<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/NCT03013894</url>
  </required_header>
  <id_info>
    <org_study_id>2015_300</org_study_id>
    <nct_id>NCT03013894</nct_id>
  </id_info>
  <brief_title>Confocal Laser Endomicroscopy in the Lower Urinary Tract</brief_title>
  <official_title>Feasibility of Confocal Laser Endomicroscopy in Bladder Cancer Diagnosis</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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Cystoscopy and cytology, the current 'gold standard' for detection and follow-up&#xD;
      of primary and recurrent bladder cancer have some limitations. CLE, a high resolution imaging&#xD;
      technique, that can be used combined with endo-urological procedures, seems promising to&#xD;
      improve diagnosis of bladder cancer. The diagnostic accuracy of cystoscopic applied confocal&#xD;
      laser endomicroscopy (CLE) still has to be defined.&#xD;
&#xD;
      Objective: To directly correlate CLE images with histopathology, and identify and define CLE&#xD;
      characteristics of normal urothelium, benign bladder urothelium, and bladder tumors&#xD;
      (low-grade, high-grade and carcinoma in situ (CIS)) of the lower urinary tract.&#xD;
&#xD;
      Primary objective: to develop descriptive image interpretation criteria and a classification&#xD;
      of CLE images of bladder tissue through a review of prospectively obtained CLE videos from&#xD;
      bladder tissue correlated with histopathology.&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  Assessing procedure related adverse events of CLE&#xD;
&#xD;
        -  Assessing technical feasibility of CLE&#xD;
&#xD;
        -  To develop a CLE image atlas for urothelium of the lower urinary tract (normal, benign,&#xD;
           low-grade or high-grade and CIS)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, multicenter, observational study; the investigators will establish&#xD;
      sensitivity and specificity of CLE ex vivo and in vivo, in the diagnosis of bladder&#xD;
      carcinoma.&#xD;
&#xD;
      Eligible patients are diagnosed with a bladder tumor at the outpatient clinic and scheduled&#xD;
      for transurethral resection of bladder tumor (TURB). In total the investigators want to&#xD;
      include 60 patients. Yearly approximately 70 patients are diagnosed with primary and&#xD;
      recurrent bladder carcinoma in the Academic Medical Center (AMC) and will undergo TURB.&#xD;
&#xD;
      Their Urologist will inform patients diagnosed with a bladder tumor who will be scheduled for&#xD;
      treatment by means of TURB about the study. Information about the study will be provided both&#xD;
      orally and in written form.&#xD;
&#xD;
      CLE images are recorded using a probe-based system (Cellvizio 100 series, Mauna Kea&#xD;
      Technologies, Paris, France). The probe (Cystoflex UHD-R, Mauna Kea Technologies, Paris,&#xD;
      France) has an outer diameter of 2.8 mm, a field of view of 240 µm and has a resolution of 1&#xD;
      µm. Images are collected at a scan rate of 12 frames per second. Using the Cellvizio Viewer&#xD;
      system, the investigators can observe mucosal microarchitecture with an increased field of&#xD;
      view through mosaic post processing. This system also enables virtual staining of mucosal&#xD;
      structures to further enhance tissue contrast.&#xD;
&#xD;
      A fluorescent contrast agent is needed to obtain CLE images. Fluorescein&#xD;
      (fluoresceinedisodium, Fresenius Kabi, Zeist, Netherlands), a non-toxic and commonly used&#xD;
      fluorescent dye will be administered intravesical (300-400 mL 0.1% fluorescein diluted in&#xD;
      saline) and left indwelling for 5 minutes to stain the extracellular matrix.&#xD;
&#xD;
      The study consists of three CLE measurements, one in vivo prior to tumor resection, the&#xD;
      second ex vivo of the resected specimen, and the last measurement is ex vivo after fixating&#xD;
      the tumor on formaldehyde. In the case of multiple tumors, multiple CLE measurements will be&#xD;
      done. The measurement per-operatively will add approximately 15 minutes to operating time. In&#xD;
      the ex vivo set up, additional images will be acquired using Optical Coherence Tomography&#xD;
      (OCT). During tumor resection, a small chip of normal urothelium will be resected&#xD;
      additionally to act as control. Resected bladder tissue will be fixed and laminated by the&#xD;
      pathology department, to correlate to CLE images.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2016</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</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>Confocal laser endomicroscopy characteristics of urothelium of the lower urinary tract</measure>
    <time_frame>1.5 years</time_frame>
    <description>Qualitatively correlating CLE images to histopathology to define CLE characteristics</description>
  </primary_outcome>
  <enrollment type="Actual">73</enrollment>
  <condition>Bladder Neoplasm</condition>
  <condition>Urothelial Carcinoma</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      CLE images (without DNA) and histopathology (with DNA)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients &gt;18 years old with primary or recurrent bladder tumor(s), who are scheduled for&#xD;
        TURB are eligible for this study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;18 years old&#xD;
&#xD;
          -  Bladder tumor(s)&#xD;
&#xD;
          -  Candidate for TURB&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt;18 years old&#xD;
&#xD;
          -  Patients with known allergy for fluorescein&#xD;
&#xD;
          -  Possible pregnancy or lactating women&#xD;
&#xD;
          -  No signed informed consent&#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>Jean J de la Rosette, prof. dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Academic Medical Center</name>
      <address>
        <city>Amsterdam</city>
        <zip>1105AZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>June 5, 2018</last_update_submitted>
  <last_update_submitted_qc>June 5, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2018</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>Prof.dr. J.J.M.C.H. de la Rosette</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>bladder neoplasm</keyword>
  <keyword>urothelium carcinoma</keyword>
  <keyword>confocal laser endomicroscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urinary Bladder Neoplasms</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/NCT03013894
org study id: 2015_300
nct id: NCT03013894
lead sponsor: 
has dmc: No
Rationale: Cystoscopy and cytology, the current 'gold standard' for detection and follow-up
      of primary and recurrent bladder cancer have some limitations. CLE, a high resolution imaging
      technique, that can be used combined with endo-urological procedures, seems promising to
      improve diagnosis of bladder cancer. The diagnostic accuracy of cystoscopic applied confocal
      laser endomicroscopy (CLE) still has to be defined.

      Objective: To directly correlate CLE images with histopathology, and identify and define CLE
      characteristics of normal urothelium, benign bladder urothelium, and bladder tumors
      (low-grade, high-grade and carcinoma in situ (CIS)) of the lower urinary tract.

      Primary objective: to develop descriptive image interpretation criteria and a classification
      of CLE images of bladder tissue through a review of prospectively obtained CLE videos from
      bladder tissue correlated with histopathology.

      Secondary objectives:

        -  Assessing procedure related adverse events of CLE

        -  Assessing technical feasibility of CLE

        -  To develop a CLE image atlas for urothelium of the lower urinary tract (normal, benign,
           low-grade or high-grade and CIS)
This is a prospective, multicenter, observational study; the investigators will establish
      sensitivity and specificity of CLE ex vivo and in vivo, in the diagnosis of bladder
      carcinoma.

      Eligible patients are diagnosed with a bladder tumor at the outpatient clinic and scheduled
      for transurethral resection of bladder tumor (TURB). In total the investigators want to
      include 60 patients. Yearly approximately 70 patients are diagnosed with primary and
      recurrent bladder carcinoma in the Academic Medical Center (AMC) and will undergo TURB.

      Their Urologist will inform patients diagnosed with a bladder tumor who will be scheduled for
      treatment by means of TURB about the study. Information about the study will be provided both
      orally and in written form.

      CLE images are recorded using a probe-based system (Cellvizio 100 series, Mauna Kea
      Technologies, Paris, France). The probe (Cystoflex UHD-R, Mauna Kea Technologies, Paris,
      France) has an outer diameter of 2.8 mm, a field of view of 240 µm and has a resolution of 1
      µm. Images are collected at a scan rate of 12 frames per second. Using the Cellvizio Viewer
      system, the investigators can observe mucosal microarchitecture with an increased field of
      view through mosaic post processing. This system also enables virtual staining of mucosal
      structures to further enhance tissue contrast.

      A fluorescent contrast agent is needed to obtain CLE images. Fluorescein
      (fluoresceinedisodium, Fresenius Kabi, Zeist, Netherlands), a non-toxic and commonly used
      fluorescent dye will be administered intravesical (300-400 mL 0.1% fluorescein diluted in
      saline) and left indwelling for 5 minutes to stain the extracellular matrix.

      The study consists of three CLE measurements, one in vivo prior to tumor resection, the
      second ex vivo of the resected specimen, and the last measurement is ex vivo after fixating
      the tumor on formaldehyde. In the case of multiple tumors, multiple CLE measurements will be
      done. The measurement per-operatively will add approximately 15 minutes to operating time. In
      the ex vivo set up, additional images will be acquired using Optical Coherence Tomography
      (OCT). During tumor resection, a small chip of normal urothelium will be resected
      additionally to act as control. Resected bladder tissue will be fixed and laminated by the
      pathology department, to correlate to CLE images.
observational model: Cohort
time perspective: Prospective
measure: Confocal laser endomicroscopy characteristics of urothelium of the lower urinary tract
time frame: 1.5 years
description: Qualitatively correlating CLE images to histopathology to define CLE characteristics
CLE images (without DNA) and histopathology (with DNA)
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean J de la Rosette, prof. dr.
role: Principal Investigator
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
investigator full name: Prof.dr. J.J.M.C.H. de la Rosette
investigator title: Principal Investigator
mesh term: Urinary Bladder Neoplasms
sharing ipd: No