<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/NCT02238327</url>
  </required_header>
  <id_info>
    <org_study_id>PRO14070355</org_study_id>
    <secondary_id>1R01HL125049-01</secondary_id>
    <nct_id>NCT02238327</nct_id>
  </id_info>
  <brief_title>Longitudinal Evaluation of HIV-associated Lung Disease Phenotypes</brief_title>
  <acronym>LEAP</acronym>
  <official_title>The Study is a Multicenter, Prospective Observational Study of Pathogenesis of HIV Pulmonary Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall hypotheses of this proposal are that discrete phenotypes of HIV Chronic&#xD;
      Obstructive Pulmonary disease (COPD) differ in their trajectories, biomarkers, and risk&#xD;
      factors and that persistent viral infection including residual HIV is linked to HIV COPD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is a multicenter, prospective observational study of pathogenesis of HIV pulmonary&#xD;
      disease. We will determine the prevalence and risk factors for lung dysfunction as quantified&#xD;
      by pulmonary function testing in HIV+ subjects. We will build on our existing longitudinal&#xD;
      cohorts while adjusting for important co-variates such as antiretroviral therapy (ART),&#xD;
      smoking history, co-infections, and illicit drug use. Evaluations will be scheduled at&#xD;
      baseline, 18 months, and 36 months. (6, 12, 18 and 36 months for ART initiators at the UCSF).&#xD;
      Study visits will consist of blood draw, questionnaires, pulmonary function testing, 6-minute&#xD;
      walk test, CT of the chest at visit two. Oral specimen collection and glycocalyx and&#xD;
      echocardiogram (visit two) at the Pittsburgh site only.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">March 2, 2020</completion_date>
  <primary_completion_date type="Actual">March 2, 2020</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>differences in the trajectory of FEV1 in clinical COPD phenotypes,</measure>
    <time_frame>36 months</time_frame>
    <description>PFT's at baseline, 18 months and 36months to determine modifying risk factors and relationship of phenotypes to mortality, and delineate the association of ART and lung dysfunction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>will measure biomarkers of these phenotypes and ability to predict HIV COPD</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">232</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>HIV</condition>
  <condition>Emphysema</condition>
  <arm_group>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <description>HIV positive DLCO percent predicted &gt;=.80 FEV1/FVC percent predicted &gt;=0.70</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
    <description>HIV positive DLco percent predicted &lt;=0.80% FEV1/FVC percent predicted&lt;=0.70%</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>blood draw</intervention_name>
    <description>Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>questionnaires</intervention_name>
    <description>The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Lung function testing</intervention_name>
    <description>The routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured before and after bronchodilator administration (4 puffs of albuterol). The best of three reproducible forced expiratory attempts is used in analysis. Percent- predicted spirometric values are based on age, height, gender, and ethnicity. DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms to ATS standards. DLco will be adjusted for hemoglobin and carboxyhemoglobin.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
    <other_name>Spirometry</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Six-Minute walk test</intervention_name>
    <description>Six-minute walk tests are performed in a 100 foot (30.48 m) segment of straight hallway marked at 10 foot (3 m) intervals. In addition to the usual ATS protocol, the patient is monitored, when available, with Bluetooth wireless pulse oximetry and the time and distance recorded after six minutes and if they desaturate to &lt;88%. Dyspnea (Borg 0-10) and perceived exertion (Borg 6-20) scales are completed at the beginning and the end of test.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Quantitative CT scans</intervention_name>
    <description>Subjects will undergo a standard chest CT. The CT scans will use a phantom shipped between sites to standardize results and capture contiguous volume scans acquired at slice thicknesses of 5.0 mm in the axial plane and reconstructed with 512 x 512 pixel matrices. CT examinations will encompass the entire thorax and be performed during a breath-hold at end-inspiration. We will measure % of lung tissue below a threshold for emphysema (i.e. -950 Hounsfield units). Measurements have been histologically-verified and give reproducible measurements. The data set is assembled and analyzed with the image data anonymized.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
    <other_name>CT scan of the chest</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nasal secretion and cell collection</intervention_name>
    <description>Participants will be instructed to blow their nose to remove accumulated mucus. Two sprays of commercially available nasal saline will be instilled in each nostril. The participant will then be ask to exhale through the rinsed nostril into a specimen cup. We will repeat this up to 5 times on each side depending on the participants' tolerance to the procedure. Using an otoscope, a small curette will then be used to collect 3 to 5 samples of nasal cells from each nostril. These samples will be used immediately for analysis or banked for future study.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
    <other_name>Nasal wash</other_name>
    <other_name>Nasal scrapping</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Echocardiogram</intervention_name>
    <description>The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.</description>
    <arm_group_label>HIV positive normal pulmonary function</arm_group_label>
    <arm_group_label>HIV positive with pulmonary dysfuntion</arm_group_label>
    <other_name>Echo</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood, serum, bronchial wash and cells&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will be HIV positive subjects previously seen for other studies. There&#xD;
        will be three centers enrolling, the University of Pittsburgh, the University of California&#xD;
        San Francisco, and the University of California Los Angeles. Recruitment will occur from&#xD;
        participants in ongoing lung studies at these sites.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-1 infection, documented in medical record at any time prior to study entry.&#xD;
&#xD;
          -  Men and women age 18 to 80.&#xD;
&#xD;
          -  Ability and willingness to complete all tests.&#xD;
&#xD;
          -  Participant in HLRC studies, MACS, Women's Interagency Health Study, and local HIV&#xD;
             clinics.&#xD;
&#xD;
          -  For UCSF only, new ART initiators from Women's Interagency Health Study or the HIV&#xD;
             clinic&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breast-feeding.&#xD;
&#xD;
          -  Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery&#xD;
             within 3 months, recent myocardial infarction, etc.).&#xD;
&#xD;
          -  Increasing respiratory symptoms or febrile (temperature &gt;100.40F [380C]) within 4&#xD;
             weeks of study entry.&#xD;
&#xD;
          -  Hospitalization within 4 weeks prior to study entry (excluding mental health).&#xD;
&#xD;
          -  Uncontrolled hypertension at screening visit (systolic &gt; 180 mm Hg or diastolic &gt; 100&#xD;
             mm Hg) from an average of two or more readings. Subject may return for screening after&#xD;
             blood pressure is controlled.&#xD;
&#xD;
          -  Active cancer requiring systemic chemotherapy or radiation.&#xD;
&#xD;
          -  Active infection of lungs, brain, or abdomen.&#xD;
&#xD;
          -  Intravenous drug use or alcohol use that will impair ability to complete study&#xD;
             investigations in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, Rom W, Weiden MD, Zhao E, Thompson B, Crothers K. Factors associated with abnormal spirometry among HIV-infected individuals. AIDS. 2015 Aug 24;29(13):1691-700. doi: 10.1097/QAD.0000000000000750.</citation>
    <PMID>26372280</PMID>
  </reference>
  <reference>
    <citation>Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.</citation>
    <PMID>29313714</PMID>
  </reference>
  <reference>
    <citation>Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, Huang L, Ghedin E, Greenblatt RM, Morris A. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018 Oct 4;13(10):e0205065. doi: 10.1371/journal.pone.0205065. eCollection 2018.</citation>
    <PMID>30286195</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>October 6, 2020</last_update_submitted>
  <last_update_submitted_qc>October 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Alison Morris</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Antiretroviral therapy</keyword>
  <keyword>pulmonary function</keyword>
  <keyword>biomarkers</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>
    <mesh_term>Emphysema</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/NCT02238327
org study id: PRO14070355
secondary id: 1R01HL125049-01
nct id: NCT02238327
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The overall hypotheses of this proposal are that discrete phenotypes of HIV Chronic
      Obstructive Pulmonary disease (COPD) differ in their trajectories, biomarkers, and risk
      factors and that persistent viral infection including residual HIV is linked to HIV COPD.
The study is a multicenter, prospective observational study of pathogenesis of HIV pulmonary
      disease. We will determine the prevalence and risk factors for lung dysfunction as quantified
      by pulmonary function testing in HIV+ subjects. We will build on our existing longitudinal
      cohorts while adjusting for important co-variates such as antiretroviral therapy (ART),
      smoking history, co-infections, and illicit drug use. Evaluations will be scheduled at
      baseline, 18 months, and 36 months. (6, 12, 18 and 36 months for ART initiators at the UCSF).
      Study visits will consist of blood draw, questionnaires, pulmonary function testing, 6-minute
      walk test, CT of the chest at visit two. Oral specimen collection and glycocalyx and
      echocardiogram (visit two) at the Pittsburgh site only.
observational model: Cohort
time perspective: Prospective
measure: differences in the trajectory of FEV1 in clinical COPD phenotypes,
time frame: 36 months
description: PFT's at baseline, 18 months and 36months to determine modifying risk factors and relationship of phenotypes to mortality, and delineate the association of ART and lung dysfunction.
measure: will measure biomarkers of these phenotypes and ability to predict HIV COPD
time frame: 36 months
arm group label: HIV positive normal pulmonary function
description: HIV positive DLCO percent predicted >=.80 FEV1/FVC percent predicted >=0.70
arm group label: HIV positive with pulmonary dysfuntion
description: HIV positive DLco percent predicted <=0.80% FEV1/FVC percent predicted<=0.70%
intervention type: Procedure
intervention name: blood draw
description: Blood will be drawn for plasma, serum, and PBMCs. Clinical labs drawn will be for hepatitis, CMV, hemoglobin and carboxyhemoglobin.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
intervention type: Procedure
intervention name: questionnaires
description: The following questionnaires are administered to participants by study personnel at each visit: LEAP questionnaire, St. George's, and MMRC.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
intervention type: Procedure
intervention name: Lung function testing
description: The routine lung function endpoints of FVC, FEV1, FEV1/FVC, and FEF25-75% will be measured before and after bronchodilator administration (4 puffs of albuterol). The best of three reproducible forced expiratory attempts is used in analysis. Percent- predicted spirometric values are based on age, height, gender, and ethnicity. DLco will be measured using the automated single-breath procedure of the integrated testing system, which conforms to ATS standards. DLco will be adjusted for hemoglobin and carboxyhemoglobin.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
other name: Spirometry
intervention type: Procedure
intervention name: Six-Minute walk test
description: Six-minute walk tests are performed in a 100 foot (30.48 m) segment of straight hallway marked at 10 foot (3 m) intervals. In addition to the usual ATS protocol, the patient is monitored, when available, with Bluetooth wireless pulse oximetry and the time and distance recorded after six minutes and if they desaturate to <88%. Dyspnea (Borg 0-10) and perceived exertion (Borg 6-20) scales are completed at the beginning and the end of test.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
intervention type: Radiation
intervention name: Quantitative CT scans
description: Subjects will undergo a standard chest CT. The CT scans will use a phantom shipped between sites to standardize results and capture contiguous volume scans acquired at slice thicknesses of 5.0 mm in the axial plane and reconstructed with 512 x 512 pixel matrices. CT examinations will encompass the entire thorax and be performed during a breath-hold at end-inspiration. We will measure % of lung tissue below a threshold for emphysema (i.e. -950 Hounsfield units). Measurements have been histologically-verified and give reproducible measurements. The data set is assembled and analyzed with the image data anonymized.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
other name: CT scan of the chest
intervention type: Procedure
intervention name: Nasal secretion and cell collection
description: Participants will be instructed to blow their nose to remove accumulated mucus. Two sprays of commercially available nasal saline will be instilled in each nostril. The participant will then be ask to exhale through the rinsed nostril into a specimen cup. We will repeat this up to 5 times on each side depending on the participants' tolerance to the procedure. Using an otoscope, a small curette will then be used to collect 3 to 5 samples of nasal cells from each nostril. These samples will be used immediately for analysis or banked for future study.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
other name: Nasal wash
other name: Nasal scrapping
intervention type: Procedure
intervention name: Echocardiogram
description: The cardiac ultrasound will use standard ultrasound techniques to image two-dimensional slices of the heart using 3D real-time imaging.
arm group label: HIV positive normal pulmonary function
arm group label: HIV positive with pulmonary dysfuntion
other name: Echo
Whole blood, serum, bronchial wash and cells
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: United States
citation: Drummond MB, Huang L, Diaz PT, Kirk GD, Kleerup EC, Morris A, Rom W, Weiden MD, Zhao E, Thompson B, Crothers K. Factors associated with abnormal spirometry among HIV-infected individuals. AIDS. 2015 Aug 24;29(13):1691-700. doi: 10.1097/QAD.0000000000000750.
PMID: 26372280
citation: Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, Kingsley L, McMahon DK, Morris A. Decreased Lung Function and All-Cause Mortality in HIV-infected Individuals. Ann Am Thorac Soc. 2018 Feb;15(2):192-199. doi: 10.1513/AnnalsATS.201606-492OC.
PMID: 29313714
citation: Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, Huang L, Ghedin E, Greenblatt RM, Morris A. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018 Oct 4;13(10):e0205065. doi: 10.1371/journal.pone.0205065. eCollection 2018.
PMID: 30286195
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Alison Morris
investigator title: Professor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Emphysema