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 monthDifference in improvement in composite clinical endpoint comprising weight, cough clearance and FEV1 at 2 months.
Secondary outcome: Change in plasma L-arginine concentrationChange 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
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