High-Dose Vitamin D<sub>3</sub> during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial

Ganmaa, Davaasambuu; Baatar, Munkhzul; Fawzi, Wafaie W.; Spiegelman, Donna; Willett, Walter C.; Bayasgalan, Purev; Erkhembayar, Baasansuren; Burneebaatar, Buyankhishig; Oyun-Erdene, Sereeter; Jolliffe, David A.; Xenakis, Theodoros; Bromage, Sabri; Bloom, Barry R.; Martineau, Adrian R.

doi:10.1164/rccm.201705-0936oc

Cited by 75 publications

(82 citation statements)

References 18 publications

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“…Until 2017, 11 randomized trials have been published investigating the therapeutic potential of adjunctive vitD 3 treatment in TB [], but consensus on the potential beneficial effects is still lacking. Most trials were too small to demonstrate statistical power, the dosage regimen of vitD 3 was highly variable, as were baseline concentrations of 25(OH)D 3 .…”

Section: Discussionmentioning

confidence: 99%

“…The primary end‐point was mainly time to sputum conversion, while treatment efficacy including smear‐negative patients has rarely been reported. Importantly, most studies used bolus doses of vitD 3 , which have consistently failed to support clinical and microbiological efficacy in TB . VitD 3 given at an early stage of chemotherapy (0, 14, 28, and 42 days) resulted in enhanced sputum conversion only in patients with the Taq1 tt genotype of the VDR , while vitD 3 provided at later time‐points (0, 5 and 8 months) failed to increase 25(OH)D 3 levels and accordingly had no effect compared to placebo .…”

Section: Discussionmentioning

confidence: 99%

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Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

et al. 2018

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Objective. Immunotherapy using vitamin D (vitD 3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD 3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB).Methods. A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD 3 and 2 9 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intentionto-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25 (OH)D 3 concentrations.Results. Most subjects had low baseline plasma 25 (OH)D 3 levels that increased gradually in the vitD 3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. nmol L À1). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (À0.52, 95% CI À0.93, À0.10; P = 0.015) while the modified TB score was reduced at week 8 (À0.58, 95% CI À1.02, À0.14; P = 0.01) and 16 (À0.34, 95% CI À0.64, À0.03; P = 0.03). VitD 3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD 3 + PBA group (12.6%).Conclusion. Daily supplementation with vitD 3 + PBA may ameliorate clinical TB symptoms and diseasespecific complications, while the intervention had no effect on bacterial clearance in sputum.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

et al. 2018

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“…Carefully selected patients may also improve their immune system's capability to control the bacteria by host‐directed therapeutic interventions . As an example for a host‐aimed intervention, vitamin D supplementation has not led to significant improvement of treatment outcomes except for certain subgroups of patients with specific genetic polymorphisms …”

Section: Individualized Therapy Versus Standardized Treatment Regimenmentioning

confidence: 99%

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

et al. 2018

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The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure.

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“…In the largest trial conducted to date, Datta and colleagues investigated effects of high‐dose intramuscular vitamin D 3 and reported a trend towards reduced TB symptom score and higher rates of sputum smear conversion in participants randomized to the intervention arm of the trial; however, P values for inter‐arm comparisons were not presented . Three subsequent trials, one in the Republic of Georgia (, n = 199), one in India (, n = 247) and one in Mongolia (, n = 390), investigated effects of high‐dose oral vitamin D 3 on sputum culture conversion, and reported no significant effect on this outcome.…”

Section: Randomized Controlled Trials Investigating the Effects Of VImentioning

confidence: 99%

“…As standard drugs are not expected to be as efficient, any true effect of vitamin D may be unmasked and should be possible to find in a reasonably large clinical trial. There are studies where MDR‐TB patients were included, revealing a trend towards enhanced improvement of vitamin D in MDR‐TB patients . But in most trials, MDR‐TB has usually been an exclusion criterion or the numbers of MDR‐TB patients in individual studies have not been large enough to make definite conclusions.…”

Section: Potential Future Approaches: Vitamin D Supplementation To Trmentioning

confidence: 99%

Vitamin D and tuberculosis: where next?

2018

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Tuberculosis (TB) has troubled mankind for millennia, but current treatment strategies are long and complicated and the disease remains a major global health problem. The risk of Mycobacterium tuberculosis (Mtb) infection or progression of active TB disease is elevated in individuals with vitamin D deficiency. High-dose vitamin D was used to treat TB in the preantibiotic era, and in vitro experimental data show that vitamin D supports innate immune responses that restrict growth of Mtb. Several randomized controlled trials have tested whether adjunctive vitamin D supplementation enhances the clinical and microbiological response to standard antimicrobial chemotherapy for pulmonary TB. The effects have been modest at best, and attention is turning to the question of whether vitamin D supplementation might have a role in preventing acquisition or reactivation of latent Mtb infection. In this article, we describe the effects of vitamin D on host immune responses to Mtb in vitro and in vivo and review the results of clinical trials in the field. We also reflect on the findings of clinical trials of vitamin D supplementation for the prevention of acute respiratory tract infections, and discuss how these findings might influence the design of future trials to evaluate the role of vitamin D in the prevention and treatment of TB.

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High-Dose Vitamin D₃ during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial

Abstract: Vitamin D did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Cited by 75 publications

References 18 publications

Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

Vitamin D and tuberculosis: where next?

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High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial

Abstract: Vitamin D did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Cited by 75 publications

References 18 publications

Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

Vitamin D and tuberculosis: where next?

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Product

Resources

About

High-Dose Vitamin D₃ during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial

Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia

Daily adjunctive therapy with vitamin D₃ and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia