<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/NCT03022513</url>
  </required_header>
  <id_info>
    <org_study_id>ACPM13</org_study_id>
    <nct_id>NCT03022513</nct_id>
  </id_info>
  <brief_title>Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients</brief_title>
  <official_title>Fibromyalgia-like Joint/Muscle Pain and Synovitis in Non-celiac Wheat Sensitivity Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Palermo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Palermo</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>
      Recently it has been reported that a consistent percentage of the general population consider&#xD;
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though&#xD;
      they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac&#xD;
      Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term&#xD;
      'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes&#xD;
      the symptoms in NCGS patients, and the investigators also showed that these patients had a&#xD;
      high frequency of coexistent multiple food hypersensitivity. The clinical picture of NCWS is&#xD;
      characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or&#xD;
      constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and&#xD;
      extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,'&#xD;
      tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness,&#xD;
      and anemia). Nowadays no data are available on the characteristic of 'rheumatologic' symptoms&#xD;
      of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the&#xD;
      prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible&#xD;
      ultrasonographic alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and&#xD;
      3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a&#xD;
      gluten free diet period of almost 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recently it has been reported that a consistent percentage of the general population consider&#xD;
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though&#xD;
      they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac&#xD;
      Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term&#xD;
      'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes&#xD;
      the symptoms in NCGS patients, and the investigators also showed that these patients had a&#xD;
      high frequency of coexistent multiple food hypersensitivity. CD is an immunological disorder&#xD;
      whose best-known manifestations are gastrointestinal symptoms. However, early joint&#xD;
      manifestations are common and frequently overlooked features of the disease. Similarly, the&#xD;
      clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal&#xD;
      pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux,&#xD;
      aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache,&#xD;
      depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like&#xD;
      joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the&#xD;
      characteristic of 'rheumatological' symptoms of NCWS patients. Therefore, the aims of the&#xD;
      present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in&#xD;
      NCWS patient, 2) to search for possible ultrasonographical alterations (i.e. synovitis) of&#xD;
      hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like&#xD;
      joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">June 1, 2018</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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Prevalence of fibromyalgia-like joint/muscle pain in NCWS patient using an ad hoc questionnaire and orientated clinical examination (tenders and triggers point evaluation)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hands and feet joints ultrasonography alterations</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Hands and feet joints ultrasonography alterations in NCWS patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Modification of fibromyalgia-like joint/muscle pain, by visual analogic scale, in NCWS patients after a gluten free diet period of almost 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Modifications of hands and feet joints ultrasonography alterations in NCWS patients after a gluten free diet period of almost 6 months.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Non-celiac Wheat Sensitivity</condition>
  <arm_group>
    <arm_group_label>NCWS patients</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fifty consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CD patients</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Fifty sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as first control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IBS patients</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Fifty sex- and age-matched subjects with IBS unrelated to NCWS or other food 'intolerance', diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as second control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gluten free diet</intervention_name>
    <description>The investigators will evaluate the prevalence of fibromyalgia-like joint/muscle pain and the possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints in NCWS patient at baseline (i.e. at the moment of diagnosis) and after a gluten free diet period of almost 6 months.</description>
    <arm_group_label>NCWS patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All the patients met the recently proposed criteria:&#xD;
&#xD;
          -  negative serum anti-tissue transglutaminase and antiendomysium (EmA) immunoglobulin&#xD;
             (Ig) A and IgG antibodies&#xD;
&#xD;
          -  absence of intestinal villous atrophy&#xD;
&#xD;
          -  IgE-mediated immunoallergic tests negative to wheat and cow's milk protein (skin prick&#xD;
             tests and/or serum specific IgE detection).&#xD;
&#xD;
        Adjunctive criteria adopted in our patients were:&#xD;
&#xD;
          -  resolution of the gastrointestinal and extra-intestinal symptoms on a standard&#xD;
             elimination diet, without wheat, cow's milk, egg, tomato, chocolate, or other food(s)&#xD;
             causing self-reported symptoms&#xD;
&#xD;
          -  symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge,&#xD;
             performed as described previously. DBPC cow's milk protein challenge will be also&#xD;
             performed to diagnose cow's milk protein allergy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria will be:&#xD;
&#xD;
          -  age &lt;18 years&#xD;
&#xD;
          -  positive EmA in the culture medium of the duodenal biopsies, even if the villi to&#xD;
             crypts ratio in the duodenal mucosa was normal&#xD;
&#xD;
          -  self-exclusion of wheat from the diet and refusal to reintroduce it before entering&#xD;
             the study&#xD;
&#xD;
          -  other organic gastrointestinal diseases&#xD;
&#xD;
          -  previously diagnosed rheumatic diseases&#xD;
&#xD;
          -  nervous system disease and/or major psychiatric disorder&#xD;
&#xD;
          -  physical impairment limiting physical activity&#xD;
&#xD;
          -  menopause; steroid and sex steroid therapy, hormone replacement therapy or&#xD;
             ovariectomy.&#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>Antonio Carroccio, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Palermo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Internal Medicine, Giovanni Paolo II Hospital of Sciacca</name>
      <address>
        <city>Sciacca</city>
        <state>Agrigento</state>
        <zip>92019</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Internal Medicine, University Hospital of Palermo</name>
      <address>
        <city>Palermo</city>
        <zip>90129</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <results_reference>
    <citation>Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.</citation>
    <PMID>22825366</PMID>
  </results_reference>
  <results_reference>
    <citation>Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996.</citation>
    <PMID>24533607</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.</citation>
    <PMID>24275240</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, D'Alcamo A, Mansueto P. Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy. Gastroenterology. 2015 Mar;148(3):666-7. doi: 10.1053/j.gastro.2014.11.047. Epub 2015 Jan 24. No abstract available.</citation>
    <PMID>25625764</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Soresi M, D'Alcamo A, Sciume C, Iacono G, Geraci G, Brusca I, Seidita A, Adragna F, Carta M, Mansueto P. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med. 2014 Nov 28;12:230. doi: 10.1186/s12916-014-0230-2.</citation>
    <PMID>25430806</PMID>
  </results_reference>
  <results_reference>
    <citation>Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Role of FODMAPs in Patients With Irritable Bowel Syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82. doi: 10.1177/0884533615569886. Epub 2015 Feb 18.</citation>
    <PMID>25694210</PMID>
  </results_reference>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>December 30, 2016</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>April 26, 2020</last_update_submitted>
  <last_update_submitted_qc>April 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Palermo</investigator_affiliation>
    <investigator_full_name>Pasquale Mansueto</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Non-celiac Wheat Sensitivity</keyword>
  <keyword>fibromyalgia</keyword>
  <keyword>synovitis</keyword>
  <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>
    <mesh_term>Synovitis</mesh_term>
    <mesh_term>Myalgia</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03022513
org study id: ACPM13
nct id: NCT03022513
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recently it has been reported that a consistent percentage of the general population consider
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though
      they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac
      Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term
      'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes
      the symptoms in NCGS patients, and the investigators also showed that these patients had a
      high frequency of coexistent multiple food hypersensitivity. The clinical picture of NCWS is
      characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or
      constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and
      extra-intestinal and/or systemic manifestations (headache, depression, anxiety, 'foggy mind,'
      tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness,
      and anemia). Nowadays no data are available on the characteristic of 'rheumatologic' symptoms
      of NCWS patients. Therefore, the aims of the present study are: 1) to investigate the
      prevalence of fibromyalgia-like joint/muscle pain in NCWS patient, 2) to search for possible
      ultrasonographic alterations (i.e. synovitis) of hands and feet joints of NCWS patients, and
      3) to evaluate modification of fibromyalgia-like joint/muscle pain in NCWS patients after a
      gluten free diet period of almost 6 months.
Recently it has been reported that a consistent percentage of the general population consider
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though
      they do not have CD or wheat allergy. This clinical condition has been named Non-Celiac
      Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the term
      'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat causes
      the symptoms in NCGS patients, and the investigators also showed that these patients had a
      high frequency of coexistent multiple food hypersensitivity. CD is an immunological disorder
      whose best-known manifestations are gastrointestinal symptoms. However, early joint
      manifestations are common and frequently overlooked features of the disease. Similarly, the
      clinical picture of NCWS is characterized by combined gastrointestinal (bloating, abdominal
      pain, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux,
      aphthous stomatitis) and extra-intestinal and/or systemic manifestations (headache,
      depression, anxiety, 'foggy mind,' tiredness, dermatitis or skin rash, fibromyalgia-like
      joint/muscle pain, leg or arm numbness, and anemia). Nowadays no data are available on the
      characteristic of 'rheumatological' symptoms of NCWS patients. Therefore, the aims of the
      present study are: 1) to investigate the prevalence of fibromyalgia-like joint/muscle pain in
      NCWS patient, 2) to search for possible ultrasonographical alterations (i.e. synovitis) of
      hands and feet joints of NCWS patients, and 3) to evaluate modification of fibromyalgia-like
      joint/muscle pain in NCWS patients after a gluten free diet period of almost 6 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Prevalence of fibromyalgia-like joint/muscle pain in NCWS patients
time frame: up to 12 months
description: Prevalence of fibromyalgia-like joint/muscle pain in NCWS patient using an ad hoc questionnaire and orientated clinical examination (tenders and triggers point evaluation)
measure: Hands and feet joints ultrasonography alterations
time frame: up to 12 months
description: Hands and feet joints ultrasonography alterations in NCWS patients.
measure: Modification of fibromyalgia-like joint/muscle pain in NCWS patients after gluten free diet
time frame: up to 12 months
description: Modification of fibromyalgia-like joint/muscle pain, by visual analogic scale, in NCWS patients after a gluten free diet period of almost 6 months.
measure: Modifications of hands and feet joints ultrasonography alterations in NCWS patients after gluten free diet
time frame: up to 12 months
description: Modifications of hands and feet joints ultrasonography alterations in NCWS patients after a gluten free diet period of almost 6 months.
arm group label: NCWS patients
arm group type: Active Comparator
description: Fifty consecutive adult patients with an irritable bowel syndrome (IBS)-like clinical presentation, according to Rome III criteria, and a definitive diagnosis of NCWS. The patients will be recruited between January 2017 and January 2018 at 2 centers: the Department of Internal Medicine at the University Hospital of Palermo, Italy, and the Department of Internal Medicine of the Hospital of Sciacca, Agrigento, Italy. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.
arm group label: CD patients
arm group type: No Intervention
description: Fifty sex- and age-matched subjects with CD, diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as first control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo, Italy.
arm group label: IBS patients
arm group type: No Intervention
description: Fifty sex- and age-matched subjects with IBS unrelated to NCWS or other food 'intolerance', diagnosed according to standard criteria during the same study period and enrolled, at the same 2 centers, as second control group. All subjects will undergo clinical evaluation and hands and feet joints ultrasonography at the Rheumatology Unit of the University of Palermo.
intervention type: Other
intervention name: Gluten free diet
description: The investigators will evaluate the prevalence of fibromyalgia-like joint/muscle pain and the possible ultrasonographical alterations (i.e. synovitis) of hands and feet joints in NCWS patient at baseline (i.e. at the moment of diagnosis) and after a gluten free diet period of almost 6 months.
arm group label: NCWS patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Antonio Carroccio, PhD
role: Study Director
affiliation: University of Palermo
facility: 
facility: 
country: Italy
citation: Carroccio A, Mansueto P, Iacono G, Soresi M, D'Alcamo A, Cavataio F, Brusca I, Florena AM, Ambrosiano G, Seidita A, Pirrone G, Rini GB. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907. doi: 10.1038/ajg.2012.236. Epub 2012 Jul 24.
PMID: 22825366
citation: Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr. 2014;33(1):39-54. doi: 10.1080/07315724.2014.869996.
PMID: 24533607
citation: Carroccio A, Rini G, Mansueto P. Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity. Gastroenterology. 2014 Jan;146(1):320-1. doi: 10.1053/j.gastro.2013.08.061. Epub 2013 Nov 22. No abstract available.
PMID: 24275240
citation: Carroccio A, D'Alcamo A, Mansueto P. Nonceliac wheat sensitivity in the context of multiple food hypersensitivity: new data from confocal endomicroscopy. Gastroenterology. 2015 Mar;148(3):666-7. doi: 10.1053/j.gastro.2014.11.047. Epub 2015 Jan 24. No abstract available.
PMID: 25625764
citation: Carroccio A, Soresi M, D'Alcamo A, Sciume C, Iacono G, Geraci G, Brusca I, Seidita A, Adragna F, Carta M, Mansueto P. Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study. BMC Med. 2014 Nov 28;12:230. doi: 10.1186/s12916-014-0230-2.
PMID: 25430806
citation: Mansueto P, Seidita A, D'Alcamo A, Carroccio A. Role of FODMAPs in Patients With Irritable Bowel Syndrome. Nutr Clin Pract. 2015 Oct;30(5):665-82. doi: 10.1177/0884533615569886. Epub 2015 Feb 18.
PMID: 25694210
responsible party type: Principal Investigator
investigator affiliation: University of Palermo
investigator full name: Pasquale Mansueto
investigator title: MD
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
mesh term: Synovitis
mesh term: Myalgia
mesh term: Hypersensitivity
sharing ipd: No