<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/NCT04436250</url>
  </required_header>
  <id_info>
    <org_study_id>ESKEFIB</org_study_id>
    <nct_id>NCT04436250</nct_id>
  </id_info>
  <brief_title>ESKETamine for FIBromyalgia Treatment</brief_title>
  <acronym>ESKEFIB</acronym>
  <official_title>Intravenous Infusions of S-KETAMINE in Fibromyalgia Syndromes: an Exploratory Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grand Hôpital de Charleroi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Grand Hôpital de Charleroi</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>
      Fibromyalgia is a cause of chronic pain, classified by the Internal Classification of&#xD;
      Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by the&#xD;
      American College of Rheumatology (ACR). No treatment to its complete cure is available at&#xD;
      this time, all treatments having as purpose pain relief and an improvement of quality of life&#xD;
      by combining pharmacologic and nonpharmacologic treatments. One of the mechanisms proposed in&#xD;
      fibromyalgia is the central sensitisation phenomenon, by which the central nervous system&#xD;
      becomes &quot;hypersensitive&quot; to nociceptive or non-nociceptive stimuli. The receptor involved in&#xD;
      this phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has&#xD;
      therefore been proposed as a co-treatment in chronic pain with central sensitization&#xD;
      phenomena, such as fibromyalgia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ketamine is a drug used for anesthesia since the 1970s, acting as an antagonist to the&#xD;
      N-methyl-D-aspartate receptor located in the central nervous system. It has two stereoisomers&#xD;
      : R +ketamine and S - ketamine, the latter being about two to four times more potent.&#xD;
      S-ketamine also has the advantages of producing less psychotropic effects, less tiredness and&#xD;
      a lower temporary cognitive impairment than the racemic mixture at equianalgesic doses. Being&#xD;
      first used as an anesthetic, in the last twenty years, ketamine's indications expanded to&#xD;
      other domains, such as treatment of depression or off label use for chronic pain relief.&#xD;
      Chronic pain is a multidimensional syndrome that touches 17-44% of the population of western&#xD;
      countries. Fibromyalgia is a cause of chronic pain, classified by the Internal Classification&#xD;
      of Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by&#xD;
      the American College of Rheumatology (ACR). No treatment to its complete cure is available at&#xD;
      this time, all treatments having as purpose pain relief and an improvement of quality of life&#xD;
      by combining pharmacologic and nonpharmacologic treatments (as given by the European League&#xD;
      Against Rheumatism (EULAR) guidelines). One of the mechanisms proposed in fibromyalgia is the&#xD;
      central sensitisation phenomenon, by which the central nervous system becomes&#xD;
      &quot;hypersensitive&quot; to nociceptive or non-nociceptive stimuli. The receptor involved in this&#xD;
      phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has&#xD;
      therefore been proposed as a co-treatment in chronic pain with central sensitization&#xD;
      phenomena, such as fibromyalgia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 10, 2020</start_date>
  <completion_date type="Anticipated">August 2024</completion_date>
  <primary_completion_date type="Anticipated">August 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Patients will be randomized in a 2:1 ratio (S-ketamine : placebo) per block of 15 patients sequentially into the first 2 groups, one with placebo and one with first dose of S-Ketamine Low Dose (0.2mg/kg).&#xD;
A second group will receive S-Ketamine High Dose (0.4 mg/kg) with the same randomized ratio (2:1).</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The research pharmacist prepares the syringe with a placebo or active drug (group 1 with 0.2mg/kg or group 2 with 0.4 mg/kg of S-Ketamine) and anonymizes it before giving it to care provider.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The primary outcome is twofold, aiming on one side pain relief and on the other the improvement of the patient's functional status</measure>
    <time_frame>12 weeks</time_frame>
    <description>Pain relief will be considered as a two point decrease on the Brief Pain Inventory (BPI) pain severity index at twelve weeks follow-up. (Two points being established as the Minimal Clinically Important Difference (MCID) for fibromyalgic patients).&#xD;
The functional status will be evaluated by the BPI Interference scale. An improvement will be considered as a one point reduction on this index (as established by the MCID).&#xD;
The primary outcome is to determine whether the association of S-ketamine to the analgesic treatment will increase the number of patients showing a clinically significant improvement of pain and/or functional status.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients showing 50 % reduction in the BPI (Brief Pain Inventory) pain index</measure>
    <time_frame>12 weeks</time_frame>
    <description>Measures will be done with different questionnaires</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">210</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clonidine at a dose of 1 microg/kg Magnesium sulfate at a dose of 40 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>S-Ketamine Low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>S-Ketamine at a dose of 0.2 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>S-ketamine High dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>S-ketamine at a dose of 0.4 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Active comparator</intervention_name>
    <description>The active comparator is composed of clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>S-Ketamine Low dose</arm_group_label>
    <arm_group_label>S-ketamine High dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-Ketamine Low dose</intervention_name>
    <description>The arm 1 is composed of esketamine 0.2 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.</description>
    <arm_group_label>S-Ketamine Low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-Ketamine High dose</intervention_name>
    <description>The arm 2 is composed of esketamine 0.4 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.</description>
    <arm_group_label>S-ketamine High dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients suffering from chronic pain (as defined by International Association for the&#xD;
             Study of Pain) being diagnosed as fibromyalgia according to the American College of&#xD;
             Rheumatology 2016 criteria&#xD;
&#xD;
          -  patients qualified for the treatment by S-ketamine as established by our latest&#xD;
             clinical practice&#xD;
&#xD;
          -  patients aged 18-65 years old&#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>Jean-Paul Lechat, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Grand Hôpital de Charleroi</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Paul Lechat, MD</last_name>
    <phone>00 32 71 10</phone>
    <phone_ext>4071</phone_ext>
    <email>jean-paul.lechat@ghdc.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zuzana Javorcikova, MD</last_name>
    <phone>00 32 474 64</phone>
    <phone_ext>1109</phone_ext>
    <email>z.javorcikova.pro@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Grand Hôpital de Charleroi</name>
      <address>
        <city>Gilly</city>
        <state>Hainaut</state>
        <zip>6060</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Paul Lechat, MD</last_name>
      <phone>00 32 71 10</phone>
      <phone_ext>4071</phone_ext>
      <email>jean-paul@ghdc.be</email>
    </contact>
    <contact_backup>
      <last_name>Zuzana Javorcikova, MD</last_name>
      <phone>00 32 474 64</phone>
      <phone_ext>1109</phone_ext>
      <email>z.javorcikova.pro@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Philippe Van der Linden, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michel Dangoisse, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stéphane Nikis, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Esketamine</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/NCT04436250
org study id: ESKEFIB
nct id: NCT04436250
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Fibromyalgia is a cause of chronic pain, classified by the Internal Classification of
      Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by the
      American College of Rheumatology (ACR). No treatment to its complete cure is available at
      this time, all treatments having as purpose pain relief and an improvement of quality of life
      by combining pharmacologic and nonpharmacologic treatments. One of the mechanisms proposed in
      fibromyalgia is the central sensitisation phenomenon, by which the central nervous system
      becomes "hypersensitive" to nociceptive or non-nociceptive stimuli. The receptor involved in
      this phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has
      therefore been proposed as a co-treatment in chronic pain with central sensitization
      phenomena, such as fibromyalgia.
Ketamine is a drug used for anesthesia since the 1970s, acting as an antagonist to the
      N-methyl-D-aspartate receptor located in the central nervous system. It has two stereoisomers
      : R +ketamine and S - ketamine, the latter being about two to four times more potent.
      S-ketamine also has the advantages of producing less psychotropic effects, less tiredness and
      a lower temporary cognitive impairment than the racemic mixture at equianalgesic doses. Being
      first used as an anesthetic, in the last twenty years, ketamine's indications expanded to
      other domains, such as treatment of depression or off label use for chronic pain relief.
      Chronic pain is a multidimensional syndrome that touches 17-44% of the population of western
      countries. Fibromyalgia is a cause of chronic pain, classified by the Internal Classification
      of Diseases (ICD) as a primary chronic pain with specific diagnostic criteria established by
      the American College of Rheumatology (ACR). No treatment to its complete cure is available at
      this time, all treatments having as purpose pain relief and an improvement of quality of life
      by combining pharmacologic and nonpharmacologic treatments (as given by the European League
      Against Rheumatism (EULAR) guidelines). One of the mechanisms proposed in fibromyalgia is the
      central sensitisation phenomenon, by which the central nervous system becomes
      "hypersensitive" to nociceptive or non-nociceptive stimuli. The receptor involved in this
      phenomenon is the N-methyl-D-aspartate receptor to which ketamine binds. Ketamine has
      therefore been proposed as a co-treatment in chronic pain with central sensitization
      phenomena, such as fibromyalgia.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Patients will be randomized in a 2:1 ratio (S-ketamine : placebo) per block of 15 patients sequentially into the first 2 groups, one with placebo and one with first dose of S-Ketamine Low Dose (0.2mg/kg).
A second group will receive S-Ketamine High Dose (0.4 mg/kg) with the same randomized ratio (2:1).
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
masking description: The research pharmacist prepares the syringe with a placebo or active drug (group 1 with 0.2mg/kg or group 2 with 0.4 mg/kg of S-Ketamine) and anonymizes it before giving it to care provider.
measure: The primary outcome is twofold, aiming on one side pain relief and on the other the improvement of the patient's functional status
time frame: 12 weeks
description: Pain relief will be considered as a two point decrease on the Brief Pain Inventory (BPI) pain severity index at twelve weeks follow-up. (Two points being established as the Minimal Clinically Important Difference (MCID) for fibromyalgic patients).
The functional status will be evaluated by the BPI Interference scale. An improvement will be considered as a one point reduction on this index (as established by the MCID).
The primary outcome is to determine whether the association of S-ketamine to the analgesic treatment will increase the number of patients showing a clinically significant improvement of pain and/or functional status.
measure: Number of patients showing 50 % reduction in the BPI (Brief Pain Inventory) pain index
time frame: 12 weeks
description: Measures will be done with different questionnaires
arm group label: Placebo
arm group type: Active Comparator
description: Clonidine at a dose of 1 microg/kg Magnesium sulfate at a dose of 40 mg/kg
arm group label: S-Ketamine Low dose
arm group type: Experimental
description: S-Ketamine at a dose of 0.2 mg/kg
arm group label: S-ketamine High dose
arm group type: Experimental
description: S-ketamine at a dose of 0.4 mg/kg
intervention type: Drug
intervention name: Active comparator
description: The active comparator is composed of clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride
arm group label: Placebo
arm group label: S-Ketamine Low dose
arm group label: S-ketamine High dose
intervention type: Drug
intervention name: S-Ketamine Low dose
description: The arm 1 is composed of esketamine 0.2 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.
arm group label: S-Ketamine Low dose
intervention type: Drug
intervention name: S-Ketamine High dose
description: The arm 2 is composed of esketamine 0.4 mg/kg and clonidine 1 microg/kg combined with magnesium sulfate 40 mg/kg diluted in 45 ml of sodium chloride.
arm group label: S-ketamine High dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jean-Paul Lechat, MD
role: Principal Investigator
affiliation: Grand Hôpital de Charleroi
last name: Jean-Paul Lechat, MD
phone: 00 32 71 10
phone ext: 4071
email: jean-paul.lechat@ghdc.be
last name: Zuzana Javorcikova, MD
phone: 00 32 474 64
phone ext: 1109
email: z.javorcikova.pro@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: Belgium
responsible party type: Sponsor
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
mesh term: Ketamine
mesh term: Esketamine