<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/NCT03821311</url>
  </required_header>
  <id_info>
    <org_study_id>38RC17.376</org_study_id>
    <nct_id>NCT03821311</nct_id>
  </id_info>
  <brief_title>Investigating the Effect of Nasal High Flow Oxygen Therapy on Regional Lung Function</brief_title>
  <acronym>INVENT</acronym>
  <official_title>Investigating the Effect of Nasal High Flow Oxygen Therapy on Regional Lung Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</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 study aims to assess the effect of nasal high flow oxygen therapy on regional function&#xD;
      measured by volumetric computed tomography, in patients with chronic obstructive pulmonary&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery of&#xD;
      heated and humidified air at flow rates that exceed peak inspiratory flow, via a&#xD;
      large-caliber nasal cannula. It delivers a fraction of inspired oxygen (FiO2) from 21% to&#xD;
      100%, with a flow rate up to 60 L·min-1.&#xD;
&#xD;
      The therapy is used for a variety of disease conditions including chronic obstructive&#xD;
      pulmonary disease (COPD). Patients with COPD frequently manifest flow limitation during&#xD;
      resting tidal breathing, through dynamic compression of the airways, which is attributed to a&#xD;
      loss of parenchymal tethering of the airways. In patients with severe COPD and respiratory&#xD;
      failure, improved oxygenation and ventilation may reduce mortality. There are limited&#xD;
      clinical data available in adult applications of NHF and on the effectiveness of NHF in&#xD;
      patients with stable moderate or severe COPD.&#xD;
&#xD;
      The mechanisms through which NHF affects the respiratory system are still being investigated.&#xD;
      Two of the proposed mechanisms of action of NHF therapy are the generation of 3-5 cmH20&#xD;
      positive airway pressure during expiration and washout of the nasopharyngeal dead space.&#xD;
      Positive airway pressure has been shown to improve oxygenation, ventilation-perfusion&#xD;
      matching and respiratory rates, while nasopharyngeal washout reduces the anatomical dead&#xD;
      space and thereby improves alveolar ventilation.&#xD;
&#xD;
      Our working hypothesis is that positive nasopharyngeal pressure generated by NHF particularly&#xD;
      during expiration can help maintain small peripheral airways patent, thereby reducing the&#xD;
      amount of gas trapping.&#xD;
&#xD;
      Gas trapping can be quantified based on densitometric analysis of registered computerized&#xD;
      tomography images obtained at high and low lung volumes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2018</start_date>
  <completion_date type="Actual">June 18, 2019</completion_date>
  <primary_completion_date type="Actual">June 18, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>It's a prospective, single-center, pilot, pathophysiological study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Gas trapping (expressed as percent total lung volume)</measure>
    <time_frame>30 minutes</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Regional lung ventilation distribution</measure>
    <time_frame>30 minutes</time_frame>
    <description>Regional change in attenuation between end-expiration and end-inspiration, based on CT image</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Coefficient of variation of regional lung ventilation</measure>
    <time_frame>30 minutes</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Nasal High Flow</condition>
  <condition>Dynamic Volumetric Computed Tomography</condition>
  <arm_group>
    <arm_group_label>Computed tomography examination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will undergo a low-dose supine position chest CT scan including end-inspiratory and expiratory acquisitions, corresponding to the routine protocol for COPD patients, except that this end-inspiratory/end-expiratory CT is repeated 3 times for total of 6 CT acquisitions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Computed tomography</intervention_name>
    <description>End-inspiratory/end-expiratory CT is repeated 3 times corresponding to the 3 studied conditions: At baseline, through expiratory resistive loading using an adjustable PEP mask, and after 5 min of nasal high flow therapy at 25 L/min.</description>
    <arm_group_label>Computed tomography examination</arm_group_label>
    <other_name>CT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stable, moderate to severe COPD, defined as follows:&#xD;
&#xD;
        Moderate: FEV1/FVC &lt; 0.7 or lower limit of normal, and 30 &lt; FEV1 ≤ 60 percent predicted;&#xD;
        Severe: FEV1/FVC &lt; 0.7 or lower limit of normal, and FEV1 ≤ 30 percent predicted&#xD;
&#xD;
          -  Indication for CT imaging as part of routine workup.&#xD;
&#xD;
          -  Written informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Acute disease condition such as infection, respiratory or cardiac failure&#xD;
&#xD;
          -  Persons referred to in Articles L1151-5 to L1151-8 and L1122-1-2 of the French Public&#xD;
             Health Code: Declared pregnant, parturient or lactating, persons deprived of their&#xD;
             liberty by judicial or administrative decision, minors, adults who are legally&#xD;
             protected or unable to express consent, etc.&#xD;
&#xD;
          -  Evolving neoplastic disease&#xD;
&#xD;
          -  Patient without social security health care coverage&#xD;
&#xD;
          -  Subject in an exclusion period from another study&#xD;
&#xD;
          -  Any contraindication to NHF such as nasal or upper airway bleeding, secretion, tumor,&#xD;
             recent surgery; cervical, nasal or skull fracture.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital Grenoble</name>
      <address>
        <city>Grenoble</city>
        <state>Isère</state>
        <zip>38000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.</citation>
    <PMID>22878278</PMID>
  </reference>
  <reference>
    <citation>Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J Appl Physiol Respir Environ Exerc Physiol. 1980 Sep;49(3):511-5. doi: 10.1152/jappl.1980.49.3.511.</citation>
    <PMID>7204175</PMID>
  </reference>
  <reference>
    <citation>Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage-Metreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.</citation>
    <PMID>25981908</PMID>
  </reference>
  <reference>
    <citation>Pisani L, Vega ML. Use of Nasal High Flow in Stable COPD: Rationale and Physiology. COPD. 2017 Jun;14(3):346-350. doi: 10.1080/15412555.2017.1315715. Epub 2017 May 1.</citation>
    <PMID>28459282</PMID>
  </reference>
  <reference>
    <citation>Curley GF, Laffy JG, Zhang H, Slutsky AS. Noninvasive respiratory support for acute respiratory failure-high flow nasal cannula oxygen or non-invasive ventilation? J Thorac Dis. 2015 Jul;7(7):1092-7. doi: 10.3978/j.issn.2072-1439.2015.07.18. No abstract available.</citation>
    <PMID>26380720</PMID>
  </reference>
  <reference>
    <citation>Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011 Dec;107(6):998-1004. doi: 10.1093/bja/aer265. Epub 2011 Sep 9.</citation>
    <PMID>21908497</PMID>
  </reference>
  <reference>
    <citation>Riera J, Perez P, Cortes J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013 Apr;58(4):589-96. doi: 10.4187/respcare.02086.</citation>
    <PMID>23050520</PMID>
  </reference>
  <reference>
    <citation>Spahija J, de Marchie M, Grassino A. Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD. Chest. 2005 Aug;128(2):640-50. doi: 10.1378/chest.128.2.640.</citation>
    <PMID>16100149</PMID>
  </reference>
  <reference>
    <citation>O'Donnell DE, Sanii R, Anthonisen NR, Younes M. Expiratory resistive loading in patients with severe chronic air-flow limitation. An evaluation of ventilatory mechanics and compensatory responses. Am Rev Respir Dis. 1987 Jul;136(1):102-7. doi: 10.1164/ajrccm/136.1.102.</citation>
    <PMID>3605825</PMID>
  </reference>
  <reference>
    <citation>Mueller RE, Petty TL, Filley GF. Ventilation and arterial blood gas changes induced by pursed lips breathing. J Appl Physiol. 1970 Jun;28(6):784-9. doi: 10.1152/jappl.1970.28.6.784. No abstract available.</citation>
    <PMID>5419502</PMID>
  </reference>
  <reference>
    <citation>Galban CJ, Han MK, Boes JL, Chughtai KA, Meyer CR, Johnson TD, Galban S, Rehemtulla A, Kazerooni EA, Martinez FJ, Ross BD. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med. 2012 Nov;18(11):1711-5. doi: 10.1038/nm.2971. Epub 2012 Oct 7.</citation>
    <PMID>23042237</PMID>
  </reference>
  <reference>
    <citation>Fricke K, Tatkov S, Domanski U, Franke KJ, Nilius G, Schneider H. Nasal high flow reduces hypercapnia by clearance of anatomical dead space in a COPD patient. Respir Med Case Rep. 2016 Aug 26;19:115-7. doi: 10.1016/j.rmcr.2016.08.010. eCollection 2016.</citation>
    <PMID>27668173</PMID>
  </reference>
  <reference>
    <citation>Kybic J, Unser M. Fast parametric elastic image registration. IEEE Trans Image Process. 2003;12(11):1427-42. doi: 10.1109/TIP.2003.813139.</citation>
    <PMID>18244700</PMID>
  </reference>
  <reference>
    <citation>Gibson GJ, Loddenkemper R, Lundback B, Sibille Y. Respiratory health and disease in Europe: the new European Lung White Book. Eur Respir J. 2013 Sep;42(3):559-63. doi: 10.1183/09031936.00105513. No abstract available.</citation>
    <PMID>24000245</PMID>
  </reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>December 26, 2019</last_update_submitted>
  <last_update_submitted_qc>December 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 27, 2019</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>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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/NCT03821311
org study id: 38RC17.376
nct id: NCT03821311
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to assess the effect of nasal high flow oxygen therapy on regional function
      measured by volumetric computed tomography, in patients with chronic obstructive pulmonary
      disease.
Nasal high flow (NHF) is a non-invasive breathing therapy that is based on the delivery of
      heated and humidified air at flow rates that exceed peak inspiratory flow, via a
      large-caliber nasal cannula. It delivers a fraction of inspired oxygen (FiO2) from 21% to
      100%, with a flow rate up to 60 L·min-1.

      The therapy is used for a variety of disease conditions including chronic obstructive
      pulmonary disease (COPD). Patients with COPD frequently manifest flow limitation during
      resting tidal breathing, through dynamic compression of the airways, which is attributed to a
      loss of parenchymal tethering of the airways. In patients with severe COPD and respiratory
      failure, improved oxygenation and ventilation may reduce mortality. There are limited
      clinical data available in adult applications of NHF and on the effectiveness of NHF in
      patients with stable moderate or severe COPD.

      The mechanisms through which NHF affects the respiratory system are still being investigated.
      Two of the proposed mechanisms of action of NHF therapy are the generation of 3-5 cmH20
      positive airway pressure during expiration and washout of the nasopharyngeal dead space.
      Positive airway pressure has been shown to improve oxygenation, ventilation-perfusion
      matching and respiratory rates, while nasopharyngeal washout reduces the anatomical dead
      space and thereby improves alveolar ventilation.

      Our working hypothesis is that positive nasopharyngeal pressure generated by NHF particularly
      during expiration can help maintain small peripheral airways patent, thereby reducing the
      amount of gas trapping.

      Gas trapping can be quantified based on densitometric analysis of registered computerized
      tomography images obtained at high and low lung volumes.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: It's a prospective, single-center, pilot, pathophysiological study.
primary purpose: Treatment
masking: None (Open Label)
measure: Gas trapping (expressed as percent total lung volume)
time frame: 30 minutes
measure: Regional lung ventilation distribution
time frame: 30 minutes
description: Regional change in attenuation between end-expiration and end-inspiration, based on CT image
measure: Coefficient of variation of regional lung ventilation
time frame: 30 minutes
arm group label: Computed tomography examination
arm group type: Experimental
description: Each patient will undergo a low-dose supine position chest CT scan including end-inspiratory and expiratory acquisitions, corresponding to the routine protocol for COPD patients, except that this end-inspiratory/end-expiratory CT is repeated 3 times for total of 6 CT acquisitions.
intervention type: Radiation
intervention name: Computed tomography
description: End-inspiratory/end-expiratory CT is repeated 3 times corresponding to the 3 studied conditions: At baseline, through expiratory resistive loading using an adjustable PEP mask, and after 5 min of nasal high flow therapy at 25 L/min.
arm group label: Computed tomography examination
other name: CT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
citation: Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. doi: 10.1164/rccm.201204-0596PP. Epub 2012 Aug 9.
PMID: 22878278
citation: Stubbing DG, Pengelly LD, Morse JL, Jones NL. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J Appl Physiol Respir Environ Exerc Physiol. 1980 Sep;49(3):511-5. doi: 10.1152/jappl.1980.49.3.511.
PMID: 7204175
citation: Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Beduneau G, Deletage-Metreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.
PMID: 25981908
citation: Pisani L, Vega ML. Use of Nasal High Flow in Stable COPD: Rationale and Physiology. COPD. 2017 Jun;14(3):346-350. doi: 10.1080/15412555.2017.1315715. Epub 2017 May 1.
PMID: 28459282
citation: Curley GF, Laffy JG, Zhang H, Slutsky AS. Noninvasive respiratory support for acute respiratory failure-high flow nasal cannula oxygen or non-invasive ventilation? J Thorac Dis. 2015 Jul;7(7):1092-7. doi: 10.3978/j.issn.2072-1439.2015.07.18. No abstract available.
PMID: 26380720
citation: Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth. 2011 Dec;107(6):998-1004. doi: 10.1093/bja/aer265. Epub 2011 Sep 9.
PMID: 21908497
citation: Riera J, Perez P, Cortes J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013 Apr;58(4):589-96. doi: 10.4187/respcare.02086.
PMID: 23050520
citation: Spahija J, de Marchie M, Grassino A. Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD. Chest. 2005 Aug;128(2):640-50. doi: 10.1378/chest.128.2.640.
PMID: 16100149
citation: O'Donnell DE, Sanii R, Anthonisen NR, Younes M. Expiratory resistive loading in patients with severe chronic air-flow limitation. An evaluation of ventilatory mechanics and compensatory responses. Am Rev Respir Dis. 1987 Jul;136(1):102-7. doi: 10.1164/ajrccm/136.1.102.
PMID: 3605825
citation: Mueller RE, Petty TL, Filley GF. Ventilation and arterial blood gas changes induced by pursed lips breathing. J Appl Physiol. 1970 Jun;28(6):784-9. doi: 10.1152/jappl.1970.28.6.784. No abstract available.
PMID: 5419502
citation: Galban CJ, Han MK, Boes JL, Chughtai KA, Meyer CR, Johnson TD, Galban S, Rehemtulla A, Kazerooni EA, Martinez FJ, Ross BD. Computed tomography-based biomarker provides unique signature for diagnosis of COPD phenotypes and disease progression. Nat Med. 2012 Nov;18(11):1711-5. doi: 10.1038/nm.2971. Epub 2012 Oct 7.
PMID: 23042237
citation: Fricke K, Tatkov S, Domanski U, Franke KJ, Nilius G, Schneider H. Nasal high flow reduces hypercapnia by clearance of anatomical dead space in a COPD patient. Respir Med Case Rep. 2016 Aug 26;19:115-7. doi: 10.1016/j.rmcr.2016.08.010. eCollection 2016.
PMID: 27668173
citation: Kybic J, Unser M. Fast parametric elastic image registration. IEEE Trans Image Process. 2003;12(11):1427-42. doi: 10.1109/TIP.2003.813139.
PMID: 18244700
citation: Gibson GJ, Loddenkemper R, Lundback B, Sibille Y. Respiratory health and disease in Europe: the new European Lung White Book. Eur Respir J. 2013 Sep;42(3):559-63. doi: 10.1183/09031936.00105513. No abstract available.
PMID: 24000245
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No