Tolerability of inhaled N-chlorotaurine in humans: a double-blind randomized phase I clinical study

Abstract

Background:N-chlorotaurine (NCT), a long-lived oxidant produced by human leukocytes, can be synthesized chemically and used topically as a well-tolerated antiseptic to different body regions including sensitive ones. The aim of this study was to test the tolerability of inhaled 1% NCT in aqueous solution upon repeated application.Methods:The study was performed double-blind and randomized with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). There were two Austrian centres involved, the hospitals, Natters and Vöcklabruck. Healthy, full age volunteers were included, 12 in each centre. A total of 12 patients were treated with NCT, and 12 with placebo, exactly half of each group from each centre. The single dose was 1.2 ml inhaled over a period of 10 min using an AKITA JET nebulizer. One inhalation was done every day for five consecutive days. The primary criterion of evaluation was the forced expiratory volume in 1 second (FEV1). Secondary criteria were subjective sensations, further lung function parameters such as airway resistance, physical examination, and blood analyses (gases, electrolytes, organ function values, pharmacokinetic parameters taurine and methionine, immune parameters).Results:All included 15 females and 9 males completed the treatment and the control examinations according to the study protocol. FEV1 (100.83% ± 8.04% for NCT and 92.92% ± 11.35% for controls) remained unchanged and constant during the treatment and in control examinations 1 week and 3 months after the treatment (98.75% ± 7.37% for NCT and 91.17% ± 9.46% for controls, p > 0.082 between time points within each group). The same was true for all other objective parameters. Subjective mild sensations with a higher frequency in the test group were chlorine taste (p < 0.01) and occasional tickle in the throat (p = 0.057). Taurine and methionine plasma concentrations did not change within 60 min after inhalation or later on.Conclusions:Inhaled NCT is well tolerated as in other applications of different body regions. Side effects are mild, topical and transitory. The study was registered prospectively in the European Clinical Trials Database of the European Medicines Agency. The EudraCT number is 2012-003700-12.

Successful treatment of a unique chronic multi-bacterial scalp infection with N-chlorotaurine, N-bromotaurine and bromamine T

“…None of these halogens proved toxic for the patient. This is in agreement with our previous experimental evidence for a low toxicity of halogens against human cells [59] and a remarkable tolerability by human subjects [20,21,61]. No relapse of infection occurred, as the patient remained free of symptoms for many months post-treatment.…”

Swift Cure of a Chronic Wound Infected With Multiresistant Staphylococcus aureus in an Elderly Patient With Stage 5 Renal Disease

“…11 Even inhaled NCT showed good tolerability. 12 N-bromotaurine (NBrT), the taurine-derived natural oxidant preferentially generated by eosinophil peroxidases from hypobromous acid at the site of inflammation, has also combined potent microbicidal and anti-inflammatory activities. 6,8,13 NCT in combination with NBrT cured a herpes zoster case with remarkably rapid reepithelialization.…”

N-chlorotaurine, a novel inhaled virucidal antiseptic is highly active against respiratory viruses including SARS-CoV-2 (COVID-19)

“…Tolerability of repeatedly inhaled NCT has been confirmed in the normal lung and in a streptoccoccal inflammation model each in pigs, and in the normal lung of mice [34][35][36] . In humans, tolerability was confirmed in a placebo-controlled phase I clinical study 16 .…”

“…Safe, well tolerated, affordable, and effective medications are urgently needed against COVID-19 and would be beneficial for treatment of viral bronchopneumonia caused by other viruses such as influenza and RSV. As an endogenous mild long-lived oxidant 17 , inhaled NCT has been demonstrated to be well tolerated and safe in animals (pigs and mice) and in a clinical phase I study in humans 16,[34][35][36] . As an active chlorine compound belonging to the class of chloramines, it has broad-spectrum activity against pathogens without occurrence of resistance because of the oxidizing mechanism of activity with thio-and amino-groups as the main targets 14,22,23 .…”

“…2a) and of 10 min or less ( Fig. 2b-e Further advantages of NCT would be high safety and high tolerability by human tissue 14 , absence of systemic absorption, of systemic adverse effects 16 , of systemic interaction with…”