<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/NCT02978144</url>
  </required_header>
  <id_info>
    <org_study_id>AAAR0417</org_study_id>
    <secondary_id>1R01HL131960-01</secondary_id>
    <nct_id>NCT02978144</nct_id>
  </id_info>
  <brief_title>Imaging of Apoptosis in Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>In Vivo Imaging of Destructive Processes in Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>No</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>
      This will be a prospective study examining the use of 99mTc-Annexin V-128 (AxV-128/Tc)&#xD;
      single-photon emission computed tomography (SPECT)/computerized tomography (CT) technology in&#xD;
      the imaging and functional assessment of the lung of patients with chronic obstructive&#xD;
      pulmonary disease (COPD), healthy volunteer smokers without COPD and healthy volunteer&#xD;
      subjects without smoking history. The aim of study is to determine if patients with COPD have&#xD;
      an increased AxV-128/Tc signal with SPECT/CT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is&#xD;
      characterized by clinical symptoms and spirometry. Additional measures for diagnosis can be&#xD;
      taken using imaging modalities such as CT. However, the evaluation of lung destruction in&#xD;
      COPD is limited by the inability to visualize the activation of pathological processes since&#xD;
      imaging modalities are only able to evaluate end-organ damage. In this proposal, the&#xD;
      investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process&#xD;
      known to be pathogenic in COPD. Apoptosis, a process of programmed cellular death, correlates&#xD;
      with COPD severity and is not seen in the normal adult lung. In the past several years the&#xD;
      investigators have demonstrated the successful ability of AxV-128/Tc to detect apoptosis in&#xD;
      vivo in a preclinical animal model of smoke exposure emphysema model. Additionally, Phase 1&#xD;
      studies have demonstrated safety of this agent in healthy patients. Therefore, the&#xD;
      investigators will bring AxV-128/Tc forward as a probe to image the apoptotic disease process&#xD;
      of the lung in patients with COPD. The investigators will determine if the imaging signal&#xD;
      correlates with serum biomarkers of apoptosis and inflammation. It is the investigators'&#xD;
      hypothesis that AxV-128/99mTc imaging will show increased uptake in the lungs of patients&#xD;
      with COPD, and that this signal intensity will correlate with accepted markers of apoptosis&#xD;
      and inflammation. If successful, such an approach will be a powerful tool to potentially&#xD;
      predict disease progression after diagnosis, identify patients at risk for disease&#xD;
      exacerbation related lung function decline, and monitor response to disease targeted therapy.&#xD;
&#xD;
      The total effective dose from the combined SPECT and CT scans is 6.2 millisievert (mSv). This&#xD;
      effective dose is below what a patient receives during a standard 2 dose rest and stress&#xD;
      cardiac nuclear imaging study and well within the range of current clinical nuclear imaging&#xD;
      tests. The exact long term risk for development of cancer from diagnostic radiological&#xD;
      procedures is currently under debate but all imaging procedures in this study are aimed to&#xD;
      keep total radiation burden As Low As Reasonably Achievable (ALARA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 15, 2017</start_date>
  <completion_date type="Anticipated">April 2024</completion_date>
  <primary_completion_date type="Anticipated">April 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean AxV-128/Tc Uptake</measure>
    <time_frame>Up to 18 months from the initial scan</time_frame>
    <description>Mean ± standard deviation (SD) for values for uptake of AxV-128/Tc for individual lobes and for lungs will be determined for each COPD group and compared using unpaired t-test for values with Gaussian distribution and Mann Whitney (Wilcoxon rank) test for continuous variables without normal distribution.</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Current smokers</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy controls who are currently smoking (&gt; 10 pack years) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with moderate COPD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with moderate COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with severe COPD</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients with severe COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>SPECT-CT imaging</intervention_name>
    <description>Injection of AxV-128 labeled with 99mTc followed by SPECT-CT</description>
    <arm_group_label>Current smokers</arm_group_label>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Patients with moderate COPD</arm_group_label>
    <arm_group_label>Patients with severe COPD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AxV-128/Tc</intervention_name>
    <description>Injection of AxV-128 labeled with 99mTc</description>
    <arm_group_label>Current smokers</arm_group_label>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Patients with moderate COPD</arm_group_label>
    <arm_group_label>Patients with severe COPD</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with moderate COPD: Global Initiative for Chronic Obstructive Lung Disease&#xD;
             (GOLD) Stage II, forced expiratory volume 1 (FEV1)/forced vital capacity (FVC) &lt; 0.7&#xD;
             and FEV1 50-79% predicted&#xD;
&#xD;
          -  Patients with severe COPD: GOLD Stage III-IV, FEV1/FVC &lt; 0.7 and FEV1 &lt; 50% predicted&#xD;
&#xD;
          -  Healthy controls who are currently smoking (&gt; 10 pack years) with normal spirometry&#xD;
             (FEV1 &gt; 80% and FEV1/FVC &gt; 70%)&#xD;
&#xD;
          -  Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal&#xD;
             spirometry (FEV1 &gt; 80% and FEV1/FVC &gt; 70%)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gebhard Wagener, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>July 25, 2023</last_update_submitted>
  <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Obstructive Pulmonary Disease (COPD)</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>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02978144
org study id: AAAR0417
secondary id: 1R01HL131960-01
nct id: NCT02978144
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This will be a prospective study examining the use of 99mTc-Annexin V-128 (AxV-128/Tc)
      single-photon emission computed tomography (SPECT)/computerized tomography (CT) technology in
      the imaging and functional assessment of the lung of patients with chronic obstructive
      pulmonary disease (COPD), healthy volunteer smokers without COPD and healthy volunteer
      subjects without smoking history. The aim of study is to determine if patients with COPD have
      an increased AxV-128/Tc signal with SPECT/CT.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is
      characterized by clinical symptoms and spirometry. Additional measures for diagnosis can be
      taken using imaging modalities such as CT. However, the evaluation of lung destruction in
      COPD is limited by the inability to visualize the activation of pathological processes since
      imaging modalities are only able to evaluate end-organ damage. In this proposal, the
      investigators aim to assess a molecular imaging probe targeting apoptosis, a cellular process
      known to be pathogenic in COPD. Apoptosis, a process of programmed cellular death, correlates
      with COPD severity and is not seen in the normal adult lung. In the past several years the
      investigators have demonstrated the successful ability of AxV-128/Tc to detect apoptosis in
      vivo in a preclinical animal model of smoke exposure emphysema model. Additionally, Phase 1
      studies have demonstrated safety of this agent in healthy patients. Therefore, the
      investigators will bring AxV-128/Tc forward as a probe to image the apoptotic disease process
      of the lung in patients with COPD. The investigators will determine if the imaging signal
      correlates with serum biomarkers of apoptosis and inflammation. It is the investigators'
      hypothesis that AxV-128/99mTc imaging will show increased uptake in the lungs of patients
      with COPD, and that this signal intensity will correlate with accepted markers of apoptosis
      and inflammation. If successful, such an approach will be a powerful tool to potentially
      predict disease progression after diagnosis, identify patients at risk for disease
      exacerbation related lung function decline, and monitor response to disease targeted therapy.

      The total effective dose from the combined SPECT and CT scans is 6.2 millisievert (mSv). This
      effective dose is below what a patient receives during a standard 2 dose rest and stress
      cardiac nuclear imaging study and well within the range of current clinical nuclear imaging
      tests. The exact long term risk for development of cancer from diagnostic radiological
      procedures is currently under debate but all imaging procedures in this study are aimed to
      keep total radiation burden As Low As Reasonably Achievable (ALARA).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Mean AxV-128/Tc Uptake
time frame: Up to 18 months from the initial scan
description: Mean ± standard deviation (SD) for values for uptake of AxV-128/Tc for individual lobes and for lungs will be determined for each COPD group and compared using unpaired t-test for values with Gaussian distribution and Mann Whitney (Wilcoxon rank) test for continuous variables without normal distribution.
arm group label: Healthy volunteers
arm group type: Other
description: Healthy controls who never smoked (less than 100 lifetime cigarettes) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
arm group label: Current smokers
arm group type: Other
description: Healthy controls who are currently smoking (> 10 pack years) with normal spirometry will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
arm group label: Patients with moderate COPD
arm group type: Other
description: Patients with moderate COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
arm group label: Patients with severe COPD
arm group type: Other
description: Patients with severe COPD will be injected with AxV-128 labeled with 99mTc followed by SPECT-CT (AxV-128/Tc SPECT-CT imaging).
intervention type: Radiation
intervention name: SPECT-CT imaging
description: Injection of AxV-128 labeled with 99mTc followed by SPECT-CT
arm group label: Current smokers
arm group label: Healthy volunteers
arm group label: Patients with moderate COPD
arm group label: Patients with severe COPD
intervention type: Drug
intervention name: AxV-128/Tc
description: Injection of AxV-128 labeled with 99mTc
arm group label: Current smokers
arm group label: Healthy volunteers
arm group label: Patients with moderate COPD
arm group label: Patients with severe COPD
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gebhard Wagener, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: Undecided