Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.
<h4>Background</h4>Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-...
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Public Library of Science (PLoS)
2015-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0138340&type=printable |
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| author | Akhirunnesa Mily Rokeya Sultana Rekha S M Mostafa Kamal Abu Saleh Mohammad Arifuzzaman Zeaur Rahim Lamia Khan Md Ahsanul Haq Khaliqu Zaman Peter Bergman Susanna Brighenti Gudmundur H Gudmundsson Birgitta Agerberth Rubhana Raqib |
| author_facet | Akhirunnesa Mily Rokeya Sultana Rekha S M Mostafa Kamal Abu Saleh Mohammad Arifuzzaman Zeaur Rahim Lamia Khan Md Ahsanul Haq Khaliqu Zaman Peter Bergman Susanna Brighenti Gudmundur H Gudmundsson Birgitta Agerberth Rubhana Raqib |
| author_sort | Akhirunnesa Mily |
| collection | DOAJ |
| description | <h4>Background</h4>Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.<h4>Objective</h4>To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.<h4>Methods</h4>Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.<h4>Results</h4>At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).<h4>Conclusion</h4>Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.<h4>Trial registration</h4>clinicaltrials.gov NCT01580007. |
| format | Article |
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| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
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| spelling | doaj-art-08cd874e715147f996f63f7495daf33f2025-08-20T02:28:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013834010.1371/journal.pone.0138340Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.Akhirunnesa MilyRokeya Sultana RekhaS M Mostafa KamalAbu Saleh Mohammad ArifuzzamanZeaur RahimLamia KhanMd Ahsanul HaqKhaliqu ZamanPeter BergmanSusanna BrighentiGudmundur H GudmundssonBirgitta AgerberthRubhana Raqib<h4>Background</h4>Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.<h4>Objective</h4>To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.<h4>Methods</h4>Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.<h4>Results</h4>At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).<h4>Conclusion</h4>Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.<h4>Trial registration</h4>clinicaltrials.gov NCT01580007.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0138340&type=printable |
| spellingShingle | Akhirunnesa Mily Rokeya Sultana Rekha S M Mostafa Kamal Abu Saleh Mohammad Arifuzzaman Zeaur Rahim Lamia Khan Md Ahsanul Haq Khaliqu Zaman Peter Bergman Susanna Brighenti Gudmundur H Gudmundsson Birgitta Agerberth Rubhana Raqib Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. PLoS ONE |
| title | Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. |
| title_full | Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. |
| title_fullStr | Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. |
| title_full_unstemmed | Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. |
| title_short | Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial. |
| title_sort | significant effects of oral phenylbutyrate and vitamin d3 adjunctive therapy in pulmonary tuberculosis a randomized controlled trial |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0138340&type=printable |
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