Project 2: Informing oral nicotine pouch regulations to promote public health

项目 2：告知口服尼古丁袋法规以促进公共卫生

• 批准号: 10666068
• 负责人: Brittney L Keller-Hamilton
• 金额: $ 72.86万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666068
• 关键词: Acute; Address; Adult; Affect; Anabasine; Animal Model; Area; Behavior; Biochemical; Brain; Characteristics; Cigarette; Cigarette Smoker; Crossover Design; Dependence; Dimensions; Dizziness; Double-Blind Method; Drug Kinetics; Ecological momentary assessment; Ensure; Epithelium; Fostering; Gene Expression; Genes; Harm Reduction; Health; Health Benefit; High Prevalence; Human; Industry; Inflammatory; Isomerism; Laboratories; Manufacturer; Measures; Methods; Microbe; Modified Risk Tobacco Product; Nicotine; Nicotinic Agonists; Nicotinic Receptors; Ohio; Oral; Outcome; Outcome Study; Participant; Persons; Phase; Plasma; Positioning Attribute; Preparation; Prevalence; Procedures; Public Health; Randomized; Regulation; Reporting; Rewards; Risk; Sampling; Science; Smokeless Tobacco; Smoker; Standardization; Taste Perception; Time; Tobacco; Tobacco Industry; Tobacco use; Toxic effect; Universities; Visit; Youth; addiction; addiction liability; arm; base; behavioral economics; cancer biomarkers; cancer risk; cost; design; experience; follow-up; host microbiome; indexing; innovation; nicotine replacement; oral microbiome; programs; smokeless tobacco user; snus; tobacco products; tobacco user; tobacco-free; toxicant; uptake

PROJECT SUMMARY – PROJECT 2 Historically, the tobacco industry manipulated nicotine concentration and form to offer a range of smokeless tobacco (ST) products to appeal to both new and established users. Termed by the industry as the “graduation” program, they provided new users with “starter products” with low nicotine concentration and low freebase nicotine and “mature” users with higher concentrations of nicotine, mainly in the freebase form, to maintain dependence. They are now following the same playbook for oral nicotine pouches (ONPs), manipulating the nicotine dimensions of concentration and form, and more recently have begun manipulating isomer composition through the use of synthetic nicotine. While ONPs may have promise as a less harmful alternative for smokers and ST users who completely switch, the potential risk for ONP uptake among young new users is concerning. The overall integrative theme of The Ohio State University Tobacco Center for Regulatory Science is: “Flipping the Script”: Using the Industry's Nicotine Playbook to Maximize Public Health. Just as the tobacco industry manipulates nicotine to create ONPs that appeal to young people, with the evidence produced by Project 2 (P2), we posit that the FDA can regulate the nicotine dimensions in ONPs, making them unappealing to new users while still providing smokers and ST users a less harmful but appealing and satisfying alternative. P2 will inform regulations that position ONPs as a public health benefit rather than a threat by identifying the characteristics of nicotine that best support switching to ONPs and evaluating corresponding changes to the oral microbiome among adult smokers and ST users. In Phase 1, using a double-blind, cross- over design, exclusive smokers (n=80) and ST users (n=80) will be randomized to high or low nicotine concentration, and then engage in 5 single-product laboratory use sessions of their usual brand and 4 ONPs (random order) that range in freebase fraction (low, high) and isomer (racemic, >99% S-nicotine). Outcomes include plasma nicotine pharmacokinetics, subjective effects, and behavioral economic demand indicies. In Phase 2, the same participants, after a 1-week usual brand control period, will substitute a randomly assigned ONP for their usual brand for 4 weeks. Study outcomes include use behaviors, including complete switching, measured via ecological momentary assessment and biochemically confirmed (anatabine and anabasine), count of unused ONPs, subjective effects, behavioral economic demand indices, and oral microbiome assessment. P2 is significant and innovative because it uses a mix of tightly controlled in-lab procedures and ad libitum, naturalistic use of commercial tobacco products to assess how nicotine concentration, form, and isomer affect the addiction potential and health effects of ONPs. This is the first study of the combined nicotine dimensions with the intent of facilitating switching from cigarettes and ST to ONPs without increasing youth uptake. P2 addresses the FDA priority areas of Addiction, Product Composition & Design, Toxicity, Behavior, and Health Effects, and will inform ONP nicotine regulations designed to foster complete switching for established smokers and ST users.

项目摘要 – 项目 2 从历史上看，烟草业操纵尼古丁浓度和形式来提供一系列无烟产品 烟草（ST）产品以吸引新用户和老用户，被行业终止为“毕业”。 计划中，他们为新用户提供了低尼古丁浓度和低游离碱的“入门产品” 尼古丁和尼古丁浓度较高（主要以游离碱形式）的“成熟”使用者，以维持 他们现在正在遵循口服尼古丁袋（ONP）的相同策略，操纵尼古丁袋。 尼古丁的浓度和形式维度，最近开始操纵异构体 而 ONP 可能有望成为一种危害较小的替代品。 对于完全转换的吸烟者和无烟烟草使用者来说，年轻新使用者吸收 ONP 的潜在风险是 俄亥俄州立大学烟草监管科学中心的整体综合主题。 是：“翻转剧本”：利用行业的尼古丁剧本来最大限度地提高公众健康。 烟草业操纵尼古丁来制造吸引年轻人的 ONP，并提供了证据 通过项目 2 (P2)，我们假设 FDA 可以调节 ONP 中的尼古丁含量，使它们 对新用户没有吸引力，但仍然为吸烟者和无烟烟草用户提供危害较小但有吸引力和令人满意的 P2 将告知法规将 ONP 视为公共卫生益处而不是威胁。 确定最有利于改用 ONP 的尼古丁特性并评估相应的 在第一阶段，使用双盲、交叉研究来改变成年吸烟者和无烟烟草使用者的口腔微生物组。 根据设计，专门吸烟者 (n=80) 和 ST 使用者 (n=80) 将被随机分配到高尼古丁或低尼古丁组 集中精力，然后进行 5 次其常用品牌的单品实验室使用课程和 4 个 ONP （随机顺序）范围为游离碱分数（低、高）和异构体（外消旋，> 99% S-尼古丁结果）。 包括血浆尼古丁药代动力学、主观效应和行为经济需求指标。 第 2 阶段，相同的参与者在经过 1 周的常规品牌控制期后，将替代随机分配的参与者 ONP 对其常用品牌为期 4 周的研究结果包括使用行为，包括完全转换、 通过生态瞬时评估和生化确认（新竹碱和新竹碱）进行测量，计数 未使用的 ONP、主观影响、行为经济需求指数和口腔微生物组评估。 具有重要意义和创新性，因为它结合了严格控制的实验室程序和随意使用， 自然地使用商业烟草产品来评估尼古丁浓度、形式和异构体如何影响 ONP 的成瘾潜力和健康影响这是第一项综合尼古丁维度的研究。 目的是在不增加青少年吸食 P2 的情况下促进从卷烟和无烟烟草转向 ONP。 解决 FDA 的成瘾、产品成分和设计、毒性、行为和健康等优先领域 效果，并将告知 ONP 尼古丁法规，旨在促进已吸烟者完全戒烟 和ST用户。