<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/NCT04488926</url>
  </required_header>
  <id_info>
    <org_study_id>MPS-FM</org_study_id>
    <nct_id>NCT04488926</nct_id>
  </id_info>
  <brief_title>Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients</brief_title>
  <official_title>Efficacy and Tolerability of Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients: A Double-blind, Randomized, Placebo-controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Epitech Group SpA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Azienda Ospedaliera Universitaria Integrata Verona</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Epitech Group SpA</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>
      The onset of chronic Fibromyalgia symptomatology is due to central alterations, together with&#xD;
      peripheral neuroimmune modifications. Using positron emission tomography (PET), it has been&#xD;
      observed for the first time that fibromyalgia patients have a high activation of microglial&#xD;
      cells compared to normal subjects. Experimental evidence in neuroinflammation models in vitro&#xD;
      and in vivo have demonstrated the anti-inflammatory and neuroprotective effect of&#xD;
      Palmitoylethanolamide (PEA), effects confirmed by observational clinical investigations&#xD;
      conducted in patients with fibromyalgia in which micronized and ultra-micronized&#xD;
      Palmitoylethanolamide (mPEA and umPEA) reduced the intensity of pain improving the quality of&#xD;
      life. The aim of this study is to investigate the efficacy and tolerability of PEA-m + PEA-um&#xD;
      administered as an add-on therapy with a double-blind, randomized, placebo-controlled&#xD;
      clinical investigation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2020</start_date>
  <completion_date type="Actual">May 2, 2022</completion_date>
  <primary_completion_date type="Actual">May 2, 2022</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fibromyalgia symptoms assessed by Fibromyalgia Impact Questionnaire Revised</measure>
    <time_frame>90 days</time_frame>
    <description>Change of Fibromyalgia symptoms</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pain Intensity assessed by Visual Analogue Scale</measure>
    <time_frame>90 days</time_frame>
    <description>Change of Visual Analogue Scale every 30 days (0: no pain - 100 mm: maximum pain)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health assessed by Short form-12 Health Survey</measure>
    <time_frame>90 days</time_frame>
    <description>Change in Health at the end of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep Disorders assessed by Pittsburgh Sleep Quality Index</measure>
    <time_frame>90 days</time_frame>
    <description>Change in sleep disorders at the end of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Drugs consumption assessed by a daily diary</measure>
    <time_frame>90 days</time_frame>
    <description>Change in rescue drugs consumption during the entire period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>90 days</time_frame>
    <description>Monitoring of adverse event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood test</measure>
    <time_frame>90 days</time_frame>
    <description>Clinically significant changes in blood test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Normast® MPS (mPEA and umPEA 300mg + 600mg) microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) microgranules</intervention_name>
    <description>Micronized and ultra-micronized Palmitoylethanolamide is on the market in Italy as a Food for Special Medical Purposes</description>
    <arm_group_label>Group 1</arm_group_label>
    <other_name>Normast® MPS microgranules</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo microgranules 1800mg</intervention_name>
    <description>Placebo was prepared to be indistinguishable from color and flavor from the Product</description>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Therapy</intervention_name>
    <description>(antidepressants, anticonvulsants, muscle relaxants, weak opiates, etc..) consolidated for at least 3 months</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rescue Drug</intervention_name>
    <description>Use as needed allowed</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Paracetamol or Fans</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Fibromyalgia according to the criteria of the American College of&#xD;
             Rheumatology 2016 (symptoms for at least 3 months, Widespread Pain Index (WPI) ≥ 7 and&#xD;
             Symptom Severity (SS) ≥ 5 or WPI 4-6 and SS ≥ 9)&#xD;
&#xD;
          -  Pain intensity assessed on the Visual Analogue Scale (VAS) ≥ 40&#xD;
&#xD;
          -  PEA-naive patients&#xD;
&#xD;
          -  Patients who agree to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Values of WPI &lt;7 and SS &lt;5&#xD;
&#xD;
          -  Pain intensity assessed on the Visual Analogue Scale (VAS) &lt;40&#xD;
&#xD;
          -  Patients who have already taken PEA in the past&#xD;
&#xD;
          -  Allergic or hypersensitive subjects to the product and / or one or more of its&#xD;
             excipients&#xD;
&#xD;
          -  Patients who refuse to sign informed consent&#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>Enrico Polati, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliera Universitaria Integrata di Verona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anestesia e Rianimazione B - Azienda Ospedaliera Universitaria Integrata di Verona</name>
      <address>
        <city>Verona</city>
        <state>VR</state>
        <zip>37126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <link>
    <url>https://pubmed.ncbi.nlm.nih.gov/30827269/</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Schweiger V, Martini A, Bellamoli P, Donadello K, Schievano C, Balzo GD, Sarzi-Puttini P, Parolini M, Polati E. Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients. CNS Neurol Disord Drug Targets. 2019;18(4):326-333. doi: 10.2174/1871527318666190227205359.</citation>
    <PMID>30827269</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 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>Palmidrol</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/NCT04488926
org study id: MPS-FM
nct id: NCT04488926
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The onset of chronic Fibromyalgia symptomatology is due to central alterations, together with
      peripheral neuroimmune modifications. Using positron emission tomography (PET), it has been
      observed for the first time that fibromyalgia patients have a high activation of microglial
      cells compared to normal subjects. Experimental evidence in neuroinflammation models in vitro
      and in vivo have demonstrated the anti-inflammatory and neuroprotective effect of
      Palmitoylethanolamide (PEA), effects confirmed by observational clinical investigations
      conducted in patients with fibromyalgia in which micronized and ultra-micronized
      Palmitoylethanolamide (mPEA and umPEA) reduced the intensity of pain improving the quality of
      life. The aim of this study is to investigate the efficacy and tolerability of PEA-m + PEA-um
      administered as an add-on therapy with a double-blind, randomized, placebo-controlled
      clinical investigation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Fibromyalgia symptoms assessed by Fibromyalgia Impact Questionnaire Revised
time frame: 90 days
description: Change of Fibromyalgia symptoms
measure: Pain Intensity assessed by Visual Analogue Scale
time frame: 90 days
description: Change of Visual Analogue Scale every 30 days (0: no pain - 100 mm: maximum pain)
measure: Health assessed by Short form-12 Health Survey
time frame: 90 days
description: Change in Health at the end of treatment
measure: Sleep Disorders assessed by Pittsburgh Sleep Quality Index
time frame: 90 days
description: Change in sleep disorders at the end of treatment
measure: Rescue Drugs consumption assessed by a daily diary
time frame: 90 days
description: Change in rescue drugs consumption during the entire period
measure: Incidence of Adverse Events
time frame: 90 days
description: Monitoring of adverse event
measure: Blood test
time frame: 90 days
description: Clinically significant changes in blood test
arm group label: Group 1
arm group type: Active Comparator
description: Normast® MPS (mPEA and umPEA 300mg + 600mg) microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days
arm group label: Group 2
arm group type: Placebo Comparator
description: Placebo microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days
intervention type: Dietary Supplement
intervention name: micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) microgranules
description: Micronized and ultra-micronized Palmitoylethanolamide is on the market in Italy as a Food for Special Medical Purposes
arm group label: Group 1
other name: Normast® MPS microgranules
intervention type: Other
intervention name: Placebo microgranules 1800mg
description: Placebo was prepared to be indistinguishable from color and flavor from the Product
arm group label: Group 2
intervention type: Drug
intervention name: Standard Therapy
description: (antidepressants, anticonvulsants, muscle relaxants, weak opiates, etc..) consolidated for at least 3 months
arm group label: Group 1
arm group label: Group 2
intervention type: Drug
intervention name: Rescue Drug
description: Use as needed allowed
arm group label: Group 1
arm group label: Group 2
other name: Paracetamol or Fans
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Enrico Polati, MD
role: Principal Investigator
affiliation: Azienda Ospedaliera Universitaria Integrata di Verona
facility: 
country: Italy
url: https://pubmed.ncbi.nlm.nih.gov/30827269/
description: Related Info
citation: Schweiger V, Martini A, Bellamoli P, Donadello K, Schievano C, Balzo GD, Sarzi-Puttini P, Parolini M, Polati E. Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients. CNS Neurol Disord Drug Targets. 2019;18(4):326-333. doi: 10.2174/1871527318666190227205359.
PMID: 30827269
responsible party type: Sponsor
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
mesh term: Palmidrol