NCT04649645.

Study name	International randomized controlled trial evaluating changes in oral health in smokers after switching to combustion‐free nicotine delivery systems (SMILE)
Methods	RCT Setting: multicenter: Italy, Moldova, Poland, UK and Indonesia
Participants	Estimated enrolment 606 participants Inclusion criteria: Demonstrate understanding of the study and willingness to participate in the study by providing a signed written informed consent Healthy, not taking regular medications for chronic medical conditions Adults, age at least 18 years old Presence of at least 10 natural anterior teeth in total (cuspid to cuspid, lower and upper jaw) Presence of at least 18 'scorable' teeth with scorable facial and lingual surfaces. Teeth that are grossly carious, orthodontically banded, exhibiting general cervical abrasion and/or enamel abrasion, and third molars will not be included in the tooth count Willingness and ability to comply with the requirements of the study including installing an APP on their digital device, e.g. smart phone or tablet For Arms A and B, participants have to be: Regular smokers, defined as: smoked for at least 5 consecutive years prior to screening. Smoked > 10 and < 30 cigarettes per day (cpd).with an exhaled breath carbon monoxide (CO) level ≥ 7 ppm at screening willing to regularly use any nicotine or tobacco product other than their own conventional cigarettes brand within 14 days prior to screening willing to change to use of study products or if randomized to Arm A continuing to use their own brand of conventional cigarettes for the whole duration of the study For Arm C, participants have to be: Never‐smokers, defined as:never smoked or who have smoked < 100 cigarettes in their lifetime and none in the 30 days prior to screening.with an exhaled breath CO level < 7 ppm at screening willing to not smoke or use any form of tobacco or nicotine‐containing products for the whole duration of the study Exclusion criteria: Pregnancy Presence of extensive crown or bridge work, dental implants, and/or rampant decay (per Investigator/Examiner discretion) Significant oral soft tissue pathology or any type of gingival overgrowth, other than plaque‐induced gingivitis and mild periodontitis (Stage I) Moderate‐to‐severe periodontitis (Stage II, III and IV) based on 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions, which require:Detectable Interdental Clinical Attachment Loss (CAL) ≥ 3 mm at ≥ 2 non‐adjacent teeth. Buccal or Oral CAL ≥ 3 mm with pocketing ≥ 5 mm detectable at ≥ 2 teeth Removable dentures or fixed and removable orthodontic appliance (except fixed lingual wires) Significant history of alcoholism or drug abuse (other than tobacco/nicotine) within 24 months prior to screening, as determined by the Investigator A course of treatment with any medications or substances (other than tobacco/nicotine) which:interfere with the cyclo‐oxygenase pathway (e.g. anti‐inflammatory drugs including aspirin and ibuprofen) within 3 days prior to each visit.are known to have antibacterial activity (e.g. antibiotics) within 7 days prior to each visit
Interventions	Standard Arm (Arm A): own tobacco cigarette brand Intervention Arm (Arm B): combustion‐free nicotine delivery system (C‐F NDS) Control Arm (Arm C): no smoking or use of any nicotine/tobacco products
Outcomes	Oral health parameters and teeth appearance, comparing short‐ and long‐term impact on periodontal health between smokers continuing with conventional cigarette smoking, those switching to combustion‐free nicotine delivery systems (C‐F NDS), and never‐smokers over 18 months
Starting date	Not yet recruiting (last updated February 2021) Estimated study start date Feb 2021. Primary completion date Feb 2023. Completion April 2023
Contact information	Principal investigator: Antonio Pacino, DDS, Addendo srl, Catania, Italy info@addendo.net
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