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Immune Reconstitution in Tuberculosis Disease (IRETB)

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

Condition Intervention Phase
Pulmonary Tuberculosis (TB)
Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Drug: Placebo tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate

Resource links provided by NLM:

Further study details as provided by Susanna Brighenti, Karolinska Institutet:

Primary Outcome Measures:
  • Composite clinical TB score [ Time Frame: 0 (baseline) compared to 8 weeks. ]
    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).

Secondary Outcome Measures:
  • Clinical secondary endpoints [ Time Frame: 0-4, 8, 16 and 24 weeks ]

    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 ]

    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).

Enrollment: 390
Study Start Date: September 2012
Study Completion Date: August 2015
Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Placebo Comparator: Placebo tablets
Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
Drug: Placebo tablets


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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Please refer to this study by its identifier: NCT01698476

Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine
Addis Ababa, Lideta sub city, Ethiopia
Sponsors and Collaborators
Karolinska Institutet
Addis Ababa University
Armauer Hansen Research Institute, Ethiopia
Principal Investigator: Susanna Brighenti, PhD Karolinska Institutet
  More Information

Responsible Party: Susanna Brighenti, Associate professor, Karolinska Institutet Identifier: NCT01698476     History of Changes
Other Study ID Numbers: IRETB-2012
Study First Received: September 25, 2012
Last Updated: February 4, 2016

Keywords provided by Susanna Brighenti, Karolinska Institutet:
pulmonary TB
sodium phenylbutyrate
antimicrobial peptides
immune response

Additional relevant MeSH terms:
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Vitamin D
4-phenylbutyric acid
Anti-Infective Agents
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Antineoplastic Agents processed this record on May 25, 2017