Evaluating the substitutability of fruit versus menthol and tobacco-flavored e-cigarettes on combustible cigarette...

While regulations have restricted the sale of pod-style fruit-flavored e-cigarettes, observational and clinical data suggest that their use is associated with smoking cessation among adults. Surprisingly, no randomized clinical trials have tested whether fruit flavors affect smoking outcomes compared with those authorized for sale, and, if so, why. Adults who smoke cigarettes daily, who have had multiple prior unsuccessful quit attempts, and who are interested in quitting smoking by switching to an e-cigarette will be recruited. Eligible adults will be randomized to fruit, menthol, or tobacco-flavored e-cigarettes. The baseline smoking rate will be established on days 1-5. Laboratory visits on days 6 and 7 will assess flavor-associated subjective reward and the reinforcing value of flavored e-cigarettes relative to combustible cigarettes. Participants will then receive an e-cigarette device and a 6-week supply of nicotine pods (5% nicotine) in their assigned flavor, and a structured action plan to quit smoking by switching to the e-cigarette. The primary outcome is the longitudinal daily cigarette count from baseline through the end of the six-week switch period (primary endpoint) and at the 26-week follow-up (secondary endpoint). Complete switching will be verified with a carbon monoxide value < 5 ppm. Secondary outcomes include subjective reward, relative reinforcing value, and positive affect. This trial will determine if fruit-flavored e-cigarettes facilitate initial and sustained switching more than menthol or tobacco, whether greater rewarding and positively reinforcing effects drive switching, and if the unavailability of fruit-flavoring may foster continued smoking for those unable to quit with FDA-approved medication. This trial was registered at CT.gov (NCT06264154) https://clinicaltrials.gov/study/NCT06264154 on February 16, 2024.