<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/NCT03801395</url>
  </required_header>
  <id_info>
    <org_study_id>182074</org_study_id>
    <nct_id>NCT03801395</nct_id>
  </id_info>
  <brief_title>PCD New Gene Discovery</brief_title>
  <official_title>Primary Ciliary Dyskinesia New Gene Discovery to Improve Diagnostics and Clinical Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</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>
      This is a new gene discovery program for individuals with PCD who do not have a specific&#xD;
      genetic etiology identified. Research procedures involve a single blood draw from the&#xD;
      affected individual and from unaffected family members in an effort to identify new genetic&#xD;
      targets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to better define how the genes that cause primary ciliary&#xD;
      dyskinesia (PCD) are related to the clinical symptoms of individuals with PCD. PCD is a rare&#xD;
      disease that affects the function of motor cilia throughout the body. This results in a&#xD;
      variety of clinical symptoms, but chief among them are a chronic wet cough, recurrent&#xD;
      sinusitis, and frequent pneumonia. These clinical symptoms can result in further structural&#xD;
      lung disease, including bronchiectasis, with eventual worsening of lung function. The&#xD;
      treatment for this condition largely focuses on augmenting airway clearance and appropriate&#xD;
      use of antimicrobial therapies, in conjunction with monitoring for evidence of pulmonary&#xD;
      impairment. Thus, it is important to identify and diagnose individuals with PCD early in&#xD;
      life.&#xD;
&#xD;
      Making a diagnosis of PCD can be difficult as their is some overlap of the clinical symptoms&#xD;
      with other conditions and there are limitation in the current diagnostic testing modalities.&#xD;
      Historically, the diagnosis has been made by identification of structural abnormalities in&#xD;
      cilia by electron microscopy (ciliary biopsy). However, this testing has limitations&#xD;
      secondary to the somewhat invasive nature of the procedures and often inconclusive results&#xD;
      secondary to sampling challenges (getting enough cilia). Furthermore, a normal ciliary biopsy&#xD;
      result does not rule-out PCD as it is now known that there are individuals with PCD who have&#xD;
      ciliary dysfunction secondary to ciliary abnormalities that are not routinely identified on&#xD;
      standard electron micrograph. Genetic testing for PCD is available, but current testing only&#xD;
      accounts for about 60-65% of the PCD population. Thus normal results in this regard do not&#xD;
      rule-out PCD either. Nasal nitric oxide (nNO) testing is an emerging research-based testing&#xD;
      that is being used more frequently to identify individuals with PCD. More specifically, it&#xD;
      has been frequently observed that individuals with PCD have low levels of nitric oxide in&#xD;
      their sinus cavities. Measuring a low level of nitric oxide of multiple different occasions&#xD;
      has proven to have diagnostic utility in an individual with a clinical symptom history&#xD;
      consistent with PCD. While nNO testing is helpful for identifying individuals likely to have&#xD;
      PCD, this testing does not give further information as to reason for ciliary dysfunction.&#xD;
      Current testing availability has resulted in a group of individuals who are being managed as&#xD;
      &quot;probable PCD&quot; which is defined by having clinical symptoms consistent with PCD (such as&#xD;
      year-round wet cough and rhinitis) at least two separate positive (low value) nNO testing&#xD;
      results, but negative PCD genetics and a non diagnostic ciliary biopsy. While these&#xD;
      individuals are often managed the same as other individuals with more defined PCD, including&#xD;
      augmentation of airway clearance therapies, in order for more specific care to be applied in&#xD;
      the future it is important to better define the ciliary structural reason for their clinical&#xD;
      symptoms. This could also be described as needing to better understand the genotype-phenotype&#xD;
      of all individuals with PCD.&#xD;
&#xD;
      This investigation seeks to better define the genotypic-phenotypic relationship of&#xD;
      individuals by initially focusing on new gene discovery in individuals with probable PCD.&#xD;
      More specifically, through whole-exome evaluation of individuals with probable PCD and&#xD;
      unaffected first-degree relatives, we will focus on identifying new mutations in ciliary&#xD;
      structural proteins and other related pulmonary genes. New gene targets will then be further&#xD;
      studied through analysis of ciliary structure and function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">October 1, 2023</completion_date>
  <primary_completion_date type="Actual">July 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Family-Based</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>DNA analysis</measure>
    <time_frame>6 months</time_frame>
    <description>Blood will be obtained for DNA analysis and identification of new PCD genes. Genetic analysis will be done by whole exome sequencing</description>
  </primary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Primary Ciliary Dyskinesia</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>There is no intervention</intervention_name>
    <description>No intervention</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be obtained for DNA analysis&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Individuals with confirmed or suspected PCD and their unaffected family members&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Age 0-90 years&#xD;
&#xD;
               -  Confirmed diagnosis of PCD by either ciliary ultrastructure abnormality or two&#xD;
                  known disease-causing alleles in a known PCD gene OR individuals with clinical&#xD;
                  suspicion of PCD without a confirmatory test (genetics or ciliary biopsy) as&#xD;
                  defined by: low nasal nitric oxide testing (&lt;77nl/min) on two separate occasions&#xD;
                  at least two months apart or compatible clinical phenotype, but unable to do&#xD;
                  nasal nitric oxide testing secondary to age or other factors OR relative of one&#xD;
                  of the previously defined individuals with PCD&#xD;
&#xD;
               -  Ability to provide informed consent or consent of parent/guardian and assent for&#xD;
                  minors&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Inability to understand the requirements of the study or be unwilling to provide&#xD;
             written informed consent (as evidenced by signature on an informed consent document&#xD;
             approved by the IRB) OR inability of parent/guardian to understand the requirements of&#xD;
             the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Vanderbilt Children's hospital</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 9, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>November 17, 2022</last_update_submitted>
  <last_update_submitted_qc>November 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Michael O'Connor</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciliary Motility Disorders</mesh_term>
    <mesh_term>Dyskinesias</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/NCT03801395
org study id: 182074
nct id: NCT03801395
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a new gene discovery program for individuals with PCD who do not have a specific
      genetic etiology identified. Research procedures involve a single blood draw from the
      affected individual and from unaffected family members in an effort to identify new genetic
      targets.
The objective of this study is to better define how the genes that cause primary ciliary
      dyskinesia (PCD) are related to the clinical symptoms of individuals with PCD. PCD is a rare
      disease that affects the function of motor cilia throughout the body. This results in a
      variety of clinical symptoms, but chief among them are a chronic wet cough, recurrent
      sinusitis, and frequent pneumonia. These clinical symptoms can result in further structural
      lung disease, including bronchiectasis, with eventual worsening of lung function. The
      treatment for this condition largely focuses on augmenting airway clearance and appropriate
      use of antimicrobial therapies, in conjunction with monitoring for evidence of pulmonary
      impairment. Thus, it is important to identify and diagnose individuals with PCD early in
      life.

      Making a diagnosis of PCD can be difficult as their is some overlap of the clinical symptoms
      with other conditions and there are limitation in the current diagnostic testing modalities.
      Historically, the diagnosis has been made by identification of structural abnormalities in
      cilia by electron microscopy (ciliary biopsy). However, this testing has limitations
      secondary to the somewhat invasive nature of the procedures and often inconclusive results
      secondary to sampling challenges (getting enough cilia). Furthermore, a normal ciliary biopsy
      result does not rule-out PCD as it is now known that there are individuals with PCD who have
      ciliary dysfunction secondary to ciliary abnormalities that are not routinely identified on
      standard electron micrograph. Genetic testing for PCD is available, but current testing only
      accounts for about 60-65% of the PCD population. Thus normal results in this regard do not
      rule-out PCD either. Nasal nitric oxide (nNO) testing is an emerging research-based testing
      that is being used more frequently to identify individuals with PCD. More specifically, it
      has been frequently observed that individuals with PCD have low levels of nitric oxide in
      their sinus cavities. Measuring a low level of nitric oxide of multiple different occasions
      has proven to have diagnostic utility in an individual with a clinical symptom history
      consistent with PCD. While nNO testing is helpful for identifying individuals likely to have
      PCD, this testing does not give further information as to reason for ciliary dysfunction.
      Current testing availability has resulted in a group of individuals who are being managed as
      "probable PCD" which is defined by having clinical symptoms consistent with PCD (such as
      year-round wet cough and rhinitis) at least two separate positive (low value) nNO testing
      results, but negative PCD genetics and a non diagnostic ciliary biopsy. While these
      individuals are often managed the same as other individuals with more defined PCD, including
      augmentation of airway clearance therapies, in order for more specific care to be applied in
      the future it is important to better define the ciliary structural reason for their clinical
      symptoms. This could also be described as needing to better understand the genotype-phenotype
      of all individuals with PCD.

      This investigation seeks to better define the genotypic-phenotypic relationship of
      individuals by initially focusing on new gene discovery in individuals with probable PCD.
      More specifically, through whole-exome evaluation of individuals with probable PCD and
      unaffected first-degree relatives, we will focus on identifying new mutations in ciliary
      structural proteins and other related pulmonary genes. New gene targets will then be further
      studied through analysis of ciliary structure and function.
observational model: Family-Based
time perspective: Prospective
measure: DNA analysis
time frame: 6 months
description: Blood will be obtained for DNA analysis and identification of new PCD genes. Genetic analysis will be done by whole exome sequencing
intervention type: Other
intervention name: There is no intervention
description: No intervention
Blood samples will be obtained for DNA analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 0 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Michael O'Connor
investigator title: Assistant Professor
mesh term: Ciliary Motility Disorders
mesh term: Dyskinesias
sharing ipd: No