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| Name | Class |
|---|---|
| National Institute of Health Research and Development, Ministry of Health Republic of Indonesia | OTHER |
| Australian National University | OTHER |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Active L-arginine plus active vitamin D |
|
| 2 | Active Comparator | Placebo L-arginine plus active Vitamin D |
|
| 3 | Active Comparator | Active L-arginine plus placebo vitamin D |
|
| 4 | Placebo Comparator | placebo L-arginine plus placebo vitamin D |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-arginine | Drug | L-arginine 6g orally daily |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Proportion of pulmonary TB patients who are culture negative at 1 month | 1 month | |
| Difference in improvement in composite clinical endpoint comprising weight, cough clearance and FEV1 at 2 months. | 2 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in plasma L-arginine concentration | week 0, 2, 4, 8, 24 | |
| Change in plasma 25(OH)D3 concentration | week 0, 2, 4, 8, 24 | |
| Death, clinical failure and default independently, and 'death or clinical failure or default'. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nicholas M Anstey, MBBS | Menzies School of Helath Research | Study Director |
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Timika Tuberculosis Clinic and Community Hospital | Timika | Papua Province | Indonesia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23967066 | Derived | 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. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Oct 13, 2022 | |
| Reset | Aug 28, 2023 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Oct 13, 2022 | Aug 28, 2023 |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| ID | Term |
|---|---|
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
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| ID | Term |
|---|---|
| D001120 | Arginine |
| D014807 | Vitamin D |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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| Vitamin D | Drug | Cholecalciferol 50000 IU once monthly orally |
|
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| Placebo L-arginine | Drug | placebo L-arginine once daily |
|
| Placebo Vitamin D | Drug | placebo vitamin D orally once monthly |
|
| week 24 |
| Hypercalcaemia | week 0, 2, 4, 8, 24 |
| Gastrointestinal side effects | weekly to week 8 then at week 24 |
| Sputum smear conversion time | weekly to week 8 then at week 24 |
| Radiological improvement (percentage lung involvement on CXR at 2 months). | week 0, 2, 4, 8, 24 |
| Cough clearance | weekly to week 8 then at week 24 |
| Difference in improvement in percent predicted FEV1 at 2 and 6 months. | weeks 0, 4, 8, 24 |
| Weight gain | weekly to week 8 then at week 24 |
| Immunological improvement (exhaled NO) | week 0, 2, 4, 8, 24 |
| Immunological improvement (T cell CD3ΞΆ expression and T cell function) | week 0, 2, 4, 24 |
| Functional improvement measured using six minute walk test | week 0, 4, 8, 24 |
| Quality of life assessment using modified St George Respiratory Questionnaire. | weeks 0, 4, 8, 24 |
| Primary end points stratified by HIV status. | weekly to week 8 then at week 24 |
| Primary end points stratified by baseline vitamin D and L-arginine status. | weekly to week 8 then week 24 |
| Primary end points stratified by ethnicity (Papuan and non-Papuan patients). | weekly to week 8 then week 24 |
| Emiliana Tjitra, MD, PhD | National Institute of Health Research and Development, Ministry of Health Republic of Indonesia | Principal Investigator |
| Sandjaja Sandjaja, PhD | National Institute of Health Research and Development, Ministry of Health Republic of 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 | Principal Investigator |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000601 | Amino Acids, Essential |
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |