<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/NCT01735526</url>
  </required_header>
  <id_info>
    <org_study_id>33/2012</org_study_id>
    <nct_id>NCT01735526</nct_id>
  </id_info>
  <brief_title>Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide After Hematopoietic Stem-cell Transplantation</brief_title>
  <acronym>DLNO/DLCO</acronym>
  <official_title>Changes in Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide After Allogeneic Versus Autologous Hematopoietic Stem-cell Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Early after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), reductions of&#xD;
      absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are frequently&#xD;
      detected even in the absence of overt idiopathic pneumonia syndrome (IPS). It can be&#xD;
      hypothesized that these changes might be due to an occult intersitial lung disease associated&#xD;
      with infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens&#xD;
      or any combination of these. To test this hypothesis, we will simultaneously measure the lung&#xD;
      diffusing capacity for nitric oxide (DLNO) and DLCO and estimate the changes of membrane&#xD;
      diffusing capacity (DM) and pulmonary capillary volume (Vc) by the DLNO/DLCO ratio. As we&#xD;
      hypothesize that GHVD should be intuitively absent amongst autologous HSCT (auto-HSCT)&#xD;
      recipients, we will compare the changes in DLNO/DLCO ratio showed by the latter group with&#xD;
      those of subjects undergoing allo-HSCT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients, early&#xD;
      reductions of absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are&#xD;
      frequently detected even in the absence of overt idiopathic pneumonia syndrome (IPS)[PMID:&#xD;
      22221781]. Two months after allo-HSCT, we have recently shown an increase in lung tissue&#xD;
      density determined by quantitative CT scan [PMID: 22898044]. It can be hypothesized that&#xD;
      these parenchymal changes might be due to an occult intersitial lung disease associated with&#xD;
      infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens or&#xD;
      any combination of these [PMID: 21531955]. To test this hypothesis, we will simultaneously&#xD;
      measure the lung diffusing capacity for nitric oxide (DLNO) and DLCO. Assuming, for clinical&#xD;
      purposes, that the reaction rate of NO with blood hemoglobin is infinite so that DLNO = DMNO&#xD;
      = DMCO*alpha (alpha = NO/CO diffusivity ratio), as to partition the effect of HSCT on&#xD;
      membrane diffusing capacity (DM) and pulmonary capillary volume (Vc) we will use the&#xD;
      DLNO/DLCO ratio [PMID:16478855]. As we hypothesize that GHVD should be intuitively absent&#xD;
      amongst autologous HSCT (auto-HSCT) recipients, we will compare the changes in DLNO/DLCO&#xD;
      ratio showed by the latter group with those of subjects undergoing allo-HSCT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in DLNO/DLCO ratio after allo- versus autologous HSCT</measure>
    <time_frame>Before and 2-6 months after HSCT</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in lung tissue density after allo- versus autologous HSCT</measure>
    <time_frame>Before and 2-6 months after HSCT</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">40</enrollment>
  <condition>Lung Disease</condition>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive patients undergoing allogeneic and autologous HSCT for hematological&#xD;
        malignancies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  baseline spirometry, lung volumes, and DLCO of the subjects included in the analysis&#xD;
             must be within the predicted normal range&#xD;
&#xD;
          -  all patients must be in stable clinical conditions at the time of study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a history of bronchial asthma, chronic obstructive pulmonary disease, or other&#xD;
             significant respiratory disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giovanni Barisione, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro</name>
      <address>
        <city>Genoa</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Bacigalupo A, Chien J, Barisione G, Pavletic S. Late pulmonary complications after allogeneic hematopoietic stem cell transplantation: diagnosis, monitoring, prevention, and treatment. Semin Hematol. 2012 Jan;49(1):15-24. doi: 10.1053/j.seminhematol.2011.10.005.</citation>
    <PMID>22221781</PMID>
  </reference>
  <reference>
    <citation>Barisione G, Pompilio PP, Bacigalupo A, Brusasco C, Cioe A, Dellaca RL, Lamparelli T, Garlaschi A, Pellegrino R, Brusasco V. Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation. Respir Physiol Neurobiol. 2012 Oct 15;184(1):80-5. doi: 10.1016/j.resp.2012.07.021. Epub 2012 Aug 8.</citation>
    <PMID>22898044</PMID>
  </reference>
  <reference>
    <citation>Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, Cooke KR; American Thoracic Society Committee on Idiopathic Pneumonia Syndrome. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011 May 1;183(9):1262-79. doi: 10.1164/rccm.2007-413ST.</citation>
    <PMID>21531955</PMID>
  </reference>
  <reference>
    <citation>van der Lee I, Zanen P, Grutters JC, Snijder RJ, van den Bosch JMM. Diffusing capacity for nitric oxide and carbon monoxide in patients with diffuse parenchymal lung disease and pulmonary arterial hypertension. Chest. 2006 Feb;129(2):378-383. doi: 10.1378/chest.129.2.378.</citation>
    <PMID>16478855</PMID>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>November 24, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>September 21, 2014</last_update_submitted>
  <last_update_submitted_qc>September 21, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 23, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy</investigator_affiliation>
    <investigator_full_name>Giovanni Barisione</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Allogeneic and autologous</keyword>
  <keyword>hematopoietic stem-cell transplantation</keyword>
  <keyword>Lung diffusing capacity</keyword>
  <keyword>for nitric oxide</keyword>
  <keyword>carbon monoxide</keyword>
  <keyword>Lung tissue density</keyword>
  <keyword>microvascular damage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</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/NCT01735526
org study id: 33/2012
nct id: NCT01735526
lead sponsor: 
has dmc: Yes
Early after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), reductions of
      absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are frequently
      detected even in the absence of overt idiopathic pneumonia syndrome (IPS). It can be
      hypothesized that these changes might be due to an occult intersitial lung disease associated
      with infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens
      or any combination of these. To test this hypothesis, we will simultaneously measure the lung
      diffusing capacity for nitric oxide (DLNO) and DLCO and estimate the changes of membrane
      diffusing capacity (DM) and pulmonary capillary volume (Vc) by the DLNO/DLCO ratio. As we
      hypothesize that GHVD should be intuitively absent amongst autologous HSCT (auto-HSCT)
      recipients, we will compare the changes in DLNO/DLCO ratio showed by the latter group with
      those of subjects undergoing allo-HSCT.
In allogeneic hematopoietic stem-cell transplantation (allo-HSCT) recipients, early
      reductions of absolute lung volume and diffusing capacity for carbon monoxide (DLCO) are
      frequently detected even in the absence of overt idiopathic pneumonia syndrome (IPS)[PMID:
      22221781]. Two months after allo-HSCT, we have recently shown an increase in lung tissue
      density determined by quantitative CT scan [PMID: 22898044]. It can be hypothesized that
      these parenchymal changes might be due to an occult intersitial lung disease associated with
      infections, acute Graft-versus-Host Disease (aGvHD), myeloablative conditioning regimens or
      any combination of these [PMID: 21531955]. To test this hypothesis, we will simultaneously
      measure the lung diffusing capacity for nitric oxide (DLNO) and DLCO. Assuming, for clinical
      purposes, that the reaction rate of NO with blood hemoglobin is infinite so that DLNO = DMNO
      = DMCO*alpha (alpha = NO/CO diffusivity ratio), as to partition the effect of HSCT on
      membrane diffusing capacity (DM) and pulmonary capillary volume (Vc) we will use the
      DLNO/DLCO ratio [PMID:16478855]. As we hypothesize that GHVD should be intuitively absent
      amongst autologous HSCT (auto-HSCT) recipients, we will compare the changes in DLNO/DLCO
      ratio showed by the latter group with those of subjects undergoing allo-HSCT.
observational model: Cohort
time perspective: Prospective
measure: Changes in DLNO/DLCO ratio after allo- versus autologous HSCT
time frame: Before and 2-6 months after HSCT
measure: Changes in lung tissue density after allo- versus autologous HSCT
time frame: Before and 2-6 months after HSCT
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Giovanni Barisione, MD
role: Principal Investigator
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
facility: 
country: Italy
citation: Bacigalupo A, Chien J, Barisione G, Pavletic S. Late pulmonary complications after allogeneic hematopoietic stem cell transplantation: diagnosis, monitoring, prevention, and treatment. Semin Hematol. 2012 Jan;49(1):15-24. doi: 10.1053/j.seminhematol.2011.10.005.
PMID: 22221781
citation: Barisione G, Pompilio PP, Bacigalupo A, Brusasco C, Cioe A, Dellaca RL, Lamparelli T, Garlaschi A, Pellegrino R, Brusasco V. Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation. Respir Physiol Neurobiol. 2012 Oct 15;184(1):80-5. doi: 10.1016/j.resp.2012.07.021. Epub 2012 Aug 8.
PMID: 22898044
citation: Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, Cooke KR; American Thoracic Society Committee on Idiopathic Pneumonia Syndrome. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med. 2011 May 1;183(9):1262-79. doi: 10.1164/rccm.2007-413ST.
PMID: 21531955
citation: van der Lee I, Zanen P, Grutters JC, Snijder RJ, van den Bosch JMM. Diffusing capacity for nitric oxide and carbon monoxide in patients with diffuse parenchymal lung disease and pulmonary arterial hypertension. Chest. 2006 Feb;129(2):378-383. doi: 10.1378/chest.129.2.378.
PMID: 16478855
responsible party type: Principal Investigator
investigator affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
investigator full name: Giovanni Barisione
investigator title: MD
mesh term: Lung Diseases