<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/NCT03017716</url>
  </required_header>
  <id_info>
    <org_study_id>ACPM14</org_study_id>
    <nct_id>NCT03017716</nct_id>
  </id_info>
  <brief_title>Inflammatory Back Pain and Gluten Free Diet</brief_title>
  <official_title>Inflammatory Back Pain and Gluten Free Diet</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>
      Articular involvement is the most frequent extra-intestinal manifestation of inflammatory&#xD;
      bowel diseases (IBD). IBD-related spondyloarthropathy is mainly characterised by axial&#xD;
      involvement (including inflammatory back pain, isolated sacroiliitis and ankylosing&#xD;
      spondylitis) but may also be associated with peripheral symptoms (i.e peripheral arthritis,&#xD;
      dactylitis and enthesopathy, such as Achilles tendinitis, plantar fasciitis, and chest wall&#xD;
      pain). In particular, inflammatory back pain (IBP) is characterised by an insidious onset,&#xD;
      improves after exercise but not with rest, and is associated with morning stiffness. Up to&#xD;
      now, several criteria sets have been proposed to define IBP. Studies conducted in various&#xD;
      populations have confirmed a high sensitivity and specificity for the Berlin criteria. Celiac&#xD;
      disease (CD) is an autoimmune systemic disease having among its clinical manifestations&#xD;
      frequent symptoms common to rheumatologic diseases. Recently, it has been reported that a&#xD;
      consistent percentage of the general population consider themselves to be suffering from&#xD;
      problems caused by wheat and/or gluten ingestion, even though they do not have CD or wheat&#xD;
      allergy. This clinical condition has been named Non-Celiac Gluten Sensitivity' (NCGS) or&#xD;
      Non-celic Wheat Sensitivity (NCWS). The clinical picture of NCWS is characterized by combined&#xD;
      gastrointestinal and extra-intestinal or systemic manifestations. Many patients affected with&#xD;
      CD and NCWS complain of IBP-like symptoms, which generally improve, together with the other&#xD;
      clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore, the aims&#xD;
      of the present study are to investigate 1) the effect of a GFD in IBP patients, randomly&#xD;
      assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a&#xD;
      period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Articular involvement is the most frequent extra-intestinal manifestation of inflammatory&#xD;
      bowel diseases (IBD), frequently follows a course that is independent of the course of&#xD;
      intestinal involvement, and its diagnosis mainly relies on clinical evidence and imaging&#xD;
      data, because laboratory assessments are rarely useful. More in details, IBD-related&#xD;
      arthropathy is one of a group of inflammatory arthritides, known as seronegative&#xD;
      spondyloarthropathies, that also includes idiopathic ankylosing spondylitis, reactive&#xD;
      arthritis, psoriatic arthritis, and undifferentiated seronegative spondyloarthropathies, all&#xD;
      of which are classified on the basis of peripheral arthritis (asymmetrical, predominantly in&#xD;
      the lower extremities) and/or inflammatory spinal involvement in IBD patients using the&#xD;
      well-known criteria of the European Spondyloarthropathy Study Group. IBD-related&#xD;
      spondyloarthropathy is mainly characterised by axial involvement (including inflammatory back&#xD;
      pain, isolated sacroiliitis and ankylosing spondylitis) but may also be associated with&#xD;
      peripheral symptoms (i.e peripheral arthritis, dactylitis and enthesopathy, such as Achilles&#xD;
      tendinitis, plantar fasciitis, and chest wall pain). In particular, inflammatory back pain&#xD;
      (IBP) is characterised by an insidious onset, improves after exercise but not with rest, and&#xD;
      is associated with morning stiffness. It may also present as pain during the second half of&#xD;
      the night and/or alternating buttock pain. Up to now, several criteria sets have been&#xD;
      proposed to define IBP. Firstly, the Calin criteria set was developed in 1977 and has since&#xD;
      then been most widely used for defining IBP. The Calin criteria set has no entry criteria and&#xD;
      is not based on standardized questions. Studies conducted in various populations have&#xD;
      confirmed a high sensitivity for the Calin criteria, but shown much lower specificity than&#xD;
      that reported in the original study. Berlin criteria for IBP were derived from a controlled&#xD;
      study, including patients with ankylosing spondylitis and mechanical low back pain, who all&#xD;
      had chronic low back pain. Berlin criteria are applicable only to those patients with chronic&#xD;
      low back pain (&gt;3 months) and age younger than &lt;50 years old. This criteria set yielded a&#xD;
      sensitivity of 70% and a specificity of 81% if at least two of the four following criteria&#xD;
      were met: morning stiffness of &gt;30-min duration, improvement in back pain with exercise but&#xD;
      not with rest, awakening because of back pain during the second half of the night only, and&#xD;
      alternating buttock pain. Assessment of Spondyloarthritis International Society (ASAS) has&#xD;
      just recently published new criteria for classification of IBP. These were based on the&#xD;
      expert judgment of the rheumatologist as the &quot;gold standard&quot; for diagnosing IBP in patients&#xD;
      with chronic back pain of unknown origin. These new candidate IBP criteria administered by&#xD;
      the interviewing clinician included the domains &quot;improvement with exercise,&quot; &quot;nocturnal&#xD;
      pain,&quot; &quot;age at onset &lt;40 years,&quot; and &quot;no improvement with rest.&quot; They were then validated in&#xD;
      a distinct cohort of patients presenting to the rheumatologist with new-onset back pain and&#xD;
      were shown to have a sensitivity of 79.6% and specificity of 72.4%. Celiac disease (CD) is an&#xD;
      autoimmune systemic disease having among its clinical manifestations frequent symptoms common&#xD;
      to rheumatologic diseases, such as musculoskeletal pain, asthenia, and cognitive fatigue.&#xD;
      Recently, it has been reported that a consistent percentage of the general population&#xD;
      consider themselves to be suffering from problems caused by wheat and/or gluten ingestion,&#xD;
      even though they do not have CD or wheat allergy. This clinical condition has been named&#xD;
      Non-Celiac Gluten Sensitivity' (NCGS). In a previous paper the investigators suggested the&#xD;
      term 'Non-Celiac Wheat Sensitivity' (NCWS), since it is not known what component of wheat&#xD;
      causes the symptoms in NCGS patients, and the investigators also showed that these patients&#xD;
      had a high frequency of coexistent multiple food hypersensitivity. The clinical picture of&#xD;
      NCWS is characterized by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or&#xD;
      constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and&#xD;
      extra-intestinal 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). NCWS lacks of specific diagnostic tests, being its diagnosis essentially of&#xD;
      exclusion. Many patients affected with CD and NCWS complain of IBP-like symptoms, which&#xD;
      significantly affect the patients' quality of life and generally improve, together with the&#xD;
      other clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore,&#xD;
      the aims of the present study are to investigate 1) the effect of a GFD in IBP patients,&#xD;
      randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD,&#xD;
      for a period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">August 1, 2023</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2023</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Musculoskeletal (back pain) evaluation at baseline and after GFD</measure>
    <time_frame>Change from baseline at 12 months</time_frame>
    <description>Musculoskeletal (back pain) evaluation, from baseline at 12 months of GFD, according to the scores calculated on the basis of Visual Analogue Scales for Musculoskeletal (back pain), taking into account whether the patients adhered or not to the GFD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in cytokines production from peripheral blood mononuclear (PBMC) at baseline and after GFD</measure>
    <time_frame>Change from baseline at 12 months</time_frame>
    <description>Changes in cytokines production from peripheral blood mononuclear (PBMC), from baseline (i.e. at diagnosis) at 12 months of GFD, taking into account whether the patients adhered or not to the GFD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of IBP in CD and in NCWS patients.</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Prevalence of IBP in CD and in NCWS patients.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Inflammatory Back Pain</condition>
  <arm_group>
    <arm_group_label>IBP patients on standard therapy</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>IBP patients on standard therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IBP patients on standard therapy and GFD</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IBP patients on standard therapy and GFD</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gluten free diet</intervention_name>
    <description>The investigators will evaluate the effect of a gluten free diet (GFD) in IBP patients, randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a period of at least one year.</description>
    <arm_group_label>IBP patients on standard therapy and GFD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        To diagnose IBP the standard Berlin Criteria will be adopted. IBP is defined by at least 2&#xD;
        positive responses among four items:&#xD;
&#xD;
          -  morning stiffness &gt;30 min of duration&#xD;
&#xD;
          -  improvement in back pain with exercise but not with rest&#xD;
&#xD;
          -  awakening because of back pain during the second half of the night only&#xD;
&#xD;
          -  alternating buttock pain.&#xD;
&#xD;
        To diagnose CD the standard criteria will be adopted. All the patients will meet the&#xD;
        following criteria:&#xD;
&#xD;
          -  positive serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA)&#xD;
             immunoglobulin (Ig)A and IgG antibodies&#xD;
&#xD;
          -  presence of intestinal villous atrophy.&#xD;
&#xD;
        To diagnose NCWS the recently proposed criteria will be adopted. All the patients will meet&#xD;
        the following criteria:&#xD;
&#xD;
          -  negative serum anti-transglutaminase (anti-tTG) and anti-endomysium (EmA)&#xD;
             immunoglobulin (Ig)A and IgG antibodies&#xD;
&#xD;
          -  absence of intestinal villous atrophy&#xD;
&#xD;
          -  negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or serum&#xD;
             specific IgE detection)&#xD;
&#xD;
          -  resolution of the IBS symptoms on standard elimination diet, excluding wheat, cow's&#xD;
             milk, egg, tomato, chocolate, and other self-reported food(s) causing symptoms&#xD;
&#xD;
          -  symptom reappearance on double-blind placebo-controlled (DBPC) wheat challenge. As the&#xD;
             investigators previously described in other studies, DBPC cow's milk protein challenge&#xD;
             and other &quot;open&quot; food challenges will be performed too.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria for NCWS diagnosis will be:&#xD;
&#xD;
          -  positive EmA in the culture medium of the duodenal biopsies, also in the case of&#xD;
             normal villi/crypts ratio in the duodenal mucosa&#xD;
&#xD;
          -  self-exclusion of wheat from the diet and refusal to reintroduce it before entering&#xD;
             the study&#xD;
&#xD;
          -  other previously diagnosed gastrointestinal disorders&#xD;
&#xD;
          -  other previously diagnosed rheumatic diseases&#xD;
&#xD;
          -  nervous system disease and/or major psychiatric disorder&#xD;
&#xD;
          -  physical impairment limiting physical activity.&#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>
  <overall_contact>
    <last_name>Antonio Carroccio, PhD</last_name>
    <phone>+390916552884</phone>
    <email>acarroccio@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pasquale Mansueto, MD</last_name>
    <phone>+390916552884</phone>
    <email>pasquale.mansueto@unipa.it</email>
  </overall_contact_backup>
  <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>
    <contact>
      <last_name>Antonio Carroccio, MD, PhD</last_name>
      <phone>+390916554347</phone>
      <email>acarroccio@hotmail.com</email>
    </contact>
  </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>
    <contact>
      <last_name>Pasquale Mansueto, MD</last_name>
      <phone>+390916554347</phone>
      <email>pasquale.mansueto@unipa.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <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>
  <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. 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, Mansueto P, D'Alcamo A, Iacono G. Non-celiac wheat sensitivity as an allergic condition: personal experience and narrative review. Am J Gastroenterol. 2013 Dec;108(12):1845-52; quiz 1853. doi: 10.1038/ajg.2013.353. Epub 2013 Nov 5.</citation>
    <PMID>24169272</PMID>
  </results_reference>
  <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>Carroccio A, Brusca I, Mansueto P, D'alcamo A, Barrale M, Soresi M, Seidita A, La Chiusa SM, Iacono G, Sprini D. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients. Clin Chem Lab Med. 2013 Jun;51(6):1257-63. doi: 10.1515/cclm-2012-0609.</citation>
    <PMID>23183757</PMID>
  </results_reference>
  <results_reference>
    <citation>Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, Cats A, Dijkmans B, Olivieri I, Pasero G, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218-27. doi: 10.1002/art.1780341003.</citation>
    <PMID>1930310</PMID>
  </results_reference>
  <results_reference>
    <citation>Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA. 1977 Jun 13;237(24):2613-4.</citation>
    <PMID>140252</PMID>
  </results_reference>
  <results_reference>
    <citation>Rudwaleit M, Metter A, Listing J, Sieper J, Braun J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum. 2006 Feb;54(2):569-78. doi: 10.1002/art.21619.</citation>
    <PMID>16447233</PMID>
  </results_reference>
  <results_reference>
    <citation>Sieper J, van der Heijde D, Landewe R, Brandt J, Burgos-Vagas R, Collantes-Estevez E, Dijkmans B, Dougados M, Khan MA, Leirisalo-Repo M, van der Linden S, Maksymowych WP, Mielants H, Olivieri I, Rudwaleit M. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009 Jun;68(6):784-8. doi: 10.1136/ard.2008.101501. Epub 2009 Jan 15.</citation>
    <PMID>19147614</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 30, 2016</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>May 9, 2023</last_update_submitted>
  <last_update_submitted_qc>May 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2023</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>Inflammatory back pain</keyword>
  <keyword>gluten-free diet</keyword>
  <keyword>celiac disease</keyword>
  <keyword>non-celiac wheat sensitivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</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/NCT03017716
org study id: ACPM14
nct id: NCT03017716
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Articular involvement is the most frequent extra-intestinal manifestation of inflammatory
      bowel diseases (IBD). IBD-related spondyloarthropathy is mainly characterised by axial
      involvement (including inflammatory back pain, isolated sacroiliitis and ankylosing
      spondylitis) but may also be associated with peripheral symptoms (i.e peripheral arthritis,
      dactylitis and enthesopathy, such as Achilles tendinitis, plantar fasciitis, and chest wall
      pain). In particular, inflammatory back pain (IBP) is characterised by an insidious onset,
      improves after exercise but not with rest, and is associated with morning stiffness. Up to
      now, several criteria sets have been proposed to define IBP. Studies conducted in various
      populations have confirmed a high sensitivity and specificity for the Berlin criteria. Celiac
      disease (CD) is an autoimmune systemic disease having among its clinical manifestations
      frequent symptoms common to rheumatologic diseases. 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) or
      Non-celic Wheat Sensitivity (NCWS). The clinical picture of NCWS is characterized by combined
      gastrointestinal and extra-intestinal or systemic manifestations. Many patients affected with
      CD and NCWS complain of IBP-like symptoms, which generally improve, together with the other
      clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore, the aims
      of the present study are to investigate 1) the effect of a GFD in IBP patients, randomly
      assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a
      period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.
Articular involvement is the most frequent extra-intestinal manifestation of inflammatory
      bowel diseases (IBD), frequently follows a course that is independent of the course of
      intestinal involvement, and its diagnosis mainly relies on clinical evidence and imaging
      data, because laboratory assessments are rarely useful. More in details, IBD-related
      arthropathy is one of a group of inflammatory arthritides, known as seronegative
      spondyloarthropathies, that also includes idiopathic ankylosing spondylitis, reactive
      arthritis, psoriatic arthritis, and undifferentiated seronegative spondyloarthropathies, all
      of which are classified on the basis of peripheral arthritis (asymmetrical, predominantly in
      the lower extremities) and/or inflammatory spinal involvement in IBD patients using the
      well-known criteria of the European Spondyloarthropathy Study Group. IBD-related
      spondyloarthropathy is mainly characterised by axial involvement (including inflammatory back
      pain, isolated sacroiliitis and ankylosing spondylitis) but may also be associated with
      peripheral symptoms (i.e peripheral arthritis, dactylitis and enthesopathy, such as Achilles
      tendinitis, plantar fasciitis, and chest wall pain). In particular, inflammatory back pain
      (IBP) is characterised by an insidious onset, improves after exercise but not with rest, and
      is associated with morning stiffness. It may also present as pain during the second half of
      the night and/or alternating buttock pain. Up to now, several criteria sets have been
      proposed to define IBP. Firstly, the Calin criteria set was developed in 1977 and has since
      then been most widely used for defining IBP. The Calin criteria set has no entry criteria and
      is not based on standardized questions. Studies conducted in various populations have
      confirmed a high sensitivity for the Calin criteria, but shown much lower specificity than
      that reported in the original study. Berlin criteria for IBP were derived from a controlled
      study, including patients with ankylosing spondylitis and mechanical low back pain, who all
      had chronic low back pain. Berlin criteria are applicable only to those patients with chronic
      low back pain (>3 months) and age younger than <50 years old. This criteria set yielded a
      sensitivity of 70% and a specificity of 81% if at least two of the four following criteria
      were met: morning stiffness of >30-min duration, improvement in back pain with exercise but
      not with rest, awakening because of back pain during the second half of the night only, and
      alternating buttock pain. Assessment of Spondyloarthritis International Society (ASAS) has
      just recently published new criteria for classification of IBP. These were based on the
      expert judgment of the rheumatologist as the "gold standard" for diagnosing IBP in patients
      with chronic back pain of unknown origin. These new candidate IBP criteria administered by
      the interviewing clinician included the domains "improvement with exercise," "nocturnal
      pain," "age at onset <40 years," and "no improvement with rest." They were then validated in
      a distinct cohort of patients presenting to the rheumatologist with new-onset back pain and
      were shown to have a sensitivity of 79.6% and specificity of 72.4%. Celiac disease (CD) is an
      autoimmune systemic disease having among its clinical manifestations frequent symptoms common
      to rheumatologic diseases, such as musculoskeletal pain, asthenia, and cognitive fatigue.
      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 or systemic manifestations (headache, depression, anxiety, 'foggy mind,'
      tiredness, dermatitis or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness,
      and anemia). NCWS lacks of specific diagnostic tests, being its diagnosis essentially of
      exclusion. Many patients affected with CD and NCWS complain of IBP-like symptoms, which
      significantly affect the patients' quality of life and generally improve, together with the
      other clinical manifestations of the diseases, during a gluten-free diet (GFD). Therefore,
      the aims of the present study are to investigate 1) the effect of a GFD in IBP patients,
      randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD,
      for a period of at least one year, and 2) the prevalence of IBP in CD and in NCWS patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Musculoskeletal (back pain) evaluation at baseline and after GFD
time frame: Change from baseline at 12 months
description: Musculoskeletal (back pain) evaluation, from baseline at 12 months of GFD, according to the scores calculated on the basis of Visual Analogue Scales for Musculoskeletal (back pain), taking into account whether the patients adhered or not to the GFD.
measure: Changes in cytokines production from peripheral blood mononuclear (PBMC) at baseline and after GFD
time frame: Change from baseline at 12 months
description: Changes in cytokines production from peripheral blood mononuclear (PBMC), from baseline (i.e. at diagnosis) at 12 months of GFD, taking into account whether the patients adhered or not to the GFD.
measure: Prevalence of IBP in CD and in NCWS patients.
time frame: up to 12 months
description: Prevalence of IBP in CD and in NCWS patients.
arm group label: IBP patients on standard therapy
arm group type: No Intervention
description: IBP patients on standard therapy.
arm group label: IBP patients on standard therapy and GFD
arm group type: Active Comparator
description: IBP patients on standard therapy and GFD
intervention type: Other
intervention name: Gluten free diet
description: The investigators will evaluate the effect of a gluten free diet (GFD) in IBP patients, randomly assigned to receive standard therapy for IBP or standard therapy for IBP plus GFD, for a period of at least one year.
arm group label: IBP patients on standard therapy and GFD
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
last name: Antonio Carroccio, PhD
phone: +390916552884
email: acarroccio@hotmail.com
last name: Pasquale Mansueto, MD
phone: +390916552884
email: pasquale.mansueto@unipa.it
facility: 
contact: 
facility: 
contact: 
country: Italy
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
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. 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, Mansueto P, D'Alcamo A, Iacono G. Non-celiac wheat sensitivity as an allergic condition: personal experience and narrative review. Am J Gastroenterol. 2013 Dec;108(12):1845-52; quiz 1853. doi: 10.1038/ajg.2013.353. Epub 2013 Nov 5.
PMID: 24169272
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: Carroccio A, Brusca I, Mansueto P, D'alcamo A, Barrale M, Soresi M, Seidita A, La Chiusa SM, Iacono G, Sprini D. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients. Clin Chem Lab Med. 2013 Jun;51(6):1257-63. doi: 10.1515/cclm-2012-0609.
PMID: 23183757
citation: Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, Cats A, Dijkmans B, Olivieri I, Pasero G, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218-27. doi: 10.1002/art.1780341003.
PMID: 1930310
citation: Calin A, Porta J, Fries JF, Schurman DJ. Clinical history as a screening test for ankylosing spondylitis. JAMA. 1977 Jun 13;237(24):2613-4.
PMID: 140252
citation: Rudwaleit M, Metter A, Listing J, Sieper J, Braun J. Inflammatory back pain in ankylosing spondylitis: a reassessment of the clinical history for application as classification and diagnostic criteria. Arthritis Rheum. 2006 Feb;54(2):569-78. doi: 10.1002/art.21619.
PMID: 16447233
citation: Sieper J, van der Heijde D, Landewe R, Brandt J, Burgos-Vagas R, Collantes-Estevez E, Dijkmans B, Dougados M, Khan MA, Leirisalo-Repo M, van der Linden S, Maksymowych WP, Mielants H, Olivieri I, Rudwaleit M. New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis international Society (ASAS). Ann Rheum Dis. 2009 Jun;68(6):784-8. doi: 10.1136/ard.2008.101501. Epub 2009 Jan 15.
PMID: 19147614
responsible party type: Principal Investigator
investigator affiliation: University of Palermo
investigator full name: Pasquale Mansueto
investigator title: MD
mesh term: Back Pain
sharing ipd: No