<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/NCT03002389</url>
  </required_header>
  <id_info>
    <org_study_id>19569-19352</org_study_id>
    <nct_id>NCT03002389</nct_id>
  </id_info>
  <brief_title>Hyperpolarized Xenon-129 MRI: a New Multi-dimensional Biomarker to Determine Pulmonary Physiologic Responses to COPD Therapeutics</brief_title>
  <official_title>Hyperpolarized Xenon-129 MRI: a New Multi-dimensional Biomarker to Determine Pulmonary Physiologic Responses to COPD Therapeutics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Virginia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hyper polarized xenon-129 MRI (HXe MRI) is a unique imaging test which can detect how air is&#xD;
      flowing in and out of lungs and how oxygen can move from inhaled air into the blood. Chronic&#xD;
      Obstructive Pulmonary Disease (COPD) is a disease in which patients develop narrowing of&#xD;
      airways, thus, having difficulties breathing air in and out their lungs and also damaging the&#xD;
      lung tissues which patients need to move oxygen from the air into blood.&#xD;
&#xD;
      In this study, two drugs which are already approved by FDA (Anoro and Arnuity) will be&#xD;
      administered to patients who are already known to have COPD. While patients are being treated&#xD;
      with these two drugs (one drug at a time over a month), lung health by using usual testing&#xD;
      methods (CT scan of the lung, pulmonary function test, and blood test) will be assessed in&#xD;
      addition to HXe MRI.&#xD;
&#xD;
      The goal of this study is to prove that the HXe MRI is an excellent imaging test to show the&#xD;
      state of lung health among COPD patients and also to obtain new informations on how lung&#xD;
      health changes with drugs that are already approved by US FDA. This work is anticipated to&#xD;
      help develop HXe MRI as a new clinical test which can guide how to treat patients with COPD&#xD;
      and if new therapies can improve lung health of patients with COPD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 5, 2017</start_date>
  <completion_date type="Anticipated">January 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in the hyper polarized MRI xenon-129 MRI (HXe MRI) assessment pre-post 30-day treatment of umeclidinium+vilanterol or Flovent</measure>
    <time_frame>Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>In vivo lung physiology measurement obtained by HXe MRI pre and post drug intervention.&#xD;
In vivo lung physiology is measured by % of the lung that does not ventilate (dead space ventilation), among of the dissolved xenon-129 gas location among airways, interstitial tissues, or circulating red blood cells. These measures will be reported as continuous variables for data analyses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>High resolution CT of lung</measure>
    <time_frame>First baseline only=day 0</time_frame>
    <description>Quantification of emphysematous lung tissues and abnormally thickened airways in correlation with changed detectable by HXe MRI.&#xD;
% of lung tissues with emphysema will be quantified by measuring tissue density using Hounsfield Unit (HU). Based on COPDgene and other studies, we will use HU &lt; -950 as emphysematous lung tissue. The lung CT scan will then be processed to yield % of lung tissue with emphysema. The airway thickness will be measured by standardized imaging algorithm developed by VIDA imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pulmonary Function Test (PFT) from pre to post-umeclidinium+vilanterol or Flovent</measure>
    <time_frame>Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
The gas exchange capacity will be assessed by diffusion capacity of carbon monoxide represented as percent DLCO. This is a standard clinical measure being used routinely in pulmonary clinics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Baseline Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
Quality of life survey will be administered to obtain numeric number as a results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Transient Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
Quality of life survey will be administered to obtain numeric number as a results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Saint George's Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
Quality of life survey will be administered to obtain numeric number as a results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Chronic Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
Quality of life survey will be administered to obtain numeric number as a results.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in BODE score from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. BODE score is calculated by the results from the pulmonary function test, modified medical research council score, and body mass index. This will yield a score ranging from 0 to 10 with higher scores predicting higher chance of mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in GOLD Stage from pre to post-umeclidinium+vilanterol or flovent</measure>
    <time_frame>Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67</time_frame>
    <description>Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention.&#xD;
GOLD stage is calculated by a combination of pulmonary function test result, modified medical research council score, and history of frequency of COPD exacerbation previous 12 months. This score will yield GOLD stages A (mild) to , B, C, D (most severe).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">95</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>All COPD Subjects</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects will be assessed with hyper polarized xenon-129 MRI, pulmonary function test, quality of life measures (BDI, TDI, SGRQ, CRQ, BODE, GOLD), and blood test.&#xD;
Intervention: All subjects will received Anoro one puff once a day for 30 days first, then 3 day washout, then Arnuity 250 microgram one puff twice a day for 30 days to complete the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anoro Ellipta</intervention_name>
    <description>inhaler approved by FDA (strength umeclidinium 65 microgram + vilanterol 25 microgram) One puff once a day for 30 days</description>
    <arm_group_label>All COPD Subjects</arm_group_label>
    <other_name>umeclidinium + vilanterol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Arnuity Ellipta</intervention_name>
    <description>inhaler approved by FDA (strength 250 microgram) One puff twice a day for 30 days</description>
    <arm_group_label>All COPD Subjects</arm_group_label>
    <other_name>fluticasone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  post bronchodilator PFT spirometry FEV1/FVC &lt; 70% predicted&#xD;
&#xD;
          -  History of diagnosis of COPD&#xD;
&#xD;
          -  History of alpha 1 anti-trypsin deficiency&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous diagnosis of asthma, interstitial lung disease, pulmonary vascular disease,&#xD;
             inability to complete MRI or any of the assessment testings.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yun M Shim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kun Qing, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Roselove Asare, RT</last_name>
    <phone>4342436074</phone>
    <email>rnn3b@virginia.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Roselove M Asare</last_name>
    <phone>4342436074</phone>
    <email>RNN3B@VIRGINIA.EDU</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Roselove NUNOO-ASARE</name>
      <address>
        <city>Keswick</city>
        <state>Virginia</state>
        <zip>22947</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Roselove Asare, RT</last_name>
      <phone>540-295-5399</phone>
      <email>RNN3B@VIRGINIA.EDU</email>
    </contact>
    <contact_backup>
      <last_name>M</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Qing K, Ruppert K, Jiang Y, Mata JF, Miller GW, Shim YM, Wang C, Ruset IC, Hersman FW, Altes TA, Mugler JP 3rd. Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI. J Magn Reson Imaging. 2014 Feb;39(2):346-59. doi: 10.1002/jmri.24181. Epub 2013 May 16.</citation>
    <PMID>23681559</PMID>
  </results_reference>
  <results_reference>
    <citation>Qing K, Mugler JP 3rd, Altes TA, Jiang Y, Mata JF, Miller GW, Ruset IC, Hersman FW, Ruppert K. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR Biomed. 2014 Dec;27(12):1490-501. doi: 10.1002/nbm.3179. Epub 2014 Aug 22.</citation>
    <PMID>25146558</PMID>
  </results_reference>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Virginia</investigator_affiliation>
    <investigator_full_name>Y. Michael Shim, MD</investigator_full_name>
    <investigator_title>Assoicate Professor, Department of Medicine</investigator_title>
  </responsible_party>
  <keyword>chronic obstructive pulmonary disease</keyword>
  <keyword>COPD</keyword>
  <keyword>emphysema</keyword>
  <keyword>MRI</keyword>
  <keyword>hyper polarized gas MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>At the conclusion of the study, correlation data between COPD phenotypes and changes in MRI characteristics will be shared. Data from individuals will be complied with unique study-generated subject ID after removing all personal identifiers. Once this is completed, the data may be shared with hyper polarized MR imaging network currently being formed in collaboration with University of WI, U Penn, Duke, U of Cincinnati, and U Missouri. The data will be accessible by these investigators after the data sharing plans are reviewed by the IRB of the record (at the University of Virginia).</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/NCT03002389
org study id: 19569-19352
nct id: NCT03002389
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Hyper polarized xenon-129 MRI (HXe MRI) is a unique imaging test which can detect how air is
      flowing in and out of lungs and how oxygen can move from inhaled air into the blood. Chronic
      Obstructive Pulmonary Disease (COPD) is a disease in which patients develop narrowing of
      airways, thus, having difficulties breathing air in and out their lungs and also damaging the
      lung tissues which patients need to move oxygen from the air into blood.

      In this study, two drugs which are already approved by FDA (Anoro and Arnuity) will be
      administered to patients who are already known to have COPD. While patients are being treated
      with these two drugs (one drug at a time over a month), lung health by using usual testing
      methods (CT scan of the lung, pulmonary function test, and blood test) will be assessed in
      addition to HXe MRI.

      The goal of this study is to prove that the HXe MRI is an excellent imaging test to show the
      state of lung health among COPD patients and also to obtain new informations on how lung
      health changes with drugs that are already approved by US FDA. This work is anticipated to
      help develop HXe MRI as a new clinical test which can guide how to treat patients with COPD
      and if new therapies can improve lung health of patients with COPD.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Changes in the hyper polarized MRI xenon-129 MRI (HXe MRI) assessment pre-post 30-day treatment of umeclidinium+vilanterol or Flovent
time frame: Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: In vivo lung physiology measurement obtained by HXe MRI pre and post drug intervention.
In vivo lung physiology is measured by % of the lung that does not ventilate (dead space ventilation), among of the dissolved xenon-129 gas location among airways, interstitial tissues, or circulating red blood cells. These measures will be reported as continuous variables for data analyses.
measure: High resolution CT of lung
time frame: First baseline only=day 0
description: Quantification of emphysematous lung tissues and abnormally thickened airways in correlation with changed detectable by HXe MRI.
% of lung tissues with emphysema will be quantified by measuring tissue density using Hounsfield Unit (HU). Based on COPDgene and other studies, we will use HU < -950 as emphysematous lung tissue. The lung CT scan will then be processed to yield % of lung tissue with emphysema. The airway thickness will be measured by standardized imaging algorithm developed by VIDA imaging.
measure: Changes in pulmonary Function Test (PFT) from pre to post-umeclidinium+vilanterol or Flovent
time frame: Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention.
The gas exchange capacity will be assessed by diffusion capacity of carbon monoxide represented as percent DLCO. This is a standard clinical measure being used routinely in pulmonary clinics.
measure: Changes in Baseline Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 7 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.
Quality of life survey will be administered to obtain numeric number as a results.
measure: Changes in Transient Dyspnea Index from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.
Quality of life survey will be administered to obtain numeric number as a results.
measure: Changes in Saint George's Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.
Quality of life survey will be administered to obtain numeric number as a results.
measure: Changes in Chronic Respiratory Questionnaire from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology using clinical standard quality of life testing in correlation with HXe MRI changes pre and post drug intervention.
Quality of life survey will be administered to obtain numeric number as a results.
measure: Changes in BODE score from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention. BODE score is calculated by the results from the pulmonary function test, modified medical research council score, and body mass index. This will yield a score ranging from 0 to 10 with higher scores predicting higher chance of mortality.
measure: Changes in GOLD Stage from pre to post-umeclidinium+vilanterol or flovent
time frame: Time point with +/- 3 day window: first baseline=day 0, first follow-up=day 30, second baseline=day 37, second follow-up=day 67
description: Measurement of in vivo lung physiology and mortality prediction score using clinical standard testing in correlation with HXe MRI changes pre and post drug intervention.
GOLD stage is calculated by a combination of pulmonary function test result, modified medical research council score, and history of frequency of COPD exacerbation previous 12 months. This score will yield GOLD stages A (mild) to , B, C, D (most severe).
arm group label: All COPD Subjects
arm group type: Other
description: All subjects will be assessed with hyper polarized xenon-129 MRI, pulmonary function test, quality of life measures (BDI, TDI, SGRQ, CRQ, BODE, GOLD), and blood test.
Intervention: All subjects will received Anoro one puff once a day for 30 days first, then 3 day washout, then Arnuity 250 microgram one puff twice a day for 30 days to complete the study.
intervention type: Drug
intervention name: Anoro Ellipta
description: inhaler approved by FDA (strength umeclidinium 65 microgram + vilanterol 25 microgram) One puff once a day for 30 days
arm group label: All COPD Subjects
other name: umeclidinium + vilanterol
intervention type: Drug
intervention name: Arnuity Ellipta
description: inhaler approved by FDA (strength 250 microgram) One puff twice a day for 30 days
arm group label: All COPD Subjects
other name: fluticasone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Yun M Shim, MD
role: Principal Investigator
affiliation: University of Virginia
last name: Kun Qing, PhD
role: Principal Investigator
affiliation: University of Virginia
last name: Roselove Asare, RT
phone: 4342436074
email: rnn3b@virginia.edu
last name: Roselove M Asare
phone: 4342436074
email: RNN3B@VIRGINIA.EDU
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Qing K, Ruppert K, Jiang Y, Mata JF, Miller GW, Shim YM, Wang C, Ruset IC, Hersman FW, Altes TA, Mugler JP 3rd. Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon-129 MRI. J Magn Reson Imaging. 2014 Feb;39(2):346-59. doi: 10.1002/jmri.24181. Epub 2013 May 16.
PMID: 23681559
citation: Qing K, Mugler JP 3rd, Altes TA, Jiang Y, Mata JF, Miller GW, Ruset IC, Hersman FW, Ruppert K. Assessment of lung function in asthma and COPD using hyperpolarized 129Xe chemical shift saturation recovery spectroscopy and dissolved-phase MRI. NMR Biomed. 2014 Dec;27(12):1490-501. doi: 10.1002/nbm.3179. Epub 2014 Aug 22.
PMID: 25146558
responsible party type: Principal Investigator
investigator affiliation: University of Virginia
investigator full name: Y. Michael Shim, MD
investigator title: Assoicate Professor, Department of Medicine
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Fluticasone
mesh term: Xhance
sharing ipd: Undecided
ipd description: At the conclusion of the study, correlation data between COPD phenotypes and changes in MRI characteristics will be shared. Data from individuals will be complied with unique study-generated subject ID after removing all personal identifiers. Once this is completed, the data may be shared with hyper polarized MR imaging network currently being formed in collaboration with University of WI, U Penn, Duke, U of Cincinnati, and U Missouri. The data will be accessible by these investigators after the data sharing plans are reviewed by the IRB of the record (at the University of Virginia).