Evaluation of Biological and Functional Changes in Healthy Smokers Switching to the Tobacco Heating System 2.2 Versus Continued Tobacco Smoking: Protocol for a Randomized, Controlled, Multicenter Study

Abstract

BackgroundTobacco harm reduction, substituting less harmful tobacco products for combustible cigarettes, is a complementary approach for smokers who would otherwise continue to smoke. The Philip Morris International (PMI) Tobacco Heating System (THS) 2.2 is a novel tobacco product with the potential to reduce the risk of harm in smokers compared to continued smoking of combustible cigarettes. It heats tobacco electrically in a controlled manner, never allowing the temperature to exceed 350°C, thereby preventing the combustion process from taking place and producing substantially lower levels of toxicants while providing nicotine, taste, ritual, and a sensory experience that closely parallels combustible cigarettes. Previous clinical studies have demonstrated reduced exposure to the toxicants (approaching the levels observed after quitting) for smokers who switched to THS 2.2, for three months. For adult smokers who would otherwise continue smoking combustible cigarettes, switching to THS 2.2 may represent an alternative way to reduce the risk of tobacco-related diseases.ObjectiveThis study aimed to further substantiate the harm reduction potential of THS 2.2 by demonstrating favorable changes in a set of 8 coprimary endpoints, representative of pathomechanistic pathways (ie, inflammation, oxidative stress, lipid metabolism, respiratory function, and genotoxicity), linked to smoking-related diseases, in smokers switching from combustible cigarettes to THS 2.2.MethodsThis study was a randomized, controlled, two-arm parallel group, multicenter ambulatory US study conducted in healthy adult smokers switching from combustible cigarettes to THS 2.2 compared with smokers continuing to smoke combustible cigarettes for six months. Subjects had a smoking history of at least ten years and did not intend to quit within the next six months.ResultsEnrollment started in March 2015 and the trial was completed in September 2016. In total, 984 subjects were randomized (combustible cigarettes, n=483; THS 2.2, n=477), and 803 completed the study. The results are expected to be available in a subsequent publication in 2019.ConclusionsIn this paper, we describe the rationale and design for this clinical study that focused on the evaluation of THS 2.2’s potential to reduce the risk of smoking-related diseases compared with that of combustible cigarettes. This study will provide insights regarding favorable changes in biological and functional endpoints informed by effects known to be seen upon smoking cessation.Trial RegistrationClinicalTrials.gov NCT02396381; http://clinicaltrials.gov/ct2/show/NCT02396381 (Archived by WebCite at http://www.webcitation.org/71PCRdagP)Registered Report IdentifierRR1-10.2196/11294

The impact of heated tobacco products on arterial stiffness

“…In line with these findings, the combination of nicotine and other harmful compounds in smoke and vape is one of the most likely explanations for the effects on the cardiovascular system 10 and lungs. 3,11,12 These components might also trigger an endothelial dysfunction and an increase of arterial stiffness, which might trigger cardiovascular events. 13 The first limitation of our study is the number of subjects who were studied.…”

Effect of Switching to the Tobacco Heating System Versus Continued Cigarette Smoking on Chronic Generalized Periodontitis Treatment Outcome: Protocol for a Randomized Controlled Multicenter Study

“…The magnitude of reduction was comparable to that observed in smokers who abstained from smoking, which has been referred to as the "gold standard" for the assessment of candidate reduced risk products [42,43]. Longer exposure studies of at least 6 months have shown favorable biological changes in smokers switching to THS, thereby reflecting improvement of several pathophysiological pathways that may eventually lead to the development of tobacco-related diseases, such as inflammation, oxidative stress, or endothelial dysfunction [44,45]. Preclinical data on gingival [46] and oral epithelial [47] human organotypic cultures showed minor histopathological alterations and minimal cytotoxicity upon THS aerosol exposure compared with exposure to cigarette smoke as well as a very significantly reduced overall impact, as illustrated by the measurement of inflammatory mediators and by transcriptomic and metabolomic analyses.…”

US regulator adds to confusion around heated tobacco products

“…Phillip Morris’s clinical and aerosol outcome data are not comprehensive, and in fact 56 potentially harmful substances are higher in IQOS aerosol than cigarette smoke. 6 12 Concerns about Phillip Morris’s IQOS research 13 14 and failure to make data from its longer term studies public 15 16 are amplified by the tobacco industry’s history of research manipulation and hiding the harms of smoking. 13 17 With the many other products now available, including pharmaceutical nicotine, which are known to be safe, smokers looking to reduce harm rather than quit should see heated tobacco products as a last resort.…”