L-arginine and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis (TB)
L-arginine and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis (TB)
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
Inclusion Criteria:

 -  Adults >15 years with sputum smear positive pulmonary TB

 -  New cases only

 -  Agree to continue treatment in Timika for the full six month course of treatment -Not
 pregnant

 -  Consent to enroll in the study.

 Exclusion Criteria:

 -  hypercalcaemia (ionized calcium >1.32 mmol/L) identified at baseline

 -  taking arginine or vitamin D