Changes in Oral Health in Tobacco Cigarettes Smokers After Switching to Combustion-Free Nicotine Delivery Systems

NCT04649645 | Completed

• 1 other identifier: COE1-05-SMILE
• Study Type: interventional
• Target: 460
• Locations: 1 country
• Sites: 1

Brief Summary

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 moderate to severe periodontitis. This study aims to investigate whether cigarette smokers who switch to combustion-free nicotine delivery systems (C-F NDS) undergo measurable improvements in 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. The investigator propose a prospective, multicenter, interventional, open label, randomized, controlled, three parallel-arms study assessing oral health parameters and teeth appearance of 18 months duration.

Conditions

Gingivitis; Periodontal Diseases

Keywords

Electronic cigarettes; Tobacco Harm Reduction; Heated tobacco products; Smokers; Gingivitis; Modified gingival index; Oral Health; Tooth stain; Periodontitis; Dental plaque imaging; Dental discoloration

Outcome Measures

Primary Outcomes (1)

• Modified Gingival Index (MGI)

  Percentage (%) mean changes in MGI from baseline at different study time-points

  Changes in the severity of gingivitis from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

Secondary Outcomes (5)

• Macpherson Modification of Lobene Tooth Stain Index (MLSI)

  Changes in extent and severity of tooth stains from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

• Dental Discolorations

  Changes in dental discolouration from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

• Plaque Score Imaging (QLF)

  Changes in dental plaque from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

• Oral Health Quality of Life (OHQOL)

  Changes in OHQOL score from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

• EuroQoL Visual Analog Scale (EQ VAS - QoL)

  Changes in the EQ VAS - QoL score from baseline will be assessed at 3 months, 6 months, 12 months and 18 months

Study Arms (3)

Standard Arm (Arm A)

ACTIVE COMPARATOR

Participant continues smoking their own cigarette brand.

Other: TOBACCO CIGARETTES

Intervention Arm (Arm B)

ACTIVE COMPARATOR

Participant switches to using C-F NDS.

Other: COMBUSTION-FREE NICOTINE DELIVERY SYSTEMS (C-F NDS)

Control Arm (Arm C)

ACTIVE COMPARATOR

Participant continues to not smoking or using of any nicotine/tobacco products.

Other: NOT SMOKING

Interventions

TOBACCO CIGARETTES OTHER

Participants in Arm A will continue smoking their own cigarette brand as usual.

Standard Arm (Arm A)

COMBUSTION-FREE NICOTINE DELIVERY SYSTEMS (C-F NDS) OTHER

Participants in Arm B will trial and familiarize with a selection of C-F NDS in order to choose the product of their preference. They will be trained and counselled on the chosen C-F NDS. Prior to check-out, participants wishing to use a heated tobacco device will receive one kit and a full 2 weeks supply of tobacco sticks of their choice (they will receive a number of tobacco sticks per day corresponding to the number of cigarettes smoked at baseline); those wishing to use a vaping product will receive one vaping kit and a full 2 weeks supply of e-liquids of their choice (they will receive twelve 10 ml refill containers).

Intervention Arm (Arm B)

NOT SMOKING OTHER

Participants in Arm C will continue not smoking or use any form of tobacco or nicotine-containing products.

Control Arm (Arm C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Demonstrate understanding of the study and willingness to participate in the study by providing a signed written informed consent
• Healthy subjects, 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, subject have to be:
• Regular smokers, defined as:
• Smoked for at least five 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 of 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, subjects have to be:
• Never-smokers, defined as:

You may not qualify if:

• 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 cyclooxygenase 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.

Sponsors & Collaborators

• Eclat Srl.: lead
• University of Catania: collaborator

Study Sites (1)

Addendo srl

Catania, Catania, 95100, Italy

Location

Related Publications (23)

• Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol. 1996 Nov;1(1):821-78. doi: 10.1902/annals.1996.1.1.821. No abstract available.

  PMID: 9118282 BACKGROUND

• Research, Science and Therapy Committee. Position Paper: Diagnosis of Periodontal Diseases. J Periodontol. 2003 Aug;74(8):1237-1247. doi: 10.1902/jop.2003.74.8.1237.

  PMID: 29539063 BACKGROUND

• Armitage GC. Clinical evaluation of periodontal diseases. Periodontol 2000. 1995 Feb;7:39-53. doi: 10.1111/j.1600-0757.1995.tb00035.x. No abstract available.

  PMID: 9567929 BACKGROUND

• Czesnikiewicz-Guzik M, D'Aiuto F, Deanfield JE. Understanding residual inflammatory risk sheds new light on the clinical importance of periodontitis in cardiovascular disease. Eur Heart J. 2020 Feb 14;41(7):818-819. doi: 10.1093/eurheartj/ehaa107. No abstract available.

  PMID: 32058578 BACKGROUND

• Armitage GC. Periodontal infections and cardiovascular disease--how strong is the association? Oral Dis. 2000 Nov;6(6):335-50. doi: 10.1111/j.1601-0825.2000.tb00126.x.

  PMID: 11355266 BACKGROUND

• Bergstrom J. Cigarette smoking as risk factor in chronic periodontal disease. Community Dent Oral Epidemiol. 1989 Oct;17(5):245-7. doi: 10.1111/j.1600-0528.1989.tb00626.x.

  PMID: 2791514 BACKGROUND

• Bergstrom J, Preber H. Tobacco Use as a Risk Factor. J Periodontol. 1994 May;65(5):545-550. doi: 10.1902/jop.1994.65.5.545.

  PMID: 29539746 BACKGROUND

• Haber J. Smoking is a major risk factor for periodontitis. Curr Opin Periodontol. 1994:12-8.

  PMID: 8032453 BACKGROUND

• Bergstrom J. Tobacco smoking and chronic destructive periodontal disease. Odontology. 2004 Sep;92(1):1-8. doi: 10.1007/s10266-004-0043-4.

  PMID: 15490298 BACKGROUND

• Ueno M, Ohara S, Sawada N, Inoue M, Tsugane S, Kawaguchi Y. The association of active and secondhand smoking with oral health in adults: Japan public health center-based study. Tob Induc Dis. 2015 Jul 29;13(1):19. doi: 10.1186/s12971-015-0047-6. eCollection 2015.

  PMID: 26225132 BACKGROUND

• Eriksen HM, Nordbo H. Extrinsic discoloration of teeth. J Clin Periodontol. 1978 Nov;5(4):229-36. doi: 10.1111/j.1600-051x.1978.tb01916.x.

  PMID: 363748 BACKGROUND

• Christen AG. The impact of tobacco use and cessation on oral and dental diseases and conditions. Am J Med. 1992 Jul 15;93(1A):25S-31S. doi: 10.1016/0002-9343(92)90624-k.

  PMID: 1497000 BACKGROUND

• Zhu S, Melcer T, Sun J, Rosbrook B, Pierce JP. Smoking cessation with and without assistance: a population-based analysis. Am J Prev Med. 2000 May;18(4):305-11. doi: 10.1016/s0749-3797(00)00124-0.

  PMID: 10788733 BACKGROUND

• West R, Zhou X. Is nicotine replacement therapy for smoking cessation effective in the "real world"? Findings from a prospective multinational cohort study. Thorax. 2007 Nov;62(11):998-1002. doi: 10.1136/thx.2007.078758. Epub 2007 Jun 15.

  PMID: 17573444 BACKGROUND

• Polosa R, Farsalinos K, Prisco D. Health impact of electronic cigarettes and heated tobacco systems. Intern Emerg Med. 2019 Sep;14(6):817-820. doi: 10.1007/s11739-019-02167-4. Epub 2019 Aug 14. No abstract available.

  PMID: 31414334 BACKGROUND

• Polosa R, Rodu B, Caponnetto P, Maglia M, Raciti C. A fresh look at tobacco harm reduction: the case for the electronic cigarette. Harm Reduct J. 2013 Oct 4;10:19. doi: 10.1186/1477-7517-10-19.

  PMID: 24090432 BACKGROUND

• Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014 Apr;5(2):67-86. doi: 10.1177/2042098614524430.

  PMID: 25083263 BACKGROUND

• McNeill A, Brose L S, Calder R, Bauld L and Robson D. Evidence review of e-cigarettes and heated tobacco products 2018. A report commissioned by Public Health England.

  BACKGROUND

• Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018 Jun;89 Suppl 1:S173-S182. doi: 10.1002/JPER.17-0721.

  PMID: 29926951 BACKGROUND

• Lobene RR, Weatherford T, Ross NM, Lamm RA, Menaker L. A modified gingival index for use in clinical trials. Clin Prev Dent. 1986 Jan-Feb;8(1):3-6. No abstract available.

  PMID: 3485495 BACKGROUND

• Conte G, Pacino SA, Urso S, Greiling D, Caponnetto P, Pedulla E, Generali L, Consolo U, Checchi V, Gospodaru S, Bordeniuc G, Fala V, Kowalski J, Nowak M, Gorska R, Amaliya A, Chapple I, Milward M, Maclure R, Nardi GM, Polosa R. Changes in Oral Health and Dental Esthetic in Smokers Switching to Combustion-Free Nicotine Alternatives: Protocol for a Multicenter and Prospective Randomized Controlled Trial. JMIR Res Protoc. 2024 Feb 23;13:e53222. doi: 10.2196/53222.

  PMID: 38393754 DERIVED

• Conte G, Amaliya A, Gupta S, Emma R, Gospodaru S, Bordeniuc G, Fala V, Pacino SA, Urso S, Zucchelli G, Polosa R. Repeatability of dental plaque quantitation by light induced fluorescence technology in current, former, and never smokers. BMC Oral Health. 2023 Jul 13;23(1):480. doi: 10.1186/s12903-023-03154-0.

  PMID: 37443061 DERIVED

• Conte G, Pacino SA, Urso S, Emma R, Pedulla E, Cibella F, Stefanini M, Zucchelli G, Polosa R. Repeatability of dental shade by digital spectrophotometry in current, former, and never smokers. Odontology. 2022 Jul;110(3):605-618. doi: 10.1007/s10266-022-00692-x. Epub 2022 Mar 10.

  PMID: 35266059 DERIVED

MeSH Terms

Conditions

Gingivitis; Periodontal Diseases; Vaping; Tooth Discoloration; Periodontitis

Interventions

Tobacco Products

Condition Hierarchy (Ancestors)

Infections; Gingival Diseases; Mouth Diseases; Stomatognathic Diseases; Smoking; Behavior; Tooth Diseases

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Antonio Pacino, D.D.S.

  Addendo srl, Catania, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Smokers participants who were eligible and consent to take part will be randomized to either continuing smoking their own cigarette brand (Arm A) or switching to using C-F NDS (Arm B). Never-smokers participants who were eligible and consent to take part will be assigned to Arm C. The randomization sequence will be computer generated, with an allocation ratio of 1:4 (Study Arm A : Study Arm B; Smokers : N-C NDS users) to compensate for an estimated 25% success rate (combined smoking abstinence rate + \>90% smoking reduction rate) in the long term. The randomization scheme will be provided to clinical sites via a web-based application set up by the CRO. The staff randomizing the participant will access the web-based application when the participant is with them, entering their participant identification number, date of birth and initials into the program. The allocation will be immediately provided by the program/software.

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 2, 2020
• Study Start: October 18, 2021
• Primary Completion: December 19, 2024
• Study Completion: December 19, 2024
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)