<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/NCT01676142</url>
  </required_header>
  <id_info>
    <org_study_id>201012082RC</org_study_id>
    <nct_id>NCT01676142</nct_id>
  </id_info>
  <brief_title>Establishing a Diagnostic Test for Non-tuberculous Mycobacteria Lung Infection Using Non-tuberculous Mycobacteria Antigen Stimulation Test: From Immune Base, Standardized Setup to Validation</brief_title>
  <official_title>Establishing a Diagnostic Test for Non-tuberculous Mycobacteria Lung Infection Using Non-tuberculous Mycobacteria Antigen Stimulation Test: From Immune Base, Standardized Setup to Validation</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>
      1. To compare TLR-2 expression of peripheral blood mononuclear cells and serum downstream&#xD;
           cytokines in those with MAC or MAB pulmonary infection and those with MAC or MAB&#xD;
           pulmonary colonization and controls.&#xD;
&#xD;
        2. To investigate the response of TLR-2 expression and cytokines activation to NTM&#xD;
           stimulation test in patients with MAC or MAB pulmonary infection and colonization and&#xD;
           controls.&#xD;
&#xD;
        3. To validate the NTM stimulation test for NTM pulmonary infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The increase of nontuberculous mycobacteria lung infection Nontuberculous mycobacteria lung&#xD;
      infection (NTM-LD) becomes an important clinical concern [1] because the rate of NTM&#xD;
      infection has increased over the past ten years [2-3]. According to a study in Taiwan, NTM-LD&#xD;
      increased from 1.26 to 7.94 per 100,000 inpatients/year during 2000 to 2008 [2]. The reasons&#xD;
      for this increase are not readily clear, but could be related to the growth in numbers of the&#xD;
      acquired immunocompromised population and advances of technique for mycobacterial culture&#xD;
      [4-7]. Among the NTM infection in Taiwan, Mycobacterium avium complex (MAC) and M. abscessus&#xD;
      (MAB) were most frequently isolated [2].&#xD;
&#xD;
      The difficulty in early diagnosing and confirming true NTM-LD However, NTM exists in the&#xD;
      environment ubiquitously, so the relevance (true disease patient number over the number of&#xD;
      patients with disease or just colonization) is far less than 100% and varied in different NTM&#xD;
      species. For example, previous studies have shown that the presence of M. kansasii and MAC&#xD;
      had a clinical relevance around 47~70% and 35~42%, respectively [8-9]. As for MAB which is&#xD;
      emerging pathogen worldwide, has a relevance of 33% [9]. According to contemporary NTM&#xD;
      guidelines established by American thoracic society, NTM pulmonary infection is diagnosed by&#xD;
      multiple criteria including microbiology of respiratory specimen and clinical findings as&#xD;
      well as radiographic findings [1]. In microbiology criteria, two or more sets of positive&#xD;
      sputum mycobacterial culture for the same NTM species within one year is needed.&#xD;
&#xD;
      Because NTM colonization is not uncommon in respiratory tract, diagnosis of true pulmonary&#xD;
      NTM infection is a great challenge in clinical practice. Actually, microbiology tests for&#xD;
      mycobacteria are neither timely nor efficient. Mycobacterial culture is time-consuming, which&#xD;
      needed weeks to wait the results even though it's current gold standard for micro-organism&#xD;
      identification [10]. The nucleic acid amplification method such as polymerase chain reaction&#xD;
      could not discriminate true NTM infection and solely colonization because the micro-organism&#xD;
      is present in both situations [11].&#xD;
&#xD;
      To early diagnose and then start treatment of NTM infection is important because NTM&#xD;
      pulmonary infection might be rapid lethal infection in intensive care unit or in patients who&#xD;
      had not received early proper treatment [6]. In addition, MAC or MAB which are most common in&#xD;
      Taiwan are resistant to most of anti-tuberculosis regimen. Hence, more rapid and accurate&#xD;
      diagnostic test should be developed [1-2, 6] The help of innate immunity in diagnosing NTM-LD&#xD;
      The body inflammatory marker, represent our immune response, would be an indicator for&#xD;
      differentiating true mycobacterial pulmonary infection from colonization while the first set&#xD;
      of mycobacterial culture grew NTM [12-15]. Both interferon-gamma and tumor necrosis&#xD;
      factor-alpha play critical roles in protective immunity to mycobacterial infections [16-17].&#xD;
      These responses are linked to engagement of Toll-like receptor 2 (TLR2) that is critical for&#xD;
      mycobacterial infection [18]. However, the TLR-2 expression has not been evaluated between&#xD;
      patients with NTM infection and colonization. According to the success of application of&#xD;
      interferon-gamma release assay for tuberculosis detection [19], we understand the specific&#xD;
      immune response is helpful to diagnose mycobacterial infection. We therefore focus on the&#xD;
      expression of TLR-2 and associated downstream cytokines in our patients with MAC or MAB lung&#xD;
      disease, which accounts the most of NTM infection [2].&#xD;
&#xD;
      The design in our study for diagnosis In order to investigate the help of host immune in&#xD;
      diagnosing NTM pulmonary infection, we initially compare the baseline expression of TLR-2 and&#xD;
      downstream cytokines in the MAC or MAB infected patients and colonized subjects. Then, we&#xD;
      perform an in-vitro stimulation test using mycobacteria (MAC or MAB) for co-culturing with&#xD;
      peripheral blood mononuclear cells of patients. The TLR-2 expression and cytokines activation&#xD;
      will be examined after the stimulation test. We then analyze the expression difference&#xD;
      between NTM-LD and colonization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2011</start_date>
  <completion_date type="Anticipated">January 2014</completion_date>
  <primary_completion_date type="Anticipated">January 2014</primary_completion_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>Patients with non-tuberculous pulmonary infection</measure>
    <time_frame>3 year</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>mortality</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>To Set up NTM Stimulation Test Foar Diagnosing NTM Pulmonary Infectionon.</condition>
  <arm_group>
    <arm_group_label>Patients with NTM pulmonary infection</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with other pathogen related lung infection</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Patient with NTM pulmonary colonization</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        1. Patients with NTM pulmonary infection: diagnosed by NTM guidelines by American&#xD;
             Thoracic Society(ATS)&#xD;
&#xD;
          2. Patients with NTM pulmonary colonization: Patients are not fulfilling the ATS&#xD;
             diagnostic criteria but having at least one set of positive sputum for NTM&#xD;
             (colonization).&#xD;
&#xD;
          3. Patients have pulmonary infiltrates, not related by NTM: three sets of respiratory&#xD;
             specimens that are negative for NTM.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  A patient has at least 3 sets of respiratory specimen for mycobacterial culture.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age younger than 18 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;
&#xD;
          -  In NTM infection group, patients having received anti-NTM treatment for one week will&#xD;
             be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</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>886972653087</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>886972653087</phone>
    </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 2011</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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycobacterium Infections</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/NCT01676142
org study id: 201012082RC
nct id: NCT01676142
lead sponsor: 
has dmc: No
1. To compare TLR-2 expression of peripheral blood mononuclear cells and serum downstream
           cytokines in those with MAC or MAB pulmonary infection and those with MAC or MAB
           pulmonary colonization and controls.

        2. To investigate the response of TLR-2 expression and cytokines activation to NTM
           stimulation test in patients with MAC or MAB pulmonary infection and colonization and
           controls.

        3. To validate the NTM stimulation test for NTM pulmonary infection.
The increase of nontuberculous mycobacteria lung infection Nontuberculous mycobacteria lung
      infection (NTM-LD) becomes an important clinical concern [1] because the rate of NTM
      infection has increased over the past ten years [2-3]. According to a study in Taiwan, NTM-LD
      increased from 1.26 to 7.94 per 100,000 inpatients/year during 2000 to 2008 [2]. The reasons
      for this increase are not readily clear, but could be related to the growth in numbers of the
      acquired immunocompromised population and advances of technique for mycobacterial culture
      [4-7]. Among the NTM infection in Taiwan, Mycobacterium avium complex (MAC) and M. abscessus
      (MAB) were most frequently isolated [2].

      The difficulty in early diagnosing and confirming true NTM-LD However, NTM exists in the
      environment ubiquitously, so the relevance (true disease patient number over the number of
      patients with disease or just colonization) is far less than 100% and varied in different NTM
      species. For example, previous studies have shown that the presence of M. kansasii and MAC
      had a clinical relevance around 47~70% and 35~42%, respectively [8-9]. As for MAB which is
      emerging pathogen worldwide, has a relevance of 33% [9]. According to contemporary NTM
      guidelines established by American thoracic society, NTM pulmonary infection is diagnosed by
      multiple criteria including microbiology of respiratory specimen and clinical findings as
      well as radiographic findings [1]. In microbiology criteria, two or more sets of positive
      sputum mycobacterial culture for the same NTM species within one year is needed.

      Because NTM colonization is not uncommon in respiratory tract, diagnosis of true pulmonary
      NTM infection is a great challenge in clinical practice. Actually, microbiology tests for
      mycobacteria are neither timely nor efficient. Mycobacterial culture is time-consuming, which
      needed weeks to wait the results even though it's current gold standard for micro-organism
      identification [10]. The nucleic acid amplification method such as polymerase chain reaction
      could not discriminate true NTM infection and solely colonization because the micro-organism
      is present in both situations [11].

      To early diagnose and then start treatment of NTM infection is important because NTM
      pulmonary infection might be rapid lethal infection in intensive care unit or in patients who
      had not received early proper treatment [6]. In addition, MAC or MAB which are most common in
      Taiwan are resistant to most of anti-tuberculosis regimen. Hence, more rapid and accurate
      diagnostic test should be developed [1-2, 6] The help of innate immunity in diagnosing NTM-LD
      The body inflammatory marker, represent our immune response, would be an indicator for
      differentiating true mycobacterial pulmonary infection from colonization while the first set
      of mycobacterial culture grew NTM [12-15]. Both interferon-gamma and tumor necrosis
      factor-alpha play critical roles in protective immunity to mycobacterial infections [16-17].
      These responses are linked to engagement of Toll-like receptor 2 (TLR2) that is critical for
      mycobacterial infection [18]. However, the TLR-2 expression has not been evaluated between
      patients with NTM infection and colonization. According to the success of application of
      interferon-gamma release assay for tuberculosis detection [19], we understand the specific
      immune response is helpful to diagnose mycobacterial infection. We therefore focus on the
      expression of TLR-2 and associated downstream cytokines in our patients with MAC or MAB lung
      disease, which accounts the most of NTM infection [2].

      The design in our study for diagnosis In order to investigate the help of host immune in
      diagnosing NTM pulmonary infection, we initially compare the baseline expression of TLR-2 and
      downstream cytokines in the MAC or MAB infected patients and colonized subjects. Then, we
      perform an in-vitro stimulation test using mycobacteria (MAC or MAB) for co-culturing with
      peripheral blood mononuclear cells of patients. The TLR-2 expression and cytokines activation
      will be examined after the stimulation test. We then analyze the expression difference
      between NTM-LD and colonization.
observational model: Case-Control
time perspective: Prospective
measure: Patients with non-tuberculous pulmonary infection
time frame: 3 year
measure: mortality
time frame: 3 years
arm group label: Patients with NTM pulmonary infection
arm group label: Patients with other pathogen related lung infection
arm group label: Patient with NTM pulmonary colonization
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chin-Chung Shu, MD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chin-Chung Shu, MD
phone: 886972653087
email: chinchungshu@ntu.edu.tw
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Mycobacterium Infections