Exploring the cessation efficacy and harm reduction potential of heated tobacco and nicotine pouch products in smokers and smokeless tobacco users: study protocol of a 6-month randomized controlled switching trial
DOI:
https://doi.org/10.18203/2349-3259.ijct20240964Keywords:
Smoking cessation, Cessation efficacy, Compliance, Harm reduction, Heated tobacco product, Nicotine pouchAbstract
Background: Despite decades of research on pharmacological and behavioural smoking cessation treatments, current quit aids are of limited success. The introduction of new, combustion-free nicotine and tobacco products extended the tool kit for people who smoke to switch away from their risky habit. We performed a systematic review including 120 studies resulting in several recommendations for a robust study design to determine the cessation efficacy of a new nicotine or tobacco product. Consequently, we prepared this study protocol to assess the cessation efficacy of heated tobacco products (HTPs) and nicotine pouches (NPs).
Methods: 250 subjects (125 exclusive smokers and 125 exclusive smokeless tobacco (SLT) users) will be recruited and offered a choice of HTPs in case of smokers and a choice of NPs in case of SLT users in order to switch. Subjects will undergo four visits (baseline, 1, 3, and 6 months) to collect biospecimens and for physical examinations. Use behaviour and questionnaires will be monitored on a regular basis by means of a smartphone-app. We describe a sensitive and specific compliance monitoring using suitable biomarkers of exposure. The sample size of 250 subjects and duration of 6 months will allow the quit rates to be assessed with sufficient statistical power. Finally, the choice between different products shall reflect the individuals’ preferences.
Conclusions: This protocol can be applied generically, providing a robust determination of a products’ cessation efficacy.
Trial Registration: The trial will be registered in the International Clinical Trials Registry Platform.
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References
GBD 2019 Tobacco Collaborators. Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet. 2021;397(10292):2337-60.
US Department of Health and Human Services. The health consequences of smoking—50 years of progress: a report of the Surgeon General; 2014.
Cohen G, Goldenson NI, Bailey PC, Chan S, Shiffman S. Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers. Nicotine Tob Res. 2021;23(12):2153-61.
Gale N, McEwan M, Eldridge AC, Fearon IM, Sherwood N, Bowen E, et al. Changes in Biomarkers of Exposure on Switching From a Conventional Cigarette to Tobacco Heating Products: A Randomized, Controlled Study in Healthy Japanese Subjects. Nicotine Tob Res. 2019;21(9):1220-7.
Haziza C, de La Bourdonnaye G, Merlet S, Benzimra M, Ancerewicz J, Donelli A, et al. Assessment of the reduction in levels of exposure to harmful and potentially harmful constituents in Japanese subjects using a novel tobacco heating system compared with conventional cigarettes and smoking abstinence: A randomized controlled study in confinement. Regul Toxicol Pharmacol. 2016;81:489-99.
Lee PN, Fry JS, Ljung T. Estimating the public health impact had tobacco-free nicotine pouches been introduced into the US in 2000. BMC Public Health. 2022;22(1):1025.
Hartmann-Boyce J, Lindson N, Butler AR, McRobbie H, Bullen C, Begh R, et al. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2022;11(11):CD010216.
Hori A, Tabuchi T, Kunugita N. The spread of heated tobacco product (HTP) use across various subgroups during 2015-16 and 2017-18 in Japan. Environ Health Prev Med. 2023;28:5.
Caponnetto P, Campagna D, Maglia M, Benfatto F, Emma R, Caruso M, et al. Comparing the Effectiveness, Tolerability, and Acceptability of Heated Tobacco Products and Refillable Electronic Cigarettes for Cigarette Substitution (CEASEFIRE): Randomized Controlled Trial. JMIR Public Health Surveill. 2023;9:e42628.
Zettergren A, Sompa S, Palmberg L, Ljungman P, Pershagen G, Andersson N, et al. Assessing tobacco use in Swedish young adults from self-report and urinary cotinine: a validation study using the BAMSE birth cohort. BMJ Open. 2023;13(7):e072582
Camacho OM, McEwan M, Gale N, Pluym N, Scherer M, Hardie G, et al. Adduct N‑(2‑cyanoethyl)valine as a Biomarker Of Compliance in Smokers Switching to Tobacco Heating Products. Preprints 2021, 2021080085.
Scherer G, Newland K, Papadopoulou E, Minet, E. A correlation study applied to biomarkers of internal and effective dose for acrylonitrile and 4-aminobiphenyl in smokers. Biomarkers. 2014;19(4):291-301.
Mulot C, Stücker I, Clavel J, Beaune P, Loriot MA. Collection of human genomic DNA from buccal cells for genetics studies: comparison between cytobrush, mouthwash, and treated card. J Biomed Biotechnol. 2005;2005(3):291-6.
Sykes K, Roberts A. The Chester step test—a simple yet effective tool for the prediction of aerobic capacity. Physiotherapy. 2004;90(4):183-8.
Vansickel A, Baxter S, Sherwood N, Kong M, Campbell L. Human Abuse Liability Assessment of Tobacco and Nicotine Products: Approaches for Meeting Current Regulatory Recommendations. Nicotine Tob Res. 2022;24(3):295-305.
Franks AS, Sando K, McBane S. Do Electronic Cigarettes Have a Role in Tobacco Cessation? Pharmacotherapy. 2018;38(5):555-68.
Harrell PT, Simmons VN, Correa JB, Padhya TA, Brandon TH. Electronic nicotine delivery systems ("e-cigarettes"): review of safety and smoking cessation efficacy. Otolaryngol Head Neck Surg. 2014;151(3):381-93.
Ibrahim S, Habiballah M, Sayed IE. Efficacy of Electronic Cigarettes for Smoking Cessation: A Systematic Review and Meta-Analysis. Am J Health Promot. 2021;35(3)442-55.
Harada S, Sata M, Matsumoto M, Iida M, Takeuchi A, Kato S, et al. Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV(1) Decline: A Longitudinal Cohort Study. J Epidemiol. 2022;32(4):180-7.
Odani S, Tabuchi, T. Prevalence and denial of current tobacco product use: Combustible and heated tobacco products, Japan, 2022. Prev Med Rep. 2022;30:102031.
Schaller JP, Keller D, Poget L, Pratte P, Kaelin E, McHugh D, et al. Evaluation of the Tobacco Heating System 2.2. Part 2: Chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. Regul Toxicol Pharmacol. 2016;81:S27-S47.
Forster M, Fiebelkorn S, Yurteri C, Mariner D, Liu C, Wright C, et al. Assessment of novel tobacco heating product THP1.0. Part 3: Comprehensive chemical characterisation of harmful and potentially harmful aerosol emissions. Regul Toxicol Pharmacol. 2018;93:14-33.
McNeill A, Munafo MR. Reducing harm from tobacco use. J Psychopharmacol. 2013;27(1):13-8.
Hatsukami DK, Joseph AM, Lesage M, Jensen J, Murphy SE, Pentel PR, et al. Developing the science base for reducing tobacco harm. Nicotine Tob Res. 2007;9Suppl4(04):S537-53.
Back S, Masser AE, Rutqvist LE, Lindholm J. Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). BMC Chem. 2023;17(1):9.
Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y. Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987;77(11):1435-8.
Kim SS, Kim S, Gona PN. Determining Optimal Cutoffs for Exhaled Carbon Monoxide and Salivary Cotinine to Identify Smokers among Korean Americans in a Smoking Cessation Clinical Trial. J Smok Cessat. 2021;2021:6678237.
Pan KT, Leonardi GS, Ucci M, Croxford B. Can Exhaled Carbon Monoxide Be Used as a Marker of Exposure? A Cross-Sectional Study in Young Adults. Int J Environ Res Public Health. 2021;18(22).