Smear Positive Pulmonary Tuberculosis Clinical Trial
Official title:
Phase 3 Trial of Oral L-arginine and / or Vitamin D as Adjunctive Therapies in Pulmonary Tuberculosis in Papua Province, Indonesia.
The purpose of this study is to determine whether adjunctive L-arginine and vitamin D can improve response to standard short course TB therapy in people with newly diagnosed pulmonary TB.
The two major pathways proposed to mediate macrophage mycobacterial killing in humans are
the arginine-nitric oxide and Vitamin D-1,25 dihydroxyvitamin D pathways. Our aim is to
determine if the key immunomodulatory agents L-arginine and vitamin D can improve the
rapidity and magnitude of the microbiological and clinical response in pulmonary TB. We will
test the following hypotheses in newly-diagnosed TB patients in Timika, Papua, Indonesia:
Our specific aims are to:
1. Determine whether supplementation with L-arginine and/or vitamin D is safe, and results
in more rapid improvement in clinical, mycobacterial, immunological, radiological,
physiological and functional measures of treatment outcome. We will randomise patients
with pulmonary TB to receive, in addition to standard TB therapy, adjunctive arginine,
vitamin D and / or placebo in a randomised, double-blind factorial 2x2 design. We will
relate serial measurements of plasma concentrations of L-arginine and vitamin D, and
immunological responses (pulmonary NO production, T cell function and phenotype) to
measures of treatment outcome [mycobacterial (sputum smear clearance and culture
conversion), physiological (spirometry), clinical (symptoms and weight), radiological
(chest Xray) and functional (six-minute walk test, modified St George Respiratory
Questionnaire)].
2. Determine whether pulmonary production of NO is inversely related to disease severity
at presentation. Baseline and serial measures of NO production will be related to
disease severity and the magnitude and rapidity of clinical response
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment