<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/NCT02203201</url>
  </required_header>
  <id_info>
    <org_study_id>ACPM04</org_study_id>
    <nct_id>NCT02203201</nct_id>
  </id_info>
  <brief_title>Diagnostic Significance of Positive EmA Antibodies in the Duodenal Culture Medium of Not-Celiac Wheat Sensitivity (NCWS)</brief_title>
  <acronym>NCWS</acronym>
  <official_title>Diagnostic Significance of Positive Anti-endomysium Antibodies in the Culture Medium of the Intestinal Biopsies in Not-Celiac Wheat Sensitivity (NCWS)</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e.&#xD;
      celiac disease and immunoglobulin E (IgE)-mediated allergic reactions. However, besides&#xD;
      celiac disease and wheat allergy, there are cases of gluten reactions in which neither&#xD;
      autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as&#xD;
      GS or Not-celiac wheat sensitivity (NCWS). Typically, NCWS diagnosis is made by exclusion,&#xD;
      and an elimination diet and an &quot;open challenge&quot; (i.e., the monitored reintroduction of&#xD;
      gluten-containing foods) are most often used to evaluate whether health improves or worsen&#xD;
      with the elimination or reintroduction of gluten in the diet, respectively. In some&#xD;
      circumstances, it is very difficult to distinguish between NCWS and celiac disease. The&#xD;
      presence of positive celiac disease specific serum antibodies (anti-tissue transglutaminase&#xD;
      (anti-tTG), and anti-endomysium (EmAs) antibodies) is of paramount importance to pose the&#xD;
      diagnosis. However, it is well known that the frequency of a positive serology is dependent&#xD;
      by the severity of the intestinal damage. Consequently, patients with less severe histology&#xD;
      damage (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that&#xD;
      EmAs are produced by the intestinal lymphocytes and previous data from our group showed that&#xD;
      EmAs assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy&#xD;
      than serum EmAs in diagnosis. Therefore, the aims of our study are to evaluate the&#xD;
      clinical-serologic-histology course of NCWS patients, showing positive EmAs assay in the&#xD;
      culture medium of the duodenal biopsies at the time of the first evaluation, and the&#xD;
      adherence to a gluten-free diet in NCWS patients after a previous full evaluation and a NCWS&#xD;
      diagnosis based on double-blinded placebo-controlled (DBPC) challenge.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gluten is the most important protein component of some grains, notably wheat, rye, and&#xD;
      barley, which are the basis for a variety of wheat-derived alimentary products consumed&#xD;
      throughout the world (bread, pasta, pizza etc). However the &quot;engineering&quot; of&#xD;
      gluten-containing grains created the conditions for human diseases related to gluten&#xD;
      exposure. These forms of gluten intolerance represent a heterogeneous set of conditions,&#xD;
      including celiac disease, wheat allergy and gluten sensitivity (GS), that, combined, seems to&#xD;
      affect about 10% of the general population.&#xD;
&#xD;
      The immune responsiveness to wheat antigens represents a complex process, and its&#xD;
      establishment and maintenance are not completely elucidated. The most frequent diseases&#xD;
      caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and IgE-mediated&#xD;
      allergic reactions. However, besides celiac disease and wheat allergy, there are cases of&#xD;
      gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are&#xD;
      involved. These are generally defined as GS or Not-celiac wheat sensitivity (NCWS), because&#xD;
      it is not known what component of the cereals causes the symptoms. Some subjects, who&#xD;
      experience symptoms when eating gluten-containing products and show improvement when&#xD;
      following a gluten-free diet (GFD) may have NCWS instead of celiac disease or wheat allergy.&#xD;
      NCWS patients are unable to tolerate gluten and develop an adverse reaction when eating&#xD;
      gluten, that, usually, and differently from celiac disease, does not lead to small intestinal&#xD;
      damage. Gastrointestinal symptoms in NCWS patients may resemble those associated with celiac&#xD;
      disease, but the overall clinical picture is generally less severe.&#xD;
&#xD;
      Typically, NCWS diagnosis is made by exclusion, and an elimination diet and an &quot;open&#xD;
      challenge&quot; (i.e., the monitored reintroduction of gluten-containing foods) are most often&#xD;
      used to evaluate whether health improves or worsen with the elimination or reintroduction of&#xD;
      gluten in the diet, respectively.&#xD;
&#xD;
      The frequency of NCWS is however still unknown, even though some studies indicated that it is&#xD;
      higher than that of celiac disease; consequently, it is very probable that this condition&#xD;
      have been undiagnosed and under-diagnosed by the physicians for a long time. However, it is&#xD;
      very difficult, in some circumstances, to distinguish between NCWS and celiac disease. In&#xD;
      fact, NCWS patients can show an intestinal histology characterized by intra-epithelial&#xD;
      lymphocytosis (Marsh 1), a finding considered compatible with a celiac disease diagnosis. In&#xD;
      this difficult, possible, celiac disease diagnosis, the presence of positive specific serum&#xD;
      antibodies (anti-tTG and EmAs) is of paramount importance to pose the diagnosis. However, it&#xD;
      is well known that the frequency of a positive serology is dependent by the severity of the&#xD;
      intestinal damage. Consequently, celiac disease patients with less severe histology damage&#xD;
      (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that EmAs are&#xD;
      produced by the intestinal lymphocytes and previous data from our group showed that EmAs&#xD;
      assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy than&#xD;
      serum EmAs in celiac disease diagnosis.&#xD;
&#xD;
      Therefore, this study has one major aim: 1. Evaluation of the clinical-serologic-histology&#xD;
      course of NCWS patients showing positive EmAs assay in the culture medium of the duodenal&#xD;
      biopsies at the time of the first evaluation; and one secondary aim: 2. Evaluation of the&#xD;
      adherence to a GFD in NCWS patients after a previous full evaluation and a NCWS diagnosis&#xD;
      based on double-blinded placebo-controlled (DBPC) challenge.&#xD;
&#xD;
      For our research, the investigators will select adult patients, both genders, affected with&#xD;
      NCWS (i.e. with symptoms/signs which disappeared on gluten-free diet and worsen on a gluten&#xD;
      containing diet, testing negative for celiac disease, [anti-tTG and EmAs negative, and with&#xD;
      biopsy Marsh 0-1] and wheat allergy [serum specific IgE for wheat negative]).&#xD;
&#xD;
      The investigators will include exclusively patients who had been previously fully evaluated&#xD;
      for suspected celiac disease in our Hospitals (Department of Internal Medicine, Giovanni&#xD;
      Paolo II Hospital of Sciacca, Agrigento, and of Internal Medicine of the University of&#xD;
      Palermo) from January 2002 to December 2012. In all patients NCWS diagnosis had been posed by&#xD;
      means of a DBPC challenge with wheat flour. At the time of the first evaluation, gluten-free&#xD;
      diet was not prescribed, but simply suggested, as these patients were not considered as&#xD;
      suffering from celiac disease.&#xD;
&#xD;
      The investigators will recruit, as a study group, those NCWS patients who had showed a&#xD;
      negative celiac disease serology and Marsh 0-1 duodenal histology, but who had displayed a&#xD;
      positive EmAs assay in the culture medium of the duodenal biopsies (EmA-biopsy). As control&#xD;
      group, NCWS patients with negative EmA-biopsy will be included.&#xD;
&#xD;
      The investigators will include at least one year before evaluated patients. At the time of&#xD;
      the recruitment it will be evaluated both the adherence to the gluten-free diet, by means of&#xD;
      a previously validated dietary form containing a printed list of the most common foods, and&#xD;
      the symptoms score (Gastrointestinal Symptom Rating Scale, GSRS). Then, the investigators&#xD;
      will re-evaluate the patients for a possible celiac disease diagnosis. Serum anti-tTG IgA and&#xD;
      IgG, anti-deamidated peptides of gliadin (DPG) IgA and IgG, and anti-gliadin (AGA) IgA and&#xD;
      IgG will be assayed. Duodenal biopsies will be taken for histological evaluation and for&#xD;
      culture EmAs assay.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2014</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">October 1, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in the intestinal histology of NCWS patients who tested positives for EmAs in the culture medium of the intestinal biopsies, at the time of the first evaluation.</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>Intestinal histology re-evaluation after at least one year since the initial NCWS diagnosis was posed. Marsh classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation.&#xD;
The above parameter will be evaluated taking into account whether the patients adhered or not to a wheat-free diet.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum anti-tTG antibodies evaluation.</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>Evaluation of changes in serum levels of anti-tTG antibodies after at least one year since the initial NCWS diagnosis was posed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum DPG antibodies evaluation.</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>Evaluation of changes in serum levels of DPG antibodies after at least one year since the initial NCWS diagnosis was posed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum AGA evaluation.</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>Evaluation of changes in serum levels of AGA after at least one year since the initial NCWS diagnosis was posed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to a wheat-free diet</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>Degree of adherence to a wheat-free diet since the initial diagnosis of NCWS was posed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms/signs evaluation.</measure>
    <time_frame>At baseline and after at least one year since the initial NCWS diagnosis was posed.</time_frame>
    <description>The evaluation of changes in symptoms/signs will be made according to the score calculated on the basis of the Visual Analogue Scale since the initial diagnosis of NCWS was posed.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">50</enrollment>
  <condition>Not-celiac Gluten Sensitivity</condition>
  <arm_group>
    <arm_group_label>Study group</arm_group_label>
    <description>NCWS patients who had showed a negative celiac disease serology and a Marsh 0-1 duodenal histology, but who had displayed a positive EmA assay in the culture medium of the duodenal biopsies (EmA-biopsy).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>NCWS patients with negative EmA-biopsy.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators will include exclusively patients who had been previously fully evaluated&#xD;
        for suspected celiac disease in our Hospitals (Department of Internal Medicine, Giovanni&#xD;
        Paolo II Hospital of Sciacca, Agrigento, and of Internal Medicine of the University of&#xD;
        Palermo) from January 2002 to December 2012. In all patients NCWS diagnosis had been posed&#xD;
        by means of a double-blind placebo-controlled (DBPC) challenge with wheat flour.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients, both genders, with age between 18-65 years, that has been previously&#xD;
             diagnosed as NCWS, according to a DBPC method&#xD;
&#xD;
          -  Patients testing negative for celiac disease ( anti-tTG and EMA negative, and with&#xD;
             biopsy Marsh 0-1) and wheat allergy (serum specific igE for wheat negative)&#xD;
&#xD;
          -  Patients showed positive EmAs in the culture medium of the duodenal biopsies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects diagnosed with celiac disease (positive anti-tTG and/or EMA, and positive&#xD;
             histology, with Marsh 2 or above)&#xD;
&#xD;
          -  Subjects diagnosed with wheat allergy (positive serum specific IgE for wheat)&#xD;
&#xD;
          -  Subjects with Type 1 Diabetes&#xD;
&#xD;
          -  Subjects with Inflammatory Bowel Diseases (Crohn's disease or ulcerative colitis)&#xD;
&#xD;
          -  Subjects with Helicobacter pylori infection and other gastrointestinal infection&#xD;
&#xD;
          -  Pregnancy&#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, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Palermo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pasquale Mansueto, MD</last_name>
    <role>Principal Investigator</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>
  <reference>
    <citation>Carroccio A, Iacono G, Di Prima L, Pirrone G, Cavataio F, Ambrosiano G, Sciume C, Geraci G, Florena A, Teresi S, Barbaria F, Pepe I, Campisi G, Mansueto P, Soresi M, Di Fede G. Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis. Eur J Gastroenterol Hepatol. 2011 Nov;23(11):1018-23. doi: 10.1097/MEG.0b013e328349b8a5.</citation>
    <PMID>21885984</PMID>
  </reference>
  <reference>
    <citation>Carroccio A, Iacono G, D'Amico D, Cavataio F, Teresi S, Caruso C, Di PL, Colombo A, D'Arpa F, Florena A, Notarbartolo A, Montalto G. Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis. Scand J Gastroenterol. 2002 Jan;37(1):32-8. doi: 10.1080/003655202753387329.</citation>
    <PMID>11843032</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>June 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 26, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>October 7, 2020</last_update_submitted>
  <last_update_submitted_qc>October 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 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>Researcher</investigator_title>
  </responsible_party>
  <keyword>Not-celiac gluten sensitivity</keyword>
  <keyword>Celiac Disease</keyword>
  <keyword>Gluten-free diet</keyword>
  <keyword>EMA assay</keyword>
  <keyword>Duodenal culture medium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiac Disease</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_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/NCT02203201
org study id: ACPM04
nct id: NCT02203201
lead sponsor: 
has dmc: No
The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, i.e.
      celiac disease and immunoglobulin E (IgE)-mediated allergic reactions. However, besides
      celiac disease and wheat allergy, there are cases of gluten reactions in which neither
      autoimmune nor IgE-mediated allergic mechanisms are involved. These are generally defined as
      GS or Not-celiac wheat sensitivity (NCWS). Typically, NCWS diagnosis is made by exclusion,
      and an elimination diet and an "open challenge" (i.e., the monitored reintroduction of
      gluten-containing foods) are most often used to evaluate whether health improves or worsen
      with the elimination or reintroduction of gluten in the diet, respectively. In some
      circumstances, it is very difficult to distinguish between NCWS and celiac disease. The
      presence of positive celiac disease specific serum antibodies (anti-tissue transglutaminase
      (anti-tTG), and anti-endomysium (EmAs) antibodies) is of paramount importance to pose the
      diagnosis. However, it is well known that the frequency of a positive serology is dependent
      by the severity of the intestinal damage. Consequently, patients with less severe histology
      damage (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that
      EmAs are produced by the intestinal lymphocytes and previous data from our group showed that
      EmAs assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy
      than serum EmAs in diagnosis. Therefore, the aims of our study are to evaluate the
      clinical-serologic-histology course of NCWS patients, showing positive EmAs assay in the
      culture medium of the duodenal biopsies at the time of the first evaluation, and the
      adherence to a gluten-free diet in NCWS patients after a previous full evaluation and a NCWS
      diagnosis based on double-blinded placebo-controlled (DBPC) challenge.
Gluten is the most important protein component of some grains, notably wheat, rye, and
      barley, which are the basis for a variety of wheat-derived alimentary products consumed
      throughout the world (bread, pasta, pizza etc). However the "engineering" of
      gluten-containing grains created the conditions for human diseases related to gluten
      exposure. These forms of gluten intolerance represent a heterogeneous set of conditions,
      including celiac disease, wheat allergy and gluten sensitivity (GS), that, combined, seems to
      affect about 10% of the general population.

      The immune responsiveness to wheat antigens represents a complex process, and its
      establishment and maintenance are not completely elucidated. The most frequent diseases
      caused by wheat ingestion are T cell-mediated disorders, i.e. celiac disease and IgE-mediated
      allergic reactions. However, besides celiac disease and wheat allergy, there are cases of
      gluten reactions in which neither autoimmune nor IgE-mediated allergic mechanisms are
      involved. These are generally defined as GS or Not-celiac wheat sensitivity (NCWS), because
      it is not known what component of the cereals causes the symptoms. Some subjects, who
      experience symptoms when eating gluten-containing products and show improvement when
      following a gluten-free diet (GFD) may have NCWS instead of celiac disease or wheat allergy.
      NCWS patients are unable to tolerate gluten and develop an adverse reaction when eating
      gluten, that, usually, and differently from celiac disease, does not lead to small intestinal
      damage. Gastrointestinal symptoms in NCWS patients may resemble those associated with celiac
      disease, but the overall clinical picture is generally less severe.

      Typically, NCWS diagnosis is made by exclusion, and an elimination diet and an "open
      challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often
      used to evaluate whether health improves or worsen with the elimination or reintroduction of
      gluten in the diet, respectively.

      The frequency of NCWS is however still unknown, even though some studies indicated that it is
      higher than that of celiac disease; consequently, it is very probable that this condition
      have been undiagnosed and under-diagnosed by the physicians for a long time. However, it is
      very difficult, in some circumstances, to distinguish between NCWS and celiac disease. In
      fact, NCWS patients can show an intestinal histology characterized by intra-epithelial
      lymphocytosis (Marsh 1), a finding considered compatible with a celiac disease diagnosis. In
      this difficult, possible, celiac disease diagnosis, the presence of positive specific serum
      antibodies (anti-tTG and EmAs) is of paramount importance to pose the diagnosis. However, it
      is well known that the frequency of a positive serology is dependent by the severity of the
      intestinal damage. Consequently, celiac disease patients with less severe histology damage
      (Marsh 1) can have negative serum antibodies. Previous studies had demonstrated that EmAs are
      produced by the intestinal lymphocytes and previous data from our group showed that EmAs
      assay in the culture medium of the intestinal biopsies has higher diagnostic accuracy than
      serum EmAs in celiac disease diagnosis.

      Therefore, this study has one major aim: 1. Evaluation of the clinical-serologic-histology
      course of NCWS patients showing positive EmAs assay in the culture medium of the duodenal
      biopsies at the time of the first evaluation; and one secondary aim: 2. Evaluation of the
      adherence to a GFD in NCWS patients after a previous full evaluation and a NCWS diagnosis
      based on double-blinded placebo-controlled (DBPC) challenge.

      For our research, the investigators will select adult patients, both genders, affected with
      NCWS (i.e. with symptoms/signs which disappeared on gluten-free diet and worsen on a gluten
      containing diet, testing negative for celiac disease, [anti-tTG and EmAs negative, and with
      biopsy Marsh 0-1] and wheat allergy [serum specific IgE for wheat negative]).

      The investigators will include exclusively patients who had been previously fully evaluated
      for suspected celiac disease in our Hospitals (Department of Internal Medicine, Giovanni
      Paolo II Hospital of Sciacca, Agrigento, and of Internal Medicine of the University of
      Palermo) from January 2002 to December 2012. In all patients NCWS diagnosis had been posed by
      means of a DBPC challenge with wheat flour. At the time of the first evaluation, gluten-free
      diet was not prescribed, but simply suggested, as these patients were not considered as
      suffering from celiac disease.

      The investigators will recruit, as a study group, those NCWS patients who had showed a
      negative celiac disease serology and Marsh 0-1 duodenal histology, but who had displayed a
      positive EmAs assay in the culture medium of the duodenal biopsies (EmA-biopsy). As control
      group, NCWS patients with negative EmA-biopsy will be included.

      The investigators will include at least one year before evaluated patients. At the time of
      the recruitment it will be evaluated both the adherence to the gluten-free diet, by means of
      a previously validated dietary form containing a printed list of the most common foods, and
      the symptoms score (Gastrointestinal Symptom Rating Scale, GSRS). Then, the investigators
      will re-evaluate the patients for a possible celiac disease diagnosis. Serum anti-tTG IgA and
      IgG, anti-deamidated peptides of gliadin (DPG) IgA and IgG, and anti-gliadin (AGA) IgA and
      IgG will be assayed. Duodenal biopsies will be taken for histological evaluation and for
      culture EmAs assay.
observational model: Case-Control
time perspective: Prospective
measure: Changes in the intestinal histology of NCWS patients who tested positives for EmAs in the culture medium of the intestinal biopsies, at the time of the first evaluation.
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: Intestinal histology re-evaluation after at least one year since the initial NCWS diagnosis was posed. Marsh classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation.
The above parameter will be evaluated taking into account whether the patients adhered or not to a wheat-free diet.
measure: Serum anti-tTG antibodies evaluation.
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: Evaluation of changes in serum levels of anti-tTG antibodies after at least one year since the initial NCWS diagnosis was posed.
measure: Serum DPG antibodies evaluation.
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: Evaluation of changes in serum levels of DPG antibodies after at least one year since the initial NCWS diagnosis was posed.
measure: Serum AGA evaluation.
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: Evaluation of changes in serum levels of AGA after at least one year since the initial NCWS diagnosis was posed.
measure: Adherence to a wheat-free diet
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: Degree of adherence to a wheat-free diet since the initial diagnosis of NCWS was posed.
measure: Symptoms/signs evaluation.
time frame: At baseline and after at least one year since the initial NCWS diagnosis was posed.
description: The evaluation of changes in symptoms/signs will be made according to the score calculated on the basis of the Visual Analogue Scale since the initial diagnosis of NCWS was posed.
arm group label: Study group
description: NCWS patients who had showed a negative celiac disease serology and a Marsh 0-1 duodenal histology, but who had displayed a positive EmA assay in the culture medium of the duodenal biopsies (EmA-biopsy).
arm group label: Control group
description: NCWS patients with negative EmA-biopsy.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Antonio Carroccio, MD, PhD
role: Study Director
affiliation: University of Palermo
last name: Pasquale Mansueto, MD
role: Principal Investigator
affiliation: University of Palermo
facility: 
facility: 
country: Italy
citation: Carroccio A, Iacono G, Di Prima L, Pirrone G, Cavataio F, Ambrosiano G, Sciume C, Geraci G, Florena A, Teresi S, Barbaria F, Pepe I, Campisi G, Mansueto P, Soresi M, Di Fede G. Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis. Eur J Gastroenterol Hepatol. 2011 Nov;23(11):1018-23. doi: 10.1097/MEG.0b013e328349b8a5.
PMID: 21885984
citation: Carroccio A, Iacono G, D'Amico D, Cavataio F, Teresi S, Caruso C, Di PL, Colombo A, D'Arpa F, Florena A, Notarbartolo A, Montalto G. Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis. Scand J Gastroenterol. 2002 Jan;37(1):32-8. doi: 10.1080/003655202753387329.
PMID: 11843032
responsible party type: Principal Investigator
investigator affiliation: University of Palermo
investigator full name: Pasquale Mansueto
investigator title: Researcher
mesh term: Celiac Disease
mesh term: Hypersensitivity