International Randomized Controlled Trial Evaluating Changes in Oral Health in Smokers after Switching to Combustion-Free Nicotine Delivery Systems: SMILE Study protocol

Although the well-known detrimental effects of conventional cigarette smoking on oral health, there are still lack of evidences about the impact of less harmful alternatives (such as electronic cigarettes or heat not burn products), especially in young smokers with clinical absence of signs of periodontitis. SMILE will be a prospective, multicenter, interventional, open label, randomized, controlled, three parallel-arms study assessing oral health parameters and teeth appearance of 18 months duration. This study aims to compare short- and long-term impact on oral health between smokers continuing with conventional cigarette smoking, those switching to combustion-free nicotine delivery systems (C-F NDS), and never-smokers by objectively evaluating changes in gingival response, as a proxy for periodontal/gingival. The total number of participants in the study planned of the trial is 606 (505 regular smokers and 101 never-smokers). Regular smokers not intending to quit will be randomized in the ratio 1:4 either in continuing to smoke commercially manufactured conventional cigarettes (n = 101; Study Arm A) or switching to C-F NDS (n = 404; Study Arm B), never-smokers will be assigned in Arm C (n= 101). The primary outcome will be to assess and compare the percentage mean change in Modified Gingival Index (MGI) score between Baseline and 18 months follow-up between the Study Arms A and B. Secondary outcomes include the assessment of within- and between-group (Arm A, Arm B and Arm C) variations from baseline to 18 months follow-up of several endpoints, such as MGI, Tooth Stains Assessment, Dental Discolorations, Plaque Score Imaging, Oral Health Quality of Life (OHQOL) assessment and EuroQoL Visual Analog Scale (EQ VAS – QoL) assessment. Patient recruitment will start in January 2021 and enrolment is expected to be completed by June 2021. This will be the first study determining overall oral health impact of using CF-NDS in smokers without sign of periodontitis. Data from this study will provide valuable insights into the overall potential of C-F NDS to reduce the risk of periodontal diseases. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT04649645 ### Funding Statement This investigator initiated research is supported by a grant from the Foundation for a Smoke free World (FSFW) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Comitato Etico Catania 2, dated 10/11/2020 (n. 73/2020/CECT2) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Results will be reported between 2023 and in 2024