Immune Reconstitution in Tuberculosis Disease (IRETB)

February 4, 2016 updated by: Susanna Brighenti, Karolinska Institutet

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

390

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Ethiopia
    • Lideta sub city
      • Addis Ababa, Lideta sub city, Ethiopia
        • Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
0 (baseline) compared to 8 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
0-4, 8, 16 and 24 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).
0, 4, 8, 16, 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Collaborators

Addis Ababa University
Armauer Hansen Research Institute, Ethiopia

Investigators

  • Principal Investigator: Susanna Brighenti, PhD, Karolinska Institutet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

September 25, 2012

First Submitted That Met QC Criteria

October 2, 2012

First Posted (Estimate)

October 3, 2012

Study Record Updates

Last Update Posted (Estimate)

February 5, 2016

Last Update Submitted That Met QC Criteria

February 4, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRETB-2012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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