Immune Reconstitution in Tuberculosis Disease

Karolinska Institutet390 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

390

Conditions

Pulmonary Tuberculosis (TB)

Interventions

vitamin D (cholecalciferol) and PBA (sodium phenylbutyrate)DRUG

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 tabletsDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

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

Addis Ababa, Lideta sub city, Ethiopia

Outcomes

Primary Outcomes

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).

Time frame: 0 (baseline) compared to 8 weeks.

Secondary Outcomes

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).

Time frame: 0-4, 8, 16 and 24 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).

Time frame: 0, 4, 8, 16, 24 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.