Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity.
BACKGROUND
Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions.


METHODS
Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks.


RESULTS
All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells.


CONCLUSIONS
This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB.
Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.|Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Catalonia, Spain.
Eva
E
Montané
Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Catalonia, Spain.|Fundació Institut Germans Trias i Pujol, Badalona, Catalonia, Spain.
Ana Maria
AM
Barriocanal
Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.|Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Catalonia, Spain.
Ana Lucía
AL
Arellano
Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
Angelica
A
Valderrama
Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain.
Yolanda
Y
Sanz
Lluita Contra la Sida Foundation, Badalona, Catalonia, Spain.|Statistics and Operations Research Department, Universitat Politècnica de Catalunya- BarcelonaTech, Barcelona, Catalonia, Spain.
Nuria
N
Perez-Alvarez
Unitat de Tuberculosi Experimental, Universitat Autònoma de Barcelona, CIBERES, Fundació Institut Germans Trias i Pujol, Badalona, Catalonia, Spain.
Paula
P
Cardona
Unitat de Tuberculosi Experimental, Universitat Autònoma de Barcelona, CIBERES, Fundació Institut Germans Trias i Pujol, Badalona, Catalonia, Spain.
Cristina
C
Vilaplana
Unitat de Tuberculosi Experimental, Universitat Autònoma de Barcelona, CIBERES, Fundació Institut Germans Trias i Pujol, Badalona, Catalonia, Spain.
Pere-Joan
http://orcid.org/0000-0001-5623-7873
PJ
Cardona
D000328:Adult; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D055985:Latent Tuberculosis / Q000178:diet therapy* / Q000276:immunology; D008297:Male; D050296:Microbial Viability; D009161:Mycobacterium / Q000276:immunology; D010865:Pilot Projects; D010919:Placebos; D019936:Probiotics / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
D010919:Placebos