASL
measure: Putative changes on brain functional connectivity at rest at V2
time frame: 5 days after iTBS sessions
description: by using the resting state sequence using MRI-ASL
measure: Putative changes on brain functional connectivity at V4
time frame: 3 months after iTBS sessions
description: by using the resting state sequence using MRI-ASL
measure: Anatomical connectivity abnormalities
time frame: At V1 : 5 days before iTBS sessions
description: by using the diffusion tensor imaging sequence (DTI) using MRI-ASL
measure: BDNF/COMT polymorphisms
time frame: 5 days after baseline
description: Research of BDNF/COMT polymorphisms on salivary samples
arm group label: Active transcranial magnetic stimulation
arm group type: Active Comparator
description: excitatory TMS will be applied to the right posterior STS
arm group label: Sham transcranial magnetic stimulation
arm group type: Sham Comparator
description: The sham TMS follows the same procedure of the active TMS without stimulating cortical tissue
intervention type: Device
intervention name: Transcranial magnetic stimulation
description: Before the stimulation, identification of a motor "hotspot" and active motor threshold (AMT) will be performed. The TMS will be applied on the intermittent theta-burst modality (iTBS), i. e., 2 s of TBS trains (30 pulses) repeated every 10 s for 190 s, with a total number of 600 pulses (Huang et al, 2005). The whole TMS session, including preparation, will last up to 1h.
The sham TMS follows the same procedure of the active TMS without stimulating cortical tissue
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
intervention type: Device
intervention name: MRI
description: Anatomical and functional images will be acquired and review by an experienced neuro-radiologist.
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
intervention type: Device
intervention name: Neuronavigation
description: The neuronavigation system will allow to guide the stimulation using the individual anatomical MRI acquired with MRI, and to record the position and orientation of the coil during successive stimulations
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
intervention type: Device
intervention name: Eye-tracking
description: 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
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
intervention type: Genetic
intervention name: Salivary samples
description: The DNA will be extracted from the salivary sample to genotyping analyses on the BDNF (Val66Met) and COMT (Val158Met) polymorphism
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
intervention type: Other
intervention name: Clinical scales
description: CGI, E-CAR and ABC will be used for behavior and clinical evaluation
arm group label: Active transcranial magnetic stimulation
arm group label: Sham transcranial magnetic stimulation
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 25 Years
healthy volunteers: No
last name: Monica ZILBOVICIUS
role: Study Chair
affiliation: INSERM ERL "Trajectoires Developpementales en Psychiatrie"
last name: Nathalie BODDAERT, MD, PhD
phone: +33171396530
email: nathalie.boddaert@aphp.fr
last name: Laure CHOUPEAUX, Master
phone: +33144381711
email: laure.choupeaux@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
sharing ipd: No