Project 3: Randomized Placebo-controlled Trial of Nicotine Pouches in Smokers

项目摘要/摘要：项目3 尼古丁袋在美国烟草市场上代表着一个快速增长的类别，但人们对此知之甚少 关于它们对健康的影响(包括上瘾)或对吸烟的影响。我们建议使用 向FDA通报吸烟者使用尼古丁药袋的影响的随机对照试验方法 对减少吸烟感兴趣，但不是戒烟。这项提议的具体目的是招募一名 对330名有兴趣减少吸烟的当前每日吸烟者进行队列调查，并对 一组行为和健康指标，在基线和随机使用后超过16周 含有0毫克、3毫克或6毫克尼古丁的“光滑”尼古丁袋，或含有冬青口味的 随机、双盲、安慰剂对照试验。审判将在两个地点进行：宾夕法尼亚州立大学好时 和德克萨斯州的M.D.安德森，以招募不同的吸烟者样本。因此，这场审判针对的是 产品组成和设计的科学领域(特别是尼古丁含量和风味添加剂)。我们的 中心假设是毒性和健康影响的关键标志(例如，尿NNAL、呼出的CO、测量 吸烟成瘾[如FTND]、氧化应激和口服B(A)P DNA加合物)将显著减少 在吸烟者中，提供了高尼古丁(6毫克)尼古丁袋子，相对于0毫克尼古丁袋子。我们还将 评估尼古丁袋内容物对尼古丁袋成瘾的影响，以及尼古丁袋尼古丁的影响 香烟和其他烟草产品消费的剂量。我们还将比较这些方法的效果 随机选择“顺滑”口味与冬青口味。在为期16周的随机阶段之后，参与者将 鼓励戒烟并接通电话戒烟服务，并在4周后进行随访 (第20周)，以确定袋子中的尼古丁含量是否影响了意向和能力 戒烟吧。在这项严格的双盲随机试验完成后，我们将有一个更好的 了解尼古丁胶囊(及其尼古丁含量和风味特征)对健康的影响 香烟消费以及由此产生的健康风险、口腔健康和尼古丁成瘾标志物的变化。 我们还打算证明，这里使用的临床试验方法未来可能会被用来评估任何 以相对标准化的方式开发新型烟草产品。因此，本项目专门针对 (A)产品组成和设计(B)毒性(C)健康科学领域的研究优先事项 影响和(D)上瘾。

Project Summary/Abstract: Project 3 Nicotine Pouches represent a rapidly growing category in the U.S. tobacco market, but little is known about their health effects (including addiction) or effects on cigarette smoking. We propose to use a randomized controlled trial methodology to inform FDA on the effects of nicotine pouch use in smokers interested in reducing their smoking but not quitting smoking. The specific aim of this proposal is to recruit a cohort of 330 current daily smokers with an interest in reducing smoking, and to measure a comprehensive battery of behavioral and health indicators at baseline, and over 16 weeks after being randomized to use Nicotine Pouches containing either 0mg, 3mg or 6mg nicotine in “Smooth” or Wintergreen flavors in a randomized double-blind, placebo-controlled trial. The trial will be conducted at two sites: Penn State Hershey and M.D. Anderson in Texas in order to recruit a diverse sample of smokers. This trial therefore addresses the scientific domain of Product Composition and Design (specifically nicotine content and flavor additives). Our central hypothesis is that key markers of toxicity and health effects (e.g. urine NNAL, exhaled CO, measures of cigarette addiction [e.g. FTND], oxidative stress and oral B(a)P DNA adducts) will be significantly reduced in smokers who are provided high nicotine (6mg) Nicotine Pouches, relative to 0mg pouches. We will also assess the effects of Nicotine Pouch content on Nicotine Pouch addiction, and the effects of pouch nicotine dose on cigarette and other tobacco product consumption. We will also compare the effects in those randomized to “Smooth” versus Wintergreen flavors. After the 16-week randomized phase, participants will be encouraged to quit smoking and connected to telephone cessation services and then followed-up 4 weeks later (week 20) in order to ascertain whether the nicotine content of the pouches influenced intention and ability to quit smoking. At the completion of this rigorous double-blind randomized trial we will have a better understanding of the effects of Nicotine Pouches (and their nicotine content and flavor characteristics) on cigarette consumption and the resulting changes to markers of health risks, oral health and nicotine addiction. We also aim to demonstrate that the clinical trial method used here may in future be used to evaluate any novel tobacco product in a relatively standardized manner. As such, this project specifically addresses research priorities within the scientific domains of (a) Product Composition and Design (b) Toxicity (c) Health Effects and (d) Addiction.