Data_Sheet_1_Protocol for the “magnitude of cigarette substitution after initiation of e-cigarettes and its impact on biomarkers of exposure and potential harm in dual users” (MAGNIFICAT) study.doc

IntroductionMany smokers who use e-cigarettes (ECs) to quit continue smoking alongside vaping. The impact on health among individuals who simultaneously smoke conventional cigarettes (CCs) and use ECs remains unclear. The varying patterns of dual use present differing levels of overall toxin exposure and relative risks concerning smoking-related diseases. Understanding these complexities is vital to assessing the implications for human health.
ObjectiveHerein we describe a protocol designed to analyze the impact of different level of substituting CCs with ECs on exposure to toxicants. We’ll use biomarkers to measure this exposure and assess harm reduction in dual users through clinical endpoints, harm-related biomarkers, and behavioral correlations. We expect to observe progressive changes with varying patterns of dual use.
Methods and analysesFor this purpose, we planned to recruit a group of 250 smokers who will be asked to reduce their CC consumption by adopting ECs (intervention group). A separate group of 50 smokers will continue to smoke CC (reference group). Study groups will be followed up for 6 months during which biospecimens will be collected for biomarker analyses, and clinical endpoints will be assessed. The trial is structured to characterize subjects’ usage patterns over time using robust biomarkers of exposure and a standardized mobile phone application to facilitate the precise categorization of dual users along the risk continuum based on their usage behaviors. Subject recruitment will start in February 2024 and enrolment is expected to be completed by August 2024. Results will be reported early in 2025. Study findings may provide valuable insights into health benefits or risks associated with varying patterns of dual use.
Ethics and disseminationThe study protocol and informed consent forms will be approved by the local Ethical Review Boards. Study results will be disseminated through articles published in reputable, peer-reviewed, open access, scientific journals, presentations at conferences, and the University website.

引言
许多试图通过电子烟（e-cigarettes, ECs）戒烟的吸烟者，仍会在使用电子烟的同时继续吸食传统卷烟。对于同时吸食传统卷烟（conventional cigarettes, CCs）并使用电子烟的人群，其健康影响目前尚不明确。双重使用的不同模式，会导致总体毒素暴露水平以及吸烟相关疾病的相对风险存在差异。明晰这些复杂情况，对评估其对人类健康的影响至关重要。
研究目的
本研究旨在阐述一项研究方案，用于分析不同程度以电子烟替代传统卷烟对有毒物质暴露的影响。我们将通过生物标志物（biomarkers）检测此类暴露情况，并结合临床终点、损伤相关生物标志物以及行为相关性，评估双重使用者的健康损伤缓解效果。我们预期可观察到，随着双重使用模式的不同，相关指标会呈现渐进性变化。
研究方法与分析
为此，本研究计划招募250名吸烟者，要求其通过使用电子烟减少传统卷烟的吸食量，该组设为干预组；另外招募50名持续吸食传统卷烟的吸烟者，作为对照组。所有研究对象将被随访6个月，期间将收集生物样本用于生物标志物分析，并评估临床终点。本试验将采用可靠的暴露生物标志物与标准化智能手机应用程序，基于研究对象的使用行为，对双重使用者在风险连续体上的类别进行精准划分，以刻画其随时间变化的使用模式。研究对象招募工作将于2024年2月启动，预计2024年8月完成入组，研究结果将于2025年初公布。本研究结果可为明确不同双重使用模式相关的健康获益或风险提供有价值的参考。
伦理与成果发布
本研究方案与知情同意书将经当地伦理审查委员会批准。研究结果将通过以下途径发布：发表于权威同行评议开放获取科学期刊、在学术会议上汇报，以及发布于合作高校官网。