<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/NCT03008252</url>
  </required_header>
  <id_info>
    <org_study_id>ACPM12</org_study_id>
    <nct_id>NCT03008252</nct_id>
  </id_info>
  <brief_title>Lactose Intolerance and Cow's Milk Protein Allergy in Non-celiac Wheat Sensitivity Patients</brief_title>
  <official_title>Lactose Intolerance and Cow's Milk Protein Allergy 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      In the last few years a new clinical entity has emerged which includes patients who consider&#xD;
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though&#xD;
      they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named&#xD;
      non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested&#xD;
      the term &quot;non-celiac wheat sensitivity&quot; (NCWS), because it is not known to date what&#xD;
      component of wheat actually causes the symptoms. 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 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). Lactose intolerance and cow's milk protein allergy (CMPA) are two medical&#xD;
      conditions with a very high prevalence in the general population, and there is a large&#xD;
      overlap between NCWS symptoms and lactose intolerance and CMPA symptoms. Therefore, the aims&#xD;
      of the present study are to investigate 1) the prevalence of positive lactose breath test and&#xD;
      DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal&#xD;
      symptoms related to milk and/or milk derivates ingestion, 2) the clinical, serological, and&#xD;
      histological characteristics of NCWS patients with lactose intolerance and CMPA in comparison&#xD;
      to NCWS patients without lactose intolerance and CMPA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the last few years, a new clinical entity has emerged which includes patients who consider&#xD;
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though&#xD;
      they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named&#xD;
      non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested&#xD;
      the term &quot;non-celiac wheat sensitivity&quot; (NCWS), because it is not known to date what&#xD;
      component of wheat actually causes the symptoms. Other areas of doubt in NCWS regard its&#xD;
      pathogenesis, while some papers reported intestinal immunologic activation, others linked&#xD;
      NCWS to the dietary short chain carbohydrate (fermentable oligo-di-monosaccharides and&#xD;
      polyols, FODMAPs) load. The researchers recently demonstrated that higher proportions of&#xD;
      patients with NCWS develop autoimmune disorders, are antinuclear antibodies (ANA) positive,&#xD;
      and show DQ2/DQ8 haplotypes compared with patients with irritable bowel syndrome (IBS),&#xD;
      supporting an immunologic involvement in NCWS. The clinical picture of NCWS is characterized&#xD;
      by combined gastrointestinal (bloating, abdominal pain, diarrhea and/or constipation, nausea,&#xD;
      epigastric pain, gastroesophageal reflux, aphthous stomatitis) and extra-intestinal or&#xD;
      systemic manifestations (headache, depression, anxiety, 'foggy mind,' tiredness, dermatitis&#xD;
      or skin rash, fibromyalgia-like joint/muscle pain, leg or arm numbness, and anemia). Lactose&#xD;
      intolerance and cow's milk protein allergy (CMPA) are two conditions with a very high&#xD;
      prevalence in the general population and there is a large overlap between NCWS and lactose&#xD;
      intolerance and CMPA symptoms. Therefore, the aims of the present study are to investigate 1)&#xD;
      the prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS&#xD;
      patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk&#xD;
      and/or milk derivates ingestion, 2) the clinical, serological, and histological&#xD;
      characteristics of NCWS patients with lactose intolerance and CMPA in comparison to NCWS&#xD;
      patients without lactose intolerance and CMPA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Actual">June 1, 2020</completion_date>
  <primary_completion_date type="Actual">July 1, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients self-reporting symptoms related to milk and/or milk derivates ingestion.</measure>
    <time_frame>January 2017 to December 2017</time_frame>
    <description>Prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates ingestion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lactose intolerance and CMPA in NCWS patients</measure>
    <time_frame>January 2017 to December 2017</time_frame>
    <description>Frequency of lactose intolerance and CMPA in NCWS patients</description>
  </secondary_outcome>
  <enrollment type="Actual">300</enrollment>
  <condition>Non-celiac Wheat Sensitivity</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lactose breath test</intervention_name>
    <description>Lactose breath test in NCWS patients with symptoms related to milk and/or milk derivates ingestion.</description>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DBPC cow's milk protein challenge</intervention_name>
    <description>DBPC cow's milk protein challenge in NCWS patients with symptoms related to milk and/or milk derivates ingestion.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The researchers prospectively will survey adult patients with functional&#xD;
        gastroenterological symptoms (Rome III criteria) and a definitive diagnosis of NCWS,&#xD;
        referred at the Department of Internal Medicine at the University Hospital of Palermo,&#xD;
        Italy, and at the Department of Internal Medicine of the Hospital of Sciacca, Agrigento,&#xD;
        Italy, between January 2017 and January 2019, comparing the characteristics of the ones&#xD;
        suffering from lactose intolerance and CMPA with those who do not suffer from lactose&#xD;
        intolerance and CMPA.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All the NCWS patients will meet the recently proposed criteria:&#xD;
&#xD;
          -  negative serum anti-tissue transglutaminase and antiendomysium (EmA) IgA and IgG&#xD;
             antibodies&#xD;
&#xD;
          -  absence of intestinal villous atrophy&#xD;
&#xD;
          -  IgE-mediated immunoallergy 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 will be:&#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.&#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 cutaneous and/or gastrointestinal diseases&#xD;
&#xD;
          -  concomitant treatment with steroids and/or antihistamines.&#xD;
&#xD;
        Lactose intolerance and CMPA will be diagnosed, in patients with self-reported&#xD;
        gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates&#xD;
        ingestion, using lactose breath test and DBPC cow's milk protein challenge, respectively.&#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>Internal Medicine Department of the Hospital of Sciacca (Agrigento)</name>
      <address>
        <city>Sciacca</city>
        <state>Agrigento</state>
        <zip>92019</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Internal Medicine Department of the University Hospital of Palermo</name>
      <address>
        <city>Palermo</city>
        <zip>90127</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>
  <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>Carroccio A, Montalto G, Custro N, Notarbartolo A, Cavataio F, D'Amico D, Alabrese D, Iacono G. Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients. Allergy. 2000 Jun;55(6):574-9. doi: 10.1034/j.1398-9995.2000.00417.x.</citation>
    <PMID>10858991</PMID>
  </results_reference>
  <results_reference>
    <citation>Carroccio A, Montalto G, Cavera G, Notarbatolo A. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec;17(6):631-6. doi: 10.1080/07315724.1998.10718813.</citation>
    <PMID>9853544</PMID>
  </results_reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</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>MD</investigator_title>
  </responsible_party>
  <keyword>Non-celiac wheat sensitivity</keyword>
  <keyword>lactose intolerance</keyword>
  <keyword>cow's milk protein allergy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactose Intolerance</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Milk Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Caseins</mesh_term>
  </intervention_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/NCT03008252
org study id: ACPM12
nct id: NCT03008252
lead sponsor: 
has dmc: No
In the last few years a new clinical entity has emerged which includes patients who consider
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though
      they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named
      non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested
      the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what
      component of wheat actually causes the symptoms. 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). Lactose intolerance and cow's milk protein allergy (CMPA) are two medical
      conditions with a very high prevalence in the general population, and there is a large
      overlap between NCWS symptoms and lactose intolerance and CMPA symptoms. Therefore, the aims
      of the present study are to investigate 1) the prevalence of positive lactose breath test and
      DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal
      symptoms related to milk and/or milk derivates ingestion, 2) the clinical, serological, and
      histological characteristics of NCWS patients with lactose intolerance and CMPA in comparison
      to NCWS patients without lactose intolerance and CMPA.
In the last few years, a new clinical entity has emerged which includes patients who consider
      themselves to be suffering from problems caused by wheat and/or gluten ingestion, even though
      they do not have celiac disease (CD) or wheat allergy. This clinical condition has been named
      non-celiac gluten sensitivity (NCGS), although in a recent article, the researchers suggested
      the term "non-celiac wheat sensitivity" (NCWS), because it is not known to date what
      component of wheat actually causes the symptoms. Other areas of doubt in NCWS regard its
      pathogenesis, while some papers reported intestinal immunologic activation, others linked
      NCWS to the dietary short chain carbohydrate (fermentable oligo-di-monosaccharides and
      polyols, FODMAPs) load. The researchers recently demonstrated that higher proportions of
      patients with NCWS develop autoimmune disorders, are antinuclear antibodies (ANA) positive,
      and show DQ2/DQ8 haplotypes compared with patients with irritable bowel syndrome (IBS),
      supporting an immunologic involvement in NCWS. 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). Lactose
      intolerance and cow's milk protein allergy (CMPA) are two conditions with a very high
      prevalence in the general population and there is a large overlap between NCWS and lactose
      intolerance and CMPA symptoms. Therefore, the aims of the present study are to investigate 1)
      the prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS
      patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk
      and/or milk derivates ingestion, 2) the clinical, serological, and histological
      characteristics of NCWS patients with lactose intolerance and CMPA in comparison to NCWS
      patients without lactose intolerance and CMPA.
observational model: Cohort
time perspective: Prospective
measure: Positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients self-reporting symptoms related to milk and/or milk derivates ingestion.
time frame: January 2017 to December 2017
description: Prevalence of positive lactose breath test and DBPC cow's milk protein challenge in NCWS patients with self-reported gastrointestinal and extra-intestinal symptoms related to milk and/or milk derivates ingestion.
measure: Lactose intolerance and CMPA in NCWS patients
time frame: January 2017 to December 2017
description: Frequency of lactose intolerance and CMPA in NCWS patients
intervention type: Other
intervention name: Lactose breath test
description: Lactose breath test in NCWS patients with symptoms related to milk and/or milk derivates ingestion.
intervention type: Other
intervention name: DBPC cow's milk protein challenge
description: DBPC cow's milk protein challenge in NCWS patients with symptoms related to milk and/or milk derivates ingestion.
study pop: 
sampling method: Probability Sample
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
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: Carroccio A, Montalto G, Custro N, Notarbartolo A, Cavataio F, D'Amico D, Alabrese D, Iacono G. Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients. Allergy. 2000 Jun;55(6):574-9. doi: 10.1034/j.1398-9995.2000.00417.x.
PMID: 10858991
citation: Carroccio A, Montalto G, Cavera G, Notarbatolo A. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec;17(6):631-6. doi: 10.1080/07315724.1998.10718813.
PMID: 9853544
responsible party type: Principal Investigator
investigator affiliation: University of Palermo
investigator full name: Pasquale Mansueto
investigator title: MD
mesh term: Lactose Intolerance
mesh term: Hypersensitivity
mesh term: Milk Hypersensitivity
mesh term: Caseins
sharing ipd: No