xml: <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/NCT05964192</url>
    </required_header>
    <id_info>
      <org_study_id>2023-A00288-37</org_study_id>
      <nct_id>NCT05964192</nct_id>
    </id_info>
    <brief_title>Added Value of a Neuroendocrine Test Battery in the Response to Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment</brief_title>
    <acronym>Endo-rTMS</acronym>
    <official_title>Added Value of a Neuroendocrine Test Battery in the Response to Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment : a Pilot Study in Major Depression (Endo-rTMS)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Centre Hospitalier Rouffach</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Centre Hospitalier Rouffach</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The primary objective of the study is to determine the predictive value of the neuroendocrine&#xD;
        tests TRH-∆∆TSH (thyreoliberin - thyreostimulin) and DST (dexamethasone suppression test) in&#xD;
        the subsequent response to rTMS-TBS (repetitive transcranial magnetic stimulation-theta burst&#xD;
        stimulation) treatment, defined as at least a 50% decrease in depression score after 20&#xD;
        sessions of rTMS-TBS.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Conduct of research :&#xD;
  &#xD;
        This is a monocentric, non-randomized, open-label pilot study involving 50 male and female&#xD;
        patients aged 18 to 65, hospitalized for major depression and presenting with an indication&#xD;
        for treatment with repeated theta-burst transcranial magnetic stimulation (rTMS-TBS), i.e. a&#xD;
        situation of therapeutic failure following 2 well-conducted antidepressant treatments.&#xD;
  &#xD;
        At the end of the 20 rTMS-TBS sessions (one session per day, except weekends), the clinical&#xD;
        response will be assessed by an investigator &quot;blind&quot; to the endocrine results. This response&#xD;
        will be analyzed according to the status of neuroendocrine tests at inclusion (TRH-∆∆TSH and&#xD;
        DST) and at the end of the study (for those who had one or more abnormal tests at inclusion&#xD;
        and in whom the same tests were repeated at the end of the rTMS-TBS sessions).&#xD;
  &#xD;
        During the inclusion visit, the patient and investigator sign the consent form, after&#xD;
        double-checking the inclusion and non-inclusion criteria.&#xD;
  &#xD;
        Immediately after the tenth rTMS session, an assessment of depression using the HAMD (17-item&#xD;
        Hamilton Depression Scale) scale will be carried out by an independent psychiatrist, blind to&#xD;
        the results of the neuroendocrine tests. This psychiatrist, who has already administered the&#xD;
        HAMD at V0, will repeat the assessments at V1 and V2.&#xD;
  &#xD;
        Immediately after the twentieth rTMS session, an assessment of depression using the HAMD&#xD;
        scale will be carried out by an independent psychiatrist. This assessment will determine&#xD;
        responder/non-responder status to rTMS-TBS.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2029</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2028</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>17-item Hamilton Depression Scale (HAMD)</measure>
      <time_frame>Change from inclusion result at 6 weeks (after 20 rTMS-TBS sessions)</time_frame>
      <description>Clinical response will be defined by at least a 50% decrease in depression score at the end of the 20 rTMS-TBS sessions - measured by the 17-item Hamilton Depression Scale (HAMD) - compared to inclusion (Carrozzino et al, 2020). The predictive value of the TRH-∆∆TSH on the one hand, and the DST on the other, will be assessed using an ROC curve and its AUC (Area Under the Curve) calculation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Hamilton Depression Scale (HAMD)</measure>
      <time_frame>Through study completion, an average of 6 weeks</time_frame>
      <description>Functional remission will be defined by a HAMD score ≤ 8 at the end of 20 sessions of rTMS-TBS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evolution of neuroendocrine parameters</measure>
      <time_frame>Through study completion, an average of 6 weeks</time_frame>
      <description>Pre- and post-treatment difference in neuroendocrine test values</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Evolution of neuroendocrine parameters</measure>
      <time_frame>Through study completion, an average of 6 weeks</time_frame>
      <description>Proportion of patients having normalized their tests at the end of the 20 sessions of rTMs.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Relationship of the therapeutic response with the evolution of neuroendocrine parameters</measure>
      <time_frame>Through study completion, an average of 6 weeks</time_frame>
      <description>Proportion of responders/functional remission patients according to the normalization or not of neuroendocrine tests after rTMS-TBS treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Predictive factors</measure>
      <time_frame>Through study completion, an average of 6 weeks</time_frame>
      <description>Predictors of response to rTMS treatment (e.g., demographics)</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">50</enrollment>
    <condition>Major Depression</condition>
    <arm_group>
      <arm_group_label>Treatment resistant major depressed inpatients (TRDs)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
      <description>The theta burst stimulation (TBS) technique consists in administering bursts of transcranial magnetic stimulation (TMS) at very high frequency (50Hz) for 5 minutes (3 pulses of stimulation given at 50 hz; 10 bursts/1 s train; inter-train interval : 8 s; number of trains : 30; 100% resting motor threshold; number pulses/session : 900). Total number of sessions : 20 sessions (single daily session).</description>
      <arm_group_label>Treatment resistant major depressed inpatients (TRDs)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Patient with a characterized depressive episode defined according to DSM-5 (diagnostic&#xD;
               and statistical manual of mental disorders) criteria;&#xD;
  &#xD;
            2. Patient between the ages of 18 and 65 years;&#xD;
  &#xD;
            3. Inpatient with an inadequate response to two prior well-conducted antidepressant&#xD;
               treatments (Hamilton 17-item scale [HAMD-17] score at inclusion≥ 18) ;&#xD;
  &#xD;
            4. Patient with written informed consent to participate in the study;&#xD;
  &#xD;
            5. Patient enrolled in or receiving social security benefits.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patient with endocrinopathy ;&#xD;
  &#xD;
            2. Patient with a contraindication to neuroendocrine testing (hypersensitivity to the&#xD;
               active substance or to one of the excipients);&#xD;
  &#xD;
            3. Patient with a contraindication to rTMS:&#xD;
  &#xD;
                 -  cochlear implant,&#xD;
  &#xD;
                 -  cardiac pacemaker,&#xD;
  &#xD;
                 -  metal clips, stents or other electronic implants within one meter of the&#xD;
                    stimulation coil,&#xD;
  &#xD;
                 -  intracranial hypertension,&#xD;
  &#xD;
                 -  poorly balanced comitiality,&#xD;
  &#xD;
                 -  in the case of well-balanced comitiality, a neurological consultation with&#xD;
                    electroencephalogram (EEG) is planned before including the patient;&#xD;
  &#xD;
            4. Patient previously treated with monoamine oxidase inhibitor (MAOI) antidepressant or&#xD;
               lithium salts (within 6 months prior to inclusion);&#xD;
  &#xD;
            5. Pregnant or lactating patient;&#xD;
  &#xD;
            6. Patient under court protection or deprived of liberty;&#xD;
  &#xD;
            7. Patient under guardianship/guardianship.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>MIHAELA TOMSA, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>CENTRE HOSPITALIER DE ROUFFACH</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>MIHAELA TOMSA</last_name>
      <phone>+33 389787018</phone>
      <email>m.tomsa@ch-rouffach.fr</email>
    </overall_contact>
    <location>
      <facility>
        <name>Centre Hospitalier Rouffach</name>
        <address>
          <city>Rouffach</city>
          <state>Alsace</state>
          <zip>68250</zip>
          <country>France</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Fabrice Duval, MD</last_name>
        <phone>33389787018</phone>
        <email>f.duval@ch-rouffach.fr</email>
      </contact>
      <contact_backup>
        <last_name>Alexis Erb, MD</last_name>
        <phone>33389787018</phone>
        <email>a.erb@ch-rouffach.fr</email>
      </contact_backup>
      <investigator>
        <last_name>Roberta Carcangiu, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Thomas Weiss, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Alexis Erb, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>France</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 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>Depression</keyword>
    <keyword>clinical outcome</keyword>
    <keyword>rTMS (repetitive transcranial magnetic stimulation)</keyword>
    <keyword>theta burst</keyword>
    <keyword>TRH (thyreoliberin) test</keyword>
    <keyword>DST (dexamethasone suppression test)</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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05964192
  org study id: 2023-A00288-37
  nct id: NCT05964192
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The primary objective of the study is to determine the predictive value of the neuroendocrine
        tests TRH-∆∆TSH (thyreoliberin - thyreostimulin) and DST (dexamethasone suppression test) in
        the subsequent response to rTMS-TBS (repetitive transcranial magnetic stimulation-theta burst
        stimulation) treatment, defined as at least a 50% decrease in depression score after 20
        sessions of rTMS-TBS.
  Conduct of research :
  
        This is a monocentric, non-randomized, open-label pilot study involving 50 male and female
        patients aged 18 to 65, hospitalized for major depression and presenting with an indication
        for treatment with repeated theta-burst transcranial magnetic stimulation (rTMS-TBS), i.e. a
        situation of therapeutic failure following 2 well-conducted antidepressant treatments.
  
        At the end of the 20 rTMS-TBS sessions (one session per day, except weekends), the clinical
        response will be assessed by an investigator "blind" to the endocrine results. This response
        will be analyzed according to the status of neuroendocrine tests at inclusion (TRH-∆∆TSH and
        DST) and at the end of the study (for those who had one or more abnormal tests at inclusion
        and in whom the same tests were repeated at the end of the rTMS-TBS sessions).
  
        During the inclusion visit, the patient and investigator sign the consent form, after
        double-checking the inclusion and non-inclusion criteria.
  
        Immediately after the tenth rTMS session, an assessment of depression using the HAMD (17-item
        Hamilton Depression Scale) scale will be carried out by an independent psychiatrist, blind to
        the results of the neuroendocrine tests. This psychiatrist, who has already administered the
        HAMD at V0, will repeat the assessments at V1 and V2.
  
        Immediately after the twentieth rTMS session, an assessment of depression using the HAMD
        scale will be carried out by an independent psychiatrist. This assessment will determine
        responder/non-responder status to rTMS-TBS.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 17-item Hamilton Depression Scale (HAMD)
  time frame: Change from inclusion result at 6 weeks (after 20 rTMS-TBS sessions)
  description: Clinical response will be defined by at least a 50% decrease in depression score at the end of the 20 rTMS-TBS sessions - measured by the 17-item Hamilton Depression Scale (HAMD) - compared to inclusion (Carrozzino et al, 2020). The predictive value of the TRH-∆∆TSH on the one hand, and the DST on the other, will be assessed using an ROC curve and its AUC (Area Under the Curve) calculation.
  measure: Hamilton Depression Scale (HAMD)
  time frame: Through study completion, an average of 6 weeks
  description: Functional remission will be defined by a HAMD score ≤ 8 at the end of 20 sessions of rTMS-TBS
  measure: Evolution of neuroendocrine parameters
  time frame: Through study completion, an average of 6 weeks
  description: Pre- and post-treatment difference in neuroendocrine test values
  measure: Evolution of neuroendocrine parameters
  time frame: Through study completion, an average of 6 weeks
  description: Proportion of patients having normalized their tests at the end of the 20 sessions of rTMs.
  measure: Relationship of the therapeutic response with the evolution of neuroendocrine parameters
  time frame: Through study completion, an average of 6 weeks
  description: Proportion of responders/functional remission patients according to the normalization or not of neuroendocrine tests after rTMS-TBS treatment.
  measure: Predictive factors
  time frame: Through study completion, an average of 6 weeks
  description: Predictors of response to rTMS treatment (e.g., demographics)
  arm group label: Treatment resistant major depressed inpatients (TRDs)
  arm group type: Experimental
  intervention type: Procedure
  intervention name: Repetitive transcranial magnetic stimulation (rTMS)
  description: The theta burst stimulation (TBS) technique consists in administering bursts of transcranial magnetic stimulation (TMS) at very high frequency (50Hz) for 5 minutes (3 pulses of stimulation given at 50 hz; 10 bursts/1 s train; inter-train interval : 8 s; number of trains : 30; 100% resting motor threshold; number pulses/session : 900). Total number of sessions : 20 sessions (single daily session).
  arm group label: Treatment resistant major depressed inpatients (TRDs)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: MIHAELA TOMSA, PhD
  role: Principal Investigator
  affiliation: CENTRE HOSPITALIER DE ROUFFACH
  last name: MIHAELA TOMSA
  phone: +33 389787018
  email: m.tomsa@ch-rouffach.fr
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  country: France
  responsible party type: Sponsor
  mesh term: Depression
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  sharing ipd: No