<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/NCT03266471</url>
  </required_header>
  <id_info>
    <org_study_id>171198</org_study_id>
    <nct_id>NCT03266471</nct_id>
  </id_info>
  <brief_title>Cytokines and Genes in Therapeutic Response in Crohn's Disease</brief_title>
  <official_title>Cytokines and Genes in Therapeutic Response in Crohn's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</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>
      Inflammatory bowel disease (IBD), consisting of two major forms, Crohn's disease (CD) and&#xD;
      ulcerative colitis (UC), affects more than 1.6 million people in the United States alone.&#xD;
      Though the precise mechanisms underlying the inflammation and immune responses in IBD are&#xD;
      still being investigated, various inflammatory mediators, including pro-inflammatory&#xD;
      cytokines, and genes have been implicated in the disease process. At present, there are no&#xD;
      reliable mechanisms to predict response to individual IBD medications. The investigators seek&#xD;
      to evaluate whether inflammatory cytokines change longitudinally during treatment with&#xD;
      anti-cytokine agents in both treatment primary responders and primary non-responders. In&#xD;
      addition, the investigators will be evaluating the pharmacogenetics of treatment response to&#xD;
      these agents.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2017</start_date>
  <completion_date type="Actual">May 3, 2022</completion_date>
  <primary_completion_date type="Actual">May 3, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Compare longitudinal cytokine measurements in treatment responders versus nonresponders.</measure>
    <time_frame>52 weeks</time_frame>
    <description>The investigators will classify Crohn's disease subjects as primary responders or primary non-responders to anti-TNF-α, ustekinumab, or vedolizumab therapy based on clinical, endoscopic, and/or histologic data. The investigators will compare serum and tissue cytokines in CD subjects at before and after treatment initiation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare serum and tissue pro-inflammatory cytokines in CD patients and healthy subjects.</measure>
    <time_frame>26 weeks</time_frame>
    <description>The investigators will compare serum and tissue cytokine/chemokine levels to see if Crohn's disease patients express a difference versus control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess whether gene variants are associated with treatment response.</measure>
    <time_frame>52 weeks</time_frame>
    <description>The investigators will collect a one time whole blood sample from subjects starting a new anti-cytokine agent (infliximab, infliximab biosimilar, adalimumab, certolizumab, ustekinumab, or vedolizumab) and extract DNA and genotype. The investigators will look for associations between genotype and treatment response.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">96</enrollment>
  <condition>Inflammatory Bowel Diseases</condition>
  <arm_group>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
    <description>Patients that are seen in the Inflammatory Bowel Disease clinic with CD confirmed by endoscopy or radiology assessment who are initiating either an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, certolizumab, or infliximab biosimilar), ustekinumab, or vedolizumab as part of their routine clinical care will be asked to provide blood samples, stool samples, and intestinal biopsies from standard of care colonoscopy at baseline and post therapy of at least 6 weeks duration but not more than 52 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or other non-IBD related indication will be asked to provide blood samples, stool samples and intestinal biopsies from standard of care colonoscopy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Baseline blood sample</intervention_name>
    <description>Blood sample for cytokine measurements and genetics.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Baseline intestinal biopsies</intervention_name>
    <description>Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Crohn's disease activity index (CDAI)</intervention_name>
    <description>To determine response, a Crohn's Disease Activity Index (CDAI) score will be obtained at time point 1 and time point 2 in all enrolled CD patients. The CDAI is a well validated symptom index for CD which assesses 8 factors including stool frequency, abdominal pain, general well being, CD complications, HCT, and deviation from ideal body weight.</description>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Post treatment blood sample</intervention_name>
    <description>Blood sample for cytokine measurements after patients have been on therapy for at least 6 weeks but no more than 52 weeks.</description>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Post treatment intestinal biopsies</intervention_name>
    <description>Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy at least 6 weeks but no more than 52 weeks after initiation of therapy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.</description>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Baseline stool sample</intervention_name>
    <description>Stool sample for inflammatory markers or microbiome analysis.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Post treatment stool sample</intervention_name>
    <description>Stool sample for inflammatory markers or microbiome analysis.</description>
    <arm_group_label>Crohn's disease Patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Any remaining serum or tissue samples may be evaluated for other markers of IBD or stored for&#xD;
      future studies.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients who are scheduled for a colonoscopy at the Vanderbilt Endoscopy Laboratory as part&#xD;
        of their routine care and who do not meet any of the pre-defined exclusion criteria will be&#xD;
        considered for participation in the study as control subjects. Patients who are part of the&#xD;
        Vanderbilt IBD practice who initiate therapy on an anti-TNF, ustekinumab, or vedolizumab as&#xD;
        part of their routine care will be considered for participation in the study as subjects.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients that are seen in the Inflammatory Bowel Disease clinic with Crohn's disease&#xD;
             who are initiating either treatment as part of their routine clinical care.&#xD;
&#xD;
          -  Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or&#xD;
             other non-IBD related indication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnant&#xD;
&#xD;
          -  have a known coagulopathy or bleeding disorder&#xD;
&#xD;
          -  have known renal or hepatic impairment&#xD;
&#xD;
          -  have a history of organ transplantation&#xD;
&#xD;
          -  CD patients who are being seen in consultation and do not plan to receive longitudinal&#xD;
             care through initiation their new therapy at the Vanderbilt IBD center will be&#xD;
             excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elizabeth Scoville, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inflammatory Bowel Disease Clinic, Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center Endoscopy Laboratory</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Elizabeth Scoville</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Cytokines</keyword>
  <keyword>Pharmacogenetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</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/NCT03266471
org study id: 171198
nct id: NCT03266471
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Inflammatory bowel disease (IBD), consisting of two major forms, Crohn's disease (CD) and
      ulcerative colitis (UC), affects more than 1.6 million people in the United States alone.
      Though the precise mechanisms underlying the inflammation and immune responses in IBD are
      still being investigated, various inflammatory mediators, including pro-inflammatory
      cytokines, and genes have been implicated in the disease process. At present, there are no
      reliable mechanisms to predict response to individual IBD medications. The investigators seek
      to evaluate whether inflammatory cytokines change longitudinally during treatment with
      anti-cytokine agents in both treatment primary responders and primary non-responders. In
      addition, the investigators will be evaluating the pharmacogenetics of treatment response to
      these agents.
observational model: Case-Control
time perspective: Prospective
measure: Compare longitudinal cytokine measurements in treatment responders versus nonresponders.
time frame: 52 weeks
description: The investigators will classify Crohn's disease subjects as primary responders or primary non-responders to anti-TNF-α, ustekinumab, or vedolizumab therapy based on clinical, endoscopic, and/or histologic data. The investigators will compare serum and tissue cytokines in CD subjects at before and after treatment initiation.
measure: Compare serum and tissue pro-inflammatory cytokines in CD patients and healthy subjects.
time frame: 26 weeks
description: The investigators will compare serum and tissue cytokine/chemokine levels to see if Crohn's disease patients express a difference versus control.
measure: To assess whether gene variants are associated with treatment response.
time frame: 52 weeks
description: The investigators will collect a one time whole blood sample from subjects starting a new anti-cytokine agent (infliximab, infliximab biosimilar, adalimumab, certolizumab, ustekinumab, or vedolizumab) and extract DNA and genotype. The investigators will look for associations between genotype and treatment response.
arm group label: Crohn's disease Patients
description: Patients that are seen in the Inflammatory Bowel Disease clinic with CD confirmed by endoscopy or radiology assessment who are initiating either an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, certolizumab, or infliximab biosimilar), ustekinumab, or vedolizumab as part of their routine clinical care will be asked to provide blood samples, stool samples, and intestinal biopsies from standard of care colonoscopy at baseline and post therapy of at least 6 weeks duration but not more than 52 weeks.
arm group label: Controls
description: Healthy adults without IBD undergoing colonoscopy for colorectal cancer screening or other non-IBD related indication will be asked to provide blood samples, stool samples and intestinal biopsies from standard of care colonoscopy.
intervention type: Diagnostic Test
intervention name: Baseline blood sample
description: Blood sample for cytokine measurements and genetics.
arm group label: Controls
arm group label: Crohn's disease Patients
intervention type: Diagnostic Test
intervention name: Baseline intestinal biopsies
description: Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.
arm group label: Controls
arm group label: Crohn's disease Patients
intervention type: Other
intervention name: Crohn's disease activity index (CDAI)
description: To determine response, a Crohn's Disease Activity Index (CDAI) score will be obtained at time point 1 and time point 2 in all enrolled CD patients. The CDAI is a well validated symptom index for CD which assesses 8 factors including stool frequency, abdominal pain, general well being, CD complications, HCT, and deviation from ideal body weight.
arm group label: Crohn's disease Patients
intervention type: Diagnostic Test
intervention name: Post treatment blood sample
description: Blood sample for cytokine measurements after patients have been on therapy for at least 6 weeks but no more than 52 weeks.
arm group label: Crohn's disease Patients
intervention type: Diagnostic Test
intervention name: Post treatment intestinal biopsies
description: Up to 20 additional biopsies will be obtained at the time of standard of care colonoscopy at least 6 weeks but no more than 52 weeks after initiation of therapy. It is not felt that additional biopsies substantially increases the risk of a colonoscopy. Cytokine measurements will be performed on the tissue collected.
arm group label: Crohn's disease Patients
intervention type: Diagnostic Test
intervention name: Baseline stool sample
description: Stool sample for inflammatory markers or microbiome analysis.
arm group label: Controls
arm group label: Crohn's disease Patients
intervention type: Diagnostic Test
intervention name: Post treatment stool sample
description: Stool sample for inflammatory markers or microbiome analysis.
arm group label: Crohn's disease Patients
Any remaining serum or tissue samples may be evaluated for other markers of IBD or stored for
      future studies.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elizabeth Scoville, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Elizabeth Scoville
investigator title: Principal Investigator
mesh term: Crohn Disease
mesh term: Inflammatory Bowel Diseases
sharing ipd: No