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Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1).

ABSTRACT: Introduction:The menthol Tobacco Heating System 2.2 (mTHS) is a newly developed candidate modified-risk tobacco product intended to reduce exposure to the harmful and potentially harmful constituents (HPHCs) of conventional cigarette (CC) smoke. This study examined the impact of switching to mTHS on biomarkers of exposure to HPHCs relative to menthol CCs (mCCs) and smoking abstinence (SA). Methods:In this three-arm, parallel-group study, 160 Japanese adult smokers (23-65 years; smoking ?10 mCCs per day) were randomized to mTHS (n = 78), mCC (n = 42), or SA (n = 40) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to HPHCs, human puffing topography, safety, and subjective effects of smoking measures. Results:After 5 days of product use, the concentrations of carboxyhemoglobin, 3-hydroxypropylmercapturic acid, monohydroxybutenyl mercapturic acid, and S-phenylmercapturic acid were 55%, 49%, 87%, and 89% lower (p < .001), respectively, in the mTHS group than in the mCC group. Other biomarkers of exposure (measured as secondary endpoints) were 50%-94% lower in the mTHS group than in the mCC group on day 5. These reductions in the mTHS group were maintained at day 90, similar to the SA group. Switching to mTHS was associated with changes in human puffing topography (shorter puff intervals and more frequent puffs). The urge-to-smoke and smoking satisfaction levels on day 90 were similar in the mTHS and the mCC groups. Conclusion:Switching from mCCs to mTHS significantly reduced exposure to HPHCs relative to continuing smoking mCCs with concentrations similar to those observed following SA in Japanese adult smokers. Implications:This randomized study compared the impact of switching to a modified-risk tobacco product candidate mTHS on biomarkers of exposure to HPHCs of cigarette smoke relative to continuing smoking cigarettes or abstaining from smoking in sequential confinement and ambulatory settings. The study showed that switching to mTHS was associated with significant biomarker reductions within 5 days in confinement, these reductions being maintained throughout the ambulatory setting up to day 90. The results provide evidence that switching to mTHS reduces real-life exposure to HPHCs in adult smokers.

SUBMITTER: Ludicke F

PROVIDER: S-EPMC5896533 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1).

Lüdicke Frank F Picavet Patrick P Baker Gizelle G Haziza Christelle C Poux Valerie V Lama Nicola N Weitkunat Rolf R

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco 20180101 2

<h4>Introduction</h4>The menthol Tobacco Heating System 2.2 (mTHS) is a newly developed candidate modified-risk tobacco product intended to reduce exposure to the harmful and potentially harmful constituents (HPHCs) of conventional cigarette (CC) smoke. This study examined the impact of switching to mTHS on biomarkers of exposure to HPHCs relative to menthol CCs (mCCs) and smoking abstinence (SA).<h4>Methods</h4>In this three-arm, parallel-group study, 160 Japanese adult smokers (23-65 years; sm ...[more]

PMID: 28177489

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Project description:IntroductionModified-risk tobacco products are expected to reduce exposure to harmful and potentially harmful constituents of cigarette smoke, and ultimately reduce the health burden of smoking-related diseases. Clinically relevant risk markers of smoking-related diseases inform about the risk profile of new tobacco products in the absence of in-market epidemiological data. The menthol Tobacco Heating System 2.2 (mTHS) is a modified-risk tobacco product in development as an alternative to cigarettes (conventional cigarettes [CCs]).MethodsIn this parallel-group study, Japanese adult smokers (23-65 years; ≥10 mCCs/day) were randomized to mTHS, menthol CCs (mCC), or smoking abstinence (SA) for 5 days in confinement and 85 days in ambulatory settings. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents and clinically relevant risk markers of smoking-related diseases.ResultsOne-hundred and sixty participants were randomized to the mTHS (n = 78), mCC (n = 42), and SA (n = 40) groups. Switching to the mTHS was associated with reductions in biomarkers of exposure compared with continuing mCCs. Reductions in 8-epi-prostaglandin F2α (biomarker of oxidative stress), 11-dehydro-thromboxane B2 (biomarker of platelet activation), soluble intracellular adhesion molecule-1 (biomarker of endothelial function), and an increase in high-density lipoprotein cholesterol (biomarker of lipid metabolism) and forced expiratory volume in 1 second (biomarker of lung function) occurred in the mTHS group compared with the mCC group. The changes in the mTHS group approached those in the SA group.ConclusionsSwitching from mCCs to mTHS was associated with improvements in clinically relevant risk markers linked to mechanistic pathways involved in smoking-related diseases.ImplicationsIn this three-way randomized study, switching from menthol cigarettes to mTHS for 5 days in confinement and 85 days in ambulatory settings was associated with reductions in biomarkers of exposure to cigarette smoke, and changes were observed in clinically relevant biomarkers of oxidative stress (8-epi-prostaglandin F2α), platelet activity (11-dehydro-thromboxane B2), endothelial function (soluble intracellular adhesion molecule-1), lipid metabolism (high-density lipoprotein cholesterol) and lung function (forced expiratory volume in 1 second), similar to the SA group. The results suggest that switching to the mTHS has the potential to reduce the adverse health effects of conventional cigarettes.

Project description:BACKGROUND:Tobacco 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. OBJECTIVE:This 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. METHODS:This 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. RESULTS:Enrollment 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. CONCLUSIONS:In 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 REGISTRATION:ClinicalTrials.gov NCT02396381; http://clinicaltrials.gov/ct2/show/NCT02396381 (Archived by WebCite at http://www.webcitation.org/71PCRdagP). REGISTERED REPORT IDENTIFIER:RR1-10.2196/11294.

Project description:BackgroundSmoking is a significant risk factor for periodontal disease and tooth loss, as shown in several clinical studies comparing smokers and nonsmokers. Although only a few longitudinal studies have assessed the outcome of periodontal disease after smoking cessation, they indicated that recovery after nonsurgical treatment was more successful in those who had quit smoking. As part of tobacco harm reduction strategies, substituting cigarettes with alternative, less harmful tobacco products is an approach complementary to cessation for smokers who would otherwise continue to smoke. The Tobacco Heating System (THS), developed by Philip Morris International (commercialized as IQOS), is part of the heat-not-burn product category. The IQOS device electrically heats tobacco instead of burning it, at much lower temperatures than cigarettes, thereby producing substantially lower levels of harmful and potentially harmful constituents, while providing the nicotine, taste, ritual, and a sensory experience that closely parallel those of cigarettes. Phillip Morris International has published the results from a broad clinical assessment program, which was established to scientifically substantiate the harm reduction potential of the THS among adult healthy smokers switching to the THS. The program is now progressing toward including adult smokers with smoking-related diseases.ObjectiveThe goal of this study is to demonstrate favorable changes of periodontal endpoints in response to mechanical periodontal therapy in patients with generalized chronic periodontitis who completely switched to THS use compared with continued cigarette smoking.MethodsThis is a randomized controlled two-arm parallel-group multicenter Japanese study conducted in patients with chronic generalized periodontitis who switch from cigarettes to THS compared with smokers continuing to smoke cigarettes for 6 months. The patients were treated with mechanical periodontal therapy as per standard of care in Japan. The primary objective of the study is to demonstrate the beneficial effect of switching to THS use compared with continued cigarette smoking on pocket depth (PD) reduction in all sites with an initial PD?4 mm. The secondary objectives include evaluation of other periodontal parameters (eg, clinical attachment level or gingival inflammation) and overall oral health status upon switching to THS. Safety was monitored throughout the study.ResultsIn total, 172 subjects were randomized to the cigarette (n=86) or THS (n=86) groups, and all 172 completed the study. The conduct phase of the study is completed, while data cleaning and analyses are ongoing.ConclusionsThis study is the first to test a heat-not-burn tobacco product in smokers with an already established disease. The results should further strengthen the evidence that switching to THS can significantly reduce the risk of smoking-related diseases if favorable changes in the evolution of chronic generalized periodontitis after mechanical therapy are found when compared with continued cigarette smoking.Trial registrationClinicalTrials.gov NCT03364751; https://clinicaltrials.gov/ct2/show/NCT03364751.International registered report identifier (irrid)DERR1-10.2196/15350.

Project description:INTRODUCTION:Tobacco Heating System (THS) 2.2, a candidate modified-risk tobacco product, aims at offering an alternative to cigarettes for smokers while substantially reducing the exposure to harmful and potentially harmful constituents found in cigarette smoke. METHODS:One hundred and sixty healthy adult US smokers participated in this randomized, three-arm parallel group, controlled clinical study. Subjects were randomized in a 2:1:1 ratio to menthol Tobacco Heating System 2.2 (mTHS), menthol cigarette, or smoking abstinence for 5 days in confinement and 86 subsequent ambulatory days. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents (reported in our co-publication, Part 1) and biomarkers of potential harm (BOPH). RESULTS:Compliance (protocol and allocated product exposure) was 51% and 18% in the mTHS and smoking abstinence arms, respectively, on day 90. Nonetheless, favorable changes in BOPHs of lipid metabolism (total cholesterol and high- and low-density cholesterol), endothelial dysfunction (soluble intercellular adhesion molecule-1), oxidative stress (8-epi-prostaglandin F2?), and cardiovascular risk factors (eg, high-sensitivity C-reactive protein) were observed in the mTHS group. Favorable effects in other BOPHs, including ones related to platelet activation (11-dehydrothromboxane B2) and metabolic syndrome (glucose), were more pronounced in normal weight subjects. CONCLUSIONS:The results suggest that the reduced exposure demonstrated when switching to mTHS is associated with overall improvements in BOPHs, which are indicative of pathomechanistic pathways underlying the development of smoking-related diseases, with some stronger effects in normal weight subjects. IMPLICATIONS:Switching to mTHS was associated with favorable changes for some BOPHs indicative of biological pathway alterations (eg, oxidative stress and endothelial dysfunction). The results suggest that switching to mTHS has the potential to reduce the adverse health effects of smoking and ultimately the risk of smoking-related diseases. Switching to mTHS for 90 days led to reductions in a number of biomarkers of exposure in smokers, relative to those who continued smoking cigarettes, which were close to those observed when stopping smoking (reported in our co-publication, Part 1). Initial findings suggest reduced levels of 8-epi-prostaglandin F2? and intercellular adhesion molecule 1, when switching to mTHS for 90 days. These changes are comparable to what is observed upon smoking cessation. In normal weight subjects, additional favorable changes were seen in 11-dehydrothromboxane B2, fibrinogen, homocysteine, hs-CRP, percentage of predicted forced expiratory volume in 1 second, systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, apolipoprotein A1, and triglycerides. TRIAL REGISTRATION:NCT01989156.

Project description:IntroductionBans of menthol characterizing flavor in cigarettes have been implemented in some localities and have been proposed more broadly. One proposed benefit of such a ban is to increase cessation rates among current menthol smokers. There is currently relatively limited data regarding how smoking behavior changes if menthol smokers switch to non-menthol cigarettes.Aims and methodsAfrican American menthol smokers interested in quitting smoking were randomized to either continue smoking menthol (n = 60) or switch to non-menthol cigarettes (n = 62) for 1 month prior to a cessation attempt. Cessation results were reported previously; this analysis reports the results from the pre-cessation visits at which amount smoked, exhaled carbon monoxide (CO) concentration, urinary cotinine concentrations, and subjective measures were assessed.ResultsOver the 4-week study period, those switching to non-menthol (vs. continuing to smoke menthol) cigarettes smoked fewer cigarettes per day (mean ratio: 0.86; 95% confidence interval [CI]: 0.76, 0.98; p = .02), reported lower withdrawal symptom severity (mean difference -1.29; 95% CI: -2.6 to -0.01; p = .05) and higher perceived effectiveness of their skills for quitting smoking (mean difference 0.56; 95% CI: 0.02-1.10; p = .05). No significant differences were found between groups in exhaled CO, urinary cotinine concentrations, or most other subjective effects including support for a ban on menthol characterizing flavor in cigarettes.ConclusionsThese results suggest that were menthol cigarettes no longer available, those that switch to non-menthol cigarettes would not change their smoking behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefit.Clinicaltrials.gov # NCT02342327.ImplicationsA ban on menthol characterizing flavor in cigarettes has been proposed as a potential means by which to increase smoking cessation rates among current menthol cigarette smokers. This study evaluated how African American menthol cigarette smokers adjusted their smoking behavior after switching to non-menthol cigarettes. Although the overall differences between groups were modest, they were in a direction consistent with decreased smoking suggesting that current smokers would not adjust their behavior in a way that is likely to be more hazardous, with some indicators suggesting that there may be some benefits.

Project description:IntroductionTobacco heating products (THPs) generate lower machine yields of toxicants compared to those found in conventional cigarette smoke. During use, these products are likely to expose users to lower levels of particulate matter and harmful and potentially harmful compounds compared with smoking cigarettes.Aims and methodsThis randomized, controlled study is investigating whether biomarkers of exposure (BoE) to smoke toxicants are reduced when smokers switch from smoking cigarettes to using the glo THP in a naturalistic, ambulatory setting. Control groups include smokers who are abstaining from cigarette smoking and never-smokers. At a baseline study visit, 24-hour urine samples and spot blood samples were taken for BoE analysis, and exhaled carbon monoxide was also measured. N-(2-cyanoethyl) valine (CEVal) was used as a marker of compliance in subjects asked to refrain from combustible cigarette smoking. Subjects are being followed up at periodic intervals for 360 days; this article presents data following a planned interim analysis at day 90.ResultsIn continuing smokers, BoE remained stable between baseline (day 1) and day 90. In both per-protocol and CEVal-compliant analysis populations, reductions in BoE were observed in subjects switching to using glo or undergoing smoking cessation. These reductions were statistically significant for a number of BoE when switching to glo was compared with continued smoking. Furthermore, in both populations, reductions observed in subjects switching to using glo were comparable to those seen with smoking cessation and were also to levels similar to those seen in never-smokers.Conclusionglo is a reduced-exposure tobacco product.ImplicationsThis clinical study builds on a previous 5-day confinement study and demonstrates that when smokers switched from smoking combustible cigarettes to using the glo THP in a naturalistic, ambulatory setting, their exposure to tobacco smoke toxicants was significantly decreased. For most BoE examined, this was to the same extent as that seen when a control group of smokers ceased cigarette smoking, or even to levels seen in never-smoker controls. This indicates that glo is a reduced-exposure product with the potential to be a reduced-risk tobacco product, when used by smokers whose cigarette consumption is displaced completely.Clinical trial registrationISRCTN81075760.

Project description:Despite awareness of negative health outcomes associated with smoking, pregnant smokers might reduce their tobacco consumption thinking that a low smoking rate reduces smoking-related negative birth outcomes. We aimed to assess in a clinical sample whether there is a smoking rate that would not impact on birth weight (BW).Pregnant smokers ?18 years, gestational age of 9-20 weeks of amenorrhea, motivated to quit smoking, smoking ?5 cigarettes/day (cpd) and their newborns (381 singleton, live births) were included in this secondary analysis of a French smoking cessation trial.The mean BW when the mother quit smoking was 3417 g (95 % CI: 3098-3738 g); when smoking >0<5 cpd, 3081g (3003-3159 g); when smoking 5-9 cpd, 3043 g (2930-3157 g); and when smoking ?10 cpd, 2831 g (2596-3157 g) (p = .006). The corresponding effect sizes ranged from medium to large (Cohen's d for BW: 0.54, 0.57 and 0.85) compared to BW when the mother quit. In the multivariable analysis, adjusted for all significant confounders, when the mother smoked on average >0<5 cpd, the loss in BW was 228 g; when smoking 5-9 cpd, 251 g; and when smoking ?10 cpd, 262 g (all p ? .02) compared to newborns' BW of mothers who stopped smoking since quit date.Even low cigarette consumption during pregnancy is associated with BW loss. All efforts should be made to help pregnant smokers quit completely during their pregnancy.As an alternative to quitting smoking, pregnant smokers reduce their smoking rate thinking that this diminishes smoking-related negative health outcomes. No study has established whether low smoking rate (more than 0 but less than 5 cpd) during pregnancy impacts BW compared to abstinence from smoking. Among treatment-seeking pregnant smokers BW of newborns of mothers who smoked even less than 5 cpd was significantly lower than of those whose mothers quit; effect sizes of different consumption levels on BW ranged from moderate (>0<5 cpd) to large (?10 cpd). Even low smoking rate is associated with reduced BW compared to complete maternal smoking abstinence.

Dataset Information

Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1).

Publications

Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1).

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