L-arginine and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis (TB) (AVDAPT)

Menzies School of Health Research

Status and phase: Completed; Phase 3

Conditions: Smear Positive Pulmonary Tuberculosis

Treatments: Drug: Vitamin D; Drug: L-arginine; Drug: Placebo Vitamin D; Drug: Placebo L-arginine

Study type: Interventional

Funder types: Other

Identifiers

NCT00677339

AVDAPT 1

Details and patient eligibility

About

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.

Full description

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

Enrollment: 200 patients

Sex: All

Ages: 15+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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200 participants in 4 patient groups, including a placebo group

1

Active Comparator group

Description:

Active L-arginine plus active vitamin D

Treatment:

Drug: L-arginine

Drug: Vitamin D

2

Active Comparator group

Description:

Placebo L-arginine plus active Vitamin D

Treatment:

Drug: Placebo L-arginine

Drug: Vitamin D

3

Active Comparator group

Description:

Active L-arginine plus placebo vitamin D

Treatment:

Drug: Placebo Vitamin D

Drug: L-arginine

4

Placebo Comparator group

Description:

placebo L-arginine plus placebo vitamin D

Treatment:

Drug: Placebo Vitamin D

Drug: Placebo L-arginine