Immune Reconstitution in Tuberculosis Disease

Phase 2

Completed

• Conditions: Pulmonary Tuberculosis (TB)
• Interventions: Drug: vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate); Drug: Placebo tablets

• Registration Number: NCT01698476
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-09-25
• Study First Submitted QC: 2012-10-02
• Study First Posted: 2012-10-03
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-04
• Last Update Posted: 2016-02-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 390

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)	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 tablets	Placebo tablets	Placebo tablets for vitamin D once daily and placebo tablets for PBA (phenylbutyrate) twice daily for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Composite clinical TB score	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

Name	Time	Method
Laboratory secondary endpoints	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).
Clinical secondary endpoints	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).

Trial Locations

Locations (1)

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