<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/NCT04431778</url>
  </required_header>
  <id_info>
    <org_study_id>PHRC-IR 2019 DELAGE</org_study_id>
    <nct_id>NCT04431778</nct_id>
  </id_info>
  <brief_title>Evaluation of the Efficacy and Tolerance of Low Doses of Ethosuximide in the Treatment of Peripheral Neuropathic Pain</brief_title>
  <acronym>E-PENEPA</acronym>
  <official_title>Evaluation of the Efficacy and Tolerance of Low Doses of Ethosuximide in the Treatment of Peripheral Neuropathic Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Clermont-Ferrand</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Clermont-Ferrand</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>
      Evaluation of the efficacy and tolerance of low doses of ethosuximide in the treatment of&#xD;
      peripheral neuropathic pain&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter, randomized, double-blind, placebo-controlled therapeutic trial evaluating the&#xD;
      efficacy and safety of low doses of ethosuximide in neuropathic pain patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 1, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 30, 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>
    <intervention_model_description>Randomisation 1:1 placebo or ethosuximide</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-blind Placebo and ethosuximide will be indistinguishable.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Neuropathic pain intensity</measure>
    <time_frame>Day 0</time_frame>
    <description>Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neuropathic pain intensity</measure>
    <time_frame>Day 84</time_frame>
    <description>Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient's Global Impression of Change (PGIC scale)</measure>
    <time_frame>Day 0, Day 28, Day 56, Day 84</time_frame>
    <description>Assessment of the patient's feelings about the effectiveness of the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life</measure>
    <time_frame>Day 0, Day 28, Day 56, Day 84</time_frame>
    <description>Assessment of the patient's quality of life with EQ-5D-3L questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantitative sensory testing (QST)</measure>
    <time_frame>Day 0, Day 28, Day 56, Day 84</time_frame>
    <description>Assessment of mechanical sensitivity using the von Frey test (static allodynia) and the brush test (dynamic allodynia).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse event</measure>
    <time_frame>Throughout the study</time_frame>
    <description>Assessment of the tolerability of the treatment by patients and clinicians</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">64</enrollment>
  <condition>Peripheral Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>Ethosuximide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with chronic peripheral neuropathic pain</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients with chronic peripheral neuropathic pain</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ethosuximide</intervention_name>
    <description>Taking the treatment (1 daily intake during the evening meal) according to increasing dosage:&#xD;
Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).</description>
    <arm_group_label>Ethosuximide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Taking the treatment (1 daily intake during the evening meal) according to increasing dosage:&#xD;
Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female (under effective contraception: pill, implant, IUD, sterilization) aged&#xD;
             18 years or older, suffering from peripheral neuropathic pain (DN4 ≥ 4) for more than&#xD;
             3 months, of intensity ≥ 4 on a numerical scale from 0 to 10, and whose analgesic&#xD;
             treatment has been stable for more than a month,&#xD;
&#xD;
          -  Patients affiliated to the French Social Security system,&#xD;
&#xD;
          -  Patients whose free and informed consent has been obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy (βHCG+ blood) or breastfeeding,&#xD;
&#xD;
          -  Neuropathic pain due to spinal cord or brain injury, phantom limb pain or&#xD;
             algohallucinosis,&#xD;
&#xD;
          -  Fibromyalgia or algodystrophy,&#xD;
&#xD;
          -  Chronic pain syndrome that the patient cannot distinguish and/or is more intense than&#xD;
             peripheral neuropathic pain,&#xD;
&#xD;
          -  Significant abnormalities in liver (transaminases &gt; 3N, cholestasis) and renal (MDRD &lt;&#xD;
             60 mL/min) tests,&#xD;
&#xD;
          -  Ongoing comorbidities: cancer, neurodegenerative pathology&#xD;
&#xD;
          -  Severe depressive disorder in progress (as determined by the clinician), history of&#xD;
             suicide attempts or hospitalization for depression,&#xD;
&#xD;
          -  Diabetic patients (contraindicated due to the high sugar concentration of&#xD;
             ethosuximide, 3g / 5 ml),&#xD;
&#xD;
          -  Patients who have previously received ethosuximide (epilepsy or clinical trial),&#xD;
&#xD;
          -  Surgery planned throughout the entire trial,&#xD;
&#xD;
          -  Medical and surgical history incompatible with the study,&#xD;
&#xD;
          -  Dependence on alcohol and/or drugs (for compliance purposes),&#xD;
&#xD;
          -  Known allergy to succinimides (ethosuximide, methsuximide, phensuximide),&#xD;
&#xD;
          -  Psychotic disorders,&#xD;
&#xD;
          -  Epileptic patients,&#xD;
&#xD;
          -  Patients benefiting from a legal protection measure (curatorship, guardianship,&#xD;
             deprived of liberty or subject to judicial safeguard).&#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_contact>
    <last_name>Lise Laclautre</last_name>
    <phone>+33473754963</phone>
    <email>promo_interne_drci@chu-clermontferrand.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Hospital Lyon sud - Pierre Bénite</name>
      <address>
        <city>Lyon</city>
        <state>Aura</state>
        <zip>69310</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Alberta LORENZI-PERNOT</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uniervity hospital, Amiens</name>
      <address>
        <city>Amiens</city>
        <zip>80000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Sandrine SORIOT-THOMAS, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Eric SERRAT, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital of Annecy Genevois</name>
      <address>
        <city>Annecy</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Pierric Giraud, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University hospital, clermont ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <zip>63000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lise Laclautre</last_name>
      <phone>+33473754963</phone>
      <email>promo_interne_drci@chu-clermontferrand.fr</email>
    </contact>
    <investigator>
      <last_name>Noémie Delage, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CIC, Hospital University, Clermont Ferrand</name>
      <address>
        <city>Clermont-Ferrand</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Christian DUALE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital, Grenoble</name>
      <address>
        <city>Grenoble</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Caroline MAINDET-DOMINICI, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHu Limoges</name>
      <address>
        <city>Limoges</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Pascale VERGNE-SALLE</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital University, Lyon</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Christian GOV, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital, Saint Etienne</name>
      <address>
        <city>Saint-Étienne</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Christelle CREACH, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital of Valence</name>
      <address>
        <city>Valence</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Todizara RANDRIAMAMONJISOA, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital of Voiron</name>
      <address>
        <city>Voiron</city>
        <country>France</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Gérard Mick, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</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>Ethosuximide</keyword>
  <keyword>T-type calcium channel</keyword>
  <keyword>Neuropathic pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</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/NCT04431778
org study id: PHRC-IR 2019 DELAGE
nct id: NCT04431778
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Evaluation of the efficacy and tolerance of low doses of ethosuximide in the treatment of
      peripheral neuropathic pain
Multicenter, randomized, double-blind, placebo-controlled therapeutic trial evaluating the
      efficacy and safety of low doses of ethosuximide in neuropathic pain patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomisation 1:1 placebo or ethosuximide
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-blind Placebo and ethosuximide will be indistinguishable.
measure: Neuropathic pain intensity
time frame: Day 0
description: Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).
measure: Neuropathic pain intensity
time frame: Day 84
description: Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).
measure: Patient's Global Impression of Change (PGIC scale)
time frame: Day 0, Day 28, Day 56, Day 84
description: Assessment of the patient's feelings about the effectiveness of the treatment.
measure: Health related quality of life
time frame: Day 0, Day 28, Day 56, Day 84
description: Assessment of the patient's quality of life with EQ-5D-3L questionnaire
measure: Quantitative sensory testing (QST)
time frame: Day 0, Day 28, Day 56, Day 84
description: Assessment of mechanical sensitivity using the von Frey test (static allodynia) and the brush test (dynamic allodynia).
measure: adverse event
time frame: Throughout the study
description: Assessment of the tolerability of the treatment by patients and clinicians
arm group label: Ethosuximide
arm group type: Experimental
description: Patients with chronic peripheral neuropathic pain
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients with chronic peripheral neuropathic pain
intervention type: Drug
intervention name: Ethosuximide
description: Taking the treatment (1 daily intake during the evening meal) according to increasing dosage:
Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).
arm group label: Ethosuximide
intervention type: Drug
intervention name: Placebo
description: Taking the treatment (1 daily intake during the evening meal) according to increasing dosage:
Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lise Laclautre
phone: +33473754963
email: promo_interne_drci@chu-clermontferrand.fr
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Not yet recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Neuralgia
mesh term: Ethosuximide