<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/NCT04504136</url>
  </required_header>
  <id_info>
    <org_study_id>IMDDN-20-MUCOSALHEALING</org_study_id>
    <secondary_id>2R01DK095662-10A1</secondary_id>
    <nct_id>NCT04504136</nct_id>
  </id_info>
  <brief_title>Regulation of Mucosal Healing in Inflammatory Bowel Disease</brief_title>
  <official_title>Regulation of Mucosal Healing in Inflammatory Bowel Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Terrence A Barrett</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Kentucky</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 objective of the current study is to compare non-healing colonic ulcers in patients with&#xD;
      inflammatory bowel disease (IBD) with iatrogenic colonic ulcers (biopsy sites) in healthy&#xD;
      control patients and patients with rheumatoid or psoriatic arthritis. Patients will be&#xD;
      biopsied at baseline and again at a follow-up visit in a &quot;biopsy of the biopsy&quot; approach.&#xD;
      These biopsies will be used to reveal patterns about gene expression and mitochondrial&#xD;
      function during ulcer healing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Induction of mucosal healing in inflammatory bowel disease (IBD) is associated with reduced&#xD;
      hospitalizations, surgeries, and reduced cancer risk. However, previous studies have shown&#xD;
      that 54-69% of ulcerative colitis (UC) patients fail to heal ulcers after several weeks of&#xD;
      treatment, and roughly half do not maintain remission at one year. The single most important&#xD;
      factor in preventing severe medical consequences, like colon removal surgery or cancer, is&#xD;
      treatment to completely heal the top layer of the intestine as quickly as possible. Healing&#xD;
      is a complex process and the dysfunction observed in colitis can only be fully understood by&#xD;
      comparison to healing in non-IBD patients.&#xD;
&#xD;
      This is a prospective trial involving three groups of patients: 1) IBD patients with active&#xD;
      disease, newly treated with anti-TNF therapy (biologic failure or naïve); 2) non-IBD patients&#xD;
      with rheumatoid/psoriatic arthritis who are receiving anti-TNF therapy, and 3) healthy&#xD;
      control patients. Biopsies will be collected at baseline during standard of care endoscopy&#xD;
      and at a follow-up research endoscopy.&#xD;
&#xD;
      This study will probe mechanisms of ulcer healing by analyzing gene expression patterns and&#xD;
      mitochondrial function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 30, 2021</start_date>
  <completion_date type="Anticipated">May 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mitochondrial DNA copy number</measure>
    <time_frame>35 days</time_frame>
    <description>Mitochondrial DNA copy number will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in expression levels of cMyc</measure>
    <time_frame>35 days</time_frame>
    <description>Relative expression of cMyc (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in expression levels of PGC-1 alpha</measure>
    <time_frame>35 days</time_frame>
    <description>Relative expression of PGC-1 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in expression levels of Ki67</measure>
    <time_frame>35 days</time_frame>
    <description>Relative expression of Ki67 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of visible ulcers</measure>
    <time_frame>1 day (at follow-up visit)</time_frame>
    <description>The number of visible ulcers will be assessed during the follow-up endoscopy for healthy patients and rheumatoid/psoriatic arthritis patients only.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Mayo Endoscopic Score</measure>
    <time_frame>35 days</time_frame>
    <description>The Mayo Endoscopic Score will be calculated at baseline and at follow-up in patients with ulcerative colitis only. The Mayo Endoscopic score is evaluated for the macroscopically most severely inflamed segment: 0 for normal or inactive disease; 1 for erythema, decreased vascular pattern, mild friability; 2 for marked erythema, absent vascular pattern, friability, erosions; 3 ulcerations or spontaneous bleeding. Segmental scores range from 0-3; higher scores indicate more severe disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Segmental SES-CD Score</measure>
    <time_frame>35 days</time_frame>
    <description>The Simple Endoscopic Score (SES) will be calculated at baseline and follow-up in patients with Crohn's disease (CD) only. The SES-CD score incorporates ulcer size, narrowing, and the area affected by disease or ulceration. Scores range from 0-12; lower scores indicate remission while higher scores indicate severe endoscopic activity.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fecal calprotectin levels</measure>
    <time_frame>35 days</time_frame>
    <description>Levels of fecal calprotectin (ug/g) will be measured from stool samples collected from patients at any time during the study protocol.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will be healthy (not diagnosed with inflammatory bowel disease).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Inflammatory Bowel Disease</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will have been diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and have either failed treatment with biologics or be naive to biologic therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rheumatoid/Psoriatic Arthritis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will have been diagnosed with rheumatoid (RA) or psoriatic arthritis (PsA) and will be receiving anti-TNF antibody therapy at the time of enrollment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Serial Biopsy</intervention_name>
    <description>During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a &quot;biopsy of the biopsy&quot; approach.</description>
    <arm_group_label>Healthy Controls</arm_group_label>
    <arm_group_label>Inflammatory Bowel Disease</arm_group_label>
    <arm_group_label>Rheumatoid/Psoriatic Arthritis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (Group 1):&#xD;
&#xD;
          -  Diagnosed ulcerative colitis or Crohn's disease&#xD;
&#xD;
          -  Biologic failure or naive to biologic treatment&#xD;
&#xD;
          -  Eligible to be treated with anti-TNF therapy&#xD;
&#xD;
        Inclusion Criteria (Group 2):&#xD;
&#xD;
          -  Diagnosed rheumatoid or psoriatic arthritis&#xD;
&#xD;
          -  Receiving anti-TNF antibody therapy at the time of enrollment&#xD;
&#xD;
        Inclusion Criteria (Group 3):&#xD;
&#xD;
          -  Endoscopically unremarkable colonic mucosa&#xD;
&#xD;
          -  Absence of inflammatory bowel disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Classified in an anesthesia risk group, ASA Class =4&#xD;
&#xD;
          -  History of bleeding diathesis or coagulopathy&#xD;
&#xD;
          -  Stroke or transient neurological attack with the last 6 months&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Receiving anticoagulants or anti-platelet medications other than low-dose aspirin&#xD;
&#xD;
          -  Receiving steroid therapy or metformin&#xD;
&#xD;
          -  HIV positive&#xD;
&#xD;
          -  Incarceration&#xD;
&#xD;
          -  History of total proctocolectomy&#xD;
&#xD;
          -  History of system chemotherapy within 18 months&#xD;
&#xD;
          -  Uncontrolled intercurrent illness&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Terrence Barrett, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Justin Thomas, PhD</last_name>
    <phone>859-323-4887</phone>
    <email>Justin.Thomas2@uky.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Justin Thomas, PhD</last_name>
      <phone>859-323-4887</phone>
      <email>justin.thomas2@uky.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>December 2, 2022</last_update_submitted>
  <last_update_submitted_qc>December 2, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Terrence A Barrett</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>mucosal</keyword>
  <keyword>rheumatoid arthritis</keyword>
  <keyword>psoriatic arthritis</keyword>
  <keyword>ulcer</keyword>
  <keyword>colitis</keyword>
  <keyword>Crohn's</keyword>
  <keyword>mitochondria</keyword>
  <keyword>biopsy</keyword>
  <keyword>wound</keyword>
  <keyword>biologic</keyword>
  <keyword>anti-TNF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Intestinal Diseases</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/NCT04504136
org study id: IMDDN-20-MUCOSALHEALING
secondary id: 2R01DK095662-10A1
nct id: NCT04504136
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of the current study is to compare non-healing colonic ulcers in patients with
      inflammatory bowel disease (IBD) with iatrogenic colonic ulcers (biopsy sites) in healthy
      control patients and patients with rheumatoid or psoriatic arthritis. Patients will be
      biopsied at baseline and again at a follow-up visit in a "biopsy of the biopsy" approach.
      These biopsies will be used to reveal patterns about gene expression and mitochondrial
      function during ulcer healing.
Induction of mucosal healing in inflammatory bowel disease (IBD) is associated with reduced
      hospitalizations, surgeries, and reduced cancer risk. However, previous studies have shown
      that 54-69% of ulcerative colitis (UC) patients fail to heal ulcers after several weeks of
      treatment, and roughly half do not maintain remission at one year. The single most important
      factor in preventing severe medical consequences, like colon removal surgery or cancer, is
      treatment to completely heal the top layer of the intestine as quickly as possible. Healing
      is a complex process and the dysfunction observed in colitis can only be fully understood by
      comparison to healing in non-IBD patients.

      This is a prospective trial involving three groups of patients: 1) IBD patients with active
      disease, newly treated with anti-TNF therapy (biologic failure or naïve); 2) non-IBD patients
      with rheumatoid/psoriatic arthritis who are receiving anti-TNF therapy, and 3) healthy
      control patients. Biopsies will be collected at baseline during standard of care endoscopy
      and at a follow-up research endoscopy.

      This study will probe mechanisms of ulcer healing by analyzing gene expression patterns and
      mitochondrial function.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in mitochondrial DNA copy number
time frame: 35 days
description: Mitochondrial DNA copy number will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
measure: Change in expression levels of cMyc
time frame: 35 days
description: Relative expression of cMyc (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
measure: Change in expression levels of PGC-1 alpha
time frame: 35 days
description: Relative expression of PGC-1 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
measure: Change in expression levels of Ki67
time frame: 35 days
description: Relative expression of Ki67 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.
measure: Number of visible ulcers
time frame: 1 day (at follow-up visit)
description: The number of visible ulcers will be assessed during the follow-up endoscopy for healthy patients and rheumatoid/psoriatic arthritis patients only.
measure: Change in Mayo Endoscopic Score
time frame: 35 days
description: The Mayo Endoscopic Score will be calculated at baseline and at follow-up in patients with ulcerative colitis only. The Mayo Endoscopic score is evaluated for the macroscopically most severely inflamed segment: 0 for normal or inactive disease; 1 for erythema, decreased vascular pattern, mild friability; 2 for marked erythema, absent vascular pattern, friability, erosions; 3 ulcerations or spontaneous bleeding. Segmental scores range from 0-3; higher scores indicate more severe disease.
measure: Change in Segmental SES-CD Score
time frame: 35 days
description: The Simple Endoscopic Score (SES) will be calculated at baseline and follow-up in patients with Crohn's disease (CD) only. The SES-CD score incorporates ulcer size, narrowing, and the area affected by disease or ulceration. Scores range from 0-12; lower scores indicate remission while higher scores indicate severe endoscopic activity.
measure: Fecal calprotectin levels
time frame: 35 days
description: Levels of fecal calprotectin (ug/g) will be measured from stool samples collected from patients at any time during the study protocol.
arm group label: Healthy Controls
arm group type: Experimental
description: Participants in this group will be healthy (not diagnosed with inflammatory bowel disease).
arm group label: Inflammatory Bowel Disease
arm group type: Experimental
description: Participants in this group will have been diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and have either failed treatment with biologics or be naive to biologic therapy.
arm group label: Rheumatoid/Psoriatic Arthritis
arm group type: Experimental
description: Participants in this group will have been diagnosed with rheumatoid (RA) or psoriatic arthritis (PsA) and will be receiving anti-TNF antibody therapy at the time of enrollment.
intervention type: Procedure
intervention name: Serial Biopsy
description: During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a "biopsy of the biopsy" approach.
arm group label: Healthy Controls
arm group label: Inflammatory Bowel Disease
arm group label: Rheumatoid/Psoriatic Arthritis
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Terrence Barrett, MD
role: Principal Investigator
affiliation: University of Kentucky
last name: Justin Thomas, PhD
phone: 859-323-4887
email: Justin.Thomas2@uky.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Terrence A Barrett
investigator title: Professor
mesh term: Intestinal Diseases
mesh term: Inflammatory Bowel Diseases
sharing ipd: No