<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/NCT01661777</url>
  </required_header>
  <id_info>
    <org_study_id>JR08012012112856</org_study_id>
    <nct_id>NCT01661777</nct_id>
  </id_info>
  <brief_title>Refractory Eustachian Tube Dysfunction: Are the Symptoms Related to Endolymphatic Hydrops</brief_title>
  <official_title>Refractory Eustachian Tube Dysfunction: Are the Symptoms Related to Endolymphatic Hydrops?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the benefit of treatment of refractory Eustachian&#xD;
      tube dysfunction with standard treatment for endolymphatic hydrops. Eustachian tube&#xD;
      dysfunction is a common diagnosis made in otolaryngology related to abnormal pressure&#xD;
      equalization of the middle ear space related to a swollen, inflamed, or occluded Eustachian&#xD;
      tube. The symptoms of this include perceived hearing loss, a feeling of fullness in the&#xD;
      affected ear/ears, ear pain, ear popping, and occasionally imbalance. These symptoms overlap&#xD;
      with a more rare and difficult to diagnose condition known as endolymphatic hydrops, or an&#xD;
      overproduction to fluid in the inner ear. The treatment for these two conditions are distinct&#xD;
      and traditionally, patients are treated for Eustachian tube dysfunction first as it is much&#xD;
      more common and there are several treatments, namely nasal steroids, antihistamines, and&#xD;
      pressure equalization tubes. For patients who do not improve with these treatments, they are&#xD;
      often treated with diuretics and a low salt diet to treat for supposed endolymphatic hydrops.&#xD;
      There has never been a study to investigate the utility of these treatments in patients with&#xD;
      refractory Eustachian tube dysfunction. There is also reason to believe that chronic ETD with&#xD;
      effusion can lead to both inner and middle ear dysfunction. Thus, this study aims to&#xD;
      determine the benefit of standard endolymphatic hydrops treatment on patient with refractory&#xD;
      Eustachian tube dysfunction symptoms in a prospective fashion.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Patients with refractory Eustachian tube dysfunction (patients with no or minimal symptom&#xD;
      improvement despite nasal steroid and antihistamine treatment followed by myringotomy tube&#xD;
      placement) have an element of endolymphatic hydrops and these patient's symptoms will improve&#xD;
      with a low sodium diet and diuretic.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eustachian tube dysfunction is one of the most common problems encountered in general&#xD;
      otolaryngology clinical practice. Symptoms of ear pressure, decreased hearing, ear pain, ear&#xD;
      popping, and frequent ear infections are often blamed on the inability of the Eustachian tube&#xD;
      to equalize air pressure across the ear drum. If the Eustachian tube is occluded, the middle&#xD;
      ear space becomes a closed chamber in which normal gas exchange cannot occur. Treatment of&#xD;
      Eustachian dysfunction has traditionally focused on a two tier system. First, patients are&#xD;
      most often placed on a nasal steroid and an antihistamine. This medication regimen leads to&#xD;
      decreased nasal inflammation, mucosal swelling, and treats nasal allergy. In many patients,&#xD;
      this treatment improves symptoms completely or reduces them to a tolerable level. If the&#xD;
      patient's symptoms are not improved, the next step in management is to create a surgical&#xD;
      tract to the middle ear via a myringotomy (a hole across the ear drum) and placing a pressure&#xD;
      equalization tube across the tympanic membrane. This bypasses any anatomical obstruction in&#xD;
      the Eustachian tube and allows the middle ear pressure to equalize with the atmospheric&#xD;
      pressure across the tympanic membrane. Unfortunately, despite this, there are patients with&#xD;
      refractory symptoms, often ear pressure and subjectively decreased hearing. These symptoms&#xD;
      are also frequently associated with inner ear disease, specifically endolymphatic hydrops.&#xD;
      Endolymphatic hydrops is felt to be related to over production of endolymphatic fluid, the&#xD;
      fluid within the inner ear. Thus, we propose that patient's will refractory Eustachian tube&#xD;
      dysfunction are experiencing an inner ear phenomenon, and that they would benefit from&#xD;
      treatment similar to how endolymphatic hydrops (or over production of endolymphatic fluid) is&#xD;
      managed. The mainstays of management of endolymphatic hydrops are a low sodium diet and&#xD;
      diuretic treatment (hydrochlorothiazide/triamterene). Both of these treatments aim to reduce&#xD;
      endolymph production.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">August 2013</completion_date>
  <primary_completion_date type="Actual">August 2013</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement in patient ETD symptoms with nasal steroid and antihistamine alone</measure>
    <time_frame>2 years</time_frame>
    <description>Determine the degree to which ETD symptoms are relieved with nasal steroid and antihistamine alone.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Improvement in patient ETD symptoms with pressure equalization tubes</measure>
    <time_frame>2 years</time_frame>
    <description>Determine the degree to which patient's symptoms related to ETD improve after placement of pressure equalization tubes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Improvement in patients with refractory ETD symptoms with treatment for endolymphatic hydrops with a diuretic and low salt diet</measure>
    <time_frame>2 years</time_frame>
    <description>Determine the degree of improvement of patient symptoms in the setting of refractory ETD after a low salt diet and diuretic treatment.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Eustachian Tube Dysfunction</condition>
  <condition>Endolymphatic Hydrops</condition>
  <arm_group>
    <arm_group_label>Nasal steroid and Antihistamine</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with ETD will be given nasal steroid and antihistamine for 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Myringotomy tubes</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients who fail nasal steroid and antihistamine treatment will have myringotomy tubes placed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low salt diet and diuretic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient's who fail to improve with myringotomy tubes will be treated with low salt det and diuretic</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nasal steroid</intervention_name>
    <arm_group_label>Nasal steroid and Antihistamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Myringotomy tube placement</intervention_name>
    <arm_group_label>Myringotomy tubes</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Diuretic</intervention_name>
    <arm_group_label>Low salt diet and diuretic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antihistamine</intervention_name>
    <arm_group_label>Nasal steroid and Antihistamine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low salt diet</intervention_name>
    <arm_group_label>Low salt diet and diuretic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any male or female patient 18-70 years old diagnosed with Eustachian tube dysfunction,&#xD;
             as determined by clinical evaluation of symptoms and positive ETDQ-7.&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  Normotensive or hypertensive (systolic blood pressure &gt;115, diastolic blood pressure&#xD;
             &gt;75)&#xD;
&#xD;
          -  Normal renal function (Cr &lt;1.00)&#xD;
&#xD;
          -  Not currently on acetazolamide&#xD;
&#xD;
          -  Not currently on a low salt diet&#xD;
&#xD;
          -  Competent in decision making process and able to sign a written informed consent form.&#xD;
&#xD;
          -  No other previous alternative otologic diagnosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Kidney disease (Cr &gt;1.00)&#xD;
&#xD;
          -  Hypotension (systolic blood pressure &lt;115, diastolic blood pressure &lt;75)&#xD;
&#xD;
          -  Strong history of vascular disease (heart attack, stroke, heart failure, peripheral&#xD;
             vascular disease i.e. claudication, gangrene, amputation)&#xD;
&#xD;
          -  Alternative otologic diagnosis (Meniere's disease)&#xD;
&#xD;
          -  Allergy or adverse reaction to previous administration of&#xD;
             hydrochlorothiazide/triamterene&#xD;
&#xD;
          -  Concurrent aspirin use&#xD;
&#xD;
          -  Current or planned pregnancy during the course of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center--Division of Neurotology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2014</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>May 28, 2014</last_update_submitted>
  <last_update_submitted_qc>May 28, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 29, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Georges Wanna</investigator_full_name>
    <investigator_title>assistant professor</investigator_title>
  </responsible_party>
  <keyword>Eustachian tube dysfunction</keyword>
  <keyword>Endolymphatic hydrops</keyword>
  <keyword>Diuretic</keyword>
  <keyword>Low salt diet</keyword>
  <keyword>Myringotomy</keyword>
  <keyword>Pressure equalization tube</keyword>
  <keyword>Ear tube</keyword>
  <keyword>Ear fullness</keyword>
  <keyword>Ear pressure</keyword>
  <keyword>Allergy</keyword>
  <keyword>Nasal steroid</keyword>
  <keyword>Antihistamine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endolymphatic Hydrops</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diuretics</mesh_term>
    <mesh_term>Histamine Antagonists</mesh_term>
    <mesh_term>Histamine H1 Antagonists</mesh_term>
  </intervention_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/NCT01661777
org study id: JR08012012112856
nct id: NCT01661777
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the benefit of treatment of refractory Eustachian
      tube dysfunction with standard treatment for endolymphatic hydrops. Eustachian tube
      dysfunction is a common diagnosis made in otolaryngology related to abnormal pressure
      equalization of the middle ear space related to a swollen, inflamed, or occluded Eustachian
      tube. The symptoms of this include perceived hearing loss, a feeling of fullness in the
      affected ear/ears, ear pain, ear popping, and occasionally imbalance. These symptoms overlap
      with a more rare and difficult to diagnose condition known as endolymphatic hydrops, or an
      overproduction to fluid in the inner ear. The treatment for these two conditions are distinct
      and traditionally, patients are treated for Eustachian tube dysfunction first as it is much
      more common and there are several treatments, namely nasal steroids, antihistamines, and
      pressure equalization tubes. For patients who do not improve with these treatments, they are
      often treated with diuretics and a low salt diet to treat for supposed endolymphatic hydrops.
      There has never been a study to investigate the utility of these treatments in patients with
      refractory Eustachian tube dysfunction. There is also reason to believe that chronic ETD with
      effusion can lead to both inner and middle ear dysfunction. Thus, this study aims to
      determine the benefit of standard endolymphatic hydrops treatment on patient with refractory
      Eustachian tube dysfunction symptoms in a prospective fashion.

      Hypothesis:

      Patients with refractory Eustachian tube dysfunction (patients with no or minimal symptom
      improvement despite nasal steroid and antihistamine treatment followed by myringotomy tube
      placement) have an element of endolymphatic hydrops and these patient's symptoms will improve
      with a low sodium diet and diuretic.
Eustachian tube dysfunction is one of the most common problems encountered in general
      otolaryngology clinical practice. Symptoms of ear pressure, decreased hearing, ear pain, ear
      popping, and frequent ear infections are often blamed on the inability of the Eustachian tube
      to equalize air pressure across the ear drum. If the Eustachian tube is occluded, the middle
      ear space becomes a closed chamber in which normal gas exchange cannot occur. Treatment of
      Eustachian dysfunction has traditionally focused on a two tier system. First, patients are
      most often placed on a nasal steroid and an antihistamine. This medication regimen leads to
      decreased nasal inflammation, mucosal swelling, and treats nasal allergy. In many patients,
      this treatment improves symptoms completely or reduces them to a tolerable level. If the
      patient's symptoms are not improved, the next step in management is to create a surgical
      tract to the middle ear via a myringotomy (a hole across the ear drum) and placing a pressure
      equalization tube across the tympanic membrane. This bypasses any anatomical obstruction in
      the Eustachian tube and allows the middle ear pressure to equalize with the atmospheric
      pressure across the tympanic membrane. Unfortunately, despite this, there are patients with
      refractory symptoms, often ear pressure and subjectively decreased hearing. These symptoms
      are also frequently associated with inner ear disease, specifically endolymphatic hydrops.
      Endolymphatic hydrops is felt to be related to over production of endolymphatic fluid, the
      fluid within the inner ear. Thus, we propose that patient's will refractory Eustachian tube
      dysfunction are experiencing an inner ear phenomenon, and that they would benefit from
      treatment similar to how endolymphatic hydrops (or over production of endolymphatic fluid) is
      managed. The mainstays of management of endolymphatic hydrops are a low sodium diet and
      diuretic treatment (hydrochlorothiazide/triamterene). Both of these treatments aim to reduce
      endolymph production.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Improvement in patient ETD symptoms with nasal steroid and antihistamine alone
time frame: 2 years
description: Determine the degree to which ETD symptoms are relieved with nasal steroid and antihistamine alone.
measure: Improvement in patient ETD symptoms with pressure equalization tubes
time frame: 2 years
description: Determine the degree to which patient's symptoms related to ETD improve after placement of pressure equalization tubes.
measure: Improvement in patients with refractory ETD symptoms with treatment for endolymphatic hydrops with a diuretic and low salt diet
time frame: 2 years
description: Determine the degree of improvement of patient symptoms in the setting of refractory ETD after a low salt diet and diuretic treatment.
arm group label: Nasal steroid and Antihistamine
arm group type: Other
description: Patients with ETD will be given nasal steroid and antihistamine for 8 weeks.
arm group label: Myringotomy tubes
arm group type: Active Comparator
description: Patients who fail nasal steroid and antihistamine treatment will have myringotomy tubes placed.
arm group label: Low salt diet and diuretic
arm group type: Active Comparator
description: Patient's who fail to improve with myringotomy tubes will be treated with low salt det and diuretic
intervention type: Drug
intervention name: Nasal steroid
arm group label: Nasal steroid and Antihistamine
intervention type: Procedure
intervention name: Myringotomy tube placement
arm group label: Myringotomy tubes
intervention type: Drug
intervention name: Diuretic
arm group label: Low salt diet and diuretic
intervention type: Drug
intervention name: Antihistamine
arm group label: Nasal steroid and Antihistamine
intervention type: Behavioral
intervention name: Low salt diet
arm group label: Low salt diet and diuretic
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Georges Wanna
investigator title: assistant professor
mesh term: Endolymphatic Hydrops
mesh term: Edema
mesh term: Diuretics
mesh term: Histamine Antagonists
mesh term: Histamine H1 Antagonists