<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/NCT03251196</url>
  </required_header>
  <id_info>
    <org_study_id>LMU-IMPH-TB Sequel-01</org_study_id>
    <nct_id>NCT03251196</nct_id>
  </id_info>
  <brief_title>TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB</brief_title>
  <acronym>TBSEQUEL</acronym>
  <official_title>TB Sequel: Pathogenesis and Risk Factors of Long-term Sequelae of Pulmonary TB Defining Individual Outcomes and Public Health Impact</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Aurum Institute NPC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ludwig-Maximilians - University of Munich</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Center Borstel</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Witwatersrand, South Africa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mbeya Medical Research Centre NIMR</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministry of Health Instituto Nacional de Saude</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Medical Research Council Unit, The Gambia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Aurum Institute NPC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an observational cohort study. Pulmonary tuberculosis (TB) patients will be enrolled&#xD;
      at the time of TB diagnosis and prospectively followed for at least two years after&#xD;
      TB-treatment initiation with optional prolonged follow-up. Study visits will be performed in&#xD;
      the study clinics or if necessary at the participant's home at pre-defined time points after&#xD;
      TB treatment initiation. Clinical assessments, biological sample collections and collection&#xD;
      of socio-economic data will be performed according to the pre-defined schedule of events.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The African continent today is emblematic of TB as a global health emergency with little&#xD;
      known about the long-term sequelae. It is likely that TB patients from resource-constrained&#xD;
      settings, who usually present with more extensive disease, are left with greater lung&#xD;
      impairment.&#xD;
&#xD;
      This project aims to advance the understanding of the clinical, microbiologic, and host&#xD;
      immune factors affecting the long-term sequelae of pulmonary tuberculosis; to identify the&#xD;
      most important factors that contribute to lung impairment, including the immunological&#xD;
      response and genetic predisposition of the host and differences in the biology of the&#xD;
      pathogen; to determine occurrence of reversible and irreversible costs and socioeconomic&#xD;
      consequences for patients; and to facilitate novel interventions to restore and preserve&#xD;
      overall health, well-being and financial protection in patients with TB.&#xD;
&#xD;
      The core of the current project is a prospective cohort of up to 1600 patients across four&#xD;
      countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB&#xD;
      diagnosis, and followed up for at least 2 years. The overall goal of the cohort is to&#xD;
      describe and analyse the basis of the long-term clinical consequences of pulmonary TB, with a&#xD;
      particular focus on lung injury. The investigators will enroll patients during two years and&#xD;
      follow each patient up for at least two years. The project also includes a number of&#xD;
      sub-studies: Host-Immunology, Pathogen and Socio-Economic. General laboratory tests and TB&#xD;
      specific tests, X-ray, physical examination and cardio-pulmonary assessment will be performed&#xD;
      and the obtained clinical data will be recorded in study questionnaires. The investigators&#xD;
      will collect and analyse biological specimens (blood, urine and sputum) longitudinally during&#xD;
      the period of observation and after all specimens have been stored. In-depth analysis of the&#xD;
      host immune response, focusing on potential mechanisms of lung damage, including oxidative&#xD;
      injury, proteolytic matrix degradation, and neutrophil-mediated damage, neutrophil-macrophage&#xD;
      ratios and markers; and molecular analysis of mycobacterial dynamics and markers in relation&#xD;
      to pulmonary and microbiological treatment outcomes, including success, failure, relapse,&#xD;
      reinfection and death will be carried out. Socio-economic data, including patient costs, will&#xD;
      be collected at the time of TB diagnosis, during treatment, at the end of treatment and&#xD;
      during the follow-up period, and analysed to determine how the risk of TB sequelae is linked&#xD;
      with the socioeconomic position of the patient, to establish the occurrence of catastrophic&#xD;
      costs due to TB and the proportion of patients that resort to potentially irreversible&#xD;
      socioeconomic coping strategies.&#xD;
&#xD;
      Accurate data source will be maintained and confidentiality will be guaranteed. Data will be&#xD;
      analysed according to the statistical plan. Results of the study will be disseminated to all&#xD;
      relevant stakeholders through meetings, reports and publications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">September 22, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2022</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>2 Years</target_duration>
  <primary_outcome>
    <measure>Severe pulmonary function impairment</measure>
    <time_frame>2 years</time_frame>
    <description>Measured by spirometry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in impairment of pulmonary function</measure>
    <time_frame>2 years</time_frame>
    <description>Measured by six minute walking test</description>
  </secondary_outcome>
  <enrollment type="Actual">1500</enrollment>
  <condition>Respiratory Tract Infections</condition>
  <condition>Tuberculosis, Pulmonary</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No Intervention, and Observational Study</intervention_name>
    <description>Observational Study</description>
    <other_name>Observational Study</other_name>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Collection Bloods, Urine and Sputum will be obtained from each patient at different&#xD;
      time-points for analysis and storage. They will include, but are not limited to: native&#xD;
      urine, native sputum, extracted DNA from positive liquid culture, sputum pellet and&#xD;
      surpernatant and whole blood (PAXgene, plasma, serum, PBMC).&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This will be a multi-country, multi-centre observational cohort study, conducted at four&#xD;
        recruiting sites in four African countries: 1) University of the Witwatersrand (WITS),&#xD;
        Johannesburg in South Africa; 2) NIMR-Mbeya Medical Research Center (NIMR-MMRC), Mbeya in&#xD;
        Tanzania; 3) Instituto Nacional de Saúde (INS), Ministry of Health, Mozambique; 4) Medical&#xD;
        Research Council (MRC) Unit The Gambia, Fajara, The Gambia.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  At least one sputum sample tested positive for Mtb by Xpert MTB/RIF assay in the study&#xD;
             clinic/study laboratory or at least one sputum sample tested positive by culture&#xD;
             methods in study laboratory or other TB laboratory&#xD;
&#xD;
          -  Be ≥ 18 years of age&#xD;
&#xD;
          -  Willingness to provide a written consent or witnessed oral consent in the case of&#xD;
             illiteracy for participation in the study, prior to patient's first sample or other&#xD;
             study-specific data being collected&#xD;
&#xD;
          -  Willing to be tested for HIV infection&#xD;
&#xD;
          -  Agrees to the collection and storage of blood, urine, and sputum specimens for use in&#xD;
             future research&#xD;
&#xD;
          -  Willing to start anti-TB treatment after TB diagnosis&#xD;
&#xD;
          -  Living within the study area and willing to inform the study team of any change of&#xD;
             address during the treatment and follow-up period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has received TB treatment in the last 6 months&#xD;
&#xD;
          -  Has incapacity to produce and provide two sputum samples of sufficient quality (3 ml)&#xD;
&#xD;
          -  Has severe medical or psychiatric condition which in the opinion of the site&#xD;
             investigator or designee, might interfere with the ability to give true informed&#xD;
             consent and to adhere to the study requirements&#xD;
&#xD;
          -  Is currently imprisoned&#xD;
&#xD;
          -  Taking part in investigational product trials related to TB and/or lung diseases&#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>Gavin J Churchyard</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chief Executive Officers</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The MRC-Unit</name>
      <address>
        <city>Fajara</city>
        <country>Gambia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Saúde</name>
      <address>
        <city>Maputo</city>
        <country>Mozambique</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clinical HIV Research Unit</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2092</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NIMR-Mbeya Medical Research Centre</name>
      <address>
        <city>Mbeya</city>
        <country>Tanzania</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Gambia</country>
    <country>Mozambique</country>
    <country>South Africa</country>
    <country>Tanzania</country>
  </location_countries>
  <link>
    <url>http://tbsequel.org</url>
    <description>TB Sequel Website</description>
  </link>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>January 12, 2021</last_update_submitted>
  <last_update_submitted_qc>January 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2021</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>Tuberculosis</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Tuberculosis, Pulmonary</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>To be shared amongst the Collaborators, on shared database when the study starts</ipd_description>
  </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/NCT03251196
org study id: LMU-IMPH-TB Sequel-01
nct id: NCT03251196
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an observational cohort study. Pulmonary tuberculosis (TB) patients will be enrolled
      at the time of TB diagnosis and prospectively followed for at least two years after
      TB-treatment initiation with optional prolonged follow-up. Study visits will be performed in
      the study clinics or if necessary at the participant's home at pre-defined time points after
      TB treatment initiation. Clinical assessments, biological sample collections and collection
      of socio-economic data will be performed according to the pre-defined schedule of events.
The African continent today is emblematic of TB as a global health emergency with little
      known about the long-term sequelae. It is likely that TB patients from resource-constrained
      settings, who usually present with more extensive disease, are left with greater lung
      impairment.

      This project aims to advance the understanding of the clinical, microbiologic, and host
      immune factors affecting the long-term sequelae of pulmonary tuberculosis; to identify the
      most important factors that contribute to lung impairment, including the immunological
      response and genetic predisposition of the host and differences in the biology of the
      pathogen; to determine occurrence of reversible and irreversible costs and socioeconomic
      consequences for patients; and to facilitate novel interventions to restore and preserve
      overall health, well-being and financial protection in patients with TB.

      The core of the current project is a prospective cohort of up to 1600 patients across four
      countries (Mozambique, Tanzania, South Africa and The Gambia), enrolled at the time of TB
      diagnosis, and followed up for at least 2 years. The overall goal of the cohort is to
      describe and analyse the basis of the long-term clinical consequences of pulmonary TB, with a
      particular focus on lung injury. The investigators will enroll patients during two years and
      follow each patient up for at least two years. The project also includes a number of
      sub-studies: Host-Immunology, Pathogen and Socio-Economic. General laboratory tests and TB
      specific tests, X-ray, physical examination and cardio-pulmonary assessment will be performed
      and the obtained clinical data will be recorded in study questionnaires. The investigators
      will collect and analyse biological specimens (blood, urine and sputum) longitudinally during
      the period of observation and after all specimens have been stored. In-depth analysis of the
      host immune response, focusing on potential mechanisms of lung damage, including oxidative
      injury, proteolytic matrix degradation, and neutrophil-mediated damage, neutrophil-macrophage
      ratios and markers; and molecular analysis of mycobacterial dynamics and markers in relation
      to pulmonary and microbiological treatment outcomes, including success, failure, relapse,
      reinfection and death will be carried out. Socio-economic data, including patient costs, will
      be collected at the time of TB diagnosis, during treatment, at the end of treatment and
      during the follow-up period, and analysed to determine how the risk of TB sequelae is linked
      with the socioeconomic position of the patient, to establish the occurrence of catastrophic
      costs due to TB and the proportion of patients that resort to potentially irreversible
      socioeconomic coping strategies.

      Accurate data source will be maintained and confidentiality will be guaranteed. Data will be
      analysed according to the statistical plan. Results of the study will be disseminated to all
      relevant stakeholders through meetings, reports and publications.
observational model: Cohort
time perspective: Prospective
measure: Severe pulmonary function impairment
time frame: 2 years
description: Measured by spirometry
measure: Changes in impairment of pulmonary function
time frame: 2 years
description: Measured by six minute walking test
intervention type: Other
intervention name: No Intervention, and Observational Study
description: Observational Study
other name: Observational Study
Collection Bloods, Urine and Sputum will be obtained from each patient at different
      time-points for analysis and storage. They will include, but are not limited to: native
      urine, native sputum, extracted DNA from positive liquid culture, sputum pellet and
      surpernatant and whole blood (PAXgene, plasma, serum, PBMC).
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gavin J Churchyard
role: Principal Investigator
affiliation: Chief Executive Officers
facility: 
facility: 
facility: 
facility: 
country: Gambia
country: Mozambique
country: South Africa
country: Tanzania
url: http://tbsequel.org
description: TB Sequel Website
responsible party type: Sponsor
mesh term: Tuberculosis
mesh term: Respiratory Tract Infections
mesh term: Tuberculosis, Pulmonary
sharing ipd: Yes
ipd description: To be shared amongst the Collaborators, on shared database when the study starts