<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/NCT03228407</url>
  </required_header>
  <id_info>
    <org_study_id>2282</org_study_id>
    <nct_id>NCT03228407</nct_id>
  </id_info>
  <brief_title>Confocal Endomicroscopy for Permeability of Esophageal Wall in Refractory Gastroesophageal Reflux Disease (GERD)</brief_title>
  <official_title>Confocal Endomicroscopy for Permeability of Esophageal Wall in Refractory Gastroesophageal Reflux Disease (GERD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McGuire Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hunter Holmes McGuire VA Medical Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>McGuire Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Confocal Endomicroscopy for Permeability of Esophageal Wall in Refractory Gastroesophageal&#xD;
      Reflux Disease (GERD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 28, 2017</start_date>
  <completion_date type="Anticipated">June 2018</completion_date>
  <primary_completion_date type="Anticipated">June 2018</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>Diagnostic</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Investigator in the lab performing Ussing's chamber analysis will be blinded to the diagnosis of the patient</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) with esophageal permeability (i.e. - epithelial barrier function).</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Compare the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) in patients with Barrett's esophagus and controls</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) in patients with symptoms of refractory GERD and Barrett's esophagus</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the Ussing's chamber findings (esophageal permeability) and confocal endomicroscopy findings of patients with symptoms of refractory GERD and Barrett's esophagus</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the Ussing's chamber findings (esophageal permeability) and confocal endomicroscopy findings of patients with symptoms of refractory GERD and controls</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the Ussing's chamber findings (esophageal permeability) and Mucosal impedance findings of patients with symptoms of refractory GERD and controls</measure>
    <time_frame>Through study completion, an average of 1 year.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Gastro Esophageal Reflux</condition>
  <condition>Barrett Esophagus</condition>
  <condition>Erosive Esophagitis</condition>
  <arm_group>
    <arm_group_label>Non-erosive reflux disease (NERD)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient's with GERD refractory to PPI with no evidence of erosive esophagitis on endoscopy. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Barrett's esophagus/erosive esophagitis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient's with Barrett's esophagus or with erosive esophagitis on endoscopy. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient's with no h/o GERD or Barrett's esophagus who are undergoing endoscopy for non-GERD related indication. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Confocal endomicroscopy</intervention_name>
    <description>Confocal laser endomicroscopy (CLE) permits real-time in-vivo histologic analysis of esophageal mucosa at the time of upper endoscopy. The technology is based on the principle of illuminating a tissue with a low-power laser and then detecting fluorescent light reflected from the tissue. Because CLE relies upon tissue fluorescence, intravenous fluorescein is generally used to highlight the vasculature and intercellular spaces of the tissue being examined.</description>
    <arm_group_label>Barrett's esophagus/erosive esophagitis</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Non-erosive reflux disease (NERD)</arm_group_label>
    <other_name>cellvizio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Endoscopic biopsies</intervention_name>
    <description>Additional biopsies will be obtained of the esophageal mucosa.These will be obtained with a standard biopsy forceps inserted through the channel in gastroscope.</description>
    <arm_group_label>Barrett's esophagus/erosive esophagitis</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Non-erosive reflux disease (NERD)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Mucosal impedance (MI)</intervention_name>
    <description>MI balloon measures epithelial impedance along a 10 cm length of esophagus. The gastroscope will be withdrawn and the MI balloon will be advanced into the esophagus through the mouth. The balloon will be inflated so that the sensors contact the esophageal mucosa. After MI measurements are obtained, the balloon will be deflated and withdrawn.</description>
    <arm_group_label>Barrett's esophagus/erosive esophagitis</arm_group_label>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Non-erosive reflux disease (NERD)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt; 18 years&#xD;
&#xD;
          2. Ability to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnancy&#xD;
&#xD;
          2. Esophageal varices&#xD;
&#xD;
          3. Prior esophageal or gastric surgery&#xD;
&#xD;
          4. Active gastrointestinal bleeding&#xD;
&#xD;
          5. Evidence of esophageal malignancy&#xD;
&#xD;
          6. Inability to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Pritesh R Mutha, MD,MPH</last_name>
    <phone>804-675-5000</phone>
    <phone_ext>5021</phone_ext>
    <email>pritesh.mutha@va.gov</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hunter Holmes McGuire VA Medical Center</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23249</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pritesh R Pritesh, MD,MPH</last_name>
      <phone>804-675-5000</phone>
      <phone_ext>5021</phone_ext>
      <email>pritesh.mutha@va.gov</email>
    </contact>
    <investigator>
      <last_name>Pritesh R Pritesh, MD,MPH</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tilak Shah, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mitchell Schubert, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alvin Zfass, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Vaezi MF, Choksi Y. Mucosal Impedance: A New Way To Diagnose Reflux Disease and How It Could Change Your Practice. Am J Gastroenterol. 2017 Jan;112(1):4-7. doi: 10.1038/ajg.2016.513. Epub 2016 Dec 13. No abstract available.</citation>
    <PMID>27958288</PMID>
  </reference>
  <results_reference>
    <citation>Cui R, Zhou L, Lin S, Xue Y, Duan L, Xia Z, Jin Z, Zhang H, Zhang J, Song Z, Yan X. The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients. Dis Esophagus. 2011 Jan;24(1):1-5. doi: 10.1111/j.1442-2050.2010.01083.x.</citation>
    <PMID>20626453</PMID>
  </results_reference>
  <results_reference>
    <citation>Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium. Gastroenterology. 1996 Nov;111(5):1200-5. doi: 10.1053/gast.1996.v111.pm8898633.</citation>
    <PMID>8898633</PMID>
  </results_reference>
  <results_reference>
    <citation>Chu CL, Zhen YB, Lv GP, Li CQ, Li Z, Qi QQ, Gu XM, Yu T, Zhang TG, Zhou CJ, Rui-Ji, Li YQ. Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012 Jun;107(6):864-74. doi: 10.1038/ajg.2012.44. Epub 2012 Mar 13.</citation>
    <PMID>22415199</PMID>
  </results_reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>July 6, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>January 11, 2018</last_update_submitted>
  <last_update_submitted_qc>January 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 16, 2018</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>Barrett Esophagus</mesh_term>
    <mesh_term>Gastroesophageal Reflux</mesh_term>
    <mesh_term>Esophagitis</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/NCT03228407
org study id: 2282
nct id: NCT03228407
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
Confocal Endomicroscopy for Permeability of Esophageal Wall in Refractory Gastroesophageal
      Reflux Disease (GERD)
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: Single (Investigator)
masking description: Investigator in the lab performing Ussing's chamber analysis will be blinded to the diagnosis of the patient
measure: Correlation between the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) with esophageal permeability (i.e. - epithelial barrier function).
time frame: Through study completion, an average of 1 year.
measure: Compare the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) in patients with Barrett's esophagus and controls
time frame: Through study completion, an average of 1 year.
measure: Compare the time from intravenous injection of fluorescein to visualization of fluorescein on probe based confocal endomicroscopy (pCLE) in patients with symptoms of refractory GERD and Barrett's esophagus
time frame: Through study completion, an average of 1 year.
measure: Correlation between the Ussing's chamber findings (esophageal permeability) and confocal endomicroscopy findings of patients with symptoms of refractory GERD and Barrett's esophagus
time frame: Through study completion, an average of 1 year.
measure: Correlation between the Ussing's chamber findings (esophageal permeability) and confocal endomicroscopy findings of patients with symptoms of refractory GERD and controls
time frame: Through study completion, an average of 1 year.
measure: Correlation between the Ussing's chamber findings (esophageal permeability) and Mucosal impedance findings of patients with symptoms of refractory GERD and controls
time frame: Through study completion, an average of 1 year.
arm group label: Non-erosive reflux disease (NERD)
arm group type: Active Comparator
description: Patient's with GERD refractory to PPI with no evidence of erosive esophagitis on endoscopy. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.
arm group label: Barrett's esophagus/erosive esophagitis
arm group type: Active Comparator
description: Patient's with Barrett's esophagus or with erosive esophagitis on endoscopy. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.
arm group label: Control
arm group type: Placebo Comparator
description: Patient's with no h/o GERD or Barrett's esophagus who are undergoing endoscopy for non-GERD related indication. Confocal endomicroscopy, endoscopic biopsies and mucosal impedance (MI) will be performed.
intervention type: Procedure
intervention name: Confocal endomicroscopy
description: Confocal laser endomicroscopy (CLE) permits real-time in-vivo histologic analysis of esophageal mucosa at the time of upper endoscopy. The technology is based on the principle of illuminating a tissue with a low-power laser and then detecting fluorescent light reflected from the tissue. Because CLE relies upon tissue fluorescence, intravenous fluorescein is generally used to highlight the vasculature and intercellular spaces of the tissue being examined.
arm group label: Barrett's esophagus/erosive esophagitis
arm group label: Control
arm group label: Non-erosive reflux disease (NERD)
other name: cellvizio
intervention type: Diagnostic Test
intervention name: Endoscopic biopsies
description: Additional biopsies will be obtained of the esophageal mucosa.These will be obtained with a standard biopsy forceps inserted through the channel in gastroscope.
arm group label: Barrett's esophagus/erosive esophagitis
arm group label: Control
arm group label: Non-erosive reflux disease (NERD)
intervention type: Diagnostic Test
intervention name: Mucosal impedance (MI)
description: MI balloon measures epithelial impedance along a 10 cm length of esophagus. The gastroscope will be withdrawn and the MI balloon will be advanced into the esophagus through the mouth. The balloon will be inflated so that the sensors contact the esophageal mucosa. After MI measurements are obtained, the balloon will be deflated and withdrawn.
arm group label: Barrett's esophagus/erosive esophagitis
arm group label: Control
arm group label: Non-erosive reflux disease (NERD)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Pritesh R Mutha, MD,MPH
phone: 804-675-5000
phone ext: 5021
email: pritesh.mutha@va.gov
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
citation: Vaezi MF, Choksi Y. Mucosal Impedance: A New Way To Diagnose Reflux Disease and How It Could Change Your Practice. Am J Gastroenterol. 2017 Jan;112(1):4-7. doi: 10.1038/ajg.2016.513. Epub 2016 Dec 13. No abstract available.
PMID: 27958288
citation: Cui R, Zhou L, Lin S, Xue Y, Duan L, Xia Z, Jin Z, Zhang H, Zhang J, Song Z, Yan X. The feasibility of light microscopic measurements of intercellular spaces in squamous epithelium in the lower-esophagus of GERD patients. Dis Esophagus. 2011 Jan;24(1):1-5. doi: 10.1111/j.1442-2050.2010.01083.x.
PMID: 20626453
citation: Tobey NA, Carson JL, Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium. Gastroenterology. 1996 Nov;111(5):1200-5. doi: 10.1053/gast.1996.v111.pm8898633.
PMID: 8898633
citation: Chu CL, Zhen YB, Lv GP, Li CQ, Li Z, Qi QQ, Gu XM, Yu T, Zhang TG, Zhou CJ, Rui-Ji, Li YQ. Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Am J Gastroenterol. 2012 Jun;107(6):864-74. doi: 10.1038/ajg.2012.44. Epub 2012 Mar 13.
PMID: 22415199
responsible party type: Sponsor
mesh term: Barrett Esophagus
mesh term: Gastroesophageal Reflux
mesh term: Esophagitis
sharing ipd: No