Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.
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-mycobacter...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4578887?pdf=render |
| _version_ | 1811221384678866944 |
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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 | 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.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.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.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).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.clinicaltrials.gov NCT01580007. |
| first_indexed | 2024-04-12T07:58:22Z |
| format | Article |
| id | doaj.art-08cd874e715147f996f63f7495daf33f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T07:58:22Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-08cd874e715147f996f63f7495daf33f2022-12-22T03:41:24ZengPublic 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 RaqibDevelopment 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.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.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.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).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.clinicaltrials.gov NCT01580007.http://europepmc.org/articles/PMC4578887?pdf=render |
| 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 | http://europepmc.org/articles/PMC4578887?pdf=render |
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