xml: <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/NCT06006039</url>
    </required_header>
    <id_info>
      <org_study_id>NL82888.018.22</org_study_id>
      <nct_id>NCT06006039</nct_id>
    </id_info>
    <brief_title>The Role of IL-23-Responsive Immune Cell Subsets in Post-Operative Recurrence in Patients With Crohn's Disease.</brief_title>
    <acronym>DIVE-23</acronym>
    <official_title>An Explorative Study to Examine the Role of IL-23-Responsive Immune Cell Subsets in Post-Operative Recurrence in Patients With Crohn's Disease.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</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>
        Inflammatory Bowel Diseases (IBDs), including ulcerative colitis and Crohn's disease (CD),&#xD;
        constitute a group of debilitating chronic diseases that profoundly impact patient quality of&#xD;
        life and incurs large costs in terms of treatment and lost productivity. Incidence of IBD is&#xD;
        rising worldwide, and there is a pressing clinical need for development of new therapies.&#xD;
        Discovery and development of effective therapies to treat IBDs depend first on a better&#xD;
        understanding of the underlying mechanisms, including how proinflammatory cells proliferate&#xD;
        unchecked.&#xD;
  &#xD;
        It has been established that the cytokine interleukin (IL)-23 plays a pivotal role in IBD&#xD;
        pathophysiology and antibodies targeting IL-23 are currently in late stage development for&#xD;
        the treatment of both CD and ulcerative colitis (UC). IL-23 is part of the IL-12 family of&#xD;
        cytokines (which includes IL-12, IL-27 and IL-35). The p40 subunit is shared among IL-23 and&#xD;
        IL-12; the p19 subunit is unique to IL-23. Thus far, the efficacy of selective anti-IL-23&#xD;
        blockade (via anti-p19 antibodies) appears 5-10% better with respect to clinical and&#xD;
        endoscopic outcomes than targeting both IL-23 and IL-12 using anti-p40 antibodies.&#xD;
        Understanding the effects of IL-23 (and IL-12) in IBDs requires identification of the most&#xD;
        relevant immune cells that respond to these cytokines. One likely cell type controlled by the&#xD;
        IL-23 pathway are innate lymphoid cells (ILCs). ILC3s (a subset of ILCs) are dominant in&#xD;
        healthy intestinal tissue and capable of producing IL-22 which maintain intestinal epithelial&#xD;
        homeostasis. Disturbances in the amounts of IL-22 caused by changes in the stimulatory&#xD;
        cytokine IL-23 in tissues, may therefore cause inflammatory responses. IL-23 may facilitate&#xD;
        the IL-12-induced shift of ILC3s to ILC1s which are contributing to the disease-causing&#xD;
        chronic inflammation.&#xD;
  &#xD;
        The DIVE 23 project is designed to understand the role of IL-23 in human IBD, in particular&#xD;
        CD. It is hypothesized that IL-23R+ cells in the gut, are drivers of chronic inflammation in&#xD;
        CD and determine the impact of IL-23 inhibition. To this end the investigators plan to&#xD;
        extensively characterize the IL-23-responsive cell populations in inflamed and non-inflamed&#xD;
        intestinal tissues of CD patients with postoperative recurrence in order to identify&#xD;
        IL-23-responsive immune cell populations that are associated with disease activity. Patients&#xD;
        will be treated in routine medical practice with biological agents and will undergo a second&#xD;
        ileocolonoscopy 12-16 weeks later to investigate the impact of the different interventions on&#xD;
        the mucosal immunology driving CD.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">June 5, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2026</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2026</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>Changes in concentration and amounts of IL-23 responsive cells in postoperative CD at baseline endoscopy and after 12-16 weeks of routine care treatment with a biological agent.</measure>
      <time_frame>Week 16</time_frame>
      <description>Single cell analysis</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Changes in concentration and amounts in IL-23 pathway cytokines and mediators, at baseline and after 12-16 weeks of biological treatment.</measure>
      <time_frame>Week 16</time_frame>
      <description>Single cell analysis</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in modified Rutgeerts' score at baseline endoscopy and follow-up endoscopy (12-16 weeks after biological treatment)</measure>
      <time_frame>Week 16</time_frame>
      <description>Endoscopic outcome measurement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in SES-CD score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment)</measure>
      <time_frame>Week 16</time_frame>
      <description>Endoscopic outcome measurement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in the Harvey-Bradshaw Index (HBI) score at baseline visit and follow-up visits at week 8 and week 12-16.</measure>
      <time_frame>Week 16</time_frame>
      <description>Clinical outcome measurement</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Robarts histopathology index (RHI) score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment).</measure>
      <time_frame>Week 16</time_frame>
      <description>Histology outcome measurement</description>
    </secondary_outcome>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Crohn´s Disease</condition>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        The investigators will retain mucosal biopsies and blood samples.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          The study will be performed in CD patients with postoperative recurrence. Patients will be&#xD;
          counselled prior to their routine endoscopy (typically 6-9 months after surgery). In&#xD;
          practice, this will be approximately be between one and two weeks before the routine&#xD;
          endoscopy. The investigators intend to evaluate 20-30 patients for this study and recruit&#xD;
          40 patients. The reason for this, is that there is a possibility that patients do not have&#xD;
          enough inflammation (Rutgeerts ≤i2a) and therefore cannot be included.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age &gt;/= 18 years;&#xD;
  &#xD;
            -  Male or non-pregnant, non-lactating females;&#xD;
  &#xD;
            -  Patients with postoperative recurrence at routine endoscopy 6-24 months following&#xD;
               resection, defined by presence of ulcerations (endoscopic Rutgeerts' score &gt;i2a) in&#xD;
               the neoterminal ileum;&#xD;
  &#xD;
            -  In the opinion of the investigator, the subject is capable of understanding and&#xD;
               complying with protocol requirements;&#xD;
  &#xD;
            -  The subject signs and dates a written informed consent form and any required privacy&#xD;
               authorization prior to the initiation of any study procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Any conditions (eg, history of alcohol or substance abuse, or lack of compliance)&#xD;
               which, in the opinion of the investigator, may interfere with the patient's ability to&#xD;
               comply with study procedures;&#xD;
  &#xD;
            -  Any condition in which one of the potential treatments are contraindicated in the&#xD;
               opinion of the investigator (eg, cardiac failure class 3-4 according to the New York&#xD;
               Heart Association [NYHA], multiple sclerosis, active infections).&#xD;
  &#xD;
            -  Received any investigational drug in the past 30 days or 5 half-lives, whichever is&#xD;
               longer.&#xD;
  &#xD;
            -  Currently participating or planning to participate in a study involving an&#xD;
               investigational product.&#xD;
  &#xD;
            -  Active or planned pregnancy during the study.&#xD;
  &#xD;
            -  Prior diagnosis of dysplasia in the colon (excluding in resected adenomas).&#xD;
  &#xD;
            -  History of malignancy in the 3 years prior to randomization except for non-melanoma&#xD;
               skin cancer.&#xD;
  &#xD;
            -  Received a biologic treatment between surgery and first endoscopy.&#xD;
  &#xD;
            -  Positive Clostridium difficile toxin B in faeces. Patients who test positive can be&#xD;
               treated per local practice and still enter the study if no longer than 4 weeks after&#xD;
               the screening visit, they test negative for Clostridium difficile toxin B.&#xD;
  &#xD;
            -  Presence of a stoma without ileocolonic anastomosis or pouch.&#xD;
  &#xD;
            -  Active perianal abscess or draining fistula&#xD;
  &#xD;
            -  ALT or AST &gt; 3x the upper limit of normal measured at screening&#xD;
  &#xD;
            -  Increased risk of bleeding: coagulation disorder, use of anticoagulants and DOACs&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
    </eligibility>
    <overall_contact>
      <last_name>Medical Ethics Committee</last_name>
      <phone>020 566 9111</phone>
      <email>metc@amsterdamumc.nl</email>
    </overall_contact>
    <location>
      <facility>
        <name>Amsterdam UMC</name>
        <address>
          <city>Amsterdam</city>
          <state>Noord-Holland</state>
          <zip>1105</zip>
          <country>Netherlands</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Lotte Oldenburg, drs</last_name>
        <phone>+31 020 566 9111</phone>
        <email>l.oldenburg@amsterdamumc.nl</email>
      </contact>
      <investigator>
        <last_name>Lotte Oldenburg, drs</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Geert D'Haens, prof dr</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 16, 2023</last_update_submitted>
    <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</investigator_affiliation>
      <investigator_full_name>Geert D'Haens</investigator_full_name>
      <investigator_title>prof dr G.R.A.M. D'Haens</investigator_title>
    </responsible_party>
    <keyword>Crohn's Disease</keyword>
    <keyword>Interleukin-23</keyword>
    <keyword>Postoperative recurrence</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Crohn Disease</mesh_term>
      <mesh_term>Recurrence</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06006039
  org study id: NL82888.018.22
  nct id: NCT06006039
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Inflammatory Bowel Diseases (IBDs), including ulcerative colitis and Crohn's disease (CD),
        constitute a group of debilitating chronic diseases that profoundly impact patient quality of
        life and incurs large costs in terms of treatment and lost productivity. Incidence of IBD is
        rising worldwide, and there is a pressing clinical need for development of new therapies.
        Discovery and development of effective therapies to treat IBDs depend first on a better
        understanding of the underlying mechanisms, including how proinflammatory cells proliferate
        unchecked.
  
        It has been established that the cytokine interleukin (IL)-23 plays a pivotal role in IBD
        pathophysiology and antibodies targeting IL-23 are currently in late stage development for
        the treatment of both CD and ulcerative colitis (UC). IL-23 is part of the IL-12 family of
        cytokines (which includes IL-12, IL-27 and IL-35). The p40 subunit is shared among IL-23 and
        IL-12; the p19 subunit is unique to IL-23. Thus far, the efficacy of selective anti-IL-23
        blockade (via anti-p19 antibodies) appears 5-10% better with respect to clinical and
        endoscopic outcomes than targeting both IL-23 and IL-12 using anti-p40 antibodies.
        Understanding the effects of IL-23 (and IL-12) in IBDs requires identification of the most
        relevant immune cells that respond to these cytokines. One likely cell type controlled by the
        IL-23 pathway are innate lymphoid cells (ILCs). ILC3s (a subset of ILCs) are dominant in
        healthy intestinal tissue and capable of producing IL-22 which maintain intestinal epithelial
        homeostasis. Disturbances in the amounts of IL-22 caused by changes in the stimulatory
        cytokine IL-23 in tissues, may therefore cause inflammatory responses. IL-23 may facilitate
        the IL-12-induced shift of ILC3s to ILC1s which are contributing to the disease-causing
        chronic inflammation.
  
        The DIVE 23 project is designed to understand the role of IL-23 in human IBD, in particular
        CD. It is hypothesized that IL-23R+ cells in the gut, are drivers of chronic inflammation in
        CD and determine the impact of IL-23 inhibition. To this end the investigators plan to
        extensively characterize the IL-23-responsive cell populations in inflamed and non-inflamed
        intestinal tissues of CD patients with postoperative recurrence in order to identify
        IL-23-responsive immune cell populations that are associated with disease activity. Patients
        will be treated in routine medical practice with biological agents and will undergo a second
        ileocolonoscopy 12-16 weeks later to investigate the impact of the different interventions on
        the mucosal immunology driving CD.
  observational model: Cohort
  time perspective: Prospective
  measure: Changes in concentration and amounts of IL-23 responsive cells in postoperative CD at baseline endoscopy and after 12-16 weeks of routine care treatment with a biological agent.
  time frame: Week 16
  description: Single cell analysis
  measure: Changes in concentration and amounts in IL-23 pathway cytokines and mediators, at baseline and after 12-16 weeks of biological treatment.
  time frame: Week 16
  description: Single cell analysis
  measure: Change in modified Rutgeerts' score at baseline endoscopy and follow-up endoscopy (12-16 weeks after biological treatment)
  time frame: Week 16
  description: Endoscopic outcome measurement
  measure: Change in SES-CD score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment)
  time frame: Week 16
  description: Endoscopic outcome measurement
  measure: Change in the Harvey-Bradshaw Index (HBI) score at baseline visit and follow-up visits at week 8 and week 12-16.
  time frame: Week 16
  description: Clinical outcome measurement
  measure: Change in Robarts histopathology index (RHI) score at baseline endoscopy and follow-up endoscopy (week 12-16, after biological treatment).
  time frame: Week 16
  description: Histology outcome measurement
  The investigators will retain mucosal biopsies and blood samples.
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  last name: Medical Ethics Committee
  phone: 020 566 9111
  email: metc@amsterdamumc.nl
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  country: Netherlands
  responsible party type: Principal Investigator
  investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  investigator full name: Geert D'Haens
  investigator title: prof dr G.R.A.M. D'Haens
  mesh term: Crohn Disease
  mesh term: Recurrence
  sharing ipd: Undecided