Immune Reconstitution in Tuberculosis Disease (IRETB)

This study has been completed.
Sponsor:
Collaborators:
Addis Ababa University
Armauer Hansen Research Institute, Ethiopia
Information provided by (Responsible Party):
Susanna Brighenti, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT01698476
First received: September 25, 2012
Last updated: February 4, 2016
Last verified: February 2016

September 25, 2012
February 4, 2016
September 2012
August 2015   (final data collection date for primary outcome measure)
Composite clinical TB score [ Time Frame: 0 (baseline) compared to 8 weeks. ] [ Designated as safety issue: Yes ]
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).
Composite clinical TB score [ Time Frame: 0 (baseline) compared to 8 weeks. ] [ Designated as safety issue: Yes ]
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/conjunctival pallor, 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).
Complete list of historical versions of study NCT01698476 on ClinicalTrials.gov Archive Site
  • Clinical secondary endpoints [ Time Frame: 0-4, 8, 16 and 24 weeks ] [ Designated as safety issue: Yes ]

    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).

  • Laboratory secondary endpoints [ Time Frame: 0, 4, 8, 16, 24 weeks ] [ Designated as safety issue: No ]

    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).

Same as current
Not Provided
Interim analysis [ Designated as safety issue: Yes ]
An interim analysis will be performed after approx. 100-150 patients have been included into the study.
 
Immune Reconstitution in Tuberculosis Disease
Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Pulmonary Tuberculosis (TB)
  • Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
    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.
  • Drug: Placebo tablets
  • Active Comparator: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
    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.
    Intervention: Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
  • Placebo Comparator: Placebo tablets
    Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
    Intervention: Drug: Placebo tablets
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
390
August 2015
August 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

HIV negative patients, adult patients >18 years who has not started anti-TB therapy.

Newly diagnosed pulmonary TB confirmed by microscopy or culture but also sputum-negative clinical TB cases (defined according to the WHO 2006 criteria for sputum smear-negative TB ie. clinical symptoms of TB, chest X-ray findings and response to standard treatment).

Exclusion Criteria:

Patients who have already started treatment with anti-TB drugs for more that 5 days.

HIV-positive patients.

History of anti-TB treatment in the past 2 years.

Local extra-pulmonary TB in the absence of lung manifestations.

Hypercalcaemia (serum calcium > 3 mmol/L) identified at baseline.

Pregnant and breast feeding women.

Any known liver or kidney function abnormality, malignancy or patients treated with cardiac glycosides.

Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Ethiopia
 
NCT01698476
IRETB-2012
Yes
Not Provided
Not Provided
Susanna Brighenti, Karolinska Institutet
Karolinska Institutet
  • Addis Ababa University
  • Armauer Hansen Research Institute, Ethiopia
Principal Investigator: Susanna Brighenti, PhD Karolinska Institutet
Karolinska Institutet
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP