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

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.