<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/NCT02183961</url>
  </required_header>
  <id_info>
    <org_study_id>FNO-ENT-EER Peptest Restech</org_study_id>
    <nct_id>NCT02183961</nct_id>
  </id_info>
  <brief_title>Three Methods Used in the Diagnosis of EER in Children With OME</brief_title>
  <official_title>Comparison of Three Methods Used in the Diagnosis of Extraesophageal Reflux in Children With Chronic Otitis Media With Effusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Ostrava</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Ostrava</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Detection of extraesophageal reflux (EER) in children with chronic otitis media with effusion&#xD;
      (OME) using three different diagnostic methods and selection of the group of patients with&#xD;
      severe EER who could potentially benefit from antireflux therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Children aged between 1 and 7 years diagnosed with bilateral or unilateral OME who underwent&#xD;
      adenoidectomy and myringotomy with insertion of a ventilation tube were included in the&#xD;
      prospective study. OME was defined as effusion in the middle ear behind an intact eardrum for&#xD;
      longer than 3 months. Diagnosis was made on the basis of otomicroscopic findings, pneumatic&#xD;
      otoscopy, type B tympanometry and audiometry (in older, cooperative children). Children with&#xD;
      no fluid in the middle ear during myringotomy were re-diagnosed as having tympanosclerosis&#xD;
      and were excluded from the study. Children with craniofacial abnormalities (Down syndrome,&#xD;
      Treacher Collins syndrome, clefts etc.) were excluded from the study as well. Demographic&#xD;
      data and symptoms of EER disease were provided by parents, who were specifically asked about&#xD;
      hoarseness, recurrent lower respiratory infections (bronchitis, pneumonia) and bronchial&#xD;
      asthma in their child.&#xD;
&#xD;
      24 hour monitoring of oropharyngeal pH using the Restech system was performed before surgery.&#xD;
      Parents were instructed to record the time their child spent eating, drinking and in a&#xD;
      horizontal position directly to the device and manually to the diary. If there was any&#xD;
      discrepancy, periods logged in the device were modified according to the diary. A&#xD;
      standardized RYAN composite score was calculated automatically using the software supplied.&#xD;
      Patients with pathological RYAN composite scores in the vertical (higher than 9.4) and/or&#xD;
      horizontal (higher than 6.8) position were classified as having pathological EER. Severe EER&#xD;
      was diagnosed when the RYAN composite score in the vertical or horizontal position was higher&#xD;
      than 200.&#xD;
&#xD;
      Myringotomy using a microscope was done on the anterior inferior part of the tympanic&#xD;
      membrane. The type of middle ear effusion (fluid, mucous) was registered. Middle ear fluid&#xD;
      was collected using a special suction device with a collecting bottle, and a ventilation tube&#xD;
      was inserted in the tympanic membrane. In the case of bilateral OME, middle ear fluids were&#xD;
      collected and analysed separately. The specimen was first standardized. 0.1 ml of 10% citric&#xD;
      acid was added, the specimen was centrifuged for 10 minutes and subsequently the original&#xD;
      migration reagent was added. Afterwards, the specimen was examined using Peptest, which&#xD;
      contains monoclonal antibodies that target pepsin. The result of the Peptest was given as&#xD;
      positive (2 lines), negative (1 line) or invalid (no line).&#xD;
&#xD;
      Then, adenoidectomy using a cold instrument was performed. A specimen of adenoids (5x5x5mm)&#xD;
      from the area close to the torus tubarius was fixed in formaldehyde and immunohistochemically&#xD;
      analysed at the Department of Pathology. Antibody P3635Rb-h (Uscnlife, USA, concentration&#xD;
      1:100) was used as the primary antibody. Antibody N-HistofineSimple Stain MAX PO (Nichirei&#xD;
      Biosciences Inc.) was used as the secondary antibody.&#xD;
&#xD;
      Statistical analysis was done using MS Excel.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The frequency of the extraesophageal reflux in children with otitis media with effusion measured with three different methods</measure>
    <time_frame>2 years</time_frame>
    <description>Children between 1 to 7 years diagnosed with OME who underwent adenoidectomy and myringotomy with insertion of a ventilation tube were included in this prospective study. EER was detected using three methods: oropharyngeal pH was monitored for 24 hours using the Restech system; detection of pepsin in middle ear fluid obtained during myringotomy was done using Peptest, and detection of pepsin in an adenoid specimen was done immunohistochemically using antibody P3635Rb-h.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Otitis Media With Effusion</condition>
  <condition>Laryngopharyngeal Reflux</condition>
  <arm_group>
    <arm_group_label>Laryngopharyngeal reflux</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EER was detected using three methods: oropharyngeal pH was monitored for 24 hours using the Restech system; detection of pepsin in middle ear fluid obtained during myringotomy was done using Peptest, and detection of pepsin in adenoid specimen was done immunohistochemically using antibody P3635Rb-h.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Restech</intervention_name>
    <arm_group_label>Laryngopharyngeal reflux</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Peptest</intervention_name>
    <arm_group_label>Laryngopharyngeal reflux</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Detection of pepsin in adenoid specimen</intervention_name>
    <arm_group_label>Laryngopharyngeal reflux</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  children with otitis media with effusion&#xD;
&#xD;
          -  age 1-7 years&#xD;
&#xD;
          -  signing of the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - children with craniofacial abnormalities (Down syndrome, Treacher Collins syndrome,&#xD;
        clefts etc.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>7 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin Formánek, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital Ostrava</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Ostrava</name>
      <address>
        <city>Ostrava</city>
        <state>Moravian-Silesian Region</state>
        <zip>708 52</zip>
        <country>Czech Republic</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czech Republic</country>
  </location_countries>
  <reference>
    <citation>O'Reilly RC, He Z, Bloedon E, Papsin B, Lundy L, Bolling L, Soundar S, Cook S, Reilly JS, Schmidt R, Deutsch ES, Barth P, Mehta DI. The role of extraesophageal reflux in otitis media in infants and children. Laryngoscope. 2008 Jul;118(7 Part 2 Suppl 116):1-9. doi: 10.1097/MLG.0b013e31817924a3.</citation>
    <PMID>18594333</PMID>
  </reference>
  <reference>
    <citation>Zelenik K, Matousek P, Urban O, Schwarz P, Starek I, Kominek P. Globus pharyngeus and extraesophageal reflux: simultaneous pH &lt;4.0 and pH &lt;5.0 analysis. Laryngoscope. 2010 Nov;120(11):2160-4. doi: 10.1002/lary.21147.</citation>
    <PMID>20938965</PMID>
  </reference>
  <reference>
    <citation>Jiang A, Liang M, Su Z, Chai L, Lei W, Wang Z, Wang A, Wen W, Chen M. Immunohistochemical detection of pepsin in laryngeal mucosa for diagnosing laryngopharyngeal reflux. Laryngoscope. 2011 Jul;121(7):1426-30. doi: 10.1002/lary.21809. Epub 2011 Jun 6.</citation>
    <PMID>21647907</PMID>
  </reference>
  <reference>
    <citation>Wiener GJ, Tsukashima R, Kelly C, Wolf E, Schmeltzer M, Bankert C, Fisk L, Vaezi M. Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux. J Voice. 2009 Jul;23(4):498-504. doi: 10.1016/j.jvoice.2007.12.005. Epub 2008 May 12.</citation>
    <PMID>18468849</PMID>
  </reference>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 8, 2014</study_first_posted>
  <last_update_submitted>July 2, 2014</last_update_submitted>
  <last_update_submitted_qc>July 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>otitis media with effusion</keyword>
  <keyword>peptest</keyword>
  <keyword>restech</keyword>
  <keyword>oropharyngeal pH monitoring</keyword>
  <keyword>laryngopharyngeal reflux</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Laryngopharyngeal Reflux</mesh_term>
    <mesh_term>Otitis</mesh_term>
    <mesh_term>Otitis Media</mesh_term>
    <mesh_term>Otitis Media with Effusion</mesh_term>
  </condition_browse>
  <!-- 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/NCT02183961
org study id: FNO-ENT-EER Peptest Restech
nct id: NCT02183961
lead sponsor: 
has dmc: No
Detection of extraesophageal reflux (EER) in children with chronic otitis media with effusion
      (OME) using three different diagnostic methods and selection of the group of patients with
      severe EER who could potentially benefit from antireflux therapy.
Children aged between 1 and 7 years diagnosed with bilateral or unilateral OME who underwent
      adenoidectomy and myringotomy with insertion of a ventilation tube were included in the
      prospective study. OME was defined as effusion in the middle ear behind an intact eardrum for
      longer than 3 months. Diagnosis was made on the basis of otomicroscopic findings, pneumatic
      otoscopy, type B tympanometry and audiometry (in older, cooperative children). Children with
      no fluid in the middle ear during myringotomy were re-diagnosed as having tympanosclerosis
      and were excluded from the study. Children with craniofacial abnormalities (Down syndrome,
      Treacher Collins syndrome, clefts etc.) were excluded from the study as well. Demographic
      data and symptoms of EER disease were provided by parents, who were specifically asked about
      hoarseness, recurrent lower respiratory infections (bronchitis, pneumonia) and bronchial
      asthma in their child.

      24 hour monitoring of oropharyngeal pH using the Restech system was performed before surgery.
      Parents were instructed to record the time their child spent eating, drinking and in a
      horizontal position directly to the device and manually to the diary. If there was any
      discrepancy, periods logged in the device were modified according to the diary. A
      standardized RYAN composite score was calculated automatically using the software supplied.
      Patients with pathological RYAN composite scores in the vertical (higher than 9.4) and/or
      horizontal (higher than 6.8) position were classified as having pathological EER. Severe EER
      was diagnosed when the RYAN composite score in the vertical or horizontal position was higher
      than 200.

      Myringotomy using a microscope was done on the anterior inferior part of the tympanic
      membrane. The type of middle ear effusion (fluid, mucous) was registered. Middle ear fluid
      was collected using a special suction device with a collecting bottle, and a ventilation tube
      was inserted in the tympanic membrane. In the case of bilateral OME, middle ear fluids were
      collected and analysed separately. The specimen was first standardized. 0.1 ml of 10% citric
      acid was added, the specimen was centrifuged for 10 minutes and subsequently the original
      migration reagent was added. Afterwards, the specimen was examined using Peptest, which
      contains monoclonal antibodies that target pepsin. The result of the Peptest was given as
      positive (2 lines), negative (1 line) or invalid (no line).

      Then, adenoidectomy using a cold instrument was performed. A specimen of adenoids (5x5x5mm)
      from the area close to the torus tubarius was fixed in formaldehyde and immunohistochemically
      analysed at the Department of Pathology. Antibody P3635Rb-h (Uscnlife, USA, concentration
      1:100) was used as the primary antibody. Antibody N-HistofineSimple Stain MAX PO (Nichirei
      Biosciences Inc.) was used as the secondary antibody.

      Statistical analysis was done using MS Excel.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: The frequency of the extraesophageal reflux in children with otitis media with effusion measured with three different methods
time frame: 2 years
description: Children between 1 to 7 years diagnosed with OME who underwent adenoidectomy and myringotomy with insertion of a ventilation tube were included in this prospective study. EER was detected using three methods: oropharyngeal pH was monitored for 24 hours using the Restech system; detection of pepsin in middle ear fluid obtained during myringotomy was done using Peptest, and detection of pepsin in an adenoid specimen was done immunohistochemically using antibody P3635Rb-h.
arm group label: Laryngopharyngeal reflux
arm group type: Experimental
description: EER was detected using three methods: oropharyngeal pH was monitored for 24 hours using the Restech system; detection of pepsin in middle ear fluid obtained during myringotomy was done using Peptest, and detection of pepsin in adenoid specimen was done immunohistochemically using antibody P3635Rb-h.
intervention type: Other
intervention name: Restech
arm group label: Laryngopharyngeal reflux
intervention type: Other
intervention name: Peptest
arm group label: Laryngopharyngeal reflux
intervention type: Other
intervention name: Detection of pepsin in adenoid specimen
arm group label: Laryngopharyngeal reflux
criteria: 
gender: All
minimum age: 1 Year
maximum age: 7 Years
healthy volunteers: No
last name: Martin Formánek, MD
role: Principal Investigator
affiliation: University Hospital Ostrava
facility: 
country: Czech Republic
citation: O'Reilly RC, He Z, Bloedon E, Papsin B, Lundy L, Bolling L, Soundar S, Cook S, Reilly JS, Schmidt R, Deutsch ES, Barth P, Mehta DI. The role of extraesophageal reflux in otitis media in infants and children. Laryngoscope. 2008 Jul;118(7 Part 2 Suppl 116):1-9. doi: 10.1097/MLG.0b013e31817924a3.
PMID: 18594333
citation: Zelenik K, Matousek P, Urban O, Schwarz P, Starek I, Kominek P. Globus pharyngeus and extraesophageal reflux: simultaneous pH <4.0 and pH <5.0 analysis. Laryngoscope. 2010 Nov;120(11):2160-4. doi: 10.1002/lary.21147.
PMID: 20938965
citation: Jiang A, Liang M, Su Z, Chai L, Lei W, Wang Z, Wang A, Wen W, Chen M. Immunohistochemical detection of pepsin in laryngeal mucosa for diagnosing laryngopharyngeal reflux. Laryngoscope. 2011 Jul;121(7):1426-30. doi: 10.1002/lary.21809. Epub 2011 Jun 6.
PMID: 21647907
citation: Wiener GJ, Tsukashima R, Kelly C, Wolf E, Schmeltzer M, Bankert C, Fisk L, Vaezi M. Oropharyngeal pH monitoring for the detection of liquid and aerosolized supraesophageal gastric reflux. J Voice. 2009 Jul;23(4):498-504. doi: 10.1016/j.jvoice.2007.12.005. Epub 2008 May 12.
PMID: 18468849
responsible party type: Sponsor
mesh term: Laryngopharyngeal Reflux
mesh term: Otitis
mesh term: Otitis Media
mesh term: Otitis Media with Effusion