<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/NCT03000101</url>
  </required_header>
  <id_info>
    <org_study_id>RBSI14LHMB</org_study_id>
    <secondary_id>SIR Programme no. RBSI14LHMB</secondary_id>
    <nct_id>NCT03000101</nct_id>
  </id_info>
  <brief_title>Study of the Role of Pomegranate Juice Ellagitannins in the Modulation of Inflammation in Inflammatory Bowel Disease</brief_title>
  <acronym>POME2016</acronym>
  <official_title>New Insight and Knowledge on Anti-inflammatory Effectiveness of Dietary Phenolics (NIKE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Azienda Ospedaliero-Universitaria di Bologna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Bologna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Conserve Italia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>GAT Foods</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>IRCCS Azienda Ospedaliero-Universitaria di Bologna</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>
      The aim of this research is to study the effects of a pomegranate juice on calprotectin&#xD;
      levels in patients suffering of inflammatory bowel disease (IBD) in clinical remission. Fecal&#xD;
      calprotectin levels, surrogate marker of mucosal inflammation, will be measured from baseline&#xD;
      to 12 weeks later (end of intervention). Systemic and mucosal changes of biochemical and&#xD;
      molecular inflammatory response markers will be also assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main purpose of the intervention trial is to assess the possible effect of pomegranate&#xD;
      juice consumption on reducing fecal calprotectin (FC) levels in volunteers suffering from IBD&#xD;
      with a high risk of clinical relapse. In detail, the objectives of this intervention are as&#xD;
      follows: (i) assessing the changes in FC levels in the two groups (active treatment, control)&#xD;
      from baseline to 12 weeks later (primary outcome); (ii) investigating the systemic and&#xD;
      mucosal modifications of selected biochemical and molecular inflammatory response markers in&#xD;
      the two groups after 12 weeks of the intervention compared with baseline (secondary&#xD;
      outcomes); (iii) evaluating circulating and urinary ellagitannin-derived metabolites from&#xD;
      regular pomegranate juice consumption in the two groups before and after the intervention.&#xD;
&#xD;
      The detailed study protocol is published in the Trials journal.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 19, 2017</start_date>
  <completion_date type="Anticipated">December 29, 2023</completion_date>
  <primary_completion_date type="Actual">July 19, 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>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in fecal calprotectin</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in fecal neutrophil-derived protein calprotectin, surrogate marker of mucosal improvement, after 12 weeks of consumption of experimental or placebo beverage, in subjects affected by IBD in clinical remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in plasma concentration of ellagitannin metabolites</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in plasma concentration of ellagitannin metabolites after 12 weeks of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in circulating cytokines levels</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in plasma levels of cytokines after 12 weeks of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in circulating trimethylamine-N-oxide (TMAO) levels</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in plasma levels of TMAO after 12 weeks of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gene expression levels in peripheral blood mononuclear cells (PBMC)</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in expression levels of selected genes in PBMC by qPCR after 12 weeks of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gene expression levels in intestinal biopsies</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in expression levels of selected genes in intestinal biopsies by qPCR after 12 weeks of intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in urinary ellagitannin metabolite excretion</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline in urinary ellagitannin metabolite excretion after 12 weeks of intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Crohn's Disease</condition>
  <condition>Ulcerative Colitis</condition>
  <arm_group>
    <arm_group_label>Pomegranate juice</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The pomegranate juice is 100% pomegranate juice, not from concentrate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo beverage</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo beverage consists in water added with sugar and citric acid.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>100% pomegranate juice</intervention_name>
    <description>125 mL of 100% pomegranate juice twice daily for 12 weeks</description>
    <arm_group_label>Pomegranate juice</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo beverage</intervention_name>
    <description>125 mL of placebo beverage twice daily for 12 weeks</description>
    <arm_group_label>Placebo beverage</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Ulcerative Colitis (diagnosed on the base of clinic, endoscopic, and&#xD;
             histologic criteria) in clinical remission (SCCAI = 0) from at least three months and&#xD;
             in stable therapy (without therapeutic modifications in the three previous months)&#xD;
             with mesalazine, immunomodulators and/or biologics.&#xD;
&#xD;
          -  Patients affected by Crohn's Disease, particularly involving sigmoid colon and rectum&#xD;
             (diagnosed on the base of clinic, endoscopic, and histologic criteria) in clinical&#xD;
             remission (CDAI &lt; 150) from at least three months and in stable therapy (without&#xD;
             therapeutic modifications in the three previous months) with mesalazine A,&#xD;
             immunomodulators and/or biologics.&#xD;
&#xD;
          -  Fecal calprotectin at baseline ≥ 100 microg/g.&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients affected by Ulcerative Colitis and Crohn's Disease with severe endoscopic&#xD;
             disease activity (Ulcerative Colitis: Mayo Endoscopic Score = 3; Crohn's Disease:&#xD;
             Simple Endoscopic Score SES-CD &gt; 15).&#xD;
&#xD;
          -  Patients on steroid therapy in the two previous months.&#xD;
&#xD;
          -  Patients in therapy with warfarin or other anticoagulants.&#xD;
&#xD;
          -  Known or supposed hypersensitivity to fruit and/or juice of pomegranate.&#xD;
&#xD;
          -  Women in fertile age which refuse to use contraceptives specified in the study (oral&#xD;
             contraception, IUD) and breastfeed women.&#xD;
&#xD;
          -  Diabetic patients and other patients with severe clinical conditions which the&#xD;
             investigator consider to contraindicate patient participation at the study.&#xD;
&#xD;
          -  Therapy modifications and/or assumption of experimental therapies within three months&#xD;
             before the study inclusion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francesca Danesi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Agri-Food Sciences and Technologies, University of Bologna</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Luigi Ricciardiello, MD, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Medical and Surgical Sciences, University of Bologna</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>U.O. Gastroenterologia - Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi</name>
      <address>
        <city>Bologna</city>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Best WR, Becktel JM, Singleton JW. Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI). Gastroenterology. 1979 Oct;77(4 Pt 2):843-6.</citation>
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  <results_reference>
    <citation>Scaioli E, Belluzzi A, Ricciardiello L, Del Rio D, Rotondo E, Mena P, Derlindati E, Danesi F. Pomegranate juice to reduce fecal calprotectin levels in inflammatory bowel disease patients with a high risk of clinical relapse: Study protocol for a randomized controlled trial. Trials. 2019 Jun 6;20(1):327. doi: 10.1186/s13063-019-3321-8.</citation>
    <PMID>31171016</PMID>
  </results_reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS Azienda Ospedaliero-Universitaria di Bologna</investigator_affiliation>
    <investigator_full_name>andrea belluzzi, MD phD</investigator_full_name>
    <investigator_title>Andrea Belluzzi, MD PhD</investigator_title>
  </responsible_party>
  <keyword>Biomarkers</keyword>
  <keyword>Colitis</keyword>
  <keyword>Colitis, Ulcerative</keyword>
  <keyword>Colonic Diseases</keyword>
  <keyword>Crohn Disease</keyword>
  <keyword>Digestive System Diseases</keyword>
  <keyword>Fruit</keyword>
  <keyword>Fruit and Vegetable Juices</keyword>
  <keyword>Gastroenteritis</keyword>
  <keyword>Gastrointestinal Diseases</keyword>
  <keyword>Humans</keyword>
  <keyword>Hydrolysable Tannins</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Inflammatory Bowel Disease</keyword>
  <keyword>Intestinal Diseases</keyword>
  <keyword>Punicaceae</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</mesh_term>
    <mesh_term>Colitis</mesh_term>
    <mesh_term>Inflammatory Bowel Diseases</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/NCT03000101
org study id: RBSI14LHMB
secondary id: SIR Programme no. RBSI14LHMB
nct id: NCT03000101
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of this research is to study the effects of a pomegranate juice on calprotectin
      levels in patients suffering of inflammatory bowel disease (IBD) in clinical remission. Fecal
      calprotectin levels, surrogate marker of mucosal inflammation, will be measured from baseline
      to 12 weeks later (end of intervention). Systemic and mucosal changes of biochemical and
      molecular inflammatory response markers will be also assessed.
The main purpose of the intervention trial is to assess the possible effect of pomegranate
      juice consumption on reducing fecal calprotectin (FC) levels in volunteers suffering from IBD
      with a high risk of clinical relapse. In detail, the objectives of this intervention are as
      follows: (i) assessing the changes in FC levels in the two groups (active treatment, control)
      from baseline to 12 weeks later (primary outcome); (ii) investigating the systemic and
      mucosal modifications of selected biochemical and molecular inflammatory response markers in
      the two groups after 12 weeks of the intervention compared with baseline (secondary
      outcomes); (iii) evaluating circulating and urinary ellagitannin-derived metabolites from
      regular pomegranate juice consumption in the two groups before and after the intervention.

      The detailed study protocol is published in the Trials journal.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in fecal calprotectin
time frame: Baseline and 12 weeks
description: Change from baseline in fecal neutrophil-derived protein calprotectin, surrogate marker of mucosal improvement, after 12 weeks of consumption of experimental or placebo beverage, in subjects affected by IBD in clinical remission.
measure: Changes in plasma concentration of ellagitannin metabolites
time frame: Baseline and 12 weeks
description: Change from baseline in plasma concentration of ellagitannin metabolites after 12 weeks of intervention.
measure: Changes in circulating cytokines levels
time frame: Baseline and 12 weeks
description: Change from baseline in plasma levels of cytokines after 12 weeks of intervention.
measure: Changes in circulating trimethylamine-N-oxide (TMAO) levels
time frame: Baseline and 12 weeks
description: Change from baseline in plasma levels of TMAO after 12 weeks of intervention.
measure: Changes in gene expression levels in peripheral blood mononuclear cells (PBMC)
time frame: Baseline and 12 weeks
description: Change from baseline in expression levels of selected genes in PBMC by qPCR after 12 weeks of intervention.
measure: Changes in gene expression levels in intestinal biopsies
time frame: Baseline and 12 weeks
description: Change from baseline in expression levels of selected genes in intestinal biopsies by qPCR after 12 weeks of intervention.
measure: Changes in urinary ellagitannin metabolite excretion
time frame: Baseline and 12 weeks
description: Change from baseline in urinary ellagitannin metabolite excretion after 12 weeks of intervention.
arm group label: Pomegranate juice
arm group type: Experimental
description: The pomegranate juice is 100% pomegranate juice, not from concentrate.
arm group label: Placebo beverage
arm group type: Placebo Comparator
description: The placebo beverage consists in water added with sugar and citric acid.
intervention type: Other
intervention name: 100% pomegranate juice
description: 125 mL of 100% pomegranate juice twice daily for 12 weeks
arm group label: Pomegranate juice
intervention type: Other
intervention name: placebo beverage
description: 125 mL of placebo beverage twice daily for 12 weeks
arm group label: Placebo beverage
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Francesca Danesi, PhD
role: Study Director
affiliation: Department of Agri-Food Sciences and Technologies, University of Bologna
last name: Luigi Ricciardiello, MD, Prof
role: Principal Investigator
affiliation: Department of Medical and Surgical Sciences, University of Bologna
facility: 
country: Italy
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responsible party type: Principal Investigator
investigator affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
investigator full name: andrea belluzzi, MD phD
investigator title: Andrea Belluzzi, MD PhD
mesh term: Crohn Disease
mesh term: Colitis
mesh term: Inflammatory Bowel Diseases
sharing ipd: No