<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/NCT02252601</url>
  </required_header>
  <id_info>
    <org_study_id>3D-CF</org_study_id>
    <secondary_id>PB-PG-0213-30055</secondary_id>
    <nct_id>NCT02252601</nct_id>
  </id_info>
  <brief_title>Evaluation of the High Frequency Digit Triplet Test in Cystic Fibrosis</brief_title>
  <acronym>3D-CF</acronym>
  <official_title>An Evaluation of the High Frequency Digit Triplet Test as a Screening Tool for Early Detection of Hearing Loss in Individuals With Cystic Fibrosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nottingham University Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Heart of England NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Birmingham Women's and Children's NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to find out whether the High Frequency Digit Triplet test can be&#xD;
      used to screen patients with cystic fibrosis for hearing loss in conditions of health and&#xD;
      pulmonary exacerbation. It is also designed to find out the youngest age at which a child can&#xD;
      perform the test, the prevalence of hearing loss in a CF population and the prevalence of&#xD;
      genetic mutations known to be associated with hearing loss in the same population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be identified from the clinic list of four Cystic Fibrosis centres (Nottingham&#xD;
      University Hospitals NHS (National Health Service) Trust, adults and children, West Midlands&#xD;
      Adult Cystic Fibrosis Centre and Birmingham Children's Hospital).&#xD;
&#xD;
      In the first work stream patients 11 years old and over will answer some hearing screening&#xD;
      questions and an ear examination and tympanogram. They will then have the new test (the High&#xD;
      Frequency Digit Triplet, HFDT, test), the standard tests (Pure tone audiogram (PTA) including&#xD;
      high frequencies, Distortion Product Otoacoustic Emissions) and then repeat the new test to&#xD;
      look for order effect. These will be compared to validate the HFDT as a screening tool for&#xD;
      hearing loss.&#xD;
&#xD;
      In the second work stream the investigators are looking to see if the test is feasible when a&#xD;
      patient is unwell and about to start a course of IV antibiotics. The patients will have the&#xD;
      same tests as in work stream 1 (though the high-frequency PTA may be modified if they are too&#xD;
      unwell to complete it). They will then have the tests repeated at the next clinic visit&#xD;
      (approximately 6-8 weeks later).&#xD;
&#xD;
      In the third work stream children aged 5-10 years will have the same tests. This is to&#xD;
      discover the youngest age at which the HFDT test can reliably be performed. To ensure that&#xD;
      the CF condition does not itself affect the ability to perform the test the investigators&#xD;
      will compare CF children to healthy control children the same age.&#xD;
&#xD;
      The investigators will take blood and saliva samples from CF patients to look for mutations&#xD;
      in mitochondrial genes which are known to be associated with aminoglycoside induced hearing&#xD;
      loss.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2015</start_date>
  <primary_completion_date type="Anticipated">July 2018</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>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients in whom the HFDT test accurately predicts the presence of absence of hearing loss.</measure>
    <time_frame>2 years</time_frame>
    <description>This will be done in patients when they are clinically stable and at the beginning and end of a pulmonary exacerbation by comparing the HFDT test with the current gold standard test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The youngest age at which 80% of children are able to perform the HFDT test.</measure>
    <time_frame>2 years</time_frame>
    <description>This will be done in children aged 5-10 years and the</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The prevalence of hearing loss in a CF population.</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The prevalence of genetic mutations that are associated with hearing loss in a CF population.</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">388</enrollment>
  <condition>Cystic Fibrosis</condition>
  <condition>Sensorineural Hearing Loss</condition>
  <arm_group>
    <arm_group_label>Well patients aged 11 and over</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Acute exacerbation aged 11 and over</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity at the beginning of a course of IV antibiotics and at their convalescent clinic visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Children with CF aged 5-10 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control Children age 5-10 years.</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>HFDT test</intervention_name>
    <arm_group_label>Acute exacerbation aged 11 and over</arm_group_label>
    <arm_group_label>Children with CF aged 5-10 years</arm_group_label>
    <arm_group_label>Healthy Control Children age 5-10 years.</arm_group_label>
    <arm_group_label>Well patients aged 11 and over</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pure tone Audiogram</intervention_name>
    <arm_group_label>Acute exacerbation aged 11 and over</arm_group_label>
    <arm_group_label>Children with CF aged 5-10 years</arm_group_label>
    <arm_group_label>Healthy Control Children age 5-10 years.</arm_group_label>
    <arm_group_label>Well patients aged 11 and over</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
        Work stream 1&#xD;
&#xD;
          -  A diagnosis of CF, confirmed by genotype or sweat test, with characteristic clinical&#xD;
             features.&#xD;
&#xD;
          -  Aged 11 years and over.&#xD;
&#xD;
          -  Informed consent. For age 11 to 18 years, consent will be sought from both the parent&#xD;
             and young person (provided the young person is competent).&#xD;
&#xD;
        Work stream 2&#xD;
&#xD;
        • As above but the participant has a pulmonary exacerbation (as defined by Fuch's criteria)&#xD;
        requiring intravenous antibiotics.&#xD;
&#xD;
        Work stream 3&#xD;
&#xD;
          -  As for work stream 1, defined above.&#xD;
&#xD;
          -  CF patients aged 5-10 years&#xD;
&#xD;
          -  Healthy control children aged 5-10 years.&#xD;
&#xD;
          -  Informed consent from parent with assent from the child.&#xD;
&#xD;
        Genetic Testing&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Diagnosis of CF as above&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  None. In individuals with a hearing aid, we will perform PTA and HFDT tests without&#xD;
             the aid.&#xD;
&#xD;
          -  Individuals found to have conductive deafness after randomisation will be fully&#xD;
             assessed for this prior to continuing with the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan Smyth, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Nottingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sally Palser, BMBS</last_name>
    <phone>+ 44 115 823 0618</phone>
    <phone_ext>30618</phone_ext>
    <email>sally.palser@nottingham.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Birmingham Children's Hospital NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B 4 6NH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jane Clarke</last_name>
      <phone>+44 121 333 8208</phone>
      <email>jane.clarke@bch.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Jane Clarke</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Heart of England NHS Foundation Trust</name>
      <address>
        <city>Birmingham</city>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Edward Nash</last_name>
      <phone>+44 121 424 1669</phone>
      <email>ed.nash@heartofengland.nhs.uk</email>
    </contact>
    <investigator>
      <last_name>Ed Nash</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alan Smyth, MD</last_name>
      <phone>+ 44 115 823 0612</phone>
      <email>alan.smyth@nottingham.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Alan Smyth, FRCPCH, MD,</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>April 11, 2016</last_update_submitted>
  <last_update_submitted_qc>April 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cystic Fibrosis</keyword>
  <keyword>Hearing Loss</keyword>
  <keyword>High Frequency Digit Triplet Test</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Hearing Loss</mesh_term>
    <mesh_term>Deafness</mesh_term>
    <mesh_term>Hearing Loss, Sensorineural</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_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/NCT02252601
org study id: 3D-CF
secondary id: PB-PG-0213-30055
nct id: NCT02252601
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to find out whether the High Frequency Digit Triplet test can be
      used to screen patients with cystic fibrosis for hearing loss in conditions of health and
      pulmonary exacerbation. It is also designed to find out the youngest age at which a child can
      perform the test, the prevalence of hearing loss in a CF population and the prevalence of
      genetic mutations known to be associated with hearing loss in the same population.
Patients will be identified from the clinic list of four Cystic Fibrosis centres (Nottingham
      University Hospitals NHS (National Health Service) Trust, adults and children, West Midlands
      Adult Cystic Fibrosis Centre and Birmingham Children's Hospital).

      In the first work stream patients 11 years old and over will answer some hearing screening
      questions and an ear examination and tympanogram. They will then have the new test (the High
      Frequency Digit Triplet, HFDT, test), the standard tests (Pure tone audiogram (PTA) including
      high frequencies, Distortion Product Otoacoustic Emissions) and then repeat the new test to
      look for order effect. These will be compared to validate the HFDT as a screening tool for
      hearing loss.

      In the second work stream the investigators are looking to see if the test is feasible when a
      patient is unwell and about to start a course of IV antibiotics. The patients will have the
      same tests as in work stream 1 (though the high-frequency PTA may be modified if they are too
      unwell to complete it). They will then have the tests repeated at the next clinic visit
      (approximately 6-8 weeks later).

      In the third work stream children aged 5-10 years will have the same tests. This is to
      discover the youngest age at which the HFDT test can reliably be performed. To ensure that
      the CF condition does not itself affect the ability to perform the test the investigators
      will compare CF children to healthy control children the same age.

      The investigators will take blood and saliva samples from CF patients to look for mutations
      in mitochondrial genes which are known to be associated with aminoglycoside induced hearing
      loss.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Proportion of patients in whom the HFDT test accurately predicts the presence of absence of hearing loss.
time frame: 2 years
description: This will be done in patients when they are clinically stable and at the beginning and end of a pulmonary exacerbation by comparing the HFDT test with the current gold standard test.
measure: The youngest age at which 80% of children are able to perform the HFDT test.
time frame: 2 years
description: This will be done in children aged 5-10 years and the
measure: The prevalence of hearing loss in a CF population.
time frame: 2 years
measure: The prevalence of genetic mutations that are associated with hearing loss in a CF population.
time frame: 2 years
arm group label: Well patients aged 11 and over
arm group type: Experimental
description: Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.
arm group label: Acute exacerbation aged 11 and over
arm group type: Experimental
description: Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity at the beginning of a course of IV antibiotics and at their convalescent clinic visit.
arm group label: Children with CF aged 5-10 years
arm group type: Experimental
description: Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.
arm group label: Healthy Control Children age 5-10 years.
arm group type: Active Comparator
description: Will have the HFDT test compared to the gold standard (the Pure tone Audiogram) as well as other tests that have previously been suggested as a screening test for ototoxicity.
intervention type: Other
intervention name: HFDT test
arm group label: Acute exacerbation aged 11 and over
arm group label: Children with CF aged 5-10 years
arm group label: Healthy Control Children age 5-10 years.
arm group label: Well patients aged 11 and over
intervention type: Other
intervention name: Pure tone Audiogram
arm group label: Acute exacerbation aged 11 and over
arm group label: Children with CF aged 5-10 years
arm group label: Healthy Control Children age 5-10 years.
arm group label: Well patients aged 11 and over
criteria: 
gender: All
minimum age: 5 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Alan Smyth, MD
role: Principal Investigator
affiliation: The University of Nottingham
last name: Sally Palser, BMBS
phone: + 44 115 823 0618
phone ext: 30618
email: sally.palser@nottingham.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Hearing Loss
mesh term: Deafness
mesh term: Hearing Loss, Sensorineural
mesh term: Fibrosis