<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/NCT02973542</url>
  </required_header>
  <id_info>
    <org_study_id>CHU-289</org_study_id>
    <secondary_id>2016-002110-42</secondary_id>
    <nct_id>NCT02973542</nct_id>
  </id_info>
  <brief_title>Ethosuximide to Treat IBS</brief_title>
  <acronym>IBSET</acronym>
  <official_title>Evaluation of the Efficacy and Tolerance of Ethosuximide in the Treatment of Abdominal Pain Associated With Irritable Bowel Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SFETD (Socièté Française d'Etude et de Traitement de la Douleur)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</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>
      Abdominal pain remains the most deleterious symptom for patients with irritable bowel&#xD;
      syndrome (IBS) and is causing a significant alteration of their quality of life. The visceral&#xD;
      hypersensitivity seems to be one of the key mechanisms that could explain the abdominal pain&#xD;
      in these patients. Current treatments, mainly symptomatic, are of limited effectiveness,&#xD;
      especially in terms of relief of abdominal pain. The study will aim to evaluate the&#xD;
      effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its&#xD;
      impact on patient quality of life, severity of symptoms related to IBS and the use of&#xD;
      analgesics / antispasmodic / regulators transit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The irritable bowel syndrome (IBS) is characterized by a combination of discomfort and / or&#xD;
      abdominal pain and bowel habits in the absence of identifiable organic pathology. This&#xD;
      condition is extremely common because it is the first cause of consultation in&#xD;
      gastroenterology and would cover 10-15% of the French. This chronic condition, although&#xD;
      functional, impact significantly on the quality of life of patients and causes considerable&#xD;
      health spending, making it a major public health problem. Especially as the currently used&#xD;
      treatments are of limited effectiveness.&#xD;
&#xD;
      Among the pathophysiological mechanisms involved in IBS, visceral hypersensitivity (VHS)&#xD;
      seems to be a major factor causing pain in patients. VHS involves sensitization of colonic&#xD;
      nerve fibers, resulting in an increase of neuronal excitability. In several animal models of&#xD;
      chronic pain, this hyperexcitability was related to a change in the expression or activity of&#xD;
      ion channels, including calcium channel Cav3.2.&#xD;
&#xD;
      Investigators especially shown the involvement of Cav3.2 channels in visceral pain in an&#xD;
      animal model of VHS. Furthermore, overexpression of these channels at the peripheral level&#xD;
      (dorsal root ganglion innervating the colon) has been demonstrated in this animal model and&#xD;
      pharmacological blockade, including ethosuximide, prevented the development of the VHS. Note&#xD;
      that Cav3.2 channels have been widely demonstrated as involved in nociceptive phenomena in&#xD;
      various animal models of chronic pain and that by blocking their ethosuximide induce an&#xD;
      analgesic effect in these models.&#xD;
&#xD;
      Finally, we have recently demonstrated the involvement of Cav3.2 channel in patients with&#xD;
      IBS, in a clinical case-control study. The Cav3.2 channels were overexpressed in the colonic&#xD;
      mucosa of patients with IBS compared to asymptomatic controls.&#xD;
&#xD;
      The Cav3.2 channels are therefore a potential pharmacological target and ethosuximide a&#xD;
      promising therapy to effectively treat the abdominal pain associated with IBS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 30, 2018</start_date>
  <completion_date type="Anticipated">May 2023</completion_date>
  <primary_completion_date type="Anticipated">April 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>30% reduction in abdominal pain</measure>
    <time_frame>through study completion, an average of 12 weeks.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Score of 4 or 5 on the SGA scale</measure>
    <time_frame>through study completion, an average of 12 weeks.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Monthly assessment of abdominal pain</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly assessment of score of Bristol scale</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of GIQLI questionnaire</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of EQ-5D questionnaire</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of IBS-SSS questionnaire</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of SGA scale.</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of the use of analgesics</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of the use of antispasmodic</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of the use of regulators transit.</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of medical response rate</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Monthly evaluation of stop work related to IBS.</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the tolerance of ethosuximide throughout the study.</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the discontinuation rate study because of adverse events throughout the study</measure>
    <time_frame>at 1 month</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">162</enrollment>
  <condition>Irritable Bowel Syndrome</condition>
  <arm_group>
    <arm_group_label>ethosuximide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A responder will correspond to a decrease in abdominal pain score (11-points NRS pain) of at least 30% compared to the score before treatment and a score of 6 or 7 on the SGA scale. At endpoint (12-weeks treatment period), it will be compared the responder rate between the 2 treatment arms (ethosuximide vs placebo).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A responder will correspond to a decrease in abdominal pain score (11-points NRS pain) of at least 30% compared to the score before treatment and a score of 6 or 7 on the SGA scale. At endpoint (12-weeks treatment period), it will be compared the responder rate between the 2 treatment arms (ethosuximide vs placebo).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ethosuximide</intervention_name>
    <description>The study will aim to evaluate the effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its impact on patient quality of life, severity of symptoms related to IBS and the use of analgesics / antispasmodic / regulators transit.</description>
    <arm_group_label>ethosuximide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The study will aim to evaluate the effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its impact on patient quality of life, severity of symptoms related to IBS and the use of analgesics / antispasmodic / regulators transit.</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years,&#xD;
&#xD;
               -  Man,&#xD;
&#xD;
               -  Women, Negative pregnancy test and effective contraception,&#xD;
&#xD;
               -  IBS defined by the Rome criteria IV&#xD;
&#xD;
               -  During the previous seven days the inclusion visit, average NRS pain ≥ 4,&#xD;
&#xD;
               -  IBS Treatment stable for 1 month&#xD;
&#xD;
               -  Patients affiliated to the French Social Security,&#xD;
&#xD;
               -  Patients with the informed consent were obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Diabetic patients&#xD;
&#xD;
          -  Known renal or hepatic impairment,&#xD;
&#xD;
          -  Significant liver function abnormalities (transaminases&gt; 3N, cholestasis) and renal&#xD;
             (MDRD &lt;60 ml / min)&#xD;
&#xD;
          -  Addiction to alcohol and / or drugs,&#xD;
&#xD;
          -  AEDs taken (epilepsy or chronic pain)&#xD;
&#xD;
          -  chronic pain of greater intensity than that related to IBS,&#xD;
&#xD;
          -  Allergy succinimides (ethosuximide, methsuximide, phensuximide)&#xD;
&#xD;
          -  History or current severe depression (hospitalization, long-term antidepressant&#xD;
             treatment)&#xD;
&#xD;
          -  Psychotic disorders,&#xD;
&#xD;
          -  Patients exclusion period, or total exceeded authorized allowances&#xD;
&#xD;
          -  Patients undergoing a measure of legal protection (trusteeship, guardianship ...).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julien SCANZI, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Clermont-Ferrand</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Clermont-Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63003</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 25, 2016</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>IBS</keyword>
  <keyword>Ethosuximide</keyword>
  <keyword>Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Irritable Bowel Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ethosuximide</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/NCT02973542
org study id: CHU-289
secondary id: 2016-002110-42
nct id: NCT02973542
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Abdominal pain remains the most deleterious symptom for patients with irritable bowel
      syndrome (IBS) and is causing a significant alteration of their quality of life. The visceral
      hypersensitivity seems to be one of the key mechanisms that could explain the abdominal pain
      in these patients. Current treatments, mainly symptomatic, are of limited effectiveness,
      especially in terms of relief of abdominal pain. The study will aim to evaluate the
      effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its
      impact on patient quality of life, severity of symptoms related to IBS and the use of
      analgesics / antispasmodic / regulators transit.
The irritable bowel syndrome (IBS) is characterized by a combination of discomfort and / or
      abdominal pain and bowel habits in the absence of identifiable organic pathology. This
      condition is extremely common because it is the first cause of consultation in
      gastroenterology and would cover 10-15% of the French. This chronic condition, although
      functional, impact significantly on the quality of life of patients and causes considerable
      health spending, making it a major public health problem. Especially as the currently used
      treatments are of limited effectiveness.

      Among the pathophysiological mechanisms involved in IBS, visceral hypersensitivity (VHS)
      seems to be a major factor causing pain in patients. VHS involves sensitization of colonic
      nerve fibers, resulting in an increase of neuronal excitability. In several animal models of
      chronic pain, this hyperexcitability was related to a change in the expression or activity of
      ion channels, including calcium channel Cav3.2.

      Investigators especially shown the involvement of Cav3.2 channels in visceral pain in an
      animal model of VHS. Furthermore, overexpression of these channels at the peripheral level
      (dorsal root ganglion innervating the colon) has been demonstrated in this animal model and
      pharmacological blockade, including ethosuximide, prevented the development of the VHS. Note
      that Cav3.2 channels have been widely demonstrated as involved in nociceptive phenomena in
      various animal models of chronic pain and that by blocking their ethosuximide induce an
      analgesic effect in these models.

      Finally, we have recently demonstrated the involvement of Cav3.2 channel in patients with
      IBS, in a clinical case-control study. The Cav3.2 channels were overexpressed in the colonic
      mucosa of patients with IBS compared to asymptomatic controls.

      The Cav3.2 channels are therefore a potential pharmacological target and ethosuximide a
      promising therapy to effectively treat the abdominal pain associated with IBS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: 30% reduction in abdominal pain
time frame: through study completion, an average of 12 weeks.
measure: Score of 4 or 5 on the SGA scale
time frame: through study completion, an average of 12 weeks.
measure: Monthly assessment of abdominal pain
time frame: at 1 month
measure: Monthly assessment of score of Bristol scale
time frame: at 1 month
measure: Monthly evaluation of GIQLI questionnaire
time frame: at 1 month
measure: Monthly evaluation of EQ-5D questionnaire
time frame: at 1 month
measure: Monthly evaluation of IBS-SSS questionnaire
time frame: at 1 month
measure: Monthly evaluation of SGA scale.
time frame: at 1 month
measure: Monthly evaluation of the use of analgesics
time frame: at 1 month
measure: Monthly evaluation of the use of antispasmodic
time frame: at 1 month
measure: Monthly evaluation of the use of regulators transit.
time frame: at 1 month
measure: Monthly evaluation of medical response rate
time frame: at 1 month
measure: Monthly evaluation of stop work related to IBS.
time frame: at 1 month
measure: Evaluation of the tolerance of ethosuximide throughout the study.
time frame: at 1 month
measure: Evaluation of the discontinuation rate study because of adverse events throughout the study
time frame: at 1 month
arm group label: ethosuximide
arm group type: Experimental
description: A responder will correspond to a decrease in abdominal pain score (11-points NRS pain) of at least 30% compared to the score before treatment and a score of 6 or 7 on the SGA scale. At endpoint (12-weeks treatment period), it will be compared the responder rate between the 2 treatment arms (ethosuximide vs placebo).
arm group label: placebo
arm group type: Placebo Comparator
description: A responder will correspond to a decrease in abdominal pain score (11-points NRS pain) of at least 30% compared to the score before treatment and a score of 6 or 7 on the SGA scale. At endpoint (12-weeks treatment period), it will be compared the responder rate between the 2 treatment arms (ethosuximide vs placebo).
intervention type: Drug
intervention name: Ethosuximide
description: The study will aim to evaluate the effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its impact on patient quality of life, severity of symptoms related to IBS and the use of analgesics / antispasmodic / regulators transit.
arm group label: ethosuximide
intervention type: Other
intervention name: Placebo
description: The study will aim to evaluate the effectiveness of ethosuximide on abdominal pain in patients with IBS, its tolerance and its impact on patient quality of life, severity of symptoms related to IBS and the use of analgesics / antispasmodic / regulators transit.
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julien SCANZI, MD
role: Principal Investigator
affiliation: University Hospital, Clermont-Ferrand
facility: 
country: France
responsible party type: Sponsor
mesh term: Irritable Bowel Syndrome
mesh term: Syndrome
mesh term: Ethosuximide