<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/NCT01698476</url>
  </required_header>
  <id_info>
    <org_study_id>IRETB-2012</org_study_id>
    <nct_id>NCT01698476</nct_id>
  </id_info>
  <brief_title>Immune Reconstitution in Tuberculosis Disease</brief_title>
  <acronym>IRETB</acronym>
  <official_title>Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Addis Ababa University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Armauer Hansen Research Institute, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska Institutet</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate&#xD;
      together with standard anti-tuberculosis treatment to significantly improve clinical recovery&#xD;
      among patients with untreated, active pulmonary tuberculosis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Composite clinical TB score</measure>
    <time_frame>0 (baseline) compared to 8 weeks.</time_frame>
    <description>A previously described composite clinical TB score will be used to monitor the efficacy of vitamin D and phenylbutyrate treatment among TB patients on standard chemotherapy. The numerical TB score will include self-reported clinical symptoms (cough, night sweats and chest pain) as well as different parameters determined upon clinical examination anemia, haemoptysis, dyspnoea, tachycardia, positive finding at lung auscultation, fever, low body mass index (BMI) and low mid upper arm circumference (MUAC). The TB score will be determined at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at time point 8 weeks compared to baseline (time point 0).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical secondary endpoints</measure>
    <time_frame>0-4, 8, 16 and 24 weeks</time_frame>
    <description>Clinical composite TB score (0, 4, 16, 24 weeks).&#xD;
Modified clinical composite TB score (0, 4, 8, 16, 24 weeks).&#xD;
Chest X-ray (0, 4, 8, 16, 24 weeks).&#xD;
Time to sputum- and/or TB culture conversion (0, 1, 2, 3, 4, 8 weeks).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Laboratory secondary endpoints</measure>
    <time_frame>0, 4, 8, 16, 24 weeks</time_frame>
    <description>Peripheral CD4/CD8 T cell counts.&#xD;
Antibodies in lymphocytes secertions (ALS) (S Ashenafi, Thorax, 2012).&#xD;
Quantiferon-in-tube TB-gold (QFT).&#xD;
Plasma levels of vitamin D, LL-37 and also cytokine/chemokine profiles.&#xD;
Functional studies of immune cells (PBMCs).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">390</enrollment>
  <condition>Pulmonary Tuberculosis (TB)</condition>
  <arm_group>
    <arm_group_label>vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo tablets</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</intervention_name>
    <description>Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.</description>
    <arm_group_label>vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo tablets</intervention_name>
    <arm_group_label>Placebo tablets</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        HIV negative patients, adult patients &gt;18 years who has not started anti-TB therapy.&#xD;
&#xD;
        Newly diagnosed pulmonary TB confirmed by microscopy or culture but also sputum-negative&#xD;
        clinical TB cases (defined according to the WHO 2006 criteria for sputum smear-negative TB&#xD;
        ie. clinical symptoms of TB, chest X-ray findings and response to standard treatment).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients who have already started treatment with anti-TB drugs for more that 5 days.&#xD;
&#xD;
        HIV-positive patients.&#xD;
&#xD;
        History of anti-TB treatment in the past 2 years.&#xD;
&#xD;
        Local extra-pulmonary TB in the absence of lung manifestations.&#xD;
&#xD;
        Hypercalcaemia (serum calcium &gt; 3 mmol/L) identified at baseline.&#xD;
&#xD;
        Pregnant and breast feeding women.&#xD;
&#xD;
        Any known liver or kidney function abnormality, malignancy or patients treated with cardiac&#xD;
        glycosides.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susanna Brighenti, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine</name>
      <address>
        <city>Addis Ababa</city>
        <state>Lideta sub city</state>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>February 4, 2016</last_update_submitted>
  <last_update_submitted_qc>February 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska Institutet</investigator_affiliation>
    <investigator_full_name>Susanna Brighenti</investigator_full_name>
    <investigator_title>Associate professor</investigator_title>
  </responsible_party>
  <keyword>pulmonary TB</keyword>
  <keyword>cholecalciferol</keyword>
  <keyword>sodium phenylbutyrate</keyword>
  <keyword>antimicrobial peptides</keyword>
  <keyword>immune response</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>4-phenylbutyric acid</mesh_term>
  </intervention_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/NCT01698476
org study id: IRETB-2012
nct id: NCT01698476
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The aim with study is to provide adjunctive therapy with vitamin D and phenylbutyrate
      together with standard anti-tuberculosis treatment to significantly improve clinical recovery
      among patients with untreated, active pulmonary tuberculosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Composite clinical TB score
time frame: 0 (baseline) compared to 8 weeks.
description: A previously described composite clinical TB score will be used to monitor the efficacy of vitamin D and phenylbutyrate treatment among TB patients on standard chemotherapy. The numerical TB score will include self-reported clinical symptoms (cough, night sweats and chest pain) as well as different parameters determined upon clinical examination anemia, haemoptysis, dyspnoea, tachycardia, positive finding at lung auscultation, fever, low body mass index (BMI) and low mid upper arm circumference (MUAC). The TB score will be determined at the time of diagnosis (time point 0) and at 4, 8, 16 and 24 weeks after initiation of antimicrobial treatment with vitamin D and phenylbutyrate. The primary endpoint will be assessed at time point 8 weeks compared to baseline (time point 0).
measure: Clinical secondary endpoints
time frame: 0-4, 8, 16 and 24 weeks
description: Clinical composite TB score (0, 4, 16, 24 weeks).
Modified clinical composite TB score (0, 4, 8, 16, 24 weeks).
Chest X-ray (0, 4, 8, 16, 24 weeks).
Time to sputum- and/or TB culture conversion (0, 1, 2, 3, 4, 8 weeks).
measure: Laboratory secondary endpoints
time frame: 0, 4, 8, 16, 24 weeks
description: Peripheral CD4/CD8 T cell counts.
Antibodies in lymphocytes secertions (ALS) (S Ashenafi, Thorax, 2012).
Quantiferon-in-tube TB-gold (QFT).
Plasma levels of vitamin D, LL-37 and also cytokine/chemokine profiles.
Functional studies of immune cells (PBMCs).
arm group label: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
arm group type: Active Comparator
description: Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
arm group label: Placebo tablets
arm group type: Placebo Comparator
description: Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
intervention type: Drug
intervention name: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
description: Dose of interventions: 5,000 IU of vitamin D (cholecalciferol tablets) once daily and 500 mg PBA (sodium phenylbutyrate tablets) twice daily for 16 weeks.
arm group label: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
intervention type: Drug
intervention name: Placebo tablets
arm group label: Placebo tablets
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Susanna Brighenti, PhD
role: Principal Investigator
affiliation: Karolinska Institutet
facility: 
country: Ethiopia
responsible party type: Principal Investigator
investigator affiliation: Karolinska Institutet
investigator full name: Susanna Brighenti
investigator title: Associate professor
mesh term: Tuberculosis
mesh term: Tuberculosis, Pulmonary
mesh term: Vitamin D
mesh term: Cholecalciferol
mesh term: 4-phenylbutyric acid