<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/NCT02214511</url>
  </required_header>
  <id_info>
    <org_study_id>C13-31</org_study_id>
    <secondary_id>2013-A01484-41</secondary_id>
    <nct_id>NCT02214511</nct_id>
  </id_info>
  <brief_title>Biomarkers of Social Sensitivity in Major Depression</brief_title>
  <acronym>SENSO</acronym>
  <official_title>Etude de la sensibilité Aux Signaux Sociaux Dans la dépression, Modulateurs Psychologiques, Comportementaux et Inflammatoires.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Major depression disorder (MDD) is a frequent and disabling mental disorder with great risk&#xD;
      of recurrence and chronicity. Interpersonal factors are among the strongest predictors of the&#xD;
      course and duration of an episode of depression. More specifically, social rejection is one&#xD;
      of the most environmental risk factors of MDD. Targeted rejection predicts hastened onset of&#xD;
      major depression. On the other hand, healthy subject show prosocial behavior after social&#xD;
      rejection to reconnect to new source of social interaction. In addition to the potential&#xD;
      impact of social exclusion on MDD onset, depressed patients may be more prone to be rejected&#xD;
      as they encounter interpersonal difficulties and may less be able to reconnect to the social&#xD;
      group after rejection.&#xD;
&#xD;
      Recent neuroimaging data show that brain processing of social exclusion activate brain&#xD;
      regions that are central to the pathophysiology of MDD. Some of these regions are also known&#xD;
      to be activated during physical pain and may contribute to the aversive dimension of the&#xD;
      experienced rejection. Pro-inflammatory cytokines are involved in MDD physiopathology and can&#xD;
      induce social withdrawal behavior. Inflammation can modulate social interactions in mammals.&#xD;
      Moreover, after a social stress such as social rejection, blood cytokines increase. At a&#xD;
      cognitive level, self-esteem can modulate the sensitivity to social rejection.&#xD;
&#xD;
      The major objective of the trial is to study sensitivity to social signals in MDD patient&#xD;
      compared to healthy subject.&#xD;
&#xD;
      The investigators hypothesize in MDD patient : (1) decrease of rapid facial reactions (RFR)&#xD;
      to dynamic emotional faces expressing joy, (2) increase of RFR to dynamic emotional faces&#xD;
      expressing sadness, (3) decrease of prosocial reaction after experimental social rejection.&#xD;
&#xD;
      Secondary objective is to identify psychological and biological mediators We hypothetize in&#xD;
      MDD patient: (1)mediating effect of systemic inflammatory cytokines, an (2) mediating effect&#xD;
      of state self esteem 30 MDD patients and 60 healthy subject will be included. They will&#xD;
      encounter psychiatric and psychometric evaluation. Their facial EMG will be recorded to&#xD;
      assess RFR to dynamic emotional faces created by photo morphing from KDEF emotional faces&#xD;
      database, coupled to occulometric recording. Subjects will perform cyberball game as an&#xD;
      experimental inclusion or exclusion task and the trustgame task as an implicit evaluation of&#xD;
      their prosocial behavior. Questionnaires will assess explicit measurement of social rejection&#xD;
      pain and desire of affiliation. Inflammatory markers will be measured in a blood sample&#xD;
      before the cyberball task for every subjects and 6 hours later for 20 healthy volunteers.&#xD;
      Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin,&#xD;
      PECAM1, sTie2, sVEGFR1, sVEGFR2 will be performed by luminex technique and usCRP, srIL2 ans&#xD;
      sCD14 by ELISA technique.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 23, 2014</start_date>
  <completion_date type="Actual">March 1, 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Rapid facial reactions : milliVolts amplitude of electromyographic signal of zygomaticus, corrugator, depressor &amp; frontalis muscles</measure>
    <time_frame>During stimuli presentation (emotional faces) at Day 1 from 9:40 to 10:30 am</time_frame>
    <description>During passive watching of dynamic emotional faces, electromyographic signal is recorded with skin electrodes facing zygomaticus, corrugator, depressor &amp; frontalis muscles.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Implicit pro-social behavior : invested money during a 4-round trust game</measure>
    <time_frame>At Day 1 from 11:40 to 11:50 am</time_frame>
    <description>Total amount of money invested by the subject during a 4-round trust game without feedback.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Explicit pro-social behavior : affiliation desire measured by a questionnaire</measure>
    <time_frame>At Day 1 from 11:50 to 12:00 am</time_frame>
    <description>Affiliation desire questionnaire from Park and Manner assessing total affiliation desire and affiliation desire towards close relationship or strangers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Self esteem assessed by questionnaires mediates social pain after rejection and pro-social behavior</measure>
    <time_frame>2 assessments at Day 1 : at 8:30 and at 11:50 am</time_frame>
    <description>Scoring of questionnaires of state and trait self esteem (state self esteem scale and Rosenberg scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic inflammation mediates social pain after rejection and pro-social behavior</measure>
    <time_frame>At day 1 : at 11:30 am and 5:30 pm</time_frame>
    <description>Inflammatory dosage in blood :&#xD;
IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 by luminex technique&#xD;
usCRP, srIL2 ans sCD14 by ELISA technique.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>MDD patients</arm_group_label>
    <description>emotional facial stimuli cyberball game</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy subjects</arm_group_label>
    <description>emotional facial stimuli cyberball game</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>emotional facial stimuli</intervention_name>
    <description>Subjects watch passively dynamic facial emotions obtained by emotionnal faces photos morphing. Their rapid facial reactions are recorded by faciel EMG device as eye movement by occulometric device.</description>
    <arm_group_label>MDD patients</arm_group_label>
    <arm_group_label>healthy subjects</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cyberball game</intervention_name>
    <description>Ball tossing computer game to manipulate social inclusion status : rejection or inclusion. Social behavior, social pain and inflammatory modification will be assessed after the game.</description>
    <arm_group_label>MDD patients</arm_group_label>
    <arm_group_label>healthy subjects</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples to explore inflammatory cytokines. Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1,&#xD;
      MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 will be&#xD;
      performed by luminex technique and usCRP, srIL2 ans sCD14 by ELISA technique.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        1. st group : major depression disorder patients&#xD;
&#xD;
          2. nd group : healthy volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For everybody :&#xD;
&#xD;
          -  benefit social health insurance&#xD;
&#xD;
          -  french speaker and reader&#xD;
&#xD;
          -  can stop smoking one day&#xD;
&#xD;
          -  volunteer to participate&#xD;
&#xD;
        For 1st group :&#xD;
&#xD;
          -  actual MDD diagnosed by a psychiatrist and meet the DSM IV criterias of MDD&#xD;
&#xD;
          -  no antidepressant treatment or antidepressant treatment for less than 7 days.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI &gt; 40&#xD;
&#xD;
          -  weekly sport &gt; 3 hours&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  fever or other infection symptoms during the last month&#xD;
&#xD;
          -  significant or unstable disease, especially neurologic or inflammatory.&#xD;
&#xD;
          -  recent history of coronary disease, ulcer, COPD, severe dyslipemia, kidney or liver&#xD;
             failure.&#xD;
&#xD;
          -  severe smoking addiction (fagerström &gt; 8)&#xD;
&#xD;
          -  antiinflammatory or immunomodulatory treatment during last month&#xD;
&#xD;
        For 1st group :&#xD;
&#xD;
          -  no psychiatric treatment except benzodiazepin if no severe vigilance trouble and&#xD;
             antidepressant treatment more than 7 days&#xD;
&#xD;
          -  subjects under legal protection&#xD;
&#xD;
          -  constraint hospitalization&#xD;
&#xD;
          -  significant suicidal risk&#xD;
&#xD;
          -  resistant MDD&#xD;
&#xD;
          -  psychiatric comorbidity&#xD;
&#xD;
        For 2nd group :&#xD;
&#xD;
        - psychiatric disease, actual or past according to DSM IV criterias&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>ICM, Pitié Salpêtrière Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>August 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 12, 2014</study_first_posted>
  <last_update_submitted>August 27, 2021</last_update_submitted>
  <last_update_submitted_qc>August 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>major depressive disorder</keyword>
  <keyword>social rejection</keyword>
  <keyword>rapid facial reaction</keyword>
  <keyword>facial mimicry</keyword>
  <keyword>prosocial behavior</keyword>
  <keyword>inflammation</keyword>
  <keyword>self esteem</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <!-- 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/NCT02214511
org study id: C13-31
secondary id: 2013-A01484-41
nct id: NCT02214511
lead sponsor: 
has dmc: No
Major depression disorder (MDD) is a frequent and disabling mental disorder with great risk
      of recurrence and chronicity. Interpersonal factors are among the strongest predictors of the
      course and duration of an episode of depression. More specifically, social rejection is one
      of the most environmental risk factors of MDD. Targeted rejection predicts hastened onset of
      major depression. On the other hand, healthy subject show prosocial behavior after social
      rejection to reconnect to new source of social interaction. In addition to the potential
      impact of social exclusion on MDD onset, depressed patients may be more prone to be rejected
      as they encounter interpersonal difficulties and may less be able to reconnect to the social
      group after rejection.

      Recent neuroimaging data show that brain processing of social exclusion activate brain
      regions that are central to the pathophysiology of MDD. Some of these regions are also known
      to be activated during physical pain and may contribute to the aversive dimension of the
      experienced rejection. Pro-inflammatory cytokines are involved in MDD physiopathology and can
      induce social withdrawal behavior. Inflammation can modulate social interactions in mammals.
      Moreover, after a social stress such as social rejection, blood cytokines increase. At a
      cognitive level, self-esteem can modulate the sensitivity to social rejection.

      The major objective of the trial is to study sensitivity to social signals in MDD patient
      compared to healthy subject.

      The investigators hypothesize in MDD patient : (1) decrease of rapid facial reactions (RFR)
      to dynamic emotional faces expressing joy, (2) increase of RFR to dynamic emotional faces
      expressing sadness, (3) decrease of prosocial reaction after experimental social rejection.

      Secondary objective is to identify psychological and biological mediators We hypothetize in
      MDD patient: (1)mediating effect of systemic inflammatory cytokines, an (2) mediating effect
      of state self esteem 30 MDD patients and 60 healthy subject will be included. They will
      encounter psychiatric and psychometric evaluation. Their facial EMG will be recorded to
      assess RFR to dynamic emotional faces created by photo morphing from KDEF emotional faces
      database, coupled to occulometric recording. Subjects will perform cyberball game as an
      experimental inclusion or exclusion task and the trustgame task as an implicit evaluation of
      their prosocial behavior. Questionnaires will assess explicit measurement of social rejection
      pain and desire of affiliation. Inflammatory markers will be measured in a blood sample
      before the cyberball task for every subjects and 6 hours later for 20 healthy volunteers.
      Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin,
      PECAM1, sTie2, sVEGFR1, sVEGFR2 will be performed by luminex technique and usCRP, srIL2 ans
      sCD14 by ELISA technique.
observational model: Cohort
time perspective: Prospective
measure: Rapid facial reactions : milliVolts amplitude of electromyographic signal of zygomaticus, corrugator, depressor & frontalis muscles
time frame: During stimuli presentation (emotional faces) at Day 1 from 9:40 to 10:30 am
description: During passive watching of dynamic emotional faces, electromyographic signal is recorded with skin electrodes facing zygomaticus, corrugator, depressor & frontalis muscles.
measure: Implicit pro-social behavior : invested money during a 4-round trust game
time frame: At Day 1 from 11:40 to 11:50 am
description: Total amount of money invested by the subject during a 4-round trust game without feedback.
measure: Explicit pro-social behavior : affiliation desire measured by a questionnaire
time frame: At Day 1 from 11:50 to 12:00 am
description: Affiliation desire questionnaire from Park and Manner assessing total affiliation desire and affiliation desire towards close relationship or strangers.
measure: Self esteem assessed by questionnaires mediates social pain after rejection and pro-social behavior
time frame: 2 assessments at Day 1 : at 8:30 and at 11:50 am
description: Scoring of questionnaires of state and trait self esteem (state self esteem scale and Rosenberg scale)
measure: Systemic inflammation mediates social pain after rejection and pro-social behavior
time frame: At day 1 : at 11:30 am and 5:30 pm
description: Inflammatory dosage in blood :
IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 by luminex technique
usCRP, srIL2 ans sCD14 by ELISA technique.
arm group label: MDD patients
description: emotional facial stimuli cyberball game
arm group label: healthy subjects
description: emotional facial stimuli cyberball game
intervention type: Behavioral
intervention name: emotional facial stimuli
description: Subjects watch passively dynamic facial emotions obtained by emotionnal faces photos morphing. Their rapid facial reactions are recorded by faciel EMG device as eye movement by occulometric device.
arm group label: MDD patients
arm group label: healthy subjects
intervention type: Behavioral
intervention name: Cyberball game
description: Ball tossing computer game to manipulate social inclusion status : rejection or inclusion. Social behavior, social pain and inflammatory modification will be assessed after the game.
arm group label: MDD patients
arm group label: healthy subjects
Blood samples to explore inflammatory cytokines. Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1,
      MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 will be
      performed by luminex technique and usCRP, srIL2 ans sCD14 by ELISA technique.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: France
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major