<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/NCT03279965</url>
  </required_header>
  <id_info>
    <org_study_id>2016LI002B</org_study_id>
    <nct_id>NCT03279965</nct_id>
  </id_info>
  <brief_title>MRI in Cystic Fibrosis and Primary Ciliary Dyskinesia</brief_title>
  <official_title>A Pilot Study to Assess the Use of MRI in the Assessment of Patients With Cystic Fibrosis and Primary Ciliary Dyskinesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Royal Brompton &amp; Harefield NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bioxydyn Ltd, Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Basel, Switzerland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Brompton &amp; Harefield NHS Foundation Trust</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 small pilot / feasibility study (Approximately 50 patients) to assess the&#xD;
      possibility of clinical implementation of MRI assessment of patients with cystic fibrosis and&#xD;
      primary ciliary dyskinesia.&#xD;
&#xD;
      Patients will undergo their standard CT imaging and lung function investigations and&#xD;
      additionally will undergo MRI examination. Reports from CT (the current gold standard) and&#xD;
      MRI will be assessed for concordance and patient acceptability and examination implementation&#xD;
      costs will also be assessed. Novel MRI-based potential markers of CF and PCD disease state&#xD;
      will also be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this small single site pilot / feasibility study we aim to recruit approximately 50&#xD;
      patients over the age of 6 years with known cystic fibrosis (CF) or primary ciliary&#xD;
      dyskinesia (PCD).&#xD;
&#xD;
      Patients will be recruited from routine clinic appointments or at admission for inpatient&#xD;
      investigation and/or treatment at the point of referral for computed tomography (CT)&#xD;
      examination. If they consent to participation they will undergo MRI examination in addition&#xD;
      to their standard clinical CT (within 7 days of the CT scan - on the same day if&#xD;
      practicable).&#xD;
&#xD;
      The magnetic resonance imaging (MRI) scans will be anonymised and reported by radiologists,&#xD;
      blinded to the CT findings. The reports and scores (Eichinger and Brody2) will then be&#xD;
      compared those of the standard CT to assess concordance between the modalities and inter and&#xD;
      intra observer variability.&#xD;
&#xD;
      Potential novel biomarkers (pulmonary ventilation and perfusion (non-contrast) and sinus&#xD;
      mucus and liver tissue characteristics) will be compared with established markers (including&#xD;
      lung clearance index) and known CF mutation / PCD type.&#xD;
&#xD;
      Patients or their carers will also be asked to fill in a short questionnaire comparing the&#xD;
      differential patient acceptability of CT and MRI examinations. The cost (time, resources etc)&#xD;
      of each examination will be calculated and compared.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 5, 2017</start_date>
  <completion_date type="Anticipated">May 5, 2018</completion_date>
  <primary_completion_date type="Anticipated">May 5, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Structural and quantitative MRI vs CT in cystic fibrosis and primary ciliary dyskinesia assessment</measure>
    <time_frame>18 months</time_frame>
    <description>To determine whether MRI with ventilation imaging can produce sufficiently diagnostic images, in the setting of CF or PCD, to replace CT imaging follow up. This will be assessed via semi-quantitative visual scoring (CT-based Brody / CFCT score and MRI-based Eichinger score) with both scoring systems applied to both CT and MRI. Scoring of the &quot;air-trapping&quot; component of CFCT will be substituted with scoring of ventilation defects on MRI. Scores will come from 2 observers, blinded to each others opinion, with a 3rd observer acting to resolve discrepancies. Intermodality variation will be assessed via ICC and Bland-Altman</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilation MRI vs Lung clearance index (LCI)</measure>
    <time_frame>18 months</time_frame>
    <description>Dynamic oxygen enhanced MRI measures will be compared to equivalent measurements from lung clearance testing. Bland Altman and ICC analysis of time to oxygen wash in (in seconds) on MRI, to time to nitrogen washout in seconds from lung clearance testing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sinus disease and exacerbations 1</measure>
    <time_frame>18 months</time_frame>
    <description>Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with frequency of infective exacerbations (number per month)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sinus disease and exacerbations 2</measure>
    <time_frame>18 months</time_frame>
    <description>Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with rate of decline in spirometry measures (percentage drop in predicted FEV1 and FEV1/FVC over the 6 months prior to scanning)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sinus disease and exacerbations 3</measure>
    <time_frame>18 months</time_frame>
    <description>Simple correlative statistics of presence of susceptibility artefact in sinus mucus (binary; yes, no) with micro-organism cultured (nominal)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver disease 1</measure>
    <time_frame>18 months</time_frame>
    <description>Simple correlation of liver volume (cm3) and T1 relaxation time (ms) with serologic markers of liver function (AST, ALT and ALP in IU/L and albumin in g/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver disease 2</measure>
    <time_frame>18 months</time_frame>
    <description>Simple correlation of liver T1 relaxation time (ms) with ultrasound elastography markers of liver fibrosis (sheer wave speed in m/s)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient acceptability</measure>
    <time_frame>18 months</time_frame>
    <description>To determine whether MRI is as acceptable to patients with CF or PCD as CT. This is via simple descriptive statistics from a bespoke questionnaire consisting of 5-point Likert scale questions regarding each scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical implementation</measure>
    <time_frame>18 months</time_frame>
    <description>To determine the operational cost differences in implementing MRI follow up vs CT follow up. Simple comparison of cost (in GBP) of diagnostic CT vs lung MRI.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Cystic Fibrosis</condition>
  <condition>Primary Ciliary Dyskinesia</condition>
  <arm_group>
    <arm_group_label>Cystic fibrosis</arm_group_label>
    <description>Patients with known cystic fibrosis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Primary ciliary dyskinesia</arm_group_label>
    <description>Patients with known primary ciliary dyskinesia</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>MRI of lungs, paranasal sinuses and liver in addition to established clinical examinations (lung CT, pulmonary function testing)</description>
    <arm_group_label>Cystic fibrosis</arm_group_label>
    <arm_group_label>Primary ciliary dyskinesia</arm_group_label>
    <other_name>Nuclear magnetic resonance (NMR)</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with known cystic fibrosis or primary ciliary dyskinesia referred for CT chest as&#xD;
        part of routine outpatient or inpatient investigations.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Known CF or PCD Referred for CT chest&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to MRI (Pacemaker etc) Unable to stay still for MRI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anand Devaraj</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Brompton Hospital London</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Anand Devaraj</last_name>
    <phone>02073528121</phone>
    <email>A.Devaraj@rbht.nhs.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Thomas Semple, MBBS, BSc</last_name>
    <phone>02073528121</phone>
    <email>T.Semple@rbht.nhs.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal Brompton Hospital</name>
      <address>
        <city>London</city>
        <zip>SW3 6NP</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Semple, FRCR MBBS</last_name>
      <phone>02073528121</phone>
      <email>T.Semple@rbht.nhs.uk</email>
    </contact>
    <contact_backup>
      <last_name>Anand Devaraj</last_name>
      <phone>02073528121</phone>
      <email>A.Devaraj@rbht.nhs.uk</email>
    </contact_backup>
    <investigator>
      <last_name>Anand Devaraj</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Simon Padley</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thomas Semple</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>June 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>September 11, 2017</last_update_submitted>
  <last_update_submitted_qc>September 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung MRI cystic fibrosis primary ciliary dyskinesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Ciliary Motility Disorders</mesh_term>
    <mesh_term>Dyskinesias</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no plan to share individual participant data outside the research team at this time.</ipd_description>
  </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/NCT03279965
org study id: 2016LI002B
nct id: NCT03279965
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a small pilot / feasibility study (Approximately 50 patients) to assess the
      possibility of clinical implementation of MRI assessment of patients with cystic fibrosis and
      primary ciliary dyskinesia.

      Patients will undergo their standard CT imaging and lung function investigations and
      additionally will undergo MRI examination. Reports from CT (the current gold standard) and
      MRI will be assessed for concordance and patient acceptability and examination implementation
      costs will also be assessed. Novel MRI-based potential markers of CF and PCD disease state
      will also be assessed.
In this small single site pilot / feasibility study we aim to recruit approximately 50
      patients over the age of 6 years with known cystic fibrosis (CF) or primary ciliary
      dyskinesia (PCD).

      Patients will be recruited from routine clinic appointments or at admission for inpatient
      investigation and/or treatment at the point of referral for computed tomography (CT)
      examination. If they consent to participation they will undergo MRI examination in addition
      to their standard clinical CT (within 7 days of the CT scan - on the same day if
      practicable).

      The magnetic resonance imaging (MRI) scans will be anonymised and reported by radiologists,
      blinded to the CT findings. The reports and scores (Eichinger and Brody2) will then be
      compared those of the standard CT to assess concordance between the modalities and inter and
      intra observer variability.

      Potential novel biomarkers (pulmonary ventilation and perfusion (non-contrast) and sinus
      mucus and liver tissue characteristics) will be compared with established markers (including
      lung clearance index) and known CF mutation / PCD type.

      Patients or their carers will also be asked to fill in a short questionnaire comparing the
      differential patient acceptability of CT and MRI examinations. The cost (time, resources etc)
      of each examination will be calculated and compared.
observational model: Case-Only
time perspective: Prospective
measure: Structural and quantitative MRI vs CT in cystic fibrosis and primary ciliary dyskinesia assessment
time frame: 18 months
description: To determine whether MRI with ventilation imaging can produce sufficiently diagnostic images, in the setting of CF or PCD, to replace CT imaging follow up. This will be assessed via semi-quantitative visual scoring (CT-based Brody / CFCT score and MRI-based Eichinger score) with both scoring systems applied to both CT and MRI. Scoring of the "air-trapping" component of CFCT will be substituted with scoring of ventilation defects on MRI. Scores will come from 2 observers, blinded to each others opinion, with a 3rd observer acting to resolve discrepancies. Intermodality variation will be assessed via ICC and Bland-Altman
measure: Ventilation MRI vs Lung clearance index (LCI)
time frame: 18 months
description: Dynamic oxygen enhanced MRI measures will be compared to equivalent measurements from lung clearance testing. Bland Altman and ICC analysis of time to oxygen wash in (in seconds) on MRI, to time to nitrogen washout in seconds from lung clearance testing
measure: Sinus disease and exacerbations 1
time frame: 18 months
description: Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with frequency of infective exacerbations (number per month)
measure: Sinus disease and exacerbations 2
time frame: 18 months
description: Simple correlative statistics of degree of sinus opacification (percentage volume occupied by mucus and polyps) with rate of decline in spirometry measures (percentage drop in predicted FEV1 and FEV1/FVC over the 6 months prior to scanning)
measure: Sinus disease and exacerbations 3
time frame: 18 months
description: Simple correlative statistics of presence of susceptibility artefact in sinus mucus (binary; yes, no) with micro-organism cultured (nominal)
measure: Liver disease 1
time frame: 18 months
description: Simple correlation of liver volume (cm3) and T1 relaxation time (ms) with serologic markers of liver function (AST, ALT and ALP in IU/L and albumin in g/L)
measure: Liver disease 2
time frame: 18 months
description: Simple correlation of liver T1 relaxation time (ms) with ultrasound elastography markers of liver fibrosis (sheer wave speed in m/s)
measure: Patient acceptability
time frame: 18 months
description: To determine whether MRI is as acceptable to patients with CF or PCD as CT. This is via simple descriptive statistics from a bespoke questionnaire consisting of 5-point Likert scale questions regarding each scan.
measure: Clinical implementation
time frame: 18 months
description: To determine the operational cost differences in implementing MRI follow up vs CT follow up. Simple comparison of cost (in GBP) of diagnostic CT vs lung MRI.
arm group label: Cystic fibrosis
description: Patients with known cystic fibrosis
arm group label: Primary ciliary dyskinesia
description: Patients with known primary ciliary dyskinesia
intervention type: Diagnostic Test
intervention name: MRI
description: MRI of lungs, paranasal sinuses and liver in addition to established clinical examinations (lung CT, pulmonary function testing)
arm group label: Cystic fibrosis
arm group label: Primary ciliary dyskinesia
other name: Nuclear magnetic resonance (NMR)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: No
last name: Anand Devaraj
role: Principal Investigator
affiliation: Royal Brompton Hospital London
last name: Anand Devaraj
phone: 02073528121
email: A.Devaraj@rbht.nhs.uk
last name: Thomas Semple, MBBS, BSc
phone: 02073528121
email: T.Semple@rbht.nhs.uk
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cystic Fibrosis
mesh term: Ciliary Motility Disorders
mesh term: Dyskinesias
mesh term: Fibrosis
sharing ipd: No
ipd description: There is no plan to share individual participant data outside the research team at this time.