Pilot, double-blind, randomized, placebocontrolled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity

PLoS ONE

Volumn 12, Issue 2, 2017, Pages

  Montané, Eva ^a,b   Barriocanal, Ana Maria ^b,c   Arellano, Ana Lucía ^a,b   Valderramal, Angelica ^a   Sanz, Yolanda ^a   Perez Alvarez, Nuria ^d,e   Cardona, Paula ^b   Vilaplana, Cristina ^b   Cardona, Pere Joan ^b  

^a HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^b UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^c Fundacio Institut DInvestigacio Germans Trias i Pujol   (Spain)

^d Lluita Contra la SIDA Foundation   (Spain)

^e UNIVERSITAT POLITÈCNICA DE CATALUNYA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CD39 ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA; LIVER ENZYME; MICROBIAL PRODUCTS NOT CLASSIFIED ELSEWHERE; NYADITUM RESAE; PLACEBO; UNCLASSIFIED DRUG; PROBIOTIC AGENT;

ABDOMINAL PAIN; ADULT; ARTICLE; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; DEFECATION; DIARRHEA; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; EFFECTOR CELL; EPIGASTRIC PAIN; FEMALE; FLATULENCE; GASTROINTESTINAL DISEASE; HEADACHE; HEMATOLOGICAL PARAMETERS; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; IMMUNOGENICITY; LATENT TUBERCULOSIS; LOW DRUG DOSE; MALE; MEMORY T LYMPHOCYTE; MIGRAINE; MYCOBACTERIUM; MYCOBACTERIUM MANRESENSIS; NAUSEA; PILOT STUDY; RANDOMIZED CONTROLLED TRIAL; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT INFECTION; SIDE EFFECT; TENESMUS; THROMBOCYTOPENIA; VOMITING; ADVERSE EFFECTS; CLINICAL TRIAL; DIET THERAPY; DIETARY SUPPLEMENT; IMMUNOLOGY; MICROBIAL VIABILITY; PHASE 1 CLINICAL TRIAL; YOUNG ADULT;

ADULT; DIETARY SUPPLEMENTS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; LATENT TUBERCULOSIS; MALE; MICROBIAL VIABILITY; MYCOBACTERIUM; PILOT PROJECTS; PLACEBOS; PROBIOTICS; YOUNG ADULT;

EID: 85012054087     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0171294     Document Type: Article

References (54)

1. Murray CJL, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London, England). 2014; 384: 1005-70.
2. Colditz GA, Berkey CS, Mosteller F, Brewer TF, Wilson ME, Burdick E, et al. The efficacy of bacillus Calmette-Gué rin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics. 1995; 96: 29-35. PMID: 7596718
3. Jung Y-J, Ryan L, LaCourse R, North RJ. Properties and protective value of the secondary versus primary T helper type 1 response to airborne Mycobacterium tuberculosis infection in mice. J Exp Med. 2005; 201: 1915-24. doi: 10.1084/jem.20050265 PMID: 15955839
4. North RJ, Jung YJ. Immunity to tuberculosis. Annu Rev Immunol. 2004; 22: 599-623. doi: 10.1146/ annurev.immunol.22.012703.104635 PMID: 15032590
5. Parrish NM, Dick JD, Bishai WR. Mechanisms of latency in Mycobacterium tuberculosis. Trends Microbiol. 1998; 6: 107-112. PMID: 9582936
6. Vilaplana C, Prats C, Marzo E, Barril C, Vegué M, Diaz J, et al. To achieve an earlier IFN-γ response is not sufficient to control Mycobacterium tuberculosis infection in mice. PLoS One. 2014; 9: e100830. doi: 10.1371/journal.pone.0100830 PMID: 24959669
7. Menzies D, Gardiner G, Farhat M, Greenaway C, Pai M. Thinking in three dimensions: A web-based algorithm to aid the interpretation of tuberculin skin test results. Int J Tuberc Lung Dis. 2008; 12: 498-505. PMID: 18419884
8. Vilaplana C, Cardona P-J. The lack of a big picture in tuberculosis: the clinical point of view, the problems of experimental modeling and immunomodulation. The factors we should consider when designing novel treatment strategies. Front Microbiol. 2014; 5: 55. doi: 10.3389/fmicb.2014.00055 PMID: 24592258
9. Marzo E, Vilaplana C, Tapia G, Diaz J, Garcia V, Cardona P-J. Damaging role of neutrophilic infiltration in a mouse model of progressive tuberculosis. Tuberculosis (Edinb). 2014; 94: 55-64.
10. Odone A, Houben RMGJ, White RG, Lönnroth K. The effect of diabetes and undernutrition trends on reaching 2035 global tuberculosis targets. Lancet Diabetes Endocrinol. 2014; 2: 754-764. doi: 10.1016/ S2213-8587(14)70164-0 PMID: 25194888
11. Sun Q, Zhang Q, Xiao H, Cui H, Su B. Significance of the frequency of CD4+CD25+CD127- T-cells in patients with pulmonary tuberculosis and diabetes mellitus. Respirology. Blackwell Publishing Asia; 2012; 17: 876-882.
12. Honkanen J, Nieminen JK, Gao R, Luopajarvi K, Salo HM, Ilonen J, et al. IL-17 immunity in human type 1 diabetes. J Immunol. American Association of Immunologists; 2010; 185: 1959-1967.
13. Ocejo-Vinyals JG, de Mateo EP, Hoz MÁ , Arroyo JL, Agüero R, Ausín F, et al. The IL-17 G-152A single nucleotide polymorphism is associated with pulmonary tuberculosis in northern Spain. Cytokine. 2013.
14. de Cassan SC, Pathan AA, Sander CR, Minassian A, Rowland R, Hill AVS, et al. Investigating the induction of vaccine-induced Th17 and regulatory T cells in healthy, Mycobacterium bovis BCG-immunized adults vaccinated with a new tuberculosis vaccine, MVA85A. Clin Vaccine Immunol. 2010; 17: 1066-73. doi: 10.1128/CVI.00047-10 PMID: 20484570
15. Zheng SG. Regulatory T cells vs Th17: differentiation of Th17 versus Treg, are the mutually exclusive? Am J Clin Exp Immunol. 2013; 2: 94-106. PMID: 23885327
16. Chaudhry A, Rudensky AY. Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest. American Society for Clinical Investigation; 2013; 123: 939-44.
17. Zhou L, Lopes JE, Chong MMW, Ivanov II, Min R, Victora GD, et al. TGF-beta-induced Foxp3 inhibits T (H)17 cell differentiation by antagonizing RORgammat function. Nature. 2008; 453: 236-40. doi: 10. 1038/nature06878 PMID: 18368049
18. May YL, Reddy TBK, Arend SM, Friggen AH, Franken KLMC, Van Meijgaarden KE, et al. Cross-reactive immunity to Mycobacterium tuberculosis DosR regulon-encoded antigens in individuals infected with environmental, nontuberculous mycobacteria. Infect Immun. American Society for Microbiology (ASM); 2009; 77: 5071-5079.
19. Serafini M, Stanzione A, Foddai S. Functional foods: traditional use and European legislation. Int J Food Sci Nutr. Taylor & Francis; 2012; 63 Suppl 1: 7-9.
20. Tortoli E, Nanetti A, Piersimoni C, Cichero P, Farina C, Mucignat G, et al. Performance assessment of new multiplex probe assay for identification of mycobacteria. J Clin Microbiol. American Society for Microbiology; 2001; 39: 1079-1084.
21. Rech G, Vilaplana C, Velasco J, Pluvinet R, Santín S, Prat C, et al. Draft Genome Sequences of Mycobacterium setense Type Strain DSM-45070 and the Nonpathogenic Strain Manresensis, Isolated from the Bank of the Cardener River in Manresa, Catalonia, Spain. Genome Announc. 2015; 3.
22. Cardona P, Marzo-Escartín E, Tapia G, Díaz J, García V, Varela I, et al. Oral administration of heatkilled mycobacterium manresensis delays progression toward active tuberculosis in C3HeB/FeJ mice. Front Microbiol. 2016; 6: 4-7.
23. Meyboom RHB, Royer RJ. Causality classification at pharmacovigilance centres in the european community. Pharmacoepidemiol Drug Saf. 1992; 1: 87-97.
24. Karch FE, Lasagna L. Toward the operational identification of adverse drug reactions. Clin Pharmacol Ther. 1977; 21: 247-54. PMID: 837643
25. Norquist JM, Khawaja SS, Kurian C, Mast TC, Liaw KL, Robertson MN, et al. Adaptation of a previously validated vaccination report card for use in adult vaccine clinical trials to align with the 2007 FDA Toxicity Grading Scale Guidance. Hum Vaccines Immunother. 2012; 8: 1208-1212.
26. Dwyer KM, Hanidziar D, Putheti P, Hill PA, Pommey S, McRae JL, et al. Expression of CD39 by human peripheral blood CD4+CD25 + T cells denotes a regulatory memory phenotype. Am J Transplant. 2010; 10: 2410-2420. doi: 10.1111/j.1600-6143.2010.03291.x PMID: 20977632
27. Chiacchio T, Casetti R, Butera O, Vanini V, Carrara S, Girardi E, et al. Characterization of regulatory T cells identified as CD4 +CD25 highCD39 + in patients with active tuberculosis. Clin Exp Immunol. 2009; 156: 463-470. doi: 10.1111/j.1365-2249.2009.03908.x PMID: 19438599
28. Feruglio SL, Tonby K, Kvale D, Dyrhol-Riise AM. Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection. Clin Exp Immunol. 2015; 179: 454-465. doi: 10.1111/cei.12468 PMID: 25313008
29. Guyot-Revol V, Innes JA, Hackforth S, Hinks T, Lalvani A. Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med. 2006; 173: 803-810. doi: 10. 1164/rccm.200508-1294OC PMID: 16339919
30. Rosenzweig P, Brohier S, Zipfel A. The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Clin Pharmacol Ther. 1993; 54: 578-583. PMID: 8222500
31. Rief W, Hessel A, Braehler E. Somatization symptoms and hypochondriacal features in the general population. Psychosom Med. 63: 595-602. PMID: 11485113
32. West NP, Pyne DB, Peake JM, Cripps AW. Probiotics, immunity and exercise: A review. Exercise Immunology Review. 2009. pp. 107-126. PMID: 19957873
33. Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev. 2010; 23: 37-46. doi: 10.1017/S0954422410000090 PMID: 20403231
34. Lahtinen SJ. Probiotic viability-does it matter? Microb Ecol Heal Dis. Co-Action Publishing; 2012; 23: 10-14.
35. Taverniti V, Guglielmetti S. The immunomodulatory properties of probiotic microorganisms beyond their viability (ghost probiotics: proposal of paraprobiotic concept). Genes Nutr. BioMed Central; 2011; 6: 261-74.
36. Shinkai S, Toba M, Saito T, Sato I, Tsubouchi M, Taira K, et al. Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebocontrolled trial. Br J Nutr. 2013; 109: 1856-65. doi: 10.1017/S0007114512003753 PMID: 22947249
37. Zhang B, An J, Shimada T, Liu S, Maeyama K. Oral administration of Enterococcus faecalis FK-23 suppresses Th17 cell development and attenuates allergic airway responses in mice. Int J Mol Med. 2012; 248-254. doi: 10.3892/ijmm.2012.1010 PMID: 22641478
38. Gil O, Díaz I, Vilaplana C, Tapia G, Díaz J, Fort M, et al. Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs. Doherty TM, editor. PLoS One. Public Library of Science; 2010; 5: e10030.
39. Chen X, Zhou B, Li M, Deng Q, Wu X, Le X, et al. CD4+CD25+FoxP3+ regulatory T cells suppress Mycobacterium tuberculosis immunity in patients with active disease. Clin Immunol. 2007; 123: 50-59. doi: 10.1016/j.clim.2006.11.009 PMID: 17234458
40. Hougardy JM, Place S, Hildebrand M, Drowart A, Debrie AS, Locht C, et al. Regulatory T cells depress immune responses to protective antigens in active tuberculosis. Am J Respir Crit Care Med. 2007; 176: 409-416. doi: 10.1164/rccm.200701-084OC PMID: 17541018
41. Li L, Lao S, Wu C. Increased frequency of CD4+CD25high Treg cells inhibit BCG-specific induction of IFN-γ by CD4+ T cells from TB patients. Tuberculosis. 2007; 87: 526-534. doi: 10.1016/j.tube.2007.07. 004 PMID: 17851131
42. Jaron B, Maranghi E, Leclerc C, Majlessi L. Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis. PLoS One. 2008; 3: e2833. doi: 10.1371/journal.pone.0002833 PMID: 18665224
43. Quinn KM, McHugh RS, Rich FJ, Goldsack LM, De Lisle GW, Buddle BM, et al. Inactivation of CD4 +CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load. Immunol Cell Biol. 2006; 84: 467-474. doi: 10.1111/j.1440-1711.2006.01460. x PMID: 16869940
44. Shafiani S, Tucker-Heard G, Kariyone A, Takatsu K, Urdahl KB. Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis. J Exp Med. 2010; 207: 1409-20. doi: 10.1084/jem.20091885 PMID: 20547826
45. Chen CY, Huang D, Yao S, Halliday L, Zeng G, Wang RC, et al. IL-2 simultaneously expands Foxp3+ T regulatory and T effector cells and confers resistance to severe tuberculosis (TB): implicative Treg-T effector cooperation in immunity to TB. J Immunol. 2012; 188: 4278-4288. doi: 10.4049/jimmunol. 1101291 PMID: 22474020
46. Scarlata G, Pellerito AM, Di Benedetto M, Massenti MF, Nastasi A. Isolation of Mycobacteria from drinking water in Palermo. Boll Ist Sieroter Milan. 1985; 64: 479-82. PMID: 4096841
47. Imwidthaya P, Suthiravitayavaniz K, Phongpanich S. Mycobacterium other than tubercle bacilli in various environments in Bangkok. J Med Assoc Thail. 1989; 72: 317-320.
48. Kubalek I, Mysak J. The prevalence of environmental mycobacteria in drinking water supply systems in a demarcated region in Czech Republic, in the period 1984-1989. Eur J Epidemiol. 1996; 12: 471-4. PMID: 8905307
49. Fernandez-Rendon E, Cerna-Cortes JF, Ramirez-Medina MA, Helguera-Repetto AC, Rivera-Gutierrez S, Estrada-Garcia T, et al. Mycobacterium mucogenicum and other non-tuberculous mycobacteria in potable water of a trauma hospital: A potential source for human infection. J Hosp Infect. Elsevier; 2012; 80: 74-76.
50. Nasr-Esfahani B, Sarikhani E, Moghim S, Faghri J, Fazeli H, Hoseini N, et al. Molecular characterization of environmental non-tuberculous mycobacteria using PCR- RFLP analysis of 441 Bp heat shock protein 65 fragments. Iran J Public Health. 2012; 41: 108-114. PMID: 23113172
51. Moghim S, Sarikhani E, Esfahani BN, Faghri J. Identification of nontuberculous mycobacteria species isolated from water samples using phenotypic and molecular methods and determination of their antibiotic resistance patterns by E- test method, in Isfahan, Iran. Iran J Basic Med Sci. 2012; 15: 1076-1082. PMID: 23493797
52. Martín Casabona N, Rosselló Urgell J. [Environmental mycobacteria in Spain: isolations in the 1976-1996 period]. Med cliínica. 2000; 115: 663-70.
53. Stein CM. Genetic epidemiology of tuberculosis susceptibility: Impact of study design. Manchester M, editor. PLoS Pathogens. 2011. p. e1001189. doi: 10.1371/journal.ppat.1001189 PMID: 21283783
54. Mö ller M, Hoal EG. Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis. Tuberculosis (Edinb). 2010; 90: 71-83.