<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/NCT04477239</url>
  </required_header>
  <id_info>
    <org_study_id>GRRES-2020-1551</org_study_id>
    <nct_id>NCT04477239</nct_id>
  </id_info>
  <brief_title>Diagnostic Performance of Urinary Gluten Immunogenic Peptides in Monitoring the Adherence to Gluten-free Diet.</brief_title>
  <official_title>A Randomized, Triple-blind, Placebo-controlled, Clinical Trial on the Diagnostic Performance of Gluten Immunogenic Peptides in the Evaluation of Gluten-free Diet Adherence: the GRRES Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università Politecnica delle Marche</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Università Politecnica delle Marche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the GRRES study is to assess the clinical usefulness of urinary gluten&#xD;
      immunogenic peptides test as a marker of gluten-free diet adherence using the rapid&#xD;
      immunochromatographic assay based on anti-gliadin 33-mer monoclonal antibodies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A strict and permanent gluten free diet (GFD) is the only effective treatment resulting in&#xD;
      full clinical, serological and histological remission, avoiding long-term complications in&#xD;
      celiac disease (CD) patients. Gluten immunogenic peptides (GIP) are fragments of gluten&#xD;
      proteins resistant to gastrointestinal digestion and detectable in urine after intestinal&#xD;
      digestion, providing direct evidence of recent gluten ingestion. A significant variability in&#xD;
      the amount of excreted urinary GIP has been reported in individuals administered with similar&#xD;
      doses of gluten and, so far, inadequate information is available about the amount of excreted&#xD;
      GIP in subjects ingesting traces or low amount of gluten. This is an important issue, as even&#xD;
      a strict GFD could be contaminated by traces of gluten, e.g. in wheat starch and processed&#xD;
      food. The aim of this study is to assess the clinical usefulness of urinary GIP as a marker&#xD;
      of GFD adherence using a rapid immunochromatographic assay based on anti-gliadin 33-mer&#xD;
      monoclonal antibodies. This is a prospective, randomized, triple-blind, placebo-controlled,&#xD;
      clinical trial. In this study, healthy volunteers following a normal diet will be requested&#xD;
      to be on strict GFD for 5 days. On day 4th, participants will be requested to collect a&#xD;
      baseline urine sample and in case of a negative GIP test result they will be assigned to&#xD;
      ingest a specific dose of purified gluten incorporated in a capsule (0 mg, 10 mg, 50 mg, 100&#xD;
      mg, 500 mg and 1000 mg, according to randomization). Participants will be requested to&#xD;
      collect urine samples in a container and take a 5 mL aliquote for the GIP test at the 9th and&#xD;
      24th hour from the time of the administration of the dose. During the collection, volunteers&#xD;
      will also be requested to record the volume of the excreted urine and to store the collected&#xD;
      urine at 4°C. Urine tubes will be stored at -20°C until the quantitative evaluation of GIP.&#xD;
      GIP test will be performed using the rapid immunochromatographic assay based on anti-gliadin&#xD;
      33-mer monoclonal antibodies iVYCHECK GIP Urine™ test (Biomedal, Spain) according to the&#xD;
      manufacturer's instructions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">November 30, 2020</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>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Randomization will be performed using a random sequence generator to conceal the sequence from the rest of the researchers and to ensure that only the investigator who will manipulate the gluten doses will know the allocation pertaining to each individual. This investigator will not carry out any assessment or any other intervention during the trial period. Until study completion, the enrolled subjects, the clinicians and the person who will perform the statistical analysis will be blinded to the group assigned.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-response relationship between the amount of gluten intake and urinary excretion of GIP.</measure>
    <time_frame>3 months</time_frame>
    <description>The primary objective of the study is to verify the usefulness of the quantitative GIP assay in urine as biomarker of adherence to the gluten-free diet in terms of dose-response relationship between the amount of ingested gluten and urinary excretion of GIP in a group of healthy volunteers.</description>
  </primary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Celiac Disease</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral administration of one capsule of Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Purified gluten (10 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of capsules containing 10 mg of purified gluten.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Purified gluten (50 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of capsules containing 50 mg of purified gluten.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Purified gluten (100 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of capsules containing 100 mg of purified gluten.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Purified gluten (500 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of capsules containing 500 mg of purified gluten.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Purified gluten (1000 mg)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral administration of capsules containing 1000 mg of purified gluten.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Gluten (behaviour)</intervention_name>
    <description>Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Purified gluten (10 mg)</arm_group_label>
    <arm_group_label>Purified gluten (100 mg)</arm_group_label>
    <arm_group_label>Purified gluten (1000 mg)</arm_group_label>
    <arm_group_label>Purified gluten (50 mg)</arm_group_label>
    <arm_group_label>Purified gluten (500 mg)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Placebo (behaviour)</intervention_name>
    <description>Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Purified gluten (10 mg)</arm_group_label>
    <arm_group_label>Purified gluten (100 mg)</arm_group_label>
    <arm_group_label>Purified gluten (1000 mg)</arm_group_label>
    <arm_group_label>Purified gluten (50 mg)</arm_group_label>
    <arm_group_label>Purified gluten (500 mg)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  healthy volunteers&#xD;
&#xD;
          -  20-40 years old&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  type 1 diabetes&#xD;
&#xD;
          -  chronic or acute inflammatory diseases of the gastrointestinal tract (CD, non-celiac&#xD;
             gluten sensitivity, Crohn's disease, ulcerative colitis, food allergy, acute&#xD;
             gastroenteritis ≤ 4 weeks prior to the study start)&#xD;
&#xD;
          -  pregnancy or lactation&#xD;
&#xD;
          -  chronic intake of medications and supplements&#xD;
&#xD;
          -  refusal/withdrawal of written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carlo Catassi, MD, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Univeristà Politecnica delle Marche, Ancona, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elena Lionetti, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univeristà Politecnica delle Marche, Ancona, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Simona Gatti, MD, PHD</last_name>
    <role>Study Chair</role>
    <affiliation>Univeristà Politecnica delle Marche, Ancona, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chiara Monachesi, PHD</last_name>
    <role>Study Chair</role>
    <affiliation>Univeristà Politecnica delle Marche, Ancona, Italy</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anil K Verma, PHD</last_name>
    <role>Study Chair</role>
    <affiliation>Univeristà Politecnica delle Marche, Ancona, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Department of Pediatrics</name>
      <address>
        <city>Ancona</city>
        <zip>60123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Moreno ML, Cebolla A, Munoz-Suano A, Carrillo-Carrion C, Comino I, Pizarro A, Leon F, Rodriguez-Herrera A, Sousa C. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017 Feb;66(2):250-257. doi: 10.1136/gutjnl-2015-310148. Epub 2015 Nov 25.</citation>
    <PMID>26608460</PMID>
  </reference>
  <reference>
    <citation>Stefanolo JP, Talamo M, Dodds S, de la Paz Temprano M, Costa AF, Moreno ML, Pinto-Sanchez MI, Smecuol E, Vazquez H, Gonzalez A, Niveloni SI, Maurino E, Verdu EF, Bai JC. Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples. Clin Gastroenterol Hepatol. 2021 Mar;19(3):484-491.e1. doi: 10.1016/j.cgh.2020.03.038. Epub 2020 Mar 23.</citation>
    <PMID>32217152</PMID>
  </reference>
  <reference>
    <citation>Silvester JA, Comino I, Kelly CP, Sousa C, Duerksen DR; DOGGIE BAG Study Group. Most Patients With Celiac Disease on Gluten-Free Diets Consume Measurable Amounts of Gluten. Gastroenterology. 2020 Apr;158(5):1497-1499.e1. doi: 10.1053/j.gastro.2019.12.016. Epub 2019 Dec 19. No abstract available.</citation>
    <PMID>31866245</PMID>
  </reference>
  <reference>
    <citation>Verma AK, Gatti S, Galeazzi T, Monachesi C, Padella L, Baldo GD, Annibali R, Lionetti E, Catassi C. Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy. Nutrients. 2017 Feb 7;9(2):115. doi: 10.3390/nu9020115.</citation>
    <PMID>28178205</PMID>
  </reference>
  <reference>
    <citation>Catassi C, Fabiani E, Iacono G, D'Agate C, Francavilla R, Biagi F, Volta U, Accomando S, Picarelli A, De Vitis I, Pianelli G, Gesuita R, Carle F, Mandolesi A, Bearzi I, Fasano A. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr. 2007 Jan;85(1):160-6. doi: 10.1093/ajcn/85.1.160.</citation>
    <PMID>17209192</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università Politecnica delle Marche</investigator_affiliation>
    <investigator_full_name>Carlo Catassi, M.D.</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Gluten-free diet</keyword>
  <keyword>Gluten immunogenic peptides</keyword>
  <keyword>Gluten contamination</keyword>
  <keyword>Gluten</keyword>
  <keyword>Urine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiac Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04477239
org study id: GRRES-2020-1551
nct id: NCT04477239
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of the GRRES study is to assess the clinical usefulness of urinary gluten
      immunogenic peptides test as a marker of gluten-free diet adherence using the rapid
      immunochromatographic assay based on anti-gliadin 33-mer monoclonal antibodies.
A strict and permanent gluten free diet (GFD) is the only effective treatment resulting in
      full clinical, serological and histological remission, avoiding long-term complications in
      celiac disease (CD) patients. Gluten immunogenic peptides (GIP) are fragments of gluten
      proteins resistant to gastrointestinal digestion and detectable in urine after intestinal
      digestion, providing direct evidence of recent gluten ingestion. A significant variability in
      the amount of excreted urinary GIP has been reported in individuals administered with similar
      doses of gluten and, so far, inadequate information is available about the amount of excreted
      GIP in subjects ingesting traces or low amount of gluten. This is an important issue, as even
      a strict GFD could be contaminated by traces of gluten, e.g. in wheat starch and processed
      food. The aim of this study is to assess the clinical usefulness of urinary GIP as a marker
      of GFD adherence using a rapid immunochromatographic assay based on anti-gliadin 33-mer
      monoclonal antibodies. This is a prospective, randomized, triple-blind, placebo-controlled,
      clinical trial. In this study, healthy volunteers following a normal diet will be requested
      to be on strict GFD for 5 days. On day 4th, participants will be requested to collect a
      baseline urine sample and in case of a negative GIP test result they will be assigned to
      ingest a specific dose of purified gluten incorporated in a capsule (0 mg, 10 mg, 50 mg, 100
      mg, 500 mg and 1000 mg, according to randomization). Participants will be requested to
      collect urine samples in a container and take a 5 mL aliquote for the GIP test at the 9th and
      24th hour from the time of the administration of the dose. During the collection, volunteers
      will also be requested to record the volume of the excreted urine and to store the collected
      urine at 4°C. Urine tubes will be stored at -20°C until the quantitative evaluation of GIP.
      GIP test will be performed using the rapid immunochromatographic assay based on anti-gliadin
      33-mer monoclonal antibodies iVYCHECK GIP Urine™ test (Biomedal, Spain) according to the
      manufacturer's instructions.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Randomization will be performed using a random sequence generator to conceal the sequence from the rest of the researchers and to ensure that only the investigator who will manipulate the gluten doses will know the allocation pertaining to each individual. This investigator will not carry out any assessment or any other intervention during the trial period. Until study completion, the enrolled subjects, the clinicians and the person who will perform the statistical analysis will be blinded to the group assigned.
measure: Dose-response relationship between the amount of gluten intake and urinary excretion of GIP.
time frame: 3 months
description: The primary objective of the study is to verify the usefulness of the quantitative GIP assay in urine as biomarker of adherence to the gluten-free diet in terms of dose-response relationship between the amount of ingested gluten and urinary excretion of GIP in a group of healthy volunteers.
arm group label: Placebo
arm group type: Placebo Comparator
description: Oral administration of one capsule of Placebo
arm group label: Purified gluten (10 mg)
arm group type: Active Comparator
description: Oral administration of capsules containing 10 mg of purified gluten.
arm group label: Purified gluten (50 mg)
arm group type: Active Comparator
description: Oral administration of capsules containing 50 mg of purified gluten.
arm group label: Purified gluten (100 mg)
arm group type: Active Comparator
description: Oral administration of capsules containing 100 mg of purified gluten.
arm group label: Purified gluten (500 mg)
arm group type: Active Comparator
description: Oral administration of capsules containing 500 mg of purified gluten.
arm group label: Purified gluten (1000 mg)
arm group type: Active Comparator
description: Oral administration of capsules containing 1000 mg of purified gluten.
intervention type: Behavioral
intervention name: Gluten (behaviour)
description: Gluten is a protein normally present in the daily diet of healthy volunteers not suffering from gluten related disorders, in far greater quantities (10-20 g/day) than those used in this study (10 mg-1 g/day).
arm group label: Placebo
arm group label: Purified gluten (10 mg)
arm group label: Purified gluten (100 mg)
arm group label: Purified gluten (1000 mg)
arm group label: Purified gluten (50 mg)
arm group label: Purified gluten (500 mg)
intervention type: Behavioral
intervention name: Placebo (behaviour)
description: Placebo is composed of pregelatinized maize starch Ph.Eur. 97.5%; magnesium stearate Ph.Eur. 1.5%; micronized silica Ph.Eur. 0.5%; Micronized talc Ph.Eur. 0.5% (NOT containing preservatives, colorings, or gluten).
arm group label: Placebo
arm group label: Purified gluten (10 mg)
arm group label: Purified gluten (100 mg)
arm group label: Purified gluten (1000 mg)
arm group label: Purified gluten (50 mg)
arm group label: Purified gluten (500 mg)
criteria: 
gender: All
minimum age: 20 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carlo Catassi, MD, MPH
role: Study Director
affiliation: Univeristà Politecnica delle Marche, Ancona, Italy
last name: Elena Lionetti, MD, PHD
role: Principal Investigator
affiliation: Univeristà Politecnica delle Marche, Ancona, Italy
last name: Simona Gatti, MD, PHD
role: Study Chair
affiliation: Univeristà Politecnica delle Marche, Ancona, Italy
last name: Chiara Monachesi, PHD
role: Study Chair
affiliation: Univeristà Politecnica delle Marche, Ancona, Italy
last name: Anil K Verma, PHD
role: Study Chair
affiliation: Univeristà Politecnica delle Marche, Ancona, Italy
facility: 
country: Italy
citation: Moreno ML, Cebolla A, Munoz-Suano A, Carrillo-Carrion C, Comino I, Pizarro A, Leon F, Rodriguez-Herrera A, Sousa C. Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing. Gut. 2017 Feb;66(2):250-257. doi: 10.1136/gutjnl-2015-310148. Epub 2015 Nov 25.
PMID: 26608460
citation: Stefanolo JP, Talamo M, Dodds S, de la Paz Temprano M, Costa AF, Moreno ML, Pinto-Sanchez MI, Smecuol E, Vazquez H, Gonzalez A, Niveloni SI, Maurino E, Verdu EF, Bai JC. Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples. Clin Gastroenterol Hepatol. 2021 Mar;19(3):484-491.e1. doi: 10.1016/j.cgh.2020.03.038. Epub 2020 Mar 23.
PMID: 32217152
citation: Silvester JA, Comino I, Kelly CP, Sousa C, Duerksen DR; DOGGIE BAG Study Group. Most Patients With Celiac Disease on Gluten-Free Diets Consume Measurable Amounts of Gluten. Gastroenterology. 2020 Apr;158(5):1497-1499.e1. doi: 10.1053/j.gastro.2019.12.016. Epub 2019 Dec 19. No abstract available.
PMID: 31866245
citation: Verma AK, Gatti S, Galeazzi T, Monachesi C, Padella L, Baldo GD, Annibali R, Lionetti E, Catassi C. Gluten Contamination in Naturally or Labeled Gluten-Free Products Marketed in Italy. Nutrients. 2017 Feb 7;9(2):115. doi: 10.3390/nu9020115.
PMID: 28178205
citation: Catassi C, Fabiani E, Iacono G, D'Agate C, Francavilla R, Biagi F, Volta U, Accomando S, Picarelli A, De Vitis I, Pianelli G, Gesuita R, Carle F, Mandolesi A, Bearzi I, Fasano A. A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Am J Clin Nutr. 2007 Jan;85(1):160-6. doi: 10.1093/ajcn/85.1.160.
PMID: 17209192
responsible party type: Principal Investigator
investigator affiliation: Università Politecnica delle Marche
investigator full name: Carlo Catassi, M.D.
investigator title: Professor
mesh term: Celiac Disease
sharing ipd: Undecided