<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/NCT03827564</url>
  </required_header>
  <id_info>
    <org_study_id>1919-802-019</org_study_id>
    <nct_id>NCT03827564</nct_id>
  </id_info>
  <brief_title>Goblet Cell Degranulation Produced by Intranasal Tear Neurostimulator (ITN) in Dry Eye Disease</brief_title>
  <official_title>Goblet Cell Degranulation Produced by Nasal Neurostimulation: A Randomized, Controlled Study in Patients With Dry Eye Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Allergan</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate goblet cell degranulation following acute use of the&#xD;
      Intranasal Tear Neurostimulator in participants with dry eye.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study discontinued due to business reasons.&#xD;
  </why_stopped>
  <start_date type="Actual">June 24, 2019</start_date>
  <completion_date type="Actual">June 8, 2020</completion_date>
  <primary_completion_date type="Actual">June 8, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in Ratio of Degranulated Goblet Cells.</measure>
    <time_frame>Screening (Day -60 to Day -30) to Application Visit (Day 0)</time_frame>
    <description>Mean change from Screening to Application Visit in ratio of goblet cell degranulation post-intranasal use of the Intranasal Tear Neurostimulator (ITN) at the Application visit compared to without use of the ITN at the Screening visit</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Dry Eye Syndromes</condition>
  <arm_group>
    <arm_group_label>ITN [TrueTear®] - Intranasal Application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intranasal application of the ITN. Single application at application visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ITN [TrueTear®] - Extranasal Application</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Extranasal application of the ITN. Single application at application visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Intranasal Tear Neurostimulator (ITN) [TrueTear®]</intervention_name>
    <description>The ITN applies a small electrical current to the nasal cavities to gently activate the body's natural tear production system.</description>
    <arm_group_label>ITN [TrueTear®] - Extranasal Application</arm_group_label>
    <arm_group_label>ITN [TrueTear®] - Intranasal Application</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capable of giving verbal and signed informed consent, which includes compliance with&#xD;
             the requirements and restrictions listed in the ICF and in this protocol&#xD;
&#xD;
          -  Have not worn contact lenses for at least 7 days prior to the screening visit and are&#xD;
             willing to forego the use of contact lenses for the duration of the study&#xD;
&#xD;
          -  The participant should be literate, able to speak English, and able to complete&#xD;
             questionnaires independently&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic or recurrent epistaxis, coagulation disorders or other conditions that, in the&#xD;
             opinion of the investigator, may lead to clinically significant increased bleeding&#xD;
&#xD;
          -  Nasal or sinus surgery (including history of application of nasal cautery) or&#xD;
             significant trauma to these areas&#xD;
&#xD;
          -  Cardiac demand pacemaker, implanted defibrillator or other implanted electronic device&#xD;
&#xD;
          -  Corneal transplant in either or both eyes&#xD;
&#xD;
          -  Current enrollment in an investigational drug or device study or participation in such&#xD;
             a study within 30 days of entry into this study&#xD;
&#xD;
          -  Women who are pregnant, planning a pregnancy, or nursing throughout the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stephen Pflugfelder, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine, Department of Ophthalmology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Baylor College of Medicine - Department of Ophthalmology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-3411</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <results_first_submitted>June 8, 2021</results_first_submitted>
  <results_first_submitted_qc>July 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 16, 2021</results_first_posted>
  <last_update_submitted>July 23, 2021</last_update_submitted>
  <last_update_submitted_qc>July 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dry Eye Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>After having received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published.</ipd_time_frame>
    <ipd_access_criteria>To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes.</ipd_access_criteria>
    <ipd_url>http://www.allerganclinicaltrials.com/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03827564/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>ITN [TrueTear®] - Intranasal Application</title>
          <description>Intranasal application of the ITN. Single application at application visit.</description>
        </group>
        <group group_id="P2">
          <title>ITN [TrueTear®] - Extranasal Application</title>
          <description>Extranasal application of the ITN. Single application at application visit.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Discontinued due to Study Termination</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All 14 enrolled participants were randomized to study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>ITN [TrueTear®] - Intranasal Application</title>
          <description>Intranasal application of the ITN. Single application at application visit.</description>
        </group>
        <group group_id="B2">
          <title>ITN [TrueTear®] - Extranasal Application</title>
          <description>Extranasal application of the ITN. Single application at application visit.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.2" spread="15.4"/>
                    <measurement group_id="B2" value="46.8" spread="10.4"/>
                    <measurement group_id="B3" value="52.2" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Difference in Ratio of Degranulated Goblet Cells.</title>
        <description>Mean change from Screening to Application Visit in ratio of goblet cell degranulation post-intranasal use of the Intranasal Tear Neurostimulator (ITN) at the Application visit compared to without use of the ITN at the Screening visit</description>
        <time_frame>Screening (Day -60 to Day -30) to Application Visit (Day 0)</time_frame>
        <population>Of the 14 Randomized participants, 13 received a single application of the Intranasal Tear Neurostimulator (ITN)</population>
        <group_list>
          <group group_id="O1">
            <title>ITN [TrueTear®] - Intranasal Application</title>
            <description>Intranasal application of the ITN. Single application at application visit.</description>
          </group>
          <group group_id="O2">
            <title>ITN [TrueTear®] - Extranasal Application</title>
            <description>Extranasal application of the ITN. Single application at application visit.</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Ratio of Degranulated Goblet Cells.</title>
          <description>Mean change from Screening to Application Visit in ratio of goblet cell degranulation post-intranasal use of the Intranasal Tear Neurostimulator (ITN) at the Application visit compared to without use of the ITN at the Screening visit</description>
          <population>Of the 14 Randomized participants, 13 received a single application of the Intranasal Tear Neurostimulator (ITN)</population>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.007" spread="0.171"/>
                    <measurement group_id="O2" value="0.124" spread="0.069"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse data was collected from participants at Screening (Day -60 to Day -30) to the Application Visit (Day 0), with a 30-day safety follow-up after the application. A period of 60 to 90 days in total.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ITN [TrueTear®] - Intranasal Application</title>
          <description>Intranasal application of the ITN. Single application at application visit.</description>
        </group>
        <group group_id="E2">
          <title>ITN [TrueTear®] - Extranasal Application</title>
          <description>Extranasal application of the ITN. Single application at application visit.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Allergan as the sponsor has proprietary interest in this study. Authorship and manuscript composition will reflect joint cooperation between investigators and Allergan personnel. Authorship will be established prior to the writing of the manuscript. Authorship will be determined by mutual agreement and in line with International Committee of Medical Journal Editors authorship requirements.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was terminated early, resulting in a small number of patients analyzed. Only a descriptive statistical analysis will be performed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Therapeutic Area Head</name_or_title>
      <organization>Allergan</organization>
      <phone>714-246-4500</phone>
      <email>IR-CTRegistration@allergan.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03827564
org study id: 1919-802-019
nct id: NCT03827564
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to evaluate goblet cell degranulation following acute use of the
      Intranasal Tear Neurostimulator in participants with dry eye.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Difference in Ratio of Degranulated Goblet Cells.
time frame: Screening (Day -60 to Day -30) to Application Visit (Day 0)
description: Mean change from Screening to Application Visit in ratio of goblet cell degranulation post-intranasal use of the Intranasal Tear Neurostimulator (ITN) at the Application visit compared to without use of the ITN at the Screening visit
arm group label: ITN [TrueTear®] - Intranasal Application
arm group type: Experimental
description: Intranasal application of the ITN. Single application at application visit.
arm group label: ITN [TrueTear®] - Extranasal Application
arm group type: Experimental
description: Extranasal application of the ITN. Single application at application visit.
intervention type: Device
intervention name: Intranasal Tear Neurostimulator (ITN) [TrueTear®]
description: The ITN applies a small electrical current to the nasal cavities to gently activate the body's natural tear production system.
arm group label: ITN [TrueTear®] - Extranasal Application
arm group label: ITN [TrueTear®] - Intranasal Application
criteria: 
gender: All
minimum age: 22 Years
maximum age: N/A
healthy volunteers: No
last name: Stephen Pflugfelder, MD
role: Principal Investigator
affiliation: Baylor College of Medicine, Department of Ophthalmology
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Eye Diseases
sharing ipd: Yes
ipd description: Allergan will share de-identified patient-level data and study-level data including protocols and clinical study reports for phase 2 - 4 trials completed after 2008 that are registered to ClinicalTrials.gov or EudraCT, have received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published. To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes. More information can be found on http://www.allerganclinicaltrials.com/.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: After having received regulatory approval in the United States and/or the European Union in a given indication and the primary manuscript from the trial has been published.
ipd access criteria: To request access to the data, the researcher must sign a data use agreement and any shared data is to be used for non-commercial purposes.
ipd url: http://www.allerganclinicaltrials.com/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was terminated early, resulting in a small number of patients analyzed. Only a descriptive statistical analysis will be performed.
point of contact: 