<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/NCT03250429</url>
  </required_header>
  <id_info>
    <org_study_id>17-1499</org_study_id>
    <nct_id>NCT03250429</nct_id>
  </id_info>
  <brief_title>Nasal and Peripheral Blood Biomarkers of CRS Patients Before and After Surgical Intervention</brief_title>
  <official_title>Nasal and Peripheral Blood Biomarkers of CRS Patients Before and After Surgical Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Flight Attendant Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To characterize inflammatory cells in the nose of patients with Chronic Rhinosinusitis (CRS)&#xD;
      before and after sinus surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rhinosinusitis (RS) is a heterogenous disease, with variable etiologies, manifestations, and&#xD;
      progression. Generally, RS can be divided into acute, subacute, and chronic RS, depending on&#xD;
      the symptoms and duration of the disease. Most commonly, acute RS is caused by a viral&#xD;
      infection (viral RS), which starts in the nasal passages and progresses to inflammation of&#xD;
      the sinuses. When this inflammation of the paranasal sinuses does not resolve and lasts for&#xD;
      at least 12 weeks, the disorder is broadly defined as chronic RS (CRS), which is usually&#xD;
      accompanied by bacterial infections. This inflammatory disease pathophysiology is further&#xD;
      subdivided into CRS with (CRSwNP) and without (CRSsNP) nasal polyps. Recently, several&#xD;
      studies aimed at phenotyping the diverse pathophysiology among patients suffering from CRS&#xD;
      characterized subgroups based on the presence of inflammatory clusters. CRSsNP is marked by&#xD;
      pro-inflammatory neutrophilic inflammation of the nasal mucosa and a nasal cytokine profile&#xD;
      that is characterized by increased levels of TGFβ1 and IFNγ and low or undetectable levels of&#xD;
      IL-5. In contrast, patients with CRSwNP demonstrate eosinophilic inflammation of the nasal&#xD;
      mucosa, low levels of TGFβ1, but high levels of Th2/Th17-type cytokines such as IL-17 and&#xD;
      IL-5, higher levels of eosinophil cationic protein (ECP) and mast cell tryptase, and lower&#xD;
      levels of IL-10.&#xD;
&#xD;
      Currently biomarkers associated with physician diagnosed disease severity and&#xD;
      patient-perceived quality of life impairments are lacking. Analysis of markers of&#xD;
      inflammation in the nasal mucosa and peripheral blood leukocytes in combination with quality&#xD;
      of life symptom scoring will enable us to identify biomarkers associated with CRS disease&#xD;
      severity. This study will determine if biomarkers identified in the nasal mucosa and&#xD;
      peripheral blood leukocytes correlate with physician diagnosed and patient-perceived disease&#xD;
      severity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">December 20, 2019</completion_date>
  <primary_completion_date type="Actual">December 10, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Inflammatory mediators in the nasal mucosa</measure>
    <time_frame>Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)</time_frame>
    <description>Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to Transforming growth factor beta 1 (TGFβ1), Interferon gamma (IFNγ), Interleukin 5 (IL-5), Interleukin 17 (IL-17), eosinophil cationic protein (ECP), mast cell tryptase, and Interleukin (IL-10) from the nasal mucosa.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Inflammatory mediators in the peripheral blood</measure>
    <time_frame>Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)</time_frame>
    <description>Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10 from the peripheral blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Rhinosinusitis Disability Index (RSDI) Scores</measure>
    <time_frame>Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)</time_frame>
    <description>The RSDI is a disease-specific health-related quality of life instrument with 3 domains (physical, functional, and emotional impacts of rhinosinusitis) using a 5-point Likert scale ranging from 0 to 4 where 0 is &quot;never&quot; and 4 is &quot;always a problem&quot;. Higher scores indicate more significant impact on quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in gene expression profile</measure>
    <time_frame>Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)</time_frame>
    <description>Analyze cells for gene expression of inflammatory mediators including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Nasal lavage fluid cell count</measure>
    <time_frame>Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)</time_frame>
    <description>Count cell types present in nasal lavage fluid cells.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">30</enrollment>
  <condition>Sinusitis, Chronic</condition>
  <arm_group>
    <arm_group_label>CRS subjects</arm_group_label>
    <description>CRS subjects who have sinus surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sinus surgery</intervention_name>
    <description>Standard Clinical Sinus Surgery</description>
    <arm_group_label>CRS subjects</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood, urine, nasal lavage fluid, nasal epithelial lining fluid&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects who are patients at UNC Healthcare ENT clinics&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Physician diagnosed CRS with surgical requirement for treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with physician-diagnosed:&#xD;
&#xD;
          -  cystic fibrosis,&#xD;
&#xD;
          -  vasculitis,&#xD;
&#xD;
          -  any type of nasal tumor&#xD;
&#xD;
          -  receiving ongoing immunosuppressant therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ilona Jaspers, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>UNC SOM</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Environmental Medicine, Asthma and Lung Biology</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 10, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>February 4, 2020</last_update_submitted>
  <last_update_submitted_qc>February 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 5, 2020</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>Sinusitis</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/NCT03250429
org study id: 17-1499
nct id: NCT03250429
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To characterize inflammatory cells in the nose of patients with Chronic Rhinosinusitis (CRS)
      before and after sinus surgery.
Rhinosinusitis (RS) is a heterogenous disease, with variable etiologies, manifestations, and
      progression. Generally, RS can be divided into acute, subacute, and chronic RS, depending on
      the symptoms and duration of the disease. Most commonly, acute RS is caused by a viral
      infection (viral RS), which starts in the nasal passages and progresses to inflammation of
      the sinuses. When this inflammation of the paranasal sinuses does not resolve and lasts for
      at least 12 weeks, the disorder is broadly defined as chronic RS (CRS), which is usually
      accompanied by bacterial infections. This inflammatory disease pathophysiology is further
      subdivided into CRS with (CRSwNP) and without (CRSsNP) nasal polyps. Recently, several
      studies aimed at phenotyping the diverse pathophysiology among patients suffering from CRS
      characterized subgroups based on the presence of inflammatory clusters. CRSsNP is marked by
      pro-inflammatory neutrophilic inflammation of the nasal mucosa and a nasal cytokine profile
      that is characterized by increased levels of TGFβ1 and IFNγ and low or undetectable levels of
      IL-5. In contrast, patients with CRSwNP demonstrate eosinophilic inflammation of the nasal
      mucosa, low levels of TGFβ1, but high levels of Th2/Th17-type cytokines such as IL-17 and
      IL-5, higher levels of eosinophil cationic protein (ECP) and mast cell tryptase, and lower
      levels of IL-10.

      Currently biomarkers associated with physician diagnosed disease severity and
      patient-perceived quality of life impairments are lacking. Analysis of markers of
      inflammation in the nasal mucosa and peripheral blood leukocytes in combination with quality
      of life symptom scoring will enable us to identify biomarkers associated with CRS disease
      severity. This study will determine if biomarkers identified in the nasal mucosa and
      peripheral blood leukocytes correlate with physician diagnosed and patient-perceived disease
      severity.
observational model: Cohort
time perspective: Prospective
measure: Change in Inflammatory mediators in the nasal mucosa
time frame: Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)
description: Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to Transforming growth factor beta 1 (TGFβ1), Interferon gamma (IFNγ), Interleukin 5 (IL-5), Interleukin 17 (IL-17), eosinophil cationic protein (ECP), mast cell tryptase, and Interleukin (IL-10) from the nasal mucosa.
measure: Change in Inflammatory mediators in the peripheral blood
time frame: Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)
description: Detection and analysis of inflammatory mediators previously characterized in CRS subgroups, including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10 from the peripheral blood.
measure: Change in Rhinosinusitis Disability Index (RSDI) Scores
time frame: Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)
description: The RSDI is a disease-specific health-related quality of life instrument with 3 domains (physical, functional, and emotional impacts of rhinosinusitis) using a 5-point Likert scale ranging from 0 to 4 where 0 is "never" and 4 is "always a problem". Higher scores indicate more significant impact on quality of life.
measure: Change in gene expression profile
time frame: Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)
description: Analyze cells for gene expression of inflammatory mediators including but not limited to TGFβ1, IFNγ, IL-5, IL-17, ECP, mast cell tryptase, and IL-10
measure: Change in Nasal lavage fluid cell count
time frame: Baseline (Pre-surgery), Post-surgery (approximately 12 weeks after surgery)
description: Count cell types present in nasal lavage fluid cells.
arm group label: CRS subjects
description: CRS subjects who have sinus surgery
intervention type: Procedure
intervention name: Sinus surgery
description: Standard Clinical Sinus Surgery
arm group label: CRS subjects
Whole blood, urine, nasal lavage fluid, nasal epithelial lining fluid
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Ilona Jaspers, Ph.D.
role: Principal Investigator
affiliation: UNC SOM
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sinusitis
sharing ipd: No