<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/NCT03821285</url>
  </required_header>
  <id_info>
    <org_study_id>2215CE</org_study_id>
    <nct_id>NCT03821285</nct_id>
  </id_info>
  <brief_title>Respiratory Function in Patients With Post-tuberculosis Lung Impairment</brief_title>
  <official_title>Evaluation of Respiratory Function in Patients With Post-tuberculosis Lung Impairment After Pulmonary Tuberculosis Treatment or After Spontaneous Healing</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università degli Studi dell'Insubria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondazione Salvatore Maugeri</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Azienda Ospedaliero Universitaria di Sassari</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto Nacional de Enfermedades Respiratorias</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Università degli Studi dell'Insubria</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Pulmonary tuberculosis (TB) is an important risk factor for chronic respiratory disease due&#xD;
      to residual lung damage. A recent review of the literature on TB sequelae and rehabilitation&#xD;
      has provided clear evidence that TB is definitively responsible for lung function impairment.&#xD;
      Functional evaluation of TB patients after completion of pulmonary tuberculosis treatment or&#xD;
      spontaneous healing should be considered as part of clinical care. Unfortunately, few studies&#xD;
      are available in the literature investigating the physiopathology of lung damage, its impact&#xD;
      on quality of life, the potential need for pulmonary rehabilitation (PR), and the effects of&#xD;
      a PR program.Objectives of this prospective multicentre international study are: Primary&#xD;
      Objective-to assess the exercise capacity 6-min walking test in patients with post-TB lung&#xD;
      impairment after completion of pulmonary tuberculosis treatment or after spontaneous healing.&#xD;
      Secondary Objectives-to assess the effects of the PR program on dyspnoea symptoms and muscle&#xD;
      fatigue, quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Methods Respiratory functional parameters at baseline and at the end of the 15 sessions&#xD;
      rehabilitation programme (RP) will be collected at the participating Centre. Follow-up visit&#xD;
      1 year after completion of RP Baseline assessment&#xD;
&#xD;
        1. After signature of the informed consent to the study, patients will undergo a&#xD;
           Pre-screening Visit: data on medical history, current pharmacological therapies, smoking&#xD;
           (pack/year), vaccinations, physical examination, vital parameters (blood pressure, heart&#xD;
           rate, respiratory rate, oxygen saturation in arterial blood), co-morbidities and Mini&#xD;
           Mental State Examination will be collected.&#xD;
&#xD;
        2. Screening Visit (before the RP), during the visit the following data will be collected:&#xD;
           number of TB disease episodes, detailed data on the last TB episode (age at onset of TB&#xD;
           symptoms, age at TB diagnosis, anti-TB treatment duration, anti-TB drugs administered,&#xD;
           socio-economic conditions, education level, physical examination, vital parameters,&#xD;
           oxygen saturation in arterial blood, heart rate and respiratory rate). Pulmonary&#xD;
           rehabilitation program tailored according to specific patient's needs.&#xD;
&#xD;
        3. Baseline assessment of respiratory function: arterial blood gas (ABG) analysis,&#xD;
           spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO), overnight&#xD;
           oximetry, electrocardiogram (ECG), chest X-ray (CXR), High-resolution computed&#xD;
           tomography (HRCT)&#xD;
&#xD;
        4. Assessment of the rehabilitation programme: functional evaluation (6MWT), muscle&#xD;
           strength evaluation (five-repetition sit-to-stand test (5STS)), respiratory muscle&#xD;
           strength (maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP)),&#xD;
           symptoms evaluation (Dyspnea: Medical Research Council Questionnaire (MRC), Modified&#xD;
           Borg pre/post 6MWT, Baseline and Transition Dyspnea Indexes (BDI-TDI) and Fatigue:&#xD;
           Modified Borg pre/post 6MWT)&#xD;
&#xD;
        5. Assessment of the Quality of Life (QoL): CAT and St George's Respiratory Questionnaire.&#xD;
&#xD;
      Final assessment:&#xD;
&#xD;
      A final assessment will be done at the end of the rehabilitation programme and will include:&#xD;
&#xD;
      c) Only ABG, spirometry and DLCO d) and e).&#xD;
&#xD;
      Pulmonary rehabilitation programme&#xD;
&#xD;
      PR programme will include:&#xD;
&#xD;
      At least 15 aerobic-training sessions by cycle ergometer supervised by a respiratory&#xD;
      therapist (5 session per week, 30 minutes each: 5 minutes warm up, 20 minutes training and 5&#xD;
      minutes warm-down) at constant load (calculated with Hill equation, Hill K, et al. Estimating&#xD;
      maximum work rate during incremental cycle ergometry testing from six-minute walk distance in&#xD;
      patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil.&#xD;
      2008;89(9):1782-7.) with an adherence of at least 80%.&#xD;
&#xD;
        1. At least 15 strength-training sessions for peripheral muscles (30 minutes calisthenics&#xD;
           exercise) with an adherence of at least 80%.&#xD;
&#xD;
        2. At least 3 face to face and/or group educational sessions, for:&#xD;
&#xD;
             -  Optimization of inhalation techniques&#xD;
&#xD;
             -  Exercise training and maintenance programs&#xD;
&#xD;
             -  Daily physical activity&#xD;
&#xD;
             -  Airways clearance techniques&#xD;
&#xD;
             -  Long oxygen therapy home management.&#xD;
&#xD;
        3. According to individual needs, the PR program should include:&#xD;
&#xD;
             -  airways clearance techniques&#xD;
&#xD;
             -  inspiratory muscles training (with Threshold®)&#xD;
&#xD;
      Monitoring Anonymous data will be collected in a common electronic format (excel database).&#xD;
&#xD;
      Adverse events (AEs) and severe adverse events (SAEs) will be reported and registered.&#xD;
&#xD;
      Follow-up&#xD;
&#xD;
      Follow-up visit 1 year after completion of RP will include:&#xD;
&#xD;
      c) Only ABG, spirometry, DLCO and overnight oximetry d) and e) Statistical analysis A&#xD;
      two-tailed p-value less than 0.05 will be considered statistically significant.&#xD;
&#xD;
      Qualitative and quantitative variables will be described with absolute and relative&#xD;
      (percentages) frequencies and means (standard deviations -SD) or medians (interquartile&#xD;
      ranges -IQR) depending on their normality, respectively. The mean difference between the two&#xD;
      study groups in the 6MWT will be evaluated using the Student's t-test. Differences in the&#xD;
      variables associated to the secondary objectives will be evaluated using the Chi-square or&#xD;
      Student's t-test for qualitative and quantitative variables. A two-tailed p-value less than&#xD;
      0.05 will be considered statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">February 14, 2019</start_date>
  <completion_date type="Anticipated">January 14, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Prospective, multicentre international</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>6-min walking test</measure>
    <time_frame>1 year</time_frame>
    <description>Exercise capacity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>dyspnoea</measure>
    <time_frame>1 year</time_frame>
    <description>Modified BORG scale (0-10) 0 better, 10 worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>muscle fatigue</measure>
    <time_frame>1 year</time_frame>
    <description>Modified Borg scale (0-10) 0 better, 10 worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>health related quality of life</measure>
    <time_frame>1 year</time_frame>
    <description>st. George Respiratory Questionnaire 0 better, 100 worse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>health status</measure>
    <time_frame>1 year</time_frame>
    <description>COPD Assessment test-CAT (0-40) 0 better, 40 worse</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Lung Diseases, Obstructive</condition>
  <condition>Pulmonary Rehabilitation</condition>
  <condition>Lung TB</condition>
  <arm_group>
    <arm_group_label>pulmonary rehabilitation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pulmonary rehabilitation program</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Pulmonary Rehabilitation</intervention_name>
    <description>Pulmonary rehabilitation programme:15 aerobic-training sessions, 15 strength-training sessions for peripheral muscles, 3 face to face and/or Group educational sessions, if needed airways clearance techniques and/or inspiratory muscles training</description>
    <arm_group_label>pulmonary rehabilitation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Patients with post-TB lung impairment after completion of pulmonary tuberculosis&#xD;
        treatment - Patients with post- TB impairment after spontaneous healing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any unstable medical condition&#xD;
&#xD;
          -  Musculoskeletal disorders contraindicating participation in the PR program&#xD;
&#xD;
          -  Cognitive impairment (Mini Mental State Examination &lt;22)&#xD;
&#xD;
          -  Unable to sign informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giovan Battista Migliori, Prof</last_name>
    <role>Study Director</role>
    <affiliation>ICS Maugeri, IRCCS</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dina Visca, Dr</last_name>
    <phone>+390331829111</phone>
    <email>dina.visca@icsmaugeri.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Elisabetta Zampogna, Dr</last_name>
    <phone>+390331829503</phone>
    <email>elisabetta.zampogna@icsmaugeri.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>ICS Maugeri, IRCCS</name>
      <address>
        <city>Tradate</city>
        <state>Varese</state>
        <zip>21049</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dina Visca, Dr</last_name>
      <phone>+390331829111</phone>
      <email>dina.visca@icsmaugeri.it</email>
    </contact>
    <contact_backup>
      <last_name>Elisabetta Zampogna, Dr</last_name>
      <phone>+390331829503</phone>
      <email>elisabetta.zampogna@icsmaugeri.it</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Tiberi S, Munoz-Torrico M, Duarte R, Dalcolmo M, D'Ambrosio L, Migliori GB. New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology. 2018 Mar-Apr;24(2):86-98. doi: 10.1016/j.rppnen.2017.10.009. Epub 2018 Feb 24.</citation>
    <PMID>29487031</PMID>
  </reference>
  <results_reference>
    <citation>Munoz-Torrico M, Rendon A, Centis R, D'Ambrosio L, Fuentes Z, Torres-Duque C, Mello F, Dalcolmo M, Perez-Padilla R, Spanevello A, Migliori GB. Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis? J Bras Pneumol. 2016 Sep-Oct;42(5):374-385. doi: 10.1590/S1806-37562016000000226.</citation>
    <PMID>27812638</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università degli Studi dell'Insubria</investigator_affiliation>
    <investigator_full_name>Dina Visca</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>TB</keyword>
  <keyword>Pulmonary rehabilitation</keyword>
  <keyword>Lung function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, 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/NCT03821285
org study id: 2215CE
nct id: NCT03821285
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Pulmonary tuberculosis (TB) is an important risk factor for chronic respiratory disease due
      to residual lung damage. A recent review of the literature on TB sequelae and rehabilitation
      has provided clear evidence that TB is definitively responsible for lung function impairment.
      Functional evaluation of TB patients after completion of pulmonary tuberculosis treatment or
      spontaneous healing should be considered as part of clinical care. Unfortunately, few studies
      are available in the literature investigating the physiopathology of lung damage, its impact
      on quality of life, the potential need for pulmonary rehabilitation (PR), and the effects of
      a PR program.Objectives of this prospective multicentre international study are: Primary
      Objective-to assess the exercise capacity 6-min walking test in patients with post-TB lung
      impairment after completion of pulmonary tuberculosis treatment or after spontaneous healing.
      Secondary Objectives-to assess the effects of the PR program on dyspnoea symptoms and muscle
      fatigue, quality of life.
Methods Respiratory functional parameters at baseline and at the end of the 15 sessions
      rehabilitation programme (RP) will be collected at the participating Centre. Follow-up visit
      1 year after completion of RP Baseline assessment

        1. After signature of the informed consent to the study, patients will undergo a
           Pre-screening Visit: data on medical history, current pharmacological therapies, smoking
           (pack/year), vaccinations, physical examination, vital parameters (blood pressure, heart
           rate, respiratory rate, oxygen saturation in arterial blood), co-morbidities and Mini
           Mental State Examination will be collected.

        2. Screening Visit (before the RP), during the visit the following data will be collected:
           number of TB disease episodes, detailed data on the last TB episode (age at onset of TB
           symptoms, age at TB diagnosis, anti-TB treatment duration, anti-TB drugs administered,
           socio-economic conditions, education level, physical examination, vital parameters,
           oxygen saturation in arterial blood, heart rate and respiratory rate). Pulmonary
           rehabilitation program tailored according to specific patient's needs.

        3. Baseline assessment of respiratory function: arterial blood gas (ABG) analysis,
           spirometry, diffusing capacity of the lungs for carbon monoxide (DLCO), overnight
           oximetry, electrocardiogram (ECG), chest X-ray (CXR), High-resolution computed
           tomography (HRCT)

        4. Assessment of the rehabilitation programme: functional evaluation (6MWT), muscle
           strength evaluation (five-repetition sit-to-stand test (5STS)), respiratory muscle
           strength (maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP)),
           symptoms evaluation (Dyspnea: Medical Research Council Questionnaire (MRC), Modified
           Borg pre/post 6MWT, Baseline and Transition Dyspnea Indexes (BDI-TDI) and Fatigue:
           Modified Borg pre/post 6MWT)

        5. Assessment of the Quality of Life (QoL): CAT and St George's Respiratory Questionnaire.

      Final assessment:

      A final assessment will be done at the end of the rehabilitation programme and will include:

      c) Only ABG, spirometry and DLCO d) and e).

      Pulmonary rehabilitation programme

      PR programme will include:

      At least 15 aerobic-training sessions by cycle ergometer supervised by a respiratory
      therapist (5 session per week, 30 minutes each: 5 minutes warm up, 20 minutes training and 5
      minutes warm-down) at constant load (calculated with Hill equation, Hill K, et al. Estimating
      maximum work rate during incremental cycle ergometry testing from six-minute walk distance in
      patients with chronic obstructive pulmonary disease. Arch Phys Med Rehabil.
      2008;89(9):1782-7.) with an adherence of at least 80%.

        1. At least 15 strength-training sessions for peripheral muscles (30 minutes calisthenics
           exercise) with an adherence of at least 80%.

        2. At least 3 face to face and/or group educational sessions, for:

             -  Optimization of inhalation techniques

             -  Exercise training and maintenance programs

             -  Daily physical activity

             -  Airways clearance techniques

             -  Long oxygen therapy home management.

        3. According to individual needs, the PR program should include:

             -  airways clearance techniques

             -  inspiratory muscles training (with Threshold®)

      Monitoring Anonymous data will be collected in a common electronic format (excel database).

      Adverse events (AEs) and severe adverse events (SAEs) will be reported and registered.

      Follow-up

      Follow-up visit 1 year after completion of RP will include:

      c) Only ABG, spirometry, DLCO and overnight oximetry d) and e) Statistical analysis A
      two-tailed p-value less than 0.05 will be considered statistically significant.

      Qualitative and quantitative variables will be described with absolute and relative
      (percentages) frequencies and means (standard deviations -SD) or medians (interquartile
      ranges -IQR) depending on their normality, respectively. The mean difference between the two
      study groups in the 6MWT will be evaluated using the Student's t-test. Differences in the
      variables associated to the secondary objectives will be evaluated using the Chi-square or
      Student's t-test for qualitative and quantitative variables. A two-tailed p-value less than
      0.05 will be considered statistically significant.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective, multicentre international
primary purpose: Screening
masking: None (Open Label)
measure: 6-min walking test
time frame: 1 year
description: Exercise capacity
measure: dyspnoea
time frame: 1 year
description: Modified BORG scale (0-10) 0 better, 10 worse
measure: muscle fatigue
time frame: 1 year
description: Modified Borg scale (0-10) 0 better, 10 worse
measure: health related quality of life
time frame: 1 year
description: st. George Respiratory Questionnaire 0 better, 100 worse
measure: health status
time frame: 1 year
description: COPD Assessment test-CAT (0-40) 0 better, 40 worse
arm group label: pulmonary rehabilitation
arm group type: Experimental
description: Pulmonary rehabilitation program
intervention type: Procedure
intervention name: Pulmonary Rehabilitation
description: Pulmonary rehabilitation programme:15 aerobic-training sessions, 15 strength-training sessions for peripheral muscles, 3 face to face and/or Group educational sessions, if needed airways clearance techniques and/or inspiratory muscles training
arm group label: pulmonary rehabilitation
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Giovan Battista Migliori, Prof
role: Study Director
affiliation: ICS Maugeri, IRCCS
last name: Dina Visca, Dr
phone: +390331829111
email: dina.visca@icsmaugeri.it
last name: Elisabetta Zampogna, Dr
phone: +390331829503
email: elisabetta.zampogna@icsmaugeri.it
facility: 
status: Recruiting
contact: 
contact backup: 
country: Italy
citation: Tiberi S, Munoz-Torrico M, Duarte R, Dalcolmo M, D'Ambrosio L, Migliori GB. New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology. 2018 Mar-Apr;24(2):86-98. doi: 10.1016/j.rppnen.2017.10.009. Epub 2018 Feb 24.
PMID: 29487031
citation: Munoz-Torrico M, Rendon A, Centis R, D'Ambrosio L, Fuentes Z, Torres-Duque C, Mello F, Dalcolmo M, Perez-Padilla R, Spanevello A, Migliori GB. Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis? J Bras Pneumol. 2016 Sep-Oct;42(5):374-385. doi: 10.1590/S1806-37562016000000226.
PMID: 27812638
responsible party type: Principal Investigator
investigator affiliation: Università degli Studi dell'Insubria
investigator full name: Dina Visca
investigator title: Principal Investigator
mesh term: Tuberculosis
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
sharing ipd: Undecided