<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/NCT03277339</url>
  </required_header>
  <id_info>
    <org_study_id>InsulaTOP</org_study_id>
    <nct_id>NCT03277339</nct_id>
  </id_info>
  <brief_title>Psycho-biological Substrates of Therapeutic Benefit of Thermal Cure on Generalized Anxiety Disorders</brief_title>
  <acronym>Insula-TOP</acronym>
  <official_title>Psycho-biological Substrates of Therapeutic Benefit of Thermal Cure on Generalized Anxiety Disorders (Insula-TOP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier Henri Laborit</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Association Francaise pour la Recherche Thermale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Les thermes de Saujon</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Poitiers University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre National de la Recherche Scientifique (CeRCA, umr 7295), France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre Hospitalier Henri Laborit</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>
      Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a&#xD;
      diagnosis of Generalised Anxiety Disorders&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a&#xD;
      diagnosis of Generalised Anxiety Disorders&#xD;
&#xD;
      Main objective is to quantify the therapeutic benefit of a thermal cure on generalized&#xD;
      anxiety disorders and to understand the psycho-biological substrates of this improvement.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  A decrease of Insula activity at rest during the answers to aversive pictures and during&#xD;
           the task of subjective measurement of heartbeat.&#xD;
&#xD;
        -  A decrease of sensibility to emotional interference by subliminal presentation of&#xD;
           emotional words thanks to a lexical task and a color recognition task associated to&#xD;
           simultaneous measurement of physiological indicator of emotional activity ( dermal&#xD;
           resistance)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 19, 2017</start_date>
  <completion_date type="Actual">February 5, 2020</completion_date>
  <primary_completion_date type="Actual">January 8, 2020</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Decrease Insula activity during a resting state task</measure>
    <time_frame>The evaluation of primary end point is performed between day 1 and day 24</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes of HAM-A score between day 1 and day 24.</measure>
    <time_frame>The evaluation of primary end point is performed between day 1 and day 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sensibility non conscientious to emotional interference in lexical task and in color identification task</measure>
    <time_frame>D= Day D1/D24/D56</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modulation of electrodermal response during presentation of predictive stimuli on aversive images and its links to the subjective view of emotional state</measure>
    <time_frame>D= Day D24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modulation of electrodermal response during presentation of predictive stimuli on aversive images and insula activation</measure>
    <time_frame>D= Day D24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lost of significant correlation (Day 24) between HAM-A score, introspective acuity and insula hyperactivation</measure>
    <time_frame>D= Day D24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evolution (Day 1 and Day 24) of the correlation between HAM-A global score and 1- the measure of heartbeat 2- emotional reactivity during aversive images task.</measure>
    <time_frame>D= Day D1/D24.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference (Day 1 and Day 24) of correlations between the symptoms severity and the activation of insula cortex during 1-aversive images task, 2-heartbeat measure task.</measure>
    <time_frame>D= Day D1/D24.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of efficacy of the thermal cure Day 56 using HAM-A score</measure>
    <time_frame>D= Day D56</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">52</enrollment>
  <condition>Generalized Anxious Disorders</condition>
  <arm_group>
    <arm_group_label>Paroxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Paroxetine (Deroxat®) Posology : 20 mg per day for 3 weeks. After 2 weeks of treatments, if indicated, physicians will prescribe until 50 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Thermal cure</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>This study is controlled with a comparator which is the Thermal cure. Thermal cure is realized for 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paroxetine</intervention_name>
    <description>Deroxat® (20 mg/day) 3 week; can be increase on week 2 until 50 mg.</description>
    <arm_group_label>Paroxetine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Thermal cure</intervention_name>
    <description>Thermal cure is realized for 3 weeks</description>
    <arm_group_label>Thermal cure</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnostic of generalized anxiety disorder according to the Diagnostic and Statistical&#xD;
             Manual of Mental Disorders (DSM IV)&#xD;
&#xD;
          -  No treatment by antidepressant for at least 2 months&#xD;
&#xD;
          -  No treatment by anxiolytic/neuroleptic/bete blockers/antipsychotic for at least 3&#xD;
             weeks&#xD;
&#xD;
          -  Global score of Hamilton Anxiety Scale (HAM-A) is greater or equal to 20&#xD;
&#xD;
          -  Score of HAM-A symptoms greater or equal to 8&#xD;
&#xD;
          -  Score of Hamilton Depressive Scale (HAM-D) lower or equal to 7&#xD;
&#xD;
          -  Age: Participants will be males and females, 18-75 years of age included.&#xD;
&#xD;
          -  For women, no ongoing pregnancy/ negative pregnancy test&#xD;
&#xD;
          -  No wounds&#xD;
&#xD;
          -  Affiliation to a social security system (recipient or assignee)&#xD;
&#xD;
          -  Signed written inform consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Treatment by antidepressant for at least 2 months or a treatment by anxiolytic,&#xD;
             neuroleptic for at least 3 weeks&#xD;
&#xD;
          -  Psychotropic treatment (antidepressant, anxiolytic and neuroleptic) between the&#xD;
             preinclusion and inclusion&#xD;
&#xD;
          -  Psychotherapy during the 3 months prior to the inclusion&#xD;
&#xD;
          -  Thermal cure during the 6 months prior to the inclusion&#xD;
&#xD;
          -  Treatment by paroxetine for at least 1 month with dose equal or superior to 20 mg per&#xD;
             day during the 12 months prior to the inclusion&#xD;
&#xD;
          -  Contraindication to paroxetine&#xD;
&#xD;
          -  Enhanced protection (minors, pregnancies women, nursing women,people deprived of&#xD;
             liberty by administrative or judicial decision, ...)&#xD;
&#xD;
          -  Blood donation during the 3 months prior to the inclusion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>JAAFARI Nematollah, MD-PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Henri Laborit</affiliation>
  </overall_official>
  <overall_official>
    <last_name>INGRAND Pierre, MD-PhD-PU-PH</last_name>
    <role>Study Chair</role>
    <affiliation>Centre d'investigation clinique INSERM CIC P802</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Henri Laborit</name>
      <address>
        <city>Poitiers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Les thermes de Saujon</name>
      <address>
        <city>Saujon</city>
        <zip>17600</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Jaafari N, Rachid F, Rotge JY, Polosan M, El-Hage W, Belin D, Vibert N, Pelissolo A. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: a review. World J Biol Psychiatry. 2012 Mar;13(3):164-77. doi: 10.3109/15622975.2011.575177. Epub 2011 May 30.</citation>
    <PMID>21623668</PMID>
  </reference>
  <reference>
    <citation>Jaafari N, Baup N, Bourdel MC, Olie JP, Rotge JY, Wassouf I, Sharov I, Millet B, Krebs MO. Neurological soft signs in OCD patients with early age at onset, versus patients with schizophrenia and healthy subjects. J Neuropsychiatry Clin Neurosci. 2011 Fall;23(4):409-16. doi: 10.1176/jnp.23.4.jnp409.</citation>
    <PMID>22231312</PMID>
  </reference>
  <reference>
    <citation>Jaafari N, Aouizerate B, Tignol J, El-Hage W, Wassouf I, Guehl D, Bioulac B, Daniel ML, Lacoste J, Gil R, Burbaud P, Rotge JY; Insight Study Group. The relationship between insight and uncertainty in obsessive-compulsive disorder. Psychopathology. 2011;44(4):272-6. doi: 10.1159/000323607. Epub 2011 May 6. Erratum In: Psychopathology. 2011;44(5):319.</citation>
    <PMID>21546788</PMID>
  </reference>
  <reference>
    <citation>Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, Dionne-Laporte A, Spiegelman D, Henrion E, Diallo O, Thibodeau P, Bachand I, Bao JY, Tong AH, Lin CH, Millet B, Jaafari N, Joober R, Dion PA, Lok S, Krebs MO, Rouleau GA. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011 Jul 10;43(9):860-3. doi: 10.1038/ng.886.</citation>
    <PMID>21743468</PMID>
  </reference>
  <reference>
    <citation>Dubois O, Salamon R, Germain C, Poirier MF, Vaugeois C, Banwarth B, Mouaffak F, Galinowski A, Olie JP. Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder. Complement Ther Med. 2010 Feb;18(1):1-7. doi: 10.1016/j.ctim.2009.11.003. Epub 2010 Jan 6.</citation>
    <PMID>20178872</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 11, 2017</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Generalized anxious disorders</keyword>
  <keyword>Thermal cure</keyword>
  <keyword>paroxetine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paroxetine</mesh_term>
  </intervention_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/NCT03277339
org study id: InsulaTOP
nct id: NCT03277339
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a
      diagnosis of Generalised Anxiety Disorders
Multicenter study comparing paroxetine (n=30) versus thermal cure (n=30) in patients with a
      diagnosis of Generalised Anxiety Disorders

      Main objective is to quantify the therapeutic benefit of a thermal cure on generalized
      anxiety disorders and to understand the psycho-biological substrates of this improvement.

      Secondary objectives:

        -  A decrease of Insula activity at rest during the answers to aversive pictures and during
           the task of subjective measurement of heartbeat.

        -  A decrease of sensibility to emotional interference by subliminal presentation of
           emotional words thanks to a lexical task and a color recognition task associated to
           simultaneous measurement of physiological indicator of emotional activity ( dermal
           resistance)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Decrease Insula activity during a resting state task
time frame: The evaluation of primary end point is performed between day 1 and day 24
measure: Changes of HAM-A score between day 1 and day 24.
time frame: The evaluation of primary end point is performed between day 1 and day 24
measure: Sensibility non conscientious to emotional interference in lexical task and in color identification task
time frame: D= Day D1/D24/D56
measure: Modulation of electrodermal response during presentation of predictive stimuli on aversive images and its links to the subjective view of emotional state
time frame: D= Day D24
measure: Modulation of electrodermal response during presentation of predictive stimuli on aversive images and insula activation
time frame: D= Day D24
measure: Lost of significant correlation (Day 24) between HAM-A score, introspective acuity and insula hyperactivation
time frame: D= Day D24
measure: Evolution (Day 1 and Day 24) of the correlation between HAM-A global score and 1- the measure of heartbeat 2- emotional reactivity during aversive images task.
time frame: D= Day D1/D24.
measure: Difference (Day 1 and Day 24) of correlations between the symptoms severity and the activation of insula cortex during 1-aversive images task, 2-heartbeat measure task.
time frame: D= Day D1/D24.
measure: Evaluation of efficacy of the thermal cure Day 56 using HAM-A score
time frame: D= Day D56
arm group label: Paroxetine
arm group type: Experimental
description: Paroxetine (Deroxat®) Posology : 20 mg per day for 3 weeks. After 2 weeks of treatments, if indicated, physicians will prescribe until 50 mg.
arm group label: Thermal cure
arm group type: Other
description: This study is controlled with a comparator which is the Thermal cure. Thermal cure is realized for 3 weeks.
intervention type: Drug
intervention name: Paroxetine
description: Deroxat® (20 mg/day) 3 week; can be increase on week 2 until 50 mg.
arm group label: Paroxetine
intervention type: Other
intervention name: Thermal cure
description: Thermal cure is realized for 3 weeks
arm group label: Thermal cure
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: JAAFARI Nematollah, MD-PhD
role: Principal Investigator
affiliation: Centre Hospitalier Henri Laborit
last name: INGRAND Pierre, MD-PhD-PU-PH
role: Study Chair
affiliation: Centre d'investigation clinique INSERM CIC P802
facility: 
facility: 
country: France
citation: Jaafari N, Rachid F, Rotge JY, Polosan M, El-Hage W, Belin D, Vibert N, Pelissolo A. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: a review. World J Biol Psychiatry. 2012 Mar;13(3):164-77. doi: 10.3109/15622975.2011.575177. Epub 2011 May 30.
PMID: 21623668
citation: Jaafari N, Baup N, Bourdel MC, Olie JP, Rotge JY, Wassouf I, Sharov I, Millet B, Krebs MO. Neurological soft signs in OCD patients with early age at onset, versus patients with schizophrenia and healthy subjects. J Neuropsychiatry Clin Neurosci. 2011 Fall;23(4):409-16. doi: 10.1176/jnp.23.4.jnp409.
PMID: 22231312
citation: Jaafari N, Aouizerate B, Tignol J, El-Hage W, Wassouf I, Guehl D, Bioulac B, Daniel ML, Lacoste J, Gil R, Burbaud P, Rotge JY; Insight Study Group. The relationship between insight and uncertainty in obsessive-compulsive disorder. Psychopathology. 2011;44(4):272-6. doi: 10.1159/000323607. Epub 2011 May 6. Erratum In: Psychopathology. 2011;44(5):319.
PMID: 21546788
citation: Girard SL, Gauthier J, Noreau A, Xiong L, Zhou S, Jouan L, Dionne-Laporte A, Spiegelman D, Henrion E, Diallo O, Thibodeau P, Bachand I, Bao JY, Tong AH, Lin CH, Millet B, Jaafari N, Joober R, Dion PA, Lok S, Krebs MO, Rouleau GA. Increased exonic de novo mutation rate in individuals with schizophrenia. Nat Genet. 2011 Jul 10;43(9):860-3. doi: 10.1038/ng.886.
PMID: 21743468
citation: Dubois O, Salamon R, Germain C, Poirier MF, Vaugeois C, Banwarth B, Mouaffak F, Galinowski A, Olie JP. Balneotherapy versus paroxetine in the treatment of generalized anxiety disorder. Complement Ther Med. 2010 Feb;18(1):1-7. doi: 10.1016/j.ctim.2009.11.003. Epub 2010 Jan 6.
PMID: 20178872
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Paroxetine