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Immune Reconstitution in Tuberculosis Disease (IRETB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01698476
Recruitment Status : Completed
First Posted : October 3, 2012
Last Update Posted : February 5, 2016
Addis Ababa University
Armauer Hansen Research Institute, Ethiopia
Information provided by (Responsible Party):
Susanna Brighenti, Karolinska Institutet

Brief Summary:
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 or disease Intervention/treatment Phase
Pulmonary Tuberculosis (TB) Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate) Drug: Placebo tablets Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 390 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate
Study Start Date : September 2012
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. 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).

  2. 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).

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01698476

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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
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Principal Investigator: Susanna Brighenti, PhD Karolinska Institutet

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Responsible Party: Susanna Brighenti, Associate professor, Karolinska Institutet Identifier: NCT01698476     History of Changes
Other Study ID Numbers: IRETB-2012
First Posted: October 3, 2012    Key Record Dates
Last Update Posted: February 5, 2016
Last Verified: February 2016

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

Additional relevant MeSH terms:
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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
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents
Antineoplastic Agents