An observational study in Gingivitis, Circadian Rhythm Disruption and Periodontal Inflammation, sponsored by Inonu University. Not yet recruiting at 1 site in Turkey (Türkiye). Open to participants aged 20 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by Inonu University · Observational
This prospective cross-sectional clinical study aims to investigate the relationship between circadian rhythm disruption and periodontal inflammation by evaluating circadian clock protein levels, inflammatory (IL-1beta) and anti-inflammatory (IL-10) cytokine levels in gingival crevicular fluid (GCF) of individuals with and without circadian rhythm disruption.
Participants aged 20-50 years will be classified into four groups based on their circadian rhythm status (disrupted/normal) and gingival health status (gingivitis/healthy). Clinical periodontal parameters including plaque index, gingival index, bleeding on probing, and probing depth will be assessed. Circadian rhythm status will be determined using validated questionnaires (Morningness-Eveningness Questionnaire and Munich Chronotype Questionnaire). Night-shift workers will represent the circadian rhythm disruption group.
GCF samples will be analyzed for circadian clock proteins (BMAL-1, CLOCK, PER-1, PER-2, PER-3, CRY-1, CRY-2, REV-ERB-beta, MTNR1B) and cytokines (IL-1beta, IL-10) using ELISA. Serum cortisol and melatonin levels will be measured for biochemical verification of circadian rhythm status.
Gingivitis groups will receive standard periodontal treatment and be re-evaluated at 2 weeks post-treatment. A total of 116 participants (29 per group) are planned for enrollment.
Gingival tissue plays a critical role in maintaining oral health as a fundamental component of periodontal tissues. Recent evidence suggests that circadian rhythm mechanisms, beyond microbial factors, may significantly influence periodontal disease pathogenesis through modulation of host immune responses.
The circadian rhythm is an endogenous mechanism regulating biological processes in approximately 24-hour physiological and behavioral cycles, controlled centrally by the suprachiasmatic nucleus in the hypothalamus. At the molecular level, core clock genes (CLOCK, BMAL1, PER1-3, CRY1-2) operate through the Transcription-Translation Feedback Loop (TTFL). CLOCK and BMAL1 proteins form heterodimers in the cell nucleus, bind to E-box regions on DNA, and initiate transcription of PER and CRY genes. Subsequently, PER and CRY proteins synthesized in the cytoplasm return to the nucleus and inhibit the CLOCK-BMAL1 complex, creating approximately 24-hour rhythmic gene expression cycles. Regulatory nuclear receptors such as REV-ERBa and ROR also contribute to the fine-tuning of this mechanism.
Recent studies have demonstrated the presence of functional peripheral clock mechanisms in periodontal tissues. CLOCK, BMAL1, PER1-3, and CRY1-2 gene expression has been identified in gingival fibroblasts and periodontal ligament fibroblasts. Experimental studies have shown that circadian rhythm disruption can increase inflammatory processes, enhance macrophage activation, elevate inflammatory cytokine production, and accelerate alveolar bone loss in periodontitis models.
Despite these findings, human studies evaluating the relationship between inflammatory cytokines and circadian rhythm proteins in gingival crevicular fluid (GCF) remain limited. This study addresses this gap by evaluating gingival health status using clinical periodontal parameters in individuals with and without circadian rhythm disruption.
Study Design:
Participants will be classified into four groups based on circadian rhythm status and periodontal health:
Time Points:
T0 (Baseline): Clinical periodontal examination, GCF, saliva, and serum sampling in all groups.
T1 (Day 14): Re-evaluation of clinical parameters and biological sampling in gingivitis groups after standard periodontal treatment.
Clinical Periodontal Assessment:
All periodontal measurements will be performed by a single examiner using a standard periodontal probe at six sites per tooth (mesiobuccal, buccal, distobuccal, mesiolingual, lingual, distolingual). Parameters include plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL).
GCF Sampling:
GCF samples will be collected using sterile Periopaper strips placed in the gingival sulcus for 30 seconds after supragingival plaque removal and isolation. GCF volumes will be quantified using a Periotron device. Samples contaminated with blood will be excluded.
Saliva Sampling:
Unstimulated saliva samples will be collected as an alternative biological material if circadian rhythm proteins cannot be detected at sufficient levels in GCF.
Serum Sampling:
Venous blood samples will be collected from the antecubital vein for biochemical evaluation of circadian rhythm status through cortisol and melatonin level analysis.
All biological samples will be collected during standardized morning hours (09:00-11:00) to minimize diurnal variation in biomarker levels.
Laboratory Analysis:
GCF samples will be analyzed using ELISA for circadian rhythm-related proteins (MTNR1B, BMAL-1, CLOCK, PER-1, PER-2, PER-3, CRY-1, CRY-2, REV-ERB-beta) and inflammatory biomarkers (IL-1beta and IL-10).
Statistical Analysis:
Data will be analyzed using SPSS. Normality will be assessed by Shapiro-Wilk test. Comparisons among independent groups will use one-way ANOVA or Kruskal-Wallis test, with Tukey or Dunn post-hoc tests. Pre- and post-treatment comparisons will use paired t-test or Wilcoxon signed-rank test. Correlations will be assessed by Pearson or Spearman analysis. Multivariate regression models will control for age, sex, BMI, and waist circumference as covariates. Significance level: p \< 0.05.
This study was approved by the Inonu University Health Sciences Scientific Research Ethics Committee and will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants.
631 studies on the registry are indexed under Gingivitis; 107 are open to participants now.
This study's planned enrollment of 116 is above the median of 93 across 116 observational studies indexed under Gingivitis.
Browse Gingivitis studies →Inonu University is the lead sponsor of 394 studies on the registry; 95 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Systemically healthy volunteers aged 20-50 years presenting to Inonu University Faculty of Dentistry, Department of Periodontology. The study population includes individuals with normal circadian rhythm and night-shift workers with circadian rhythm disruption. Participants are classified as periodontally healthy or with gingivitis based on clinical periodontal examination. Circadian rhythm status is verified using the Morningness-Eveningness Questionnaire (MEQ) and Munich Chronotype Questionnaire (MCTQ).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Individuals with normal circadian rhythm and periodontal health (control group). Inclusion: PD \<=3 mm, BOP \<10%, CAL=0, no radiographic bone loss. n=29
Individuals with normal circadian rhythm and gingivitis. Inclusion: PD \<=3 mm, 10%\<=BOP\<=30%, CAL=0, no radiographic bone loss. These participants will receive standard periodontal treatment and be re-evaluated at 14 days post-treatment. n=29
Other: Standard Periodontal Treatment
Night-shift workers with circadian rhythm disruption and periodontal health. Circadian rhythm status verified by MEQ and MCTQ questionnaires. Inclusion: PD \<=3 mm, BOP \<10%, CAL=0, no radiographic bone loss. n=29
Night-shift workers with circadian rhythm disruption and gingivitis. Circadian rhythm status verified by MEQ and MCTQ questionnaires. Inclusion: PD \<=3 mm, 10%\<=BOP\<=30%, CAL=0, no radiographic bone loss. These participants will receive standard periodontal treatment and be re-evaluated at 14 days post-treatment. n=29
Other: Standard Periodontal Treatment
Standard periodontal treatment including detailed oral hygiene instruction and professional dental surface cleaning (scaling and polishing). Applied to gingivitis groups (Group 2 and Group 4) at baseline, with clinical and biochemical re-evaluation at 14 days post-treatment.
GCF Circadian Rhythm Protein Levels
Concentrations of circadian clock proteins (BMAL-1, CLOCK, PER-1, PER-2, PER-3, CRY-1, CRY-2, REV-ERB-beta, MTNR1B) measured in gingival crevicular fluid (GCF) using ELISA. GCF collected with Periopaper strips placed in the gingival sulcus for 30 seconds. Volumes quantified using a Periotron device.
Time frame: Baseline (T0) and 14 days post-treatment (T1) for gingivitis groups
GCF Inflammatory Cytokine Levels
Interleukin-1 beta (IL-1beta, pro-inflammatory) and Interleukin-10 (IL-10, anti-inflammatory) cytokine concentrations in gingival crevicular fluid measured by ELISA.
Time frame: Baseline (T0) and 14 days post-treatment (T1) for gingivitis groups
Plan to share: Undecided
Start is estimated for Nov 2026; primary completion for Jan 2027, 2 months later.
Of 30 non-industry observational studies under Gingivitis, half reached primary completion within 12 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 25. This study's planned 2 months is below that.
Counting every sponsor, half of 30 studies reached it within 12 months; a quarter within 5 and three quarters within 25.
Start moved once since we started tracking on Sep 25, 2026: Aug 2026 → Nov 2026, on Oct 27, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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