Pulmonary Tuberculosis (TB)
Conditions
Keywords
pulmonary TB, cholecalciferol, sodium phenylbutyrate, antimicrobial peptides, immune response
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.
Interventions
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.
DRUGPlacebo tablets
Sponsors
Addis Ababa University
Armauer Hansen Research Institute, Ethiopia
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
Countries
Ethiopia
Outcome results
None listed