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/NCT06023004</url>
    </required_header>
    <id_info>
      <org_study_id>The Diverticulitis study</org_study_id>
      <nct_id>NCT06023004</nct_id>
    </id_info>
    <brief_title>The Diverticulitis Study</brief_title>
    <official_title>Circulating Tumor DNA Guided vs Opportunistic Colonoscopy Screening for CRC Detection After Acute Colonic Diverticulitis - the Diverticulitis Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Aarhus</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Odense University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Regional Hospital Horsens</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University of Southern Denmark</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Aarhus University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Aarhus</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>
        Acute colonic diverticulitis is when a part of the colon gets swollen and inflamed. The&#xD;
        diagnosis is based on a CT scan, which can show thickening of the colonic walls and&#xD;
        infiltration of the diverticula. These changes and the concomitant symptoms can overlap with&#xD;
        colorectal cancer (CRC). Therefore, the guidelines suggest that people with diverticulitis&#xD;
        should be offered a colonoscopy to ensure, that CRC is not the underlying cause of the&#xD;
        changes and symptoms.&#xD;
  &#xD;
        In Denmark, a lot of people get hospitalized each year due to diverticulitis, and many of&#xD;
        them end up having colonoscopies with the purpose of excluding CRC. Currently, there are no&#xD;
        methods for guiding colonoscopies following a diverticulitis episode, resulting in numerous&#xD;
        unnecessary colonoscopies each year.&#xD;
  &#xD;
        In the Diverticulitis study, we want to investigate if a simple blood test analyzed for the&#xD;
        presence of circulating tumor DNA (ctDNA), can help us decide who needs a colonoscopy. We&#xD;
        will collect blood samples from 220 people with diverticulitis and categorize them into ctDNA&#xD;
        positive and negative groups. The ctDNA category will be compared to the colonoscopy results&#xD;
        to see if there is a correlation between being ctDNA positive and having a CRC diagnosed at&#xD;
        the colonoscopy.&#xD;
  &#xD;
        This study could change clinical practice since we anticipate that ctDNA-guided triaging of&#xD;
        diverticulitis patients is a cost-effective strategy for selecting diverticulitis patients&#xD;
        needing colonoscopy, ensuring detection of the underlying CRC, and significantly reducing the&#xD;
        number of patients undergoing unnecessary colonoscopy.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        KEY POINTS&#xD;
  &#xD;
          -  Colonoscopy is recommended after acute diverticulitis to rule out CRC, and yearly more&#xD;
             than 2000 colonoscopies are performed.&#xD;
  &#xD;
          -  CRC incidence is low in the diverticulitis population and most colonoscopies are&#xD;
             unnecessary. It takes approximately 100-200 colonoscopies to diagnose just 1 CRC.&#xD;
  &#xD;
          -  ctDNA is a minimally invasive and extraordinarily powerful biomarker of cancer.&#xD;
  &#xD;
        GOALS&#xD;
  &#xD;
        ● To use ctDNA analysis to triage diverticulitis patients for colonoscopy. Diagnosing the&#xD;
        same CRCs, but minimizing the number of patients needing colonoscopy&#xD;
  &#xD;
        PERSPECTIVES&#xD;
  &#xD;
          -  Practice-changing evidence for ctDNA-guided triaging of diverticulitis patients for&#xD;
             colonoscopy, an important and well-recognized clinical dilemma in the management of CRC.&#xD;
  &#xD;
          -  Evaluation of the cost-effectiveness of ctDNA-guided triaging versus standard-of-care.&#xD;
  &#xD;
        PROJECT DESCRIPTION For patients who have experienced an episode of acute colonic&#xD;
        diverticulitis, Danish and international guidelines recommend opportunistic screening with&#xD;
        colonoscopy to rule out CRC as the underlying reason for the diverticulitis symptoms. In&#xD;
        Denmark, there are more than 4000 hospitalizations per year due to diverticulitis.&#xD;
        Accordingly, a substantial number of post-diverticulitis colonoscopies are performed each&#xD;
        year to rule out underlying CRC. Colonoscopy is an invasive procedure associated with&#xD;
        discomfort and pain in more than 50% of patients. The procedure also carries the risk of&#xD;
        complications such as perforation and hemorrhage, particularly for patients with diseased&#xD;
        intestines such as diverticulitis patients. CRC prevalence in suspected diverticulitis&#xD;
        patients is low, &lt;2% overall, and as low as 0.5% for uncomplicated diverticulitis. Thus, an&#xD;
        unreasonably high number of colonoscopies, ranging from 50 and up to more than 200, are&#xD;
        needed to diagnose 1 CRC. In comparison, a &gt;4% CRC prevalence is considered the minimal&#xD;
        acceptable among patients selected for follow-up colonoscopy in the Danish nationwide CRC&#xD;
        screening program, corresponding to less than 25 colonoscopies per CRC. Hence, it may be&#xD;
        questioned whether the current guidelines on follow-up colonoscopy after diverticulitis are&#xD;
        at all acceptable, both from a patient perspective and from a health-economy perspective.&#xD;
        However, it has been very difficult to change. Consequently, there is an urgent need for a&#xD;
        highly sensitive, low-risk, minimally invasive cancer detection test that can be used to&#xD;
        triage newly diagnosed diverticulitis patients and ensure that underlying CRC is still&#xD;
        diagnosed while minimizing the number of patients needing colonoscopy. Here, we propose to&#xD;
        conduct a case/control study to explore the feasibility of using our recently developed&#xD;
        TriMeth ctDNA analysis test for this purpose.&#xD;
  &#xD;
        We hypothesize that ctDNA analysis can triage diverticulitis patients for colonoscopy and&#xD;
        achieve a diagnosis of prevalent CRC but at a substantially lower colonoscopy/CRC ratio. For&#xD;
        this purpose, we will use our tumor-agnostic ctDNA analysis &quot;TriMeth&quot;. TriMeth was originally&#xD;
        developed as a CRC screening tool for selecting individuals from the average-risk population&#xD;
        for colonoscopy. Accordingly, the threshold for calling the test positive was set with the&#xD;
        objective of high specificity. At 99% specificity, it has a sensitivity of 85%. Based on data&#xD;
        from the original development and validation cohorts (400 CRC and 800 controls), we will&#xD;
        tailor TriMeth for this specific purpose, i.e., setting the threshold for test positivity to&#xD;
        achieve near 100% sensitivity by accepting a lower specificity. Second, we will conduct a&#xD;
        case-control study to validate this new TriMeth-diverticulitis threshold in the target&#xD;
        population. We expect a minimum of 20 cases with CRC diagnosed at colonoscopy after suspected&#xD;
        diverticulitis to be identified through the IMPROVE study (NCT03637686). For each case, 10&#xD;
        controls will be randomly selected (to a minimum of 200 total) from patients with CT-verified&#xD;
        diverticulitis and a follow-up colonoscopy without CRC. Diverticulitis patients may at the&#xD;
        time of colonoscopy exhibit symptoms, that would in any case serve as an absolute indication&#xD;
        for colonoscopy (patients age &gt;40 with changes in bowel habits &gt;1 month, rectal bleeding,&#xD;
        iron-deficiency anemia, or excessive weight-loss). Therefore, in addition to blood sampling,&#xD;
        we will at the time of CRC diagnosis or negative colonoscopy collect information on other&#xD;
        established indicators for colonoscopy. As part of the study, we will conduct a&#xD;
        health-economy assessment comparing the TriMeth-guided approach to the current practice of&#xD;
        &quot;colonoscopy for all&quot;. The primary outcome is the sensitivity and specificity of TriMeth for&#xD;
        CRC detection in this population. The secondary outcome is health economy, considering the&#xD;
        other indicators for colonoscopy. If high sensitivity and clinically and economically&#xD;
        relevant colonoscopy-sparing potential is demonstrated, the data will be presented to the&#xD;
        Danish Colorectal Cancer Group and the Danish Health Technology Council with the aim of&#xD;
        obtaining approval to change the national guideline and implement the approach.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 1, 2022</start_date>
    <completion_date type="Anticipated">May 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2024</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>ctDNA analysis</measure>
      <time_frame>After recruitment of the last patient, we expect that ctDNA analyses can be performed within 6 months</time_frame>
      <description>Blood samples will be categorized as either ctDNA positive or negative</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cost-effectiveness of treatment</measure>
      <time_frame>After recruitment of the last patient, we expect that cost-effectiveness analyses can be performed within 12 months</time_frame>
      <description>Assessment of the cost-effectiveness of &quot;ctDNA guided&quot; versus &quot;opportunistic&quot; colonoscopy screening of the diverticulitis patients</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">250</enrollment>
    <condition>Colonic Diverticulitis</condition>
    <condition>Colorectal Cancer</condition>
    <condition>Acute Diverticulitis</condition>
    <arm_group>
      <arm_group_label>Controls</arm_group_label>
      <description>Patients diagnosed with diverticulitis through CT scan and scheduled for a colonoscopy. The colonoscopy must result in no detection of colorectal cancer.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Cases</arm_group_label>
      <description>Patients diagnosed with CRC immediately after an episode of diverticulitis.</description>
    </arm_group>
    <biospec_retention>Samples With DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        From each patient, blood will be collected between 2 and 6 weeks after the diagnosis of&#xD;
        diverticulitis. The blood will be collected before initiation of the bowel cleansing&#xD;
        associated with the CRC screening colonoscopy.&#xD;
  &#xD;
        Blood draw: 80 mL - 7 x EDTA tubes, 1 x serum tube&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Patients with newly CT-verified diverticulitis will be identified by the attending&#xD;
          physician at the recruiting surgical departments. Patients fulfilling the inclusion&#xD;
          criteria are approached and invited to participate.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  CT-verified diverticulitis eligible for a follow-up colonoscopy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to provide oral and written informed consent&#xD;
  &#xD;
            -  Recent colonic imaging and no need for renewed visualization of the colonic mucosa&#xD;
               deemed by the attending doctor&#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>Thomas Bjørsum-Meyer, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Odense University Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Per V Andersen, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Odense University Hospital</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Kåre A Gotschalck, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Regional Hospital Horsens</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Liza Sopina, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Southern Denmark</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Claus L Andersen, PhD</last_name>
      <phone>+45 7845 5319</phone>
      <email>cla@clin.au.dk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Christina Demuth, PhD</last_name>
      <phone>+45 7845 5310</phone>
      <email>demuth@clin.au.dk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Herlev Hospital</name>
        <address>
          <city>Herlev</city>
          <state>Capital Region Of Denmark</state>
          <zip>2730</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mads F Klein, MD, Ph.D</last_name>
        <email>mads.falk.klein@regionh.dk</email>
      </contact>
      <contact_backup>
        <last_name>Taha AH Al-Taei, MD</last_name>
        <email>taha.alaa.hussein.al-taei@regionh.dk</email>
      </contact_backup>
    </location>
    <location>
      <facility>
        <name>Regional Hospital Horsens</name>
        <address>
          <city>Horsens</city>
          <state>Central Denmark Region</state>
          <zip>8700</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Kåre A Gotschalck, MD, Ph.D</last_name>
        <email>kaarsune@rm.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Regional Hospital Randers</name>
        <address>
          <city>Randers</city>
          <state>Central Denmark Region</state>
          <zip>8930</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Peter Bondeven, MD, PhD</last_name>
        <email>petefred@rm.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Regional Hospital Viborg</name>
        <address>
          <city>Viborg</city>
          <state>Central Denmark Region</state>
          <zip>8800</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Uffe S Løve, MD, PhD</last_name>
        <email>uffescho@rm.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Odense University Hospital</name>
        <address>
          <city>Odense</city>
          <state>The Region Of Southern Denmark</state>
          <zip>5000</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Thomas Bjørsum-Meyer, MD, PhD</last_name>
        <email>Thomas.Bjoersum-Meyer@rsyd.dk</email>
      </contact>
      <contact_backup>
        <last_name>Per V Andersen, MD, PhD</last_name>
        <email>Per.Vadgaard.Andersen@rsyd.dk</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <reference>
      <citation>Andersen JC, Bundgaard L, Elbrond H, Laurberg S, Walker LR, Stovring J; Danish Surgical Society. Danish national guidelines for treatment of diverticular disease. Dan Med J. 2012 May;59(5):C4453.</citation>
      <PMID>22549495</PMID>
    </reference>
    <reference>
      <citation>Meyer J, Orci LA, Combescure C, Balaphas A, Morel P, Buchs NC, Ris F. Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-analysis of Observational Studies. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1448-1456.e17. doi: 10.1016/j.cgh.2018.07.031. Epub 2018 Jul 26.</citation>
      <PMID>30056181</PMID>
    </reference>
    <reference>
      <citation>Jensen SO, Ogaard N, Orntoft MW, Rasmussen MH, Bramsen JB, Kristensen H, Mouritzen P, Madsen MR, Madsen AH, Sunesen KG, Iversen LH, Laurberg S, Christensen IJ, Nielsen HJ, Andersen CL. Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer-a clinical biomarker discovery and validation study. Clin Epigenetics. 2019 Nov 14;11(1):158. doi: 10.1186/s13148-019-0757-3.</citation>
      <PMID>31727158</PMID>
    </reference>
    <reference>
      <citation>Jensen SO, Ogaard N, Nielsen HJ, Bramsen JB, Andersen CL. Enhanced Performance of DNA Methylation Markers by Simultaneous Measurement of Sense and Antisense DNA Strands after Cytosine Conversion. Clin Chem. 2020 Jul 1;66(7):925-933. doi: 10.1093/clinchem/hvaa100.</citation>
      <PMID>32460325</PMID>
    </reference>
    <reference>
      <citation>Ogaard N, Reinert T, Henriksen TV, Frydendahl A, Aagaard E, Orntoft MW, Larsen MO, Knudsen AR, Mortensen FV, Andersen CL. Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study. Eur J Cancer. 2022 Mar;163:163-176. doi: 10.1016/j.ejca.2021.12.026. Epub 2022 Jan 22.</citation>
      <PMID>35074652</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diverticulitis</mesh_term>
      <mesh_term>Diverticulitis, Colonic</mesh_term>
    </condition_browse>
    <!-- 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/NCT06023004
  org study id: The Diverticulitis study
  nct id: NCT06023004
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Acute colonic diverticulitis is when a part of the colon gets swollen and inflamed. The
        diagnosis is based on a CT scan, which can show thickening of the colonic walls and
        infiltration of the diverticula. These changes and the concomitant symptoms can overlap with
        colorectal cancer (CRC). Therefore, the guidelines suggest that people with diverticulitis
        should be offered a colonoscopy to ensure, that CRC is not the underlying cause of the
        changes and symptoms.
  
        In Denmark, a lot of people get hospitalized each year due to diverticulitis, and many of
        them end up having colonoscopies with the purpose of excluding CRC. Currently, there are no
        methods for guiding colonoscopies following a diverticulitis episode, resulting in numerous
        unnecessary colonoscopies each year.
  
        In the Diverticulitis study, we want to investigate if a simple blood test analyzed for the
        presence of circulating tumor DNA (ctDNA), can help us decide who needs a colonoscopy. We
        will collect blood samples from 220 people with diverticulitis and categorize them into ctDNA
        positive and negative groups. The ctDNA category will be compared to the colonoscopy results
        to see if there is a correlation between being ctDNA positive and having a CRC diagnosed at
        the colonoscopy.
  
        This study could change clinical practice since we anticipate that ctDNA-guided triaging of
        diverticulitis patients is a cost-effective strategy for selecting diverticulitis patients
        needing colonoscopy, ensuring detection of the underlying CRC, and significantly reducing the
        number of patients undergoing unnecessary colonoscopy.
  KEY POINTS
  
          -  Colonoscopy is recommended after acute diverticulitis to rule out CRC, and yearly more
             than 2000 colonoscopies are performed.
  
          -  CRC incidence is low in the diverticulitis population and most colonoscopies are
             unnecessary. It takes approximately 100-200 colonoscopies to diagnose just 1 CRC.
  
          -  ctDNA is a minimally invasive and extraordinarily powerful biomarker of cancer.
  
        GOALS
  
        ● To use ctDNA analysis to triage diverticulitis patients for colonoscopy. Diagnosing the
        same CRCs, but minimizing the number of patients needing colonoscopy
  
        PERSPECTIVES
  
          -  Practice-changing evidence for ctDNA-guided triaging of diverticulitis patients for
             colonoscopy, an important and well-recognized clinical dilemma in the management of CRC.
  
          -  Evaluation of the cost-effectiveness of ctDNA-guided triaging versus standard-of-care.
  
        PROJECT DESCRIPTION For patients who have experienced an episode of acute colonic
        diverticulitis, Danish and international guidelines recommend opportunistic screening with
        colonoscopy to rule out CRC as the underlying reason for the diverticulitis symptoms. In
        Denmark, there are more than 4000 hospitalizations per year due to diverticulitis.
        Accordingly, a substantial number of post-diverticulitis colonoscopies are performed each
        year to rule out underlying CRC. Colonoscopy is an invasive procedure associated with
        discomfort and pain in more than 50% of patients. The procedure also carries the risk of
        complications such as perforation and hemorrhage, particularly for patients with diseased
        intestines such as diverticulitis patients. CRC prevalence in suspected diverticulitis
        patients is low, <2% overall, and as low as 0.5% for uncomplicated diverticulitis. Thus, an
        unreasonably high number of colonoscopies, ranging from 50 and up to more than 200, are
        needed to diagnose 1 CRC. In comparison, a >4% CRC prevalence is considered the minimal
        acceptable among patients selected for follow-up colonoscopy in the Danish nationwide CRC
        screening program, corresponding to less than 25 colonoscopies per CRC. Hence, it may be
        questioned whether the current guidelines on follow-up colonoscopy after diverticulitis are
        at all acceptable, both from a patient perspective and from a health-economy perspective.
        However, it has been very difficult to change. Consequently, there is an urgent need for a
        highly sensitive, low-risk, minimally invasive cancer detection test that can be used to
        triage newly diagnosed diverticulitis patients and ensure that underlying CRC is still
        diagnosed while minimizing the number of patients needing colonoscopy. Here, we propose to
        conduct a case/control study to explore the feasibility of using our recently developed
        TriMeth ctDNA analysis test for this purpose.
  
        We hypothesize that ctDNA analysis can triage diverticulitis patients for colonoscopy and
        achieve a diagnosis of prevalent CRC but at a substantially lower colonoscopy/CRC ratio. For
        this purpose, we will use our tumor-agnostic ctDNA analysis "TriMeth". TriMeth was originally
        developed as a CRC screening tool for selecting individuals from the average-risk population
        for colonoscopy. Accordingly, the threshold for calling the test positive was set with the
        objective of high specificity. At 99% specificity, it has a sensitivity of 85%. Based on data
        from the original development and validation cohorts (400 CRC and 800 controls), we will
        tailor TriMeth for this specific purpose, i.e., setting the threshold for test positivity to
        achieve near 100% sensitivity by accepting a lower specificity. Second, we will conduct a
        case-control study to validate this new TriMeth-diverticulitis threshold in the target
        population. We expect a minimum of 20 cases with CRC diagnosed at colonoscopy after suspected
        diverticulitis to be identified through the IMPROVE study (NCT03637686). For each case, 10
        controls will be randomly selected (to a minimum of 200 total) from patients with CT-verified
        diverticulitis and a follow-up colonoscopy without CRC. Diverticulitis patients may at the
        time of colonoscopy exhibit symptoms, that would in any case serve as an absolute indication
        for colonoscopy (patients age >40 with changes in bowel habits >1 month, rectal bleeding,
        iron-deficiency anemia, or excessive weight-loss). Therefore, in addition to blood sampling,
        we will at the time of CRC diagnosis or negative colonoscopy collect information on other
        established indicators for colonoscopy. As part of the study, we will conduct a
        health-economy assessment comparing the TriMeth-guided approach to the current practice of
        "colonoscopy for all". The primary outcome is the sensitivity and specificity of TriMeth for
        CRC detection in this population. The secondary outcome is health economy, considering the
        other indicators for colonoscopy. If high sensitivity and clinically and economically
        relevant colonoscopy-sparing potential is demonstrated, the data will be presented to the
        Danish Colorectal Cancer Group and the Danish Health Technology Council with the aim of
        obtaining approval to change the national guideline and implement the approach.
  observational model: Case-Control
  time perspective: Prospective
  measure: ctDNA analysis
  time frame: After recruitment of the last patient, we expect that ctDNA analyses can be performed within 6 months
  description: Blood samples will be categorized as either ctDNA positive or negative
  measure: Cost-effectiveness of treatment
  time frame: After recruitment of the last patient, we expect that cost-effectiveness analyses can be performed within 12 months
  description: Assessment of the cost-effectiveness of "ctDNA guided" versus "opportunistic" colonoscopy screening of the diverticulitis patients
  arm group label: Controls
  description: Patients diagnosed with diverticulitis through CT scan and scheduled for a colonoscopy. The colonoscopy must result in no detection of colorectal cancer.
  arm group label: Cases
  description: Patients diagnosed with CRC immediately after an episode of diverticulitis.
  From each patient, blood will be collected between 2 and 6 weeks after the diagnosis of
        diverticulitis. The blood will be collected before initiation of the bowel cleansing
        associated with the CRC screening colonoscopy.
  
        Blood draw: 80 mL - 7 x EDTA tubes, 1 x serum tube
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Thomas Bjørsum-Meyer, MD, PhD
  role: Principal Investigator
  affiliation: Odense University Hospital
  last name: Per V Andersen, MD, PhD
  role: Principal Investigator
  affiliation: Odense University Hospital
  last name: Kåre A Gotschalck, MD, PhD
  role: Principal Investigator
  affiliation: Regional Hospital Horsens
  last name: Liza Sopina, PhD
  role: Principal Investigator
  affiliation: University of Southern Denmark
  last name: Claus L Andersen, PhD
  phone: +45 7845 5319
  email: cla@clin.au.dk
  last name: Christina Demuth, PhD
  phone: +45 7845 5310
  email: demuth@clin.au.dk
  facility: 
  status: Recruiting
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  country: Denmark
  citation: Andersen JC, Bundgaard L, Elbrond H, Laurberg S, Walker LR, Stovring J; Danish Surgical Society. Danish national guidelines for treatment of diverticular disease. Dan Med J. 2012 May;59(5):C4453.
  PMID: 22549495
  citation: Meyer J, Orci LA, Combescure C, Balaphas A, Morel P, Buchs NC, Ris F. Risk of Colorectal Cancer in Patients With Acute Diverticulitis: A Systematic Review and Meta-analysis of Observational Studies. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1448-1456.e17. doi: 10.1016/j.cgh.2018.07.031. Epub 2018 Jul 26.
  PMID: 30056181
  citation: Jensen SO, Ogaard N, Orntoft MW, Rasmussen MH, Bramsen JB, Kristensen H, Mouritzen P, Madsen MR, Madsen AH, Sunesen KG, Iversen LH, Laurberg S, Christensen IJ, Nielsen HJ, Andersen CL. Novel DNA methylation biomarkers show high sensitivity and specificity for blood-based detection of colorectal cancer-a clinical biomarker discovery and validation study. Clin Epigenetics. 2019 Nov 14;11(1):158. doi: 10.1186/s13148-019-0757-3.
  PMID: 31727158
  citation: Jensen SO, Ogaard N, Nielsen HJ, Bramsen JB, Andersen CL. Enhanced Performance of DNA Methylation Markers by Simultaneous Measurement of Sense and Antisense DNA Strands after Cytosine Conversion. Clin Chem. 2020 Jul 1;66(7):925-933. doi: 10.1093/clinchem/hvaa100.
  PMID: 32460325
  citation: Ogaard N, Reinert T, Henriksen TV, Frydendahl A, Aagaard E, Orntoft MW, Larsen MO, Knudsen AR, Mortensen FV, Andersen CL. Tumour-agnostic circulating tumour DNA analysis for improved recurrence surveillance after resection of colorectal liver metastases: A prospective cohort study. Eur J Cancer. 2022 Mar;163:163-176. doi: 10.1016/j.ejca.2021.12.026. Epub 2022 Jan 22.
  PMID: 35074652
  responsible party type: Sponsor
  mesh term: Diverticulitis
  mesh term: Diverticulitis, Colonic