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Completed

NCT Number: NCT07323277

Effect of Smoking on Macrophage Polarization in Periodontitis

This observational case-control study investigates the effect of smoking on macrophage polarization in the pathogenesis of periodontitis. Adult participants who were either systemically healthy smokers or non-smokers, and who met the clinical criteria for periodontal health or periodontitis, were included. Gingival tissue samples were collected during periodontal procedures performed after completion of Phase I periodontal therapy, and the expression levels of macrophage polarization markers (iNOS and Arginase-1) were analyzed using ELISA. In addition, comprehensive clinical periodontal measurements-including probing pocket depth, clinical attachment level, bleeding on probing, Plaque Index, and Gingival Index-were recorded to evaluate the relationship between smoking status, inflammatory burden, and macrophage phenotype. The study aims to clarify how smoking modulates the balance between M1 and M2 macrophage responses in periodontal tissues.

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Süleyman Demirel University Faculty of Dentistry, Department of Periodontology

Isparta, 32000, Turkey (Türkiye)

About this study

Periodontitis is a chronic inflammatory disease in which macrophage polarization plays a key regulatory role in the host immune response. Smoking is a well-established risk factor that alters inflammatory pathways and immune cell behavior. This study was designed to examine how smoking influences macrophage polarization-specifically the balance between M1 (iNOS-mediated) and M2 (Arginase-1-mediated) phenotypes-in periodontal tissues.

Systemically healthy adult participants were recruited and categorized into four groups based on smoking status and periodontal condition: (1) healthy non-smokers, (2) periodontitis non-smokers, (3) healthy smokers, and (4) periodontitis smokers. Gingival tissue samples (approximately 2×2 mm) were collected during periodontal surgical procedures performed after completion of Phase I periodontal therapy, immediately stored at -80 °C, and processed for biochemical analysis. Comprehensive clinical periodontal measurements-including probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), Plaque Index (PI), and Gingival Index (GI)-were recorded on the same day to evaluate periodontal status and inflammatory burden. ELISA was used to quantify iNOS and Arginase-1 levels in gingival tissues.

The primary objective of this study is to determine whether smoking shifts the macrophage phenotype toward a more pro-inflammatory M1 profile or suppresses M2-associated regulatory pathways in the context of periodontitis. The findings are expected to contribute to a better understanding of smoking-related alterations in periodontal immune mechanisms.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • The study population consisted of volunteer participants aged 18-65 years who were referred to the Department of Periodontology at Süleyman Demirel University Faculty of Dentistry for periodontal treatment and who met the inclusion criteria without violating any exclusion criteria.

Exclusion criteria

  • Individuals who did not consent to participate in the study
  • History of any periodontal treatment within the past 6 months
  • Use of systemic antibiotics within the past 3 months
  • Pregnancy or lactation
  • Psychological or physical conditions that may interfere with cooperation during clinical examination
  • History of substance or alcohol abuse
  • Presence of severe malocclusion or ongoing orthodontic treatment
  • Acute dental pain due to caries, abscess, or other odontogenic infections
  • Presence of systemic diseases with oral manifestations or any systemic condition known to affect periodontal tissues
  • History of malignancy
  • Use of medications that can influence periodontal parameters (e.g., anti-inflammatory drugs) within the past 3 months
  • Participation in another scientific or clinical research study within the past 3 months

Treatment and study plan

Smoking Exposure

Other

Exposure to cigarette smoking, defined as smoking ≥10 cigarettes per day. Participants were classified as smokers or non-smokers based on self-reported smoking status.

Primary outcomes

  1. Gingival iNOS Level

    Time frame: At the time of periodontal surgery following completion of Phase I periodontal therapy.

    Concentration of inducible nitric oxide synthase (iNOS) in gingival tissue biopsies measured by ELISA (ng/mg tissue).

  2. Gingival Arginase-1 Level

    Time frame: At the time of periodontal surgery following completion of Phase I periodontal therapy.

    Concentration of Arginase-1 in gingival tissue biopsies measured by ELISA (ng/mg tissue).

Secondary outcomes

  1. Probing Pocket Depth (PPD)

    Time frame: Immediately prior to periodontal surgery, following completion of Phase I periodontal therapy.

    Mean probing pocket depth (mm) recorded at six sites per tooth using a periodontal probe.

  2. Clinical Attachment Level (CAL)

    Time frame: Immediately prior to periodontal surgery, following completion of Phase I periodontal therapy.

    Clinical attachment level (mm) recorded at six sites per tooth using a periodontal probe.

  3. Bleeding on Probing (BOP)

    Time frame: Immediately prior to periodontal surgery, following completion of Phase I periodontal therapy.

    Bleeding on probing percentage calculated as the proportion of bleeding sites to total sites examined.

  4. Plaque Index (PI)

    Time frame: Immediately prior to periodontal surgery, following completion of Phase I periodontal therapy.

    Dental plaque accumulation assessed using the Silness and Löe Plaque Index. Plaque scores were recorded at four surfaces per tooth and scored on a scale from 0 to 3, where 0 indicates no plaque and 3 indicates abundant plaque accumulation. Higher scores indicate worse plaque status.

  5. Gingival Index (GI)

    Time frame: Immediately prior to periodontal surgery, following completion of Phase I periodontal therapy.

    Gingival inflammation assessed using the Löe and Silness Gingival Index. Gingival Index scores were recorded at four surfaces per tooth and scored on a scale from 0 to 3, where 0 indicates normal gingiva and 3 indicates severe gingival inflammation. Higher scores indicate worse gingival status.

Sponsors and collaborators

Lead sponsor

Suleyman Demirel University

Other

Registry information

Official study title

The Effect of Smoking on Macrophage Polarization in the Pathogenesis of Periodontitis

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jan 7, 2026
Registry last updated
Jan 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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