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

NCT ID: NCT00677339

Last Updated: 2012-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2010-05-31

Brief Summary

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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.

Detailed Description

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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

Conditions

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Smear Positive Pulmonary Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Active L-arginine plus active vitamin D

Group Type ACTIVE_COMPARATOR

L-arginine

Intervention Type DRUG

L-arginine 6g orally daily

Vitamin D

Intervention Type DRUG

Cholecalciferol 50000 IU once monthly orally

2

Placebo L-arginine plus active Vitamin D

Group Type ACTIVE_COMPARATOR

Vitamin D

Intervention Type DRUG

Cholecalciferol 50000 IU once monthly orally

Placebo L-arginine

Intervention Type DRUG

placebo L-arginine once daily

3

Active L-arginine plus placebo vitamin D

Group Type ACTIVE_COMPARATOR

L-arginine

Intervention Type DRUG

L-arginine 6g orally daily

Placebo Vitamin D

Intervention Type DRUG

placebo vitamin D orally once monthly

4

placebo L-arginine plus placebo vitamin D

Group Type PLACEBO_COMPARATOR

Placebo L-arginine

Intervention Type DRUG

placebo L-arginine once daily

Placebo Vitamin D

Intervention Type DRUG

placebo vitamin D orally once monthly

Interventions

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L-arginine

L-arginine 6g orally daily

Intervention Type DRUG

Vitamin D

Cholecalciferol 50000 IU once monthly orally

Intervention Type DRUG

Placebo L-arginine

placebo L-arginine once daily

Intervention Type DRUG

Placebo Vitamin D

placebo vitamin D orally once monthly

Intervention Type DRUG

Other Intervention Names

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Argimax Calciferol Strong

Eligibility Criteria

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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
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Health Research and Development, Ministry of Health Republic of Indonesia

OTHER

Sponsor Role collaborator

Australian National University

OTHER

Sponsor Role collaborator

Menzies School of Health Research

OTHER

Sponsor Role lead

Responsible Party

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Dr Anna Ralph

Global and Tropical Health

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nicholas M Anstey, MBBS

Role: STUDY_DIRECTOR

Menzies School of Helath Research

Anna P Ralph, MBBS

Role: PRINCIPAL_INVESTIGATOR

Australian National University, Canberra, Australia

Franciscus Thio, MPPM

Role: PRINCIPAL_INVESTIGATOR

District Ministry of Health, Timika

Peter Morris, MBBS

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research, Northern Territory, Australia

Enny Kenangalem, MD

Role: PRINCIPAL_INVESTIGATOR

Papuan Community Health and Development Foundation

Jeanne R Poespoprodjo, MD

Role: PRINCIPAL_INVESTIGATOR

Mimika District Health Authority

Richard N Price, MD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Tonia Woodberry, PhD

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Paul M Kelly, MBBS

Role: PRINCIPAL_INVESTIGATOR

Australian Capital Territory Department of Health

Emiliana Tjitra, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Health Research and Development, Ministry of Health Republic of Indonesia

Sandjaja Sandjaja, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Health Research and Development, Ministry of Health Republic of Indonesia

Dina B Lolong, MD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Health Research and Development

Mark Chatfield, PhD

Role: PRINCIPAL_INVESTIGATOR

National Health and Medical Research Council (Australia) Clinical Trials Centre

Ivan Bastian, MBBS

Role: PRINCIPAL_INVESTIGATOR

Institute of Medical and Veterinary Pathology, South Australia

Locations

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Timika Tuberculosis Clinic and Community Hospital

Timika, Papua Province, Indonesia

Site Status

Countries

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Indonesia

References

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Ralph AP, Waramori G, Pontororing GJ, Kenangalem E, Wiguna A, Tjitra E, Sandjaja, Lolong DB, Yeo TW, Chatfield MD, Soemanto RK, Bastian I, Lumb R, Maguire GP, Eisman J, Price RN, Morris PS, Kelly PM, Anstey NM. L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial. PLoS One. 2013 Aug 14;8(8):e70032. doi: 10.1371/journal.pone.0070032. eCollection 2013.

Reference Type DERIVED
PMID: 23967066 (View on PubMed)

Other Identifiers

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AVDAPT 1

Identifier Type: -

Identifier Source: org_study_id

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