<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/NCT01685034</url>
  </required_header>
  <id_info>
    <org_study_id>NMCSD.2012.0148</org_study_id>
    <nct_id>NCT01685034</nct_id>
  </id_info>
  <brief_title>Allergy Immunotherapy in the Management of Eosinophilic Esophagitis</brief_title>
  <acronym>AIMEE</acronym>
  <official_title>Evaluation of the Clinical, Endoscopic and Histologic Effects of Environmental Allergy Immunotherapy in the Treatment of Eosinophilic Esophagitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United States Naval Medical Center, San Diego</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>United States Naval Medical Center, San Diego</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Eosinophilic esophagitis (EoE) is a disease that has increased in incidence over the past&#xD;
      decade that affects males predominantly, and in adults, is characterized by heartburn,&#xD;
      dysphagia, strictures and food impactions. These symptoms may require emergent endoscopic&#xD;
      removal of foods and esophageal dilations due to remodeling causing significant impairment in&#xD;
      quality of life. Treatment options are limited and often not well tolerated or effective.&#xD;
      There is poor understanding of the natural history and long term prognosis. It has been&#xD;
      associated with allergic sensitization; a high percentage of affected individuals having&#xD;
      associated atopy and current literature demonstrates a seasonal distribution of incidence and&#xD;
      severity of symptoms. Allergy immunotherapy (AIT) is a well established and effective&#xD;
      treatment for allergic rhinitis and asthma which can induce tolerance to environmental&#xD;
      allergens.&#xD;
&#xD;
      Given the efficacy of AIT and the association of aeroallergen sensitization and even seasonal&#xD;
      variation of EoE symptoms, we hypothesized that AIT may be a treatment option for patients&#xD;
      with EoE.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose: To evaluate the role of allergy AIT in the management of EoE.&#xD;
&#xD;
      Research design: Patients with EoE and aeroallergen sensitization will be offered AIT as a&#xD;
      treatment modality for EoE. They will be evaluated by questionnaire, laboratory tests,&#xD;
      endoscopy and biopsy before and after treatment to determine if there is clinical,&#xD;
      laboratory, endoscopic and histologic changes in their EoE.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Researcher deployed before approval&#xD;
  </why_stopped>
  <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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Histologic change</measure>
    <time_frame>1 year after after starting allergy immunotherapy</time_frame>
    <description>Subjects will be started on allergy immunotherapy. We will compare before and after pathology - changes in eosinophils per high power field in esophageal biopsy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Symptomatic changes</measure>
    <time_frame>1 year</time_frame>
    <description>Symptom questionaire will be assessed before intervention and after (about 1 year after being on allergy immunotherapy)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Endoscopic changes</measure>
    <time_frame>1 year</time_frame>
    <description>In addition to above, we will score their endoscopic findings before and after the intervention. The categories scored will include: 1. Pallor and diminished vascular markings 2. Furrowing 3. White plaques 4. Concentric rings or strictures. If 1 esophageal site is involved, 1 point will be given. If more than 1 site, 2 points allocated. If entire esophagus is involved, 3 points allocated and maximum score will be 12.</description>
  </other_outcome>
  <other_outcome>
    <measure>Eosinophilia change</measure>
    <time_frame>1 year</time_frame>
    <description>Absolute eosinophilic counts will be measured before and after intervention.</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse outcomes</measure>
    <time_frame>1 year</time_frame>
    <description>Any adverse events will be collected during the first year. Allergy immunotherapy has been used clinically for over 100 years. Local site reactions are common and expected, but we will monitor systemic reaction rates in this specific population and compare to known rates of reactions.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Eosinophilic Esophagitis</condition>
  <arm_group>
    <arm_group_label>Allergy Immunotherapy Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>There is only one active experimental group as this is a pilot study comparing clinical/histologic/endoscopic changes before and after treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Allergy immunotherapy (&quot;allergy shots&quot;)</intervention_name>
    <arm_group_label>Allergy Immunotherapy Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eligible for care at Naval Medical Center San Diego&#xD;
&#xD;
          -  Diagnosis of EoE (with or without GERD)&#xD;
&#xD;
          -  Positive skin test to aeroallergen(s)&#xD;
&#xD;
          -  Able to provide written informed consent prior to the conduct of any study related&#xD;
             procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All excluding conditions for Allergy immunotherapy (AIT) - pregnancy, severe asthma,&#xD;
             uncontrolled asthma, taking a beta blocker, history of coronary artery disease. (Note:&#xD;
             age is not typically an exclusion criteria for AIT, however this will be an adult only&#xD;
             study).&#xD;
&#xD;
          -  History of significant esophageal disease other than EoE (such as esophageal cancer,&#xD;
             surgeries…)&#xD;
&#xD;
          -  History of other systemic eosinophilic conditions (such as …)&#xD;
&#xD;
          -  Subjects with controlled asthma on inhaled steroids at the time of diagnosis of EoE&#xD;
             may be included , however if a subject develops new asthma or worsening asthma during&#xD;
             the study requiring new initiation of inhaled steroids, they may be discontinued to&#xD;
             avoid possible swallowing of the medication and &quot;treatment&quot; of their EoE.&#xD;
&#xD;
          -  If subject is judged by the investigator as unlikely to understand the scope of the&#xD;
             study and/or is unlikely to comply with the study procedures and visits.&#xD;
&#xD;
          -  Is currently or has recently been on AIT (within the past year)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Almansa C, Krishna M, Buchner AM, Ghabril MS, Talley N, DeVault KR, Wolfsen H, Raimondo M, Guarderas JC, Achem SR. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol. 2009 Apr;104(4):828-33. doi: 10.1038/ajg.2008.169. Epub 2009 Feb 24.</citation>
    <PMID>19240704</PMID>
  </reference>
  <reference>
    <citation>Simon D, Marti H, Heer P, Simon HU, Braathen LR, Straumann A. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol. 2005 May;115(5):1090-2. doi: 10.1016/j.jaci.2005.01.017. No abstract available.</citation>
    <PMID>15867873</PMID>
  </reference>
  <reference>
    <citation>Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001 Jan;107(1):83-90. doi: 10.1172/JCI10224.</citation>
    <PMID>11134183</PMID>
  </reference>
  <reference>
    <citation>Moawad FJ, Veerappan GR, Lake JM, Maydonovitch CL, Haymore BR, Kosisky SE, Wong RK. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther. 2010 Feb 15;31(4):509-15. doi: 10.1111/j.1365-2036.2009.04199.x. Epub 2009 Nov 19.</citation>
    <PMID>19925501</PMID>
  </reference>
  <reference>
    <citation>Penfield JD, Lang DM, Goldblum JR, Lopez R, Falk GW. The role of allergy evaluation in adults with eosinophilic esophagitis. J Clin Gastroenterol. 2010 Jan;44(1):22-7. doi: 10.1097/MCG.0b013e3181a1bee5.</citation>
    <PMID>19564792</PMID>
  </reference>
  <reference>
    <citation>Onbasi K, Sin AZ, Doganavsargil B, Onder GF, Bor S, Sebik F. Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season. Clin Exp Allergy. 2005 Nov;35(11):1423-31. doi: 10.1111/j.1365-2222.2005.02351.x.</citation>
    <PMID>16297137</PMID>
  </reference>
  <reference>
    <citation>Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. J Allergy Clin Immunol. 2003 Oct;112(4):796-7. doi: 10.1016/s0091-6749(03)01715-9. No abstract available.</citation>
    <PMID>14564365</PMID>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>September 5, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 13, 2012</study_first_posted>
  <last_update_submitted>August 17, 2016</last_update_submitted>
  <last_update_submitted_qc>August 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Eosinophilic esophagitis</keyword>
  <keyword>Environmental allergens</keyword>
  <keyword>Allergy immunotherapy</keyword>
  <keyword>Tolerance</keyword>
  <keyword>Allergic rhinitis</keyword>
  <keyword>Asthma</keyword>
  <keyword>Seasonal variation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophagitis</mesh_term>
    <mesh_term>Eosinophilic Esophagitis</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunomodulating Agents</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/NCT01685034
org study id: NMCSD.2012.0148
nct id: NCT01685034
lead sponsor: 
has dmc: Yes
Eosinophilic esophagitis (EoE) is a disease that has increased in incidence over the past
      decade that affects males predominantly, and in adults, is characterized by heartburn,
      dysphagia, strictures and food impactions. These symptoms may require emergent endoscopic
      removal of foods and esophageal dilations due to remodeling causing significant impairment in
      quality of life. Treatment options are limited and often not well tolerated or effective.
      There is poor understanding of the natural history and long term prognosis. It has been
      associated with allergic sensitization; a high percentage of affected individuals having
      associated atopy and current literature demonstrates a seasonal distribution of incidence and
      severity of symptoms. Allergy immunotherapy (AIT) is a well established and effective
      treatment for allergic rhinitis and asthma which can induce tolerance to environmental
      allergens.

      Given the efficacy of AIT and the association of aeroallergen sensitization and even seasonal
      variation of EoE symptoms, we hypothesized that AIT may be a treatment option for patients
      with EoE.
Purpose: To evaluate the role of allergy AIT in the management of EoE.

      Research design: Patients with EoE and aeroallergen sensitization will be offered AIT as a
      treatment modality for EoE. They will be evaluated by questionnaire, laboratory tests,
      endoscopy and biopsy before and after treatment to determine if there is clinical,
      laboratory, endoscopic and histologic changes in their EoE.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Histologic change
time frame: 1 year after after starting allergy immunotherapy
description: Subjects will be started on allergy immunotherapy. We will compare before and after pathology - changes in eosinophils per high power field in esophageal biopsy.
measure: Symptomatic changes
time frame: 1 year
description: Symptom questionaire will be assessed before intervention and after (about 1 year after being on allergy immunotherapy)
measure: Endoscopic changes
time frame: 1 year
description: In addition to above, we will score their endoscopic findings before and after the intervention. The categories scored will include: 1. Pallor and diminished vascular markings 2. Furrowing 3. White plaques 4. Concentric rings or strictures. If 1 esophageal site is involved, 1 point will be given. If more than 1 site, 2 points allocated. If entire esophagus is involved, 3 points allocated and maximum score will be 12.
measure: Eosinophilia change
time frame: 1 year
description: Absolute eosinophilic counts will be measured before and after intervention.
measure: Adverse outcomes
time frame: 1 year
description: Any adverse events will be collected during the first year. Allergy immunotherapy has been used clinically for over 100 years. Local site reactions are common and expected, but we will monitor systemic reaction rates in this specific population and compare to known rates of reactions.
arm group label: Allergy Immunotherapy Group
arm group type: Experimental
description: There is only one active experimental group as this is a pilot study comparing clinical/histologic/endoscopic changes before and after treatment.
intervention type: Biological
intervention name: Allergy immunotherapy ("allergy shots")
arm group label: Allergy Immunotherapy Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
citation: Almansa C, Krishna M, Buchner AM, Ghabril MS, Talley N, DeVault KR, Wolfsen H, Raimondo M, Guarderas JC, Achem SR. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am J Gastroenterol. 2009 Apr;104(4):828-33. doi: 10.1038/ajg.2008.169. Epub 2009 Feb 24.
PMID: 19240704
citation: Simon D, Marti H, Heer P, Simon HU, Braathen LR, Straumann A. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J Allergy Clin Immunol. 2005 May;115(5):1090-2. doi: 10.1016/j.jaci.2005.01.017. No abstract available.
PMID: 15867873
citation: Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001 Jan;107(1):83-90. doi: 10.1172/JCI10224.
PMID: 11134183
citation: Moawad FJ, Veerappan GR, Lake JM, Maydonovitch CL, Haymore BR, Kosisky SE, Wong RK. Correlation between eosinophilic oesophagitis and aeroallergens. Aliment Pharmacol Ther. 2010 Feb 15;31(4):509-15. doi: 10.1111/j.1365-2036.2009.04199.x. Epub 2009 Nov 19.
PMID: 19925501
citation: Penfield JD, Lang DM, Goldblum JR, Lopez R, Falk GW. The role of allergy evaluation in adults with eosinophilic esophagitis. J Clin Gastroenterol. 2010 Jan;44(1):22-7. doi: 10.1097/MCG.0b013e3181a1bee5.
PMID: 19564792
citation: Onbasi K, Sin AZ, Doganavsargil B, Onder GF, Bor S, Sebik F. Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season. Clin Exp Allergy. 2005 Nov;35(11):1423-31. doi: 10.1111/j.1365-2222.2005.02351.x.
PMID: 16297137
citation: Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. J Allergy Clin Immunol. 2003 Oct;112(4):796-7. doi: 10.1016/s0091-6749(03)01715-9. No abstract available.
PMID: 14564365
responsible party type: Sponsor
mesh term: Esophagitis
mesh term: Eosinophilic Esophagitis
mesh term: Hypersensitivity
mesh term: Immunomodulating Agents