<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/NCT01676155</url>
  </required_header>
  <id_info>
    <org_study_id>20110822RC</org_study_id>
    <nct_id>NCT01676155</nct_id>
  </id_info>
  <brief_title>The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis</brief_title>
  <official_title>The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To compare the serum apoptosis-associated markers between patients with active TB and&#xD;
      patients with LTBI To evaluate the efficiency of apoptosis-associated markers to&#xD;
      differentiate potential of active TB from LTBI&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Tuberculosis (TB) remains the most important infectious disease worldwide. For&#xD;
      controlling TB, the important strategy includes not only adequate anti-tuberculous treatment&#xD;
      but also well control of latent TB infection (LTBI). Latent TB infection (LTBI) has 10% of&#xD;
      reactivation or more in patients with immuno-compromised disorder. Although LTBI can be&#xD;
      detected by interferon-gamma release assay (IGRA) or tuberculin skin test, how to predict who&#xD;
      will become active TB from LTBI is still unclear but important. In overall prophylactic&#xD;
      treatment for LTBI, the lengthy duration and possible serious side effect too scared to&#xD;
      general application especially 90% of population who may not get illness. Therefore, to&#xD;
      recognize who develop active TB from LTBI is important for targeted prophylactic therapy. The&#xD;
      good marker is not discovered at present. When TB bacilli arrive our lung, macrohage is the&#xD;
      first line defense and necrosis rather than apoptosis is the dominant form of cell death,&#xD;
      which affords a protective milieu for M. tuberculosis. Though the apoptosis is suppressed in&#xD;
      TB, the apoptosis-associated markers have rarely been investigated in human LTBI vs. active&#xD;
      TB. We set up a cohort study to detect active TB developing from LTBI and first-step conduct&#xD;
      a case control study to compare apoptosis markers between LTBI and active TB for evaluating&#xD;
      the apoptosis markers in discriminating TB infection status. The significant markers should&#xD;
      be verified in further cohort study of LTBI patients.&#xD;
&#xD;
      Hypothesis: The apoptosis-associated markers, including Fas ligand, Decoy-receptor 3,&#xD;
      Lipoxin, and prostaglandin E2, are discriminative in patients with active TB from those with&#xD;
      LTBI and thus might predict the potential of being active TB from LTBI.&#xD;
&#xD;
      Study Aims:&#xD;
&#xD;
      To compare the serum apoptosis-associated markers between patients with active TB and&#xD;
      patients with LTBI To evaluate the efficiency of apoptosis-associated markers to&#xD;
      differentiate potential of active TB from LTBI Methods: We prospectively enroll patients with&#xD;
      active TB (n=100) and LTBI (n=100), defined by IGRA. Blood sample would be collected before&#xD;
      they received definite treatment after yielding informed consent. We will examine serum&#xD;
      apoptosis-associated markers including Fas ligand, Decoy-receptor 3, Lipoxin, and&#xD;
      prostaglandin E2, and other cytokines and chemokines in serum sample and supernatant from&#xD;
      T-cell after TB antigen stimulation. Their clinical characteristics will be recorded. We&#xD;
      compare the laboratory and clinical data between the two groups and analyze the efficacy of&#xD;
      diagnostic help from these markers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2011</start_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>getting active tuberculosis</measure>
    <time_frame>2 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">400</enrollment>
  <condition>To Compare the Serum Apoptosis-associated Markers Between Patients With Active TB and Patients With LTBI</condition>
  <condition>To Evaluate the Efficiency of Apoptosis-associated Markers to Differentiate Potential of Active TB From LTBI</condition>
  <arm_group>
    <arm_group_label>Patient with active tuberculosis</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with diagnosis of latent tuberculosis infection</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patient without latent tuberculosis or active tuberculosis</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        1. Patients with tuberculosis: microbiology or pathology proven tuberculosis infection&#xD;
&#xD;
          2. Patients with latent tuberculosis infection are defined by interferon-gamma release&#xD;
             assay&#xD;
&#xD;
          3. Patients without tuberculosis and latent tuberculosis are defi=ed by negative findings&#xD;
             in above-mentioned results&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 20 years&#xD;
&#xD;
          -  Latent TB group: family contacts who have positive response in IGRA (by QuantiFeron-TB&#xD;
             Gold-in-Tube, which is described detail in Part C) and have no signs of active TB.&#xD;
&#xD;
          -  Active TB group: patients with pulmonary tuberculosis diagnosed by positive&#xD;
             respiratory culture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age younger than 20 years.&#xD;
&#xD;
          -  Patients who have pregnancy.&#xD;
&#xD;
          -  Patients who have acquired immunodeficiency syndrome&#xD;
&#xD;
          -  Patients who have bleeding tendency which can not tolerate venous puncture such as&#xD;
             hemophilia, thrombocytopenia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chin-Chung Shu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chin-Chung Shu, MD</last_name>
    <phone>886-972653087</phone>
    <email>chinchungshu@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chin-Chung Shu, MD</last_name>
      <phone>886-972653087</phone>
      <email>chinchungshu@ntu.edu.tw</email>
    </contact>
    <investigator>
      <last_name>Chin-Chung Shu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>June 2012</verification_date>
  <study_first_submitted>August 28, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>August 28, 2012</last_update_submitted>
  <last_update_submitted_qc>August 28, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 30, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tuberculosis, latent tuberculosis infection, apoptosis, predictor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Tuberculosis, Pulmonary</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/NCT01676155
org study id: 20110822RC
nct id: NCT01676155
lead sponsor: 
has dmc: No
To compare the serum apoptosis-associated markers between patients with active TB and
      patients with LTBI To evaluate the efficiency of apoptosis-associated markers to
      differentiate potential of active TB from LTBI
Background: Tuberculosis (TB) remains the most important infectious disease worldwide. For
      controlling TB, the important strategy includes not only adequate anti-tuberculous treatment
      but also well control of latent TB infection (LTBI). Latent TB infection (LTBI) has 10% of
      reactivation or more in patients with immuno-compromised disorder. Although LTBI can be
      detected by interferon-gamma release assay (IGRA) or tuberculin skin test, how to predict who
      will become active TB from LTBI is still unclear but important. In overall prophylactic
      treatment for LTBI, the lengthy duration and possible serious side effect too scared to
      general application especially 90% of population who may not get illness. Therefore, to
      recognize who develop active TB from LTBI is important for targeted prophylactic therapy. The
      good marker is not discovered at present. When TB bacilli arrive our lung, macrohage is the
      first line defense and necrosis rather than apoptosis is the dominant form of cell death,
      which affords a protective milieu for M. tuberculosis. Though the apoptosis is suppressed in
      TB, the apoptosis-associated markers have rarely been investigated in human LTBI vs. active
      TB. We set up a cohort study to detect active TB developing from LTBI and first-step conduct
      a case control study to compare apoptosis markers between LTBI and active TB for evaluating
      the apoptosis markers in discriminating TB infection status. The significant markers should
      be verified in further cohort study of LTBI patients.

      Hypothesis: The apoptosis-associated markers, including Fas ligand, Decoy-receptor 3,
      Lipoxin, and prostaglandin E2, are discriminative in patients with active TB from those with
      LTBI and thus might predict the potential of being active TB from LTBI.

      Study Aims:

      To compare the serum apoptosis-associated markers between patients with active TB and
      patients with LTBI To evaluate the efficiency of apoptosis-associated markers to
      differentiate potential of active TB from LTBI Methods: We prospectively enroll patients with
      active TB (n=100) and LTBI (n=100), defined by IGRA. Blood sample would be collected before
      they received definite treatment after yielding informed consent. We will examine serum
      apoptosis-associated markers including Fas ligand, Decoy-receptor 3, Lipoxin, and
      prostaglandin E2, and other cytokines and chemokines in serum sample and supernatant from
      T-cell after TB antigen stimulation. Their clinical characteristics will be recorded. We
      compare the laboratory and clinical data between the two groups and analyze the efficacy of
      diagnostic help from these markers.
observational model: Case-Control
time perspective: Prospective
measure: getting active tuberculosis
time frame: 2 year
measure: mortality
time frame: 2 years
arm group label: Patient with active tuberculosis
arm group label: Patients with diagnosis of latent tuberculosis infection
arm group label: Patient without latent tuberculosis or active tuberculosis
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Chin-Chung Shu, MD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chin-Chung Shu, MD
phone: 886-972653087
email: chinchungshu@ntu.edu.tw
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary