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

Information source: Menzies School of Health Research
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Smear Positive Pulmonary Tuberculosis

Intervention: L-arginine (Drug); Vitamin D (Drug); Placebo L-arginine (Drug); Placebo Vitamin D (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Menzies School of Health Research

Official(s) and/or principal investigator(s):
Nicholas M Anstey, MBBS, Study Director, Affiliation: Menzies School of Helath Research
Anna P Ralph, MBBS, Principal Investigator, Affiliation: Australian National University, Canberra, Australia
Franciscus Thio, MPPM, Principal Investigator, Affiliation: District Ministry of Health, Timika
Peter Morris, MBBS, Principal Investigator, Affiliation: Menzies School of Health Research, Northern Territory, Australia
Enny Kenangalem, MD, Principal Investigator, Affiliation: Papuan Community Health and Development Foundation
Jeanne R Poespoprodjo, MD, Principal Investigator, Affiliation: Mimika District Health Authority
Richard N Price, MD, Principal Investigator, Affiliation: Menzies School of Health Research
Tonia Woodberry, PhD, Principal Investigator, Affiliation: Menzies School of Health Research
Paul M Kelly, MBBS, Principal Investigator, Affiliation: Australian Capital Territory Department of Health
Emiliana Tjitra, MD, PhD, Principal Investigator, Affiliation: National Institute of Health Research and Development, Indonesia
Sandjaja Sandjaja, PhD, Principal Investigator, Affiliation: National Institute of Health Research and Development, Indonesia
Dina B Lolong, MD, Principal Investigator, Affiliation: National Institute of Health Research and Development
Mark Chatfield, PhD, Principal Investigator, Affiliation: National Health and Medical Research Council (Australia) Clinical Trials Centre
Ivan Bastian, MBBS, Principal Investigator, Affiliation: Institute of Medical and Veterinary Pathology, South Australia

Summary

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.

Clinical Details

Official title: Phase 3 Trial of Oral L-arginine and / or Vitamin D as Adjunctive Therapies in Pulmonary Tuberculosis in Papua Province, Indonesia.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome:

Proportion of pulmonary TB patients who are culture negative at 1 month

Difference in improvement in composite clinical endpoint comprising weight, cough clearance and FEV1 at 2 months.

Secondary outcome:

Change in plasma L-arginine concentration

Change in plasma 25(OH)D3 concentration

Death, clinical failure and default independently, and 'death or clinical failure or default'.

Hypercalcaemia

Gastrointestinal side effects

Sputum smear conversion time

Radiological improvement (percentage lung involvement on CXR at 2 months).

Cough clearance

Difference in improvement in percent predicted FEV1 at 2 and 6 months.

Weight gain

Immunological improvement (exhaled NO)

Immunological improvement (T cell CD3ΞΆ expression and T cell function)

Functional improvement measured using six minute walk test

Quality of life assessment using modified St George Respiratory Questionnaire.

Primary end points stratified by HIV status.

Primary end points stratified by baseline vitamin D and L-arginine status.

Primary end points stratified by ethnicity (Papuan and non-Papuan patients).

Detailed 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

Eligibility

Minimum age: 15 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

Timika Tuberculosis Clinic and Community Hospital, Timika, Papua Province, Indonesia
Additional Information

Starting date: June 2008
Last updated: January 17, 2012

Page last updated: August 20, 2015

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