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Immune Reconstitution in Tuberculosis Disease (IRETB)

Primary Purpose

Pulmonary Tuberculosis (TB)

Status
Completed
Phase
Phase 2
Locations
Ethiopia
Study Type
Interventional
Intervention
vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Placebo tablets
Sponsored by
Karolinska Institutet
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Tuberculosis (TB) focused on measuring pulmonary TB, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)

Placebo tablets

Arm 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.

Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.

Outcomes

Primary Outcome Measures

Composite clinical TB score
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
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
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).

Full Information

First Posted
September 25, 2012
Last Updated
February 4, 2016
Sponsor
Karolinska Institutet
Collaborators
Addis Ababa University, Armauer Hansen Research Institute, Ethiopia
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1. Study Identification

Unique Protocol Identification Number
NCT01698476
Brief Title
Immune Reconstitution in Tuberculosis Disease
Acronym
IRETB
Official Title
Immune Reconstitution in Tuberculosis Disease Using Antimicrobial Treatment With Vitamin D and Phenylbutyrate
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska Institutet
Collaborators
Addis Ababa University, Armauer Hansen Research Institute, Ethiopia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Tuberculosis (TB)
Keywords
pulmonary TB, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
390 (Actual)

8. Arms, Groups, and Interventions

Arm Title
vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Arm Type
Active Comparator
Arm 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 Title
Placebo tablets
Arm Type
Placebo Comparator
Arm Description
Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.
Intervention Type
Drug
Intervention Name(s)
vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)
Intervention 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.
Intervention Type
Drug
Intervention Name(s)
Placebo tablets
Primary Outcome Measure Information:
Title
Composite clinical TB score
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).
Time Frame
0 (baseline) compared to 8 weeks.
Secondary Outcome Measure Information:
Title
Clinical secondary endpoints
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).
Time Frame
0-4, 8, 16 and 24 weeks
Title
Laboratory secondary endpoints
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).
Time Frame
0, 4, 8, 16, 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanna Brighenti, PhD
Organizational Affiliation
Karolinska Institutet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Black Lion Hospital (BLH), Addis Ababa University, Faculty of Medicine
City
Addis Ababa
State/Province
Lideta sub city
Country
Ethiopia

12. IPD Sharing Statement

Citations:
PubMed Identifier
29696707
Citation
Bekele A, Gebreselassie N, Ashenafi S, Kassa E, Aseffa G, Amogne W, Getachew M, Aseffa A, Worku A, Raqib R, Agerberth B, Hammar U, Bergman P, Aderaye G, Andersson J, Brighenti S. Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia. J Intern Med. 2018 Sep;284(3):292-306. doi: 10.1111/joim.12767. Epub 2018 May 23.
Results Reference
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Immune Reconstitution in Tuberculosis Disease

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