L-arginine and Vitamin D Adjunctive Therapy in Pulmonary Tuberculosis (TB) (AVDAPT)
This study has been completed.
Sponsor:
Menzies School of Health Research
Collaborators:
National Institute of Health Research and Development, Indonesia
Australian National University
Information provided by (Responsible Party):
Dr Anna Ralph, Menzies School of Health Research
ClinicalTrials.gov Identifier:
NCT00677339
First received: May 12, 2008
Last updated: January 17, 2012
Last verified: January 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Smear Positive Pulmonary Tuberculosis |
Drug: L-arginine Drug: Vitamin D Drug: Placebo L-arginine Drug: Placebo Vitamin D |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Phase 3 Trial of Oral L-arginine and / or Vitamin D as Adjunctive Therapies in Pulmonary Tuberculosis in Papua Province, Indonesia. |
Resource links provided by NLM:
Further study details as provided by Menzies School of Health Research:
Primary Outcome Measures:
- Proportion of pulmonary TB patients who are culture negative at 1 month [ Time Frame: 1 month ] [ Designated as safety issue: No ]
- Difference in improvement in composite clinical endpoint comprising weight, cough clearance and FEV1 at 2 months. [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Change in plasma L-arginine concentration [ Time Frame: week 0, 2, 4, 8, 24 ] [ Designated as safety issue: Yes ]
- Change in plasma 25(OH)D3 concentration [ Time Frame: week 0, 2, 4, 8, 24 ] [ Designated as safety issue: Yes ]
- Death, clinical failure and default independently, and 'death or clinical failure or default'. [ Time Frame: week 24 ] [ Designated as safety issue: Yes ]
- Hypercalcaemia [ Time Frame: week 0, 2, 4, 8, 24 ] [ Designated as safety issue: Yes ]
- Gastrointestinal side effects [ Time Frame: weekly to week 8 then at week 24 ] [ Designated as safety issue: Yes ]
- Sputum smear conversion time [ Time Frame: weekly to week 8 then at week 24 ] [ Designated as safety issue: No ]
- Radiological improvement (percentage lung involvement on CXR at 2 months). [ Time Frame: week 0, 2, 4, 8, 24 ] [ Designated as safety issue: No ]
- Cough clearance [ Time Frame: weekly to week 8 then at week 24 ] [ Designated as safety issue: No ]
- Difference in improvement in percent predicted FEV1 at 2 and 6 months. [ Time Frame: weeks 0, 4, 8, 24 ] [ Designated as safety issue: No ]
- Weight gain [ Time Frame: weekly to week 8 then at week 24 ] [ Designated as safety issue: No ]
- Immunological improvement (exhaled NO) [ Time Frame: week 0, 2, 4, 8, 24 ] [ Designated as safety issue: No ]
- Immunological improvement (T cell CD3ζ expression and T cell function) [ Time Frame: week 0, 2, 4, 24 ] [ Designated as safety issue: No ]
- Functional improvement measured using six minute walk test [ Time Frame: week 0, 4, 8, 24 ] [ Designated as safety issue: No ]
- Quality of life assessment using modified St George Respiratory Questionnaire. [ Time Frame: weeks 0, 4, 8, 24 ] [ Designated as safety issue: No ]
- Primary end points stratified by HIV status. [ Time Frame: weekly to week 8 then at week 24 ] [ Designated as safety issue: No ]
- Primary end points stratified by baseline vitamin D and L-arginine status. [ Time Frame: weekly to week 8 then week 24 ] [ Designated as safety issue: No ]
- Primary end points stratified by ethnicity (Papuan and non-Papuan patients). [ Time Frame: weekly to week 8 then week 24 ] [ Designated as safety issue: No ]
| Enrollment: | 200 |
| Study Start Date: | June 2008 |
| Study Completion Date: | May 2010 |
| Primary Completion Date: | February 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
Active L-arginine plus active vitamin D
|
Drug: L-arginine
L-arginine 6g orally daily
Other Name: Argimax
Drug: Vitamin D
Cholecalciferol 50000 IU once monthly orally
Other Name: Calciferol Strong
|
|
Active Comparator: 2
Placebo L-arginine plus active Vitamin D
|
Drug: Vitamin D
Cholecalciferol 50000 IU once monthly orally
Other Name: Calciferol Strong
Drug: Placebo L-arginine
placebo L-arginine once daily
|
|
Active Comparator: 3
Active L-arginine plus placebo vitamin D
|
Drug: L-arginine
L-arginine 6g orally daily
Other Name: Argimax
Drug: Placebo Vitamin D
placebo vitamin D orally once monthly
|
|
Placebo Comparator: 4
placebo L-arginine plus placebo vitamin D
|
Drug: Placebo L-arginine
placebo L-arginine once daily
Drug: Placebo Vitamin D
placebo vitamin D orally once monthly
|
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:
- 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)].
- 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| Ages Eligible for Study: | 15 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00677339
Locations
| Indonesia | |
| Timika Tuberculosis Clinic and Community Hospital | |
| Timika, Papua Province, Indonesia | |
Sponsors and Collaborators
Menzies School of Health Research
National Institute of Health Research and Development, Indonesia
Australian National University
Investigators
| Study Director: | Nicholas M Anstey, MBBS | Menzies School of Helath Research |
| Principal Investigator: | Anna P Ralph, MBBS | Australian National University, Canberra, Australia |
| Principal Investigator: | Franciscus Thio, MPPM | District Ministry of Health, Timika |
| Principal Investigator: | Peter Morris, MBBS | Menzies School of Health Research, Northern Territory, Australia |
| Principal Investigator: | Enny Kenangalem, MD | Papuan Community Health and Development Foundation |
| Principal Investigator: | Jeanne R Poespoprodjo, MD | Mimika District Health Authority |
| Principal Investigator: | Richard N Price, MD | Menzies School of Health Research |
| Principal Investigator: | Tonia Woodberry, PhD | Menzies School of Health Research |
| Principal Investigator: | Paul M Kelly, MBBS | Australian Capital Territory Department of Health |
| Principal Investigator: | Emiliana Tjitra, MD, PhD | National Institute of Health Research and Development, Indonesia |
| Principal Investigator: | Sandjaja Sandjaja, PhD | National Institute of Health Research and Development, Indonesia |
| Principal Investigator: | Dina B Lolong, MD | National Institute of Health Research and Development |
| Principal Investigator: | Mark Chatfield, PhD | National Health and Medical Research Council (Australia) Clinical Trials Centre |
| Principal Investigator: | Ivan Bastian, MBBS | Institute of Medical and Veterinary Pathology, South Australia |
More Information
No publications provided
| Responsible Party: | Dr Anna Ralph, Global and Tropical Health, Menzies School of Health Research |
| ClinicalTrials.gov Identifier: | NCT00677339 History of Changes |
| Other Study ID Numbers: | AVDAPT 1 |
| Study First Received: | May 12, 2008 |
| Last Updated: | January 17, 2012 |
| Health Authority: | Indonesia: Ministry of Health |
Keywords provided by Menzies School of Health Research:
|
Tuberculosis Adjunctive therapy L-arginine Nitric oxide Vitamin D |
Additional relevant MeSH terms:
|
Tuberculosis Tuberculosis, Pulmonary Mycobacterium Infections Actinomycetales Infections Gram-Positive Bacterial Infections Bacterial Infections Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections |
Ergocalciferols Vitamin D Vitamins Bone Density Conservation Agents Physiological Effects of Drugs Pharmacologic Actions Micronutrients Growth Substances |
ClinicalTrials.gov processed this record on May 23, 2013