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L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial

Ralph, Anna P; Waramori, Govert; Pontororing, Gysje J; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja, null; Lolong, Dina B; Yeo, Tsin W; Chatfield, Mark D; Soemanto, Retno K; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P; Eisman, John; Price, Ric N; Morris, Peter S; Kelly, Paul M; Anstey, Nicholas

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BACKGROUND Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). METHODS In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8...[Show more]

dc.contributor.authorRalph, Anna P
dc.contributor.authorWaramori, Govert
dc.contributor.authorPontororing, Gysje J
dc.contributor.authorKenangalem, Enny
dc.contributor.authorWiguna, Andri
dc.contributor.authorTjitra, Emiliana
dc.contributor.authorSandjaja, null
dc.contributor.authorLolong, Dina B
dc.contributor.authorYeo, Tsin W
dc.contributor.authorChatfield, Mark D
dc.contributor.authorSoemanto, Retno K
dc.contributor.authorBastian, Ivan
dc.contributor.authorLumb, Richard
dc.contributor.authorMaguire, Graeme P
dc.contributor.authorEisman, John
dc.contributor.authorPrice, Ric N
dc.contributor.authorMorris, Peter S
dc.contributor.authorKelly, Paul M
dc.contributor.authorAnstey, Nicholas
dc.date.accessioned2015-10-13T01:42:39Z
dc.date.available2015-10-13T01:42:39Z
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1885/15898
dc.description.abstractBACKGROUND Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). METHODS In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. RESULTS 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. CONCLUSION Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. REGISTRY ClinicalTrials.gov. Registry number: NCT00677339.
dc.description.sponsorshipFunding was provided by the Australian Respiratory Council, a Royal Australasian College of Physicians Covance Award to APR, and the National Health and Medical Research Council (NHMRC) of Australia (Grants 605806 and 496600; Scholarship to APR, Fellowships to APR, TWY, PMK, NMA). RNP is supported by a Wellcome Trust Senior Research Fellowship.
dc.format12 pages
dc.publisherPublic Library of Science
dc.rights© 2013 Ralph et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.sourcePloS one
dc.subjectadolescent
dc.subjectadult
dc.subjectaged
dc.subjectarginine
dc.subjectdouble-blind method
dc.subjectdrug combinations
dc.subjectfemale
dc.subjecthumans
dc.subjectmale
dc.subjectmiddle aged
dc.subjectmycobacterium tuberculosis
dc.subjectnitric oxide
dc.subjectplacebos
dc.subjecttreatment outcome
dc.subjecttuberculosis, pulmonary
dc.subjectvitamin d
dc.subjectyoung adult
dc.titleL-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume8
dcterms.dateAccepted2013-06-12
dc.date.issued2013-08-13
local.identifier.absfor111700
local.identifier.ariespublicationu4971216xPUB379
local.publisher.urlhttps://www.plos.org/
local.type.statusPublished Version
local.contributor.affiliationRalph, Anna P, Charles Darwin University, Australia
local.contributor.affiliationWaramori, G, Public Health & Malaria Control Department, Indonesia
local.contributor.affiliationPontororing, Gysje J, National Institute of Health Research and Development Research Program, Indonesia
local.contributor.affiliationKenangalem, Enny, Menzies School of Health Research, Australia
local.contributor.affiliationWiguna, Andri, International SOS, Indonesia
local.contributor.affiliationTjitra, Emiliana, National Institute of Health Research and Development, Indonesia
local.contributor.affiliationLolong, Dina B, National Institute of Health Research and Development, Indonesia
local.contributor.affiliationYeo, Tsin W., Charles Darwin University, Australia
local.contributor.affiliationChatfield, Mark D, Charles Darwin University, Australia
local.contributor.affiliationSoemanto, Retno K., University of Indonesia, Indonesia
local.contributor.affiliationKelly, Paul, College of Medicine, Biology and Environment, CMBE ANU Medical School, ANU Medical School, The Australian National University
dc.relationhttp://purl.org/au-research/grants/nhmrc/605806
dc.relationhttp://purl.org/au-research/grants/nhmrc/496600
local.identifier.essn1932-6203
local.bibliographicCitation.issue8
local.bibliographicCitation.startpagee70032
local.identifier.doi10.1371/journal.pone.0070032
dc.date.updated2016-06-14T09:10:51Z
local.identifier.scopusID2-s2.0-84880929179
CollectionsANU Research Publications

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