Investigating Efficacious E-Cigarette Interventions and Cessation Effects on Cancer-Related Biomarkers: A Randomized Trial of Varenicline in Adults - ABSTRACT Nicotine e-cigarette use in the US has increased to 13 million adult users per year. These devices are now the most popular tobacco product among young people. E-cigarettes deliver nicotine rapidly and are highly Harmful emerging evidence, including work by our team, suggests that e-cigarettes can induce DNA damage and suppress DNA repair, important mechanisms linked to cancer. addictive. In some devices, they can exceed the maximum nicotine delivery of combusted cigarettes. respiratory and cardiovascular effects have also been documented and Although many people want to quit using e-cigarettes, we currently lack evidence-based e-cigarette cessation methods. Varenicline, the most effective monotherapy for smoking cessation, shows promise for e-cigarette cessation including our recent 8-week preliminary trial in adults who reported exclusive daily e-cigarette use (N=40) and either former cigarette smoking or no cigarette smoking history. Specifically, we found that varenicline yielded numerically higher end of treatment relative risk probabilities for e-cigarette cessation (RR=1.51) than placebo and this difference was maintained at Week 12 follow-up (RR=1.36). Thus, varenicline warrants further testing for e-cigarette cessation. In the current study, we propose to conduct a randomized clinical trial in treatment-seeking adults (age 18+) who report exclusive daily e-cigarette use with and without a former cigarette smoking history (N=326) to test the hypothesis that varenicline is efficacious for quitting e-cigarettes. Specifically, we will randomly assign participants to 12-weeks of varenicline (titrated to 2mg daily) or matching placebo and simulate a primary care model in which all participants will receive study medication along with brief cessation advice and self-management resources. We will achieve the following aims. For Aim 1, we will compare the effect of varenicline vs. placebo on e- cigarette quit rates using daily smartphone EMA diaries and biochemical verification of e-cigarette use status. For Aim 2, we will test predictors and moderators of outcomes, such as participant demographics, cigarette smoking history, and e-cigarette device type to determine subgroups and characteristics that may impact treatment response to varenicline. Finally, for Aim 3, we will explore changes in cancer-related biomarkers following e-cigarette cessation treatment. Overall, the results will provide scientific evidence on effective treatment strategies for e-cigarette cessation and the health benefits of cessation.
