<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/NCT04461327</url>
  </required_header>
  <id_info>
    <org_study_id>RECHMPL20_0157</org_study_id>
    <nct_id>NCT04461327</nct_id>
  </id_info>
  <brief_title>Psychophysiological Study of Pain Perception in Depressed Patients With Suicidal Risk</brief_title>
  <acronym>R2D2</acronym>
  <official_title>Psychophysiological Study of Pain Perception in Depressed Patients With Suicidal Risk</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinea psychiatrie France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</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>
      Joiner's interpersonal theory of suicide postulates that the wish of death comes from&#xD;
      feelings of perceived burdensomeness and thwarted belongingness. But, only people who have&#xD;
      acquired the capability to kill themselves will attempt suicide. The acquired capability&#xD;
      refers to a reduction of fear to death, and a higher pain tolerance. Indeed, to commit&#xD;
      suicide involves to endure pain during the act. Thus, higher pain tolerance seems to be a&#xD;
      necessary feature for suicidal act.&#xD;
&#xD;
      Past studies have shown higher pain threshold and tolerance in suicidal patients, whatever&#xD;
      the stimulus was (electric, thermic or mechanical), compared to patients without suicide&#xD;
      history. Moreover, Caceda and colleagues demonstrated higher pain threshold in recent suicide&#xD;
      attempters (suicidal act within 72h) compared with depressed patients. Five days after the&#xD;
      initial evaluation, pain threshold of recent suicide attempters decreased to be similar to&#xD;
      depressed patients with suicidal ideation. Therefore, it may exist a specific state during&#xD;
      which the pain tolerance is increased. During this &quot;hypoalgesic state&quot; patients with suicidal&#xD;
      ideation could attempt suicide to get relief from suffering.&#xD;
&#xD;
      However, little is known about the specific mechanisms that are responsible for the higher&#xD;
      pain threshold and tolerance in suicide attempters. Pain is a dynamic system that results&#xD;
      from excitatory and inhibitory messages. The modification of one of these mechanisms could&#xD;
      explain the higher tolerance in recent suicide attempters. Three of them are of particular&#xD;
      interest:&#xD;
&#xD;
        1. The conditioned pain modulation (CPM) is a modulatory pain mechanism. CPM works through&#xD;
           descending pathway that reaches the spinal cord and modulates pain processing from the&#xD;
           first nociceptive synapse.In recent suicidal patients, an increase of the CPM could&#xD;
           explain higher pain tolerance.&#xD;
&#xD;
        2. The &quot;wind-up&quot; mechanism is defined as the highest excitability of the second order&#xD;
           nerve. Even if the stimulus remains stable, pain continuously raises. In recent suicide&#xD;
           attempters, a reduction of this mechanism could explain higher pain tolerance.&#xD;
&#xD;
        3. The threshold of Aδ and C nociceptors. If a nociceptive fiber is less excitable than the&#xD;
           other, it would explain higher pain threshold.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim: The first objective of this project is to test different pain mechanisms that could be&#xD;
      involved in the increase of pain thresholds and tolerance in suicidal patients. The second&#xD;
      objective is to test whether there's a loss of pleasantness during social touch in suicidal&#xD;
      patients.&#xD;
&#xD;
      The main aim is to compare the efficacity of CPM between three groups of depressed patients:&#xD;
      recent or former suicide attempters and non-attempters. The secondary aims are 1) to compare&#xD;
      the wind-up mechanism between groups, 2) to compare the difference of excitability of Aδ and&#xD;
      C fibers between groups, 3) to correlate these physiological results to clinical variables&#xD;
      (emotional reactivity and emotional regulation, dissociation and body perception), and 4) to&#xD;
      compare the pleasantness associated with social touch between groups.&#xD;
&#xD;
      Target population: 153 depressed women will be enrolled and divided into three groups. I)&#xD;
      Women having recently attempted suicide (less than 72 hours) - II) women having a past&#xD;
      suicide attempt (more than 72 hours) - III) Women without lifetime history of suicidal&#xD;
      behaviour (affective control group).&#xD;
&#xD;
      Materials: The heat test stimuli are performed by a thermode (TCS II, QST Lab) which produces&#xD;
      ramping heat pulses from 32°C to 52°C. For the conditioning stimulus (cold pressor task),&#xD;
      participants will insert their arm (up to the elbow) in circulating cold water (8°C). Pain&#xD;
      intensity is rated by a CoVAS (computer visual analog scale). This scale is similar to a&#xD;
      classic visual analog scale (VAS) ranging from &quot;no pain&quot; to the &quot;most intense pain&#xD;
      tolerable&quot;. The participant has just to move a cursor, thanks to the computer mouse. The&#xD;
      stroking is performed thanks to a Natural hair Blush Brush (No. 7, The Boots Company).&#xD;
&#xD;
      Clinical assessment: A clinical assessment will be made by a trained researcher. This&#xD;
      assessment will evaluate psychiatric diagnosis by the DSM-V (Diagnostic and Statistical&#xD;
      Manual of Mental Disorders), the severity of depression by the IDS-C30 (Inventory of&#xD;
      Depressive Symptomatology), the intensity of suicidal thoughts by the CSSRS (Columbia Suicide&#xD;
      Severity Rating Scale), and the suicidal life history by the RRRS (Risk-Rescue Rating Scale)&#xD;
      and SIS (Suicidal Intent Scales). It will also gather information about socio-demographic&#xD;
      variables, the number of depressed episodes, the number of psychiatric hospitalizations, the&#xD;
      hormonal status, and the current medications. All psychotropics medications taken by the&#xD;
      patient will be collected for the last 72 hours, as well as the dose and the date of the&#xD;
      beginning of the treatment. The patients will also have to complete some self-report measures&#xD;
      about the severity of their depression (BDI-II), their level of anxiety (STAI), their&#xD;
      physical and psychological pain (EVA current and past), their childhood trauma (CTQ), their&#xD;
      emotional state (PANAS), their difficulty in emotional regulation (DERS), their emotional&#xD;
      reactivity (ERS), their body perception (BIS), their dissociative experiences, their&#xD;
      borderline symptomatology (BSL-23) and the kind of non-suicidal self-injuries practiced&#xD;
      (SHI).&#xD;
&#xD;
      Blood tests: The blood test is made between 2 and 24 hours before the experimental procedure.&#xD;
      The biological collection is made to measure medications' concentration if the patient takes&#xD;
      antiepileptics and/or lithium, and to measure complete blood count (CBC).&#xD;
&#xD;
      Experimental design: All three pain mechanisms and social touch will be tested in one session&#xD;
      lasting 1h approximately.&#xD;
&#xD;
        1. To distinguish the threshold of Aδ and C, a thermal stimulus will be used to provoke&#xD;
           painful and non-painful sensations (Thermode QST lab). Successive and alternate phases&#xD;
           of painful (hot) and non-painful (warm) stimulations will be used. The warm phase will&#xD;
           remain stable at 38°C for 5 seconds whereas the hot phase will consist of ascending heat&#xD;
           pulses from 39°C to 52°C for 1 second each. At every phase, the participant will be&#xD;
           asked if she feels pain or not to determine the pain threshold. The Aδ fiber threshold&#xD;
           will be the first time when the participant will report pain during the hot phase. The C&#xD;
           fiber threshold will be the first time when the participant will report pain during the&#xD;
           warm phase. These measures will be repeated five times.&#xD;
&#xD;
        2. Wind-up and CPM will be evaluated successively in three steps:&#xD;
&#xD;
             1. To measure the activity of the wind-up, a constant temperature (individually&#xD;
                determined) will be applied during 2 minutes on the left forearm (stimulus test).&#xD;
                This temperature will correspond to a painful sensation of 40/100 on the CoVAS for&#xD;
                each patient previously evaluated. During the test, the participant will report the&#xD;
                intensity of pain on the CoVAS in a continuous manner. The patient will move the&#xD;
                cursor along the continuous line to indicate the pain she feels and every change.&#xD;
&#xD;
             2. The CPM activation will be produced by a counter nociceptive stimulation (cold&#xD;
                pressor task). The right forearm of the participant will be placed during 2 minutes&#xD;
                in a cold water maintained at 8°C (conditioning stimulus).&#xD;
&#xD;
             3. To measure the efficiency of the CPM, the hot constant temperature (corresponding&#xD;
                to CoVAS= 40/100) will be re-applied, during 2 minutes on the left forearm&#xD;
                (conditioned stimulus). As previously, participant will report her pain on the&#xD;
                CoVAS.&#xD;
&#xD;
      Before and after the painful tests, the participant will have to complete two self-report&#xD;
      measures. The PANAS to evaluate their emotional state and the STAI state to evaluate their&#xD;
      anxiety.&#xD;
&#xD;
      In a final step, the pleasure associated with social touch will be tested. The experimenter&#xD;
      stroked the participant's marked skin areas for 70 seconds with a soft brush in either&#xD;
      CT-optimal speed (3 cm/s; slow touch group associated with pleasantness) or non-CT-optimal&#xD;
      speed (18 cm/s; fast touch group associated with a neutral feeling). The pleasure associated&#xD;
      with the stroke is then assessed on a 10-point Likert scale (from really unpleasant to really&#xD;
      pleasant). In this within design, the reaped measures (slow touch vs fast touch) will be&#xD;
      counterbalanced between participants.&#xD;
&#xD;
      Pairing: A pairing will be made on age and antidepressant class (none, selective serotonin&#xD;
      reuptake inhibitor (SSRI), Serotonin-norepinephrine reuptake inhibitor (SNRI), tricyclic,&#xD;
      others). For each category of antidepressant, a 1 will be attributed if the patient takes one&#xD;
      medication of this category and a 0 if not. In each group, the sum of every classes of&#xD;
      medication will have to be equal. As a reminder, class of antidepressant are exclusive&#xD;
      between them.&#xD;
&#xD;
      Medical load: To control medication, a medication load index will be calculated as described&#xD;
      in Olié and al., 2018. Antiepileptics and lithium medications will be dosed in plasma.&#xD;
&#xD;
      There is an ancillary study associate with this project, ID RCB : 2023-A00213-42. His main&#xD;
      objective is to evaluate the rested functional connectivity between saliency's network areas&#xD;
      associated to pain sensitivity in patient presenting a characterized depressive episode, with&#xD;
      or without Suicide Attempt on his entire life. 50 patients are concerned. This study is&#xD;
      charaterized by a third visit during which a MRI is done.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 25, 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Painful stimulations (see detailed description)</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effectiveness of the conditioned pain modulation</measure>
    <time_frame>During painful stimulations which are assessed 24 hours after the inclusion</time_frame>
    <description>The criterion will be the average difference of perceived pain (CoVAS measure) before and after modulation, i.e. before and after the cold pressor task.&#xD;
It's postulated that recent suicidal patients will have a higher efficacity of CPM than past suicidal patients and depressed affective controls.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of the Wind-up mechanism</measure>
    <time_frame>During painful stimulations which are assessed 24 hours after the inclusion</time_frame>
    <description>The criterion will be the slope of the progressive rise of the painful sensation (CoVAS measure).&#xD;
It's postulated that recent suicidal patients will have a weaker wind-up mechanism than in the two other groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aδ and C fibers thresholds</measure>
    <time_frame>During painful stimulations which are assessed 24 hours after the inclusion</time_frame>
    <description>The criterion will be the first temperature for which the participant perceived pain for each fiber.&#xD;
It's postulated that recent suicidal patients will have a higher threshold for Aδ or C fiber than in the two other groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pleasantness associated with social touch</measure>
    <time_frame>During painful stimulations which are assessed 24 hours after the inclusion</time_frame>
    <description>The criterion will be the score on the Likert scale. It's postulated that recent suicidal patients will have a lower score than the 2 other groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Reactivity Score</measure>
    <time_frame>At inclusion</time_frame>
    <description>The score ranges from 0 to 84. A higher score indicates an elevated emotional reactivity. It's postulated that this score will be correlated with the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Regulation Score</measure>
    <time_frame>At inclusion</time_frame>
    <description>The score ranges from 36 to 180. A higher score indicates more difficulties to regulate her emotions. It's postulated that this score will be correlated with the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dissociative experiences score</measure>
    <time_frame>At inclusion</time_frame>
    <description>The score ranges from 0 to 100. A higher score indicates a higher frequency of dissociative experiences. It's postulated that this score will be correlated with the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body investment score</measure>
    <time_frame>At inclusion</time_frame>
    <description>The score ranges from 24 to 120. A higher score indicates more investment toward the body. It's postulated that this score will be correlated with the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acquired Capability of Suicide Scale</measure>
    <time_frame>At inclusion</time_frame>
    <description>The score ranges from 0 to 80. This scale mainly assess the fearlessness about death, about dying and a general component of fearlessness. A higher score indicates fearlessness. It's postulated that this score will be correlated with the primary outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional connectivity in saliency's network (ID-RCB :2023-A00213-42)</measure>
    <time_frame>During an IRM which is assessed 8 days after visite 1 or after inclusion until 24 months.</time_frame>
    <description>The functional connectivity will be represent by ALFF (Amplitude of Low Frenquency Fluctuations) and ReHo (RegionalHomogeneity) measures</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">153</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Major Depressive patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 groups:&#xD;
Women having recently attempted suicide (less than 72 hours).&#xD;
Women having a past suicide attempt (more than 72 hours).&#xD;
Women without lifetime history of suicidal behaviour.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Painful stimulations of major depressive patients</intervention_name>
    <description>All three pain mechanisms will be tested in one session lasting 1h approximately.&#xD;
The mechanisms are tested in the following order:&#xD;
Aδ and C threshold&#xD;
Wind-up&#xD;
CPM&#xD;
(more details in detailed description)</description>
    <arm_group_label>Major Depressive patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>The blood test is made between 2 and 24 hours before the experimental procedure. The biological collection is made to measure medications' concentration if the patient takes antiepileptics and/or lithium, and to measure complete blood count (CBC).</description>
    <arm_group_label>Major Depressive patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Clinical assessment</intervention_name>
    <description>A clinical assessment will be made by a trained researcher.&#xD;
(more details in detailed description)</description>
    <arm_group_label>Major Depressive patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Social touch</intervention_name>
    <description>Stroking</description>
    <arm_group_label>Major Depressive patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for all patients:&#xD;
&#xD;
          -  Woman;&#xD;
&#xD;
          -  Being aged between 18 and 65 years;&#xD;
&#xD;
          -  Currently meeting the DSM-5 major depressive episode criteria;&#xD;
&#xD;
          -  Being able to understand the nature, purpose and methodology of the study and agreeing&#xD;
             to cooperate during the assessments;&#xD;
&#xD;
          -  Having signed informed consent;&#xD;
&#xD;
          -  Being affiliated with a social security or equivalent.&#xD;
&#xD;
        Inclusion Criteria specific to each group:&#xD;
&#xD;
          -  Recent attempters: women having recently attempted suicide (less than 72 hours)&#xD;
&#xD;
          -  Past attempters: women having a past suicide attempt (more than 72 hours)&#xD;
&#xD;
          -  Affective control: women without lifetime history of suicidal behaviour (affective&#xD;
             control group).&#xD;
&#xD;
        Exclusion Criteria for all patients:&#xD;
&#xD;
          -  Existence of current psychotic or mixed characteristics;&#xD;
&#xD;
          -  Lifetime history of schizoaffective disorder or schizophrenia;&#xD;
&#xD;
          -  Current substance dependence (within the last 6 months);&#xD;
&#xD;
          -  Existence of mental retardation or serious medical comorbidity interfering with&#xD;
             measures (HIV, diabetes, cancer, chronic inflammatory pathology, neurological&#xD;
             disorder);&#xD;
&#xD;
          -  Having taken painkillers within the last 24 hours preceding the evaluation;&#xD;
&#xD;
          -  Existence of a usual or current treatment with analgesics or NSAIDs (daily analgesic&#xD;
             treatment more than 3 months);&#xD;
&#xD;
          -  Existence of a sensory or cognitive handicap;&#xD;
&#xD;
          -  Pregnant or lactating woman.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emilie Olie, MD-PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emilie Olie, MD-PhD</last_name>
    <phone>467338581</phone>
    <phone_ext>+33</phone_ext>
    <email>e-olie@chu-montpellier.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Nathan Risch, PhD Student</last_name>
    <email>risch.nathan@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital of Montpellier</name>
      <address>
        <city>Montpellier</city>
        <state>Occitanie</state>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathan RISCH</last_name>
      <email>risch.nathan@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clinic La Lironde</name>
      <address>
        <city>Saint Gély du Fesc</city>
        <state>Occitanie</state>
        <zip>34981</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Charlotte MULLE</last_name>
    </contact>
    <contact_backup>
      <last_name>Nathan RISCH</last_name>
      <email>risch.nathan@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>March 27, 2023</last_update_submitted>
  <last_update_submitted_qc>March 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pain</keyword>
  <keyword>Pain modulation</keyword>
  <keyword>Suicide</keyword>
  <keyword>Affective touch</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT04461327
org study id: RECHMPL20_0157
nct id: NCT04461327
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Joiner's interpersonal theory of suicide postulates that the wish of death comes from
      feelings of perceived burdensomeness and thwarted belongingness. But, only people who have
      acquired the capability to kill themselves will attempt suicide. The acquired capability
      refers to a reduction of fear to death, and a higher pain tolerance. Indeed, to commit
      suicide involves to endure pain during the act. Thus, higher pain tolerance seems to be a
      necessary feature for suicidal act.

      Past studies have shown higher pain threshold and tolerance in suicidal patients, whatever
      the stimulus was (electric, thermic or mechanical), compared to patients without suicide
      history. Moreover, Caceda and colleagues demonstrated higher pain threshold in recent suicide
      attempters (suicidal act within 72h) compared with depressed patients. Five days after the
      initial evaluation, pain threshold of recent suicide attempters decreased to be similar to
      depressed patients with suicidal ideation. Therefore, it may exist a specific state during
      which the pain tolerance is increased. During this "hypoalgesic state" patients with suicidal
      ideation could attempt suicide to get relief from suffering.

      However, little is known about the specific mechanisms that are responsible for the higher
      pain threshold and tolerance in suicide attempters. Pain is a dynamic system that results
      from excitatory and inhibitory messages. The modification of one of these mechanisms could
      explain the higher tolerance in recent suicide attempters. Three of them are of particular
      interest:

        1. The conditioned pain modulation (CPM) is a modulatory pain mechanism. CPM works through
           descending pathway that reaches the spinal cord and modulates pain processing from the
           first nociceptive synapse.In recent suicidal patients, an increase of the CPM could
           explain higher pain tolerance.

        2. The "wind-up" mechanism is defined as the highest excitability of the second order
           nerve. Even if the stimulus remains stable, pain continuously raises. In recent suicide
           attempters, a reduction of this mechanism could explain higher pain tolerance.

        3. The threshold of Aδ and C nociceptors. If a nociceptive fiber is less excitable than the
           other, it would explain higher pain threshold.
Aim: The first objective of this project is to test different pain mechanisms that could be
      involved in the increase of pain thresholds and tolerance in suicidal patients. The second
      objective is to test whether there's a loss of pleasantness during social touch in suicidal
      patients.

      The main aim is to compare the efficacity of CPM between three groups of depressed patients:
      recent or former suicide attempters and non-attempters. The secondary aims are 1) to compare
      the wind-up mechanism between groups, 2) to compare the difference of excitability of Aδ and
      C fibers between groups, 3) to correlate these physiological results to clinical variables
      (emotional reactivity and emotional regulation, dissociation and body perception), and 4) to
      compare the pleasantness associated with social touch between groups.

      Target population: 153 depressed women will be enrolled and divided into three groups. I)
      Women having recently attempted suicide (less than 72 hours) - II) women having a past
      suicide attempt (more than 72 hours) - III) Women without lifetime history of suicidal
      behaviour (affective control group).

      Materials: The heat test stimuli are performed by a thermode (TCS II, QST Lab) which produces
      ramping heat pulses from 32°C to 52°C. For the conditioning stimulus (cold pressor task),
      participants will insert their arm (up to the elbow) in circulating cold water (8°C). Pain
      intensity is rated by a CoVAS (computer visual analog scale). This scale is similar to a
      classic visual analog scale (VAS) ranging from "no pain" to the "most intense pain
      tolerable". The participant has just to move a cursor, thanks to the computer mouse. The
      stroking is performed thanks to a Natural hair Blush Brush (No. 7, The Boots Company).

      Clinical assessment: A clinical assessment will be made by a trained researcher. This
      assessment will evaluate psychiatric diagnosis by the DSM-V (Diagnostic and Statistical
      Manual of Mental Disorders), the severity of depression by the IDS-C30 (Inventory of
      Depressive Symptomatology), the intensity of suicidal thoughts by the CSSRS (Columbia Suicide
      Severity Rating Scale), and the suicidal life history by the RRRS (Risk-Rescue Rating Scale)
      and SIS (Suicidal Intent Scales). It will also gather information about socio-demographic
      variables, the number of depressed episodes, the number of psychiatric hospitalizations, the
      hormonal status, and the current medications. All psychotropics medications taken by the
      patient will be collected for the last 72 hours, as well as the dose and the date of the
      beginning of the treatment. The patients will also have to complete some self-report measures
      about the severity of their depression (BDI-II), their level of anxiety (STAI), their
      physical and psychological pain (EVA current and past), their childhood trauma (CTQ), their
      emotional state (PANAS), their difficulty in emotional regulation (DERS), their emotional
      reactivity (ERS), their body perception (BIS), their dissociative experiences, their
      borderline symptomatology (BSL-23) and the kind of non-suicidal self-injuries practiced
      (SHI).

      Blood tests: The blood test is made between 2 and 24 hours before the experimental procedure.
      The biological collection is made to measure medications' concentration if the patient takes
      antiepileptics and/or lithium, and to measure complete blood count (CBC).

      Experimental design: All three pain mechanisms and social touch will be tested in one session
      lasting 1h approximately.

        1. To distinguish the threshold of Aδ and C, a thermal stimulus will be used to provoke
           painful and non-painful sensations (Thermode QST lab). Successive and alternate phases
           of painful (hot) and non-painful (warm) stimulations will be used. The warm phase will
           remain stable at 38°C for 5 seconds whereas the hot phase will consist of ascending heat
           pulses from 39°C to 52°C for 1 second each. At every phase, the participant will be
           asked if she feels pain or not to determine the pain threshold. The Aδ fiber threshold
           will be the first time when the participant will report pain during the hot phase. The C
           fiber threshold will be the first time when the participant will report pain during the
           warm phase. These measures will be repeated five times.

        2. Wind-up and CPM will be evaluated successively in three steps:

             1. To measure the activity of the wind-up, a constant temperature (individually
                determined) will be applied during 2 minutes on the left forearm (stimulus test).
                This temperature will correspond to a painful sensation of 40/100 on the CoVAS for
                each patient previously evaluated. During the test, the participant will report the
                intensity of pain on the CoVAS in a continuous manner. The patient will move the
                cursor along the continuous line to indicate the pain she feels and every change.

             2. The CPM activation will be produced by a counter nociceptive stimulation (cold
                pressor task). The right forearm of the participant will be placed during 2 minutes
                in a cold water maintained at 8°C (conditioning stimulus).

             3. To measure the efficiency of the CPM, the hot constant temperature (corresponding
                to CoVAS= 40/100) will be re-applied, during 2 minutes on the left forearm
                (conditioned stimulus). As previously, participant will report her pain on the
                CoVAS.

      Before and after the painful tests, the participant will have to complete two self-report
      measures. The PANAS to evaluate their emotional state and the STAI state to evaluate their
      anxiety.

      In a final step, the pleasure associated with social touch will be tested. The experimenter
      stroked the participant's marked skin areas for 70 seconds with a soft brush in either
      CT-optimal speed (3 cm/s; slow touch group associated with pleasantness) or non-CT-optimal
      speed (18 cm/s; fast touch group associated with a neutral feeling). The pleasure associated
      with the stroke is then assessed on a 10-point Likert scale (from really unpleasant to really
      pleasant). In this within design, the reaped measures (slow touch vs fast touch) will be
      counterbalanced between participants.

      Pairing: A pairing will be made on age and antidepressant class (none, selective serotonin
      reuptake inhibitor (SSRI), Serotonin-norepinephrine reuptake inhibitor (SNRI), tricyclic,
      others). For each category of antidepressant, a 1 will be attributed if the patient takes one
      medication of this category and a 0 if not. In each group, the sum of every classes of
      medication will have to be equal. As a reminder, class of antidepressant are exclusive
      between them.

      Medical load: To control medication, a medication load index will be calculated as described
      in Olié and al., 2018. Antiepileptics and lithium medications will be dosed in plasma.

      There is an ancillary study associate with this project, ID RCB : 2023-A00213-42. His main
      objective is to evaluate the rested functional connectivity between saliency's network areas
      associated to pain sensitivity in patient presenting a characterized depressive episode, with
      or without Suicide Attempt on his entire life. 50 patients are concerned. This study is
      charaterized by a third visit during which a MRI is done.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Painful stimulations (see detailed description)
primary purpose: Basic Science
masking: None (Open Label)
measure: Effectiveness of the conditioned pain modulation
time frame: During painful stimulations which are assessed 24 hours after the inclusion
description: The criterion will be the average difference of perceived pain (CoVAS measure) before and after modulation, i.e. before and after the cold pressor task.
It's postulated that recent suicidal patients will have a higher efficacity of CPM than past suicidal patients and depressed affective controls.
measure: Effectiveness of the Wind-up mechanism
time frame: During painful stimulations which are assessed 24 hours after the inclusion
description: The criterion will be the slope of the progressive rise of the painful sensation (CoVAS measure).
It's postulated that recent suicidal patients will have a weaker wind-up mechanism than in the two other groups.
measure: Aδ and C fibers thresholds
time frame: During painful stimulations which are assessed 24 hours after the inclusion
description: The criterion will be the first temperature for which the participant perceived pain for each fiber.
It's postulated that recent suicidal patients will have a higher threshold for Aδ or C fiber than in the two other groups.
measure: Pleasantness associated with social touch
time frame: During painful stimulations which are assessed 24 hours after the inclusion
description: The criterion will be the score on the Likert scale. It's postulated that recent suicidal patients will have a lower score than the 2 other groups.
measure: Emotional Reactivity Score
time frame: At inclusion
description: The score ranges from 0 to 84. A higher score indicates an elevated emotional reactivity. It's postulated that this score will be correlated with the primary outcome.
measure: Emotional Regulation Score
time frame: At inclusion
description: The score ranges from 36 to 180. A higher score indicates more difficulties to regulate her emotions. It's postulated that this score will be correlated with the primary outcome.
measure: Dissociative experiences score
time frame: At inclusion
description: The score ranges from 0 to 100. A higher score indicates a higher frequency of dissociative experiences. It's postulated that this score will be correlated with the primary outcome.
measure: Body investment score
time frame: At inclusion
description: The score ranges from 24 to 120. A higher score indicates more investment toward the body. It's postulated that this score will be correlated with the primary outcome.
measure: Acquired Capability of Suicide Scale
time frame: At inclusion
description: The score ranges from 0 to 80. This scale mainly assess the fearlessness about death, about dying and a general component of fearlessness. A higher score indicates fearlessness. It's postulated that this score will be correlated with the primary outcome.
measure: Functional connectivity in saliency's network (ID-RCB :2023-A00213-42)
time frame: During an IRM which is assessed 8 days after visite 1 or after inclusion until 24 months.
description: The functional connectivity will be represent by ALFF (Amplitude of Low Frenquency Fluctuations) and ReHo (RegionalHomogeneity) measures
arm group label: Major Depressive patients
arm group type: Experimental
description: 3 groups:
Women having recently attempted suicide (less than 72 hours).
Women having a past suicide attempt (more than 72 hours).
Women without lifetime history of suicidal behaviour.
intervention type: Behavioral
intervention name: Painful stimulations of major depressive patients
description: All three pain mechanisms will be tested in one session lasting 1h approximately.
The mechanisms are tested in the following order:
Aδ and C threshold
Wind-up
CPM
(more details in detailed description)
arm group label: Major Depressive patients
intervention type: Biological
intervention name: Blood sample
description: The blood test is made between 2 and 24 hours before the experimental procedure. The biological collection is made to measure medications' concentration if the patient takes antiepileptics and/or lithium, and to measure complete blood count (CBC).
arm group label: Major Depressive patients
intervention type: Diagnostic Test
intervention name: Clinical assessment
description: A clinical assessment will be made by a trained researcher.
(more details in detailed description)
arm group label: Major Depressive patients
intervention type: Behavioral
intervention name: Social touch
description: Stroking
arm group label: Major Depressive patients
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Emilie Olie, MD-PhD
role: Principal Investigator
affiliation: University Hospital, Montpellier
last name: Emilie Olie, MD-PhD
phone: 467338581
phone ext: +33
email: e-olie@chu-montpellier.fr
last name: Nathan Risch, PhD Student
email: risch.nathan@gmail.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: France
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major