Biomarkers of Exposure and Potential Harm in Exclusive Users of Nicotine Pouches and Current, Former, and Never Smokers: Protocol for a Cross-sectional Clinical Study

BackgroundTobacco harm reduction (THR) aims to reduce the health burden of cigarettes by encouraging smokers to switch to using alternative tobacco or nicotine products. Nicotine pouches (NPs) are smokeless, tobacco-free, oral products that may be beneficial as part of a THR strategy. ObjectiveThis 2-center, cross-sectional confinement study conducted in Denmark and Sweden aimed to determine whether biomarkers of exposure (BoEs) to tobacco toxicants and biomarkers of potential harm (BoPHs) in exclusive users of NPs show favorable differences compared with current smokers. MethodsParticipants were healthy NP users (target n=100) and current, former, or never smokers (target n=40 each), as confirmed by urinary cotinine and exhaled carbon monoxide concentrations. During a 24-hour confinement period, participants were asked to use their usual product (NP or cigarette) as normal, and BoEs and BoPHs were measured in blood and 24-hour urine samples, with compliance determined using anabasine, anatabine, and N-(2-cyanoethyl)valine. BoEs and BoPHs were compared between NP users and current, former, and never smokers. Urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (BoE to nicotine-derived nitrosamine ketone) and urinary 8-epi-prostaglandin F2α type III, exhaled nitric oxide, blood carboxyhemoglobin, white blood cell count, soluble intercellular adhesion molecule-1, and high-density lipoprotein cholesterol (BoPHs) were evaluated as primary outcomes. Other measures included urinary 11-dehydrothromboxane B2, forced expiratory volume, carotid intima-media thickness, self-reported quality of life, and oral health. ResultsThe results of this study were received in mid-2022 and will be published in late 2022 to early 2023. ConclusionsThe results of this study will provide information on toxicant exposure and biomarkers associated with the development of smoking-related diseases among users of NPs compared with smokers, as well as on the potential role of NPs in THR. Trial RegistrationInternational Standard Randomised Controlled Trial Number (ISRCTN) ISRCTN16988167; https://www.isrctn.com/ISRCTN16988167 International Registered Report Identifier (IRRID)DERR1-10.2196/39785