Hyaluronic Acid as an Adjunct to Non-Surgical Periodontal Therapy in Smokers

The Effect of Adjunctive Use of Hyaluronic Acid in Non-Surgical Periodontal Treatment in Smoking Patients

The goal of this clinical trial is to evaluate whether hyaluronic acid (HA) improves periodontal healing in people with periodontal disease who smoke. Moreover, the effects of HA on biomolecules and bacteria levels will be assesed during the follow up period.

The main questions it will answer are:

Will periodontal sites treated with HA gel after non-surgical periodontal treatment (NSPT) lead to better outcomes in clinical parameters compared to the sites treated with NSPT only in smokers?

Will adjunctive use of HA gel reduce oxidative stress markers and bacteria levels during follow-up?

Researchers will compare periodontal sites receiving NSPT with adjunctive HA gel application to sites receiving NSPT alone to determine whether HA provides additional clinical, biochemical and microbiological benefits.

Participants will:

• first receive full-mouth NSPT then, randomization will be performed in selected jaw to determine the test sites. These two interproximal test sites will additionally receive HA gel application.
• attend follow-up visits at 1, 3 and 6 months for clinical periodontal measurements and to provide gingival crevicular fluid samples (GCF) and subgingival samples.

The GCF samples will be evaluted for Metallothionein (MT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels and subgingival samples for periodontal pathogens.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontitis; Oxidative Stress; Periodontal Therapy; Hyaluronic Acid; Oral Microbiota; Metallothionein; 8-OHdG
• Intervention / Treatment: Procedure: Scaling and Root Planing; Device: Hyaluronic Acid (HYADENT BG)

Detailed Description

This study is an split-mouth study that investigates the clinical, biochemical and microbiological efficacy of Hyadent BG® gel application in periodontal pockets after non-surgical periodontal treatment (NSPT) in smoking patients.

The study will include 23 smoker periodontitis patients who applied to the Department of Periodontology, Faculty of Dentistry, Marmara University, for the eligible participants will receive detailed information regarding study procedures, and written informed consent will be obtained prior to enrollment.

Treament Procedures

Two days before NSPT, radiographic and full mouth clinical evaluations will be carried out to determine which jaw will be included for the study. The intraoral photographs will be taken, and impressions of the related jaw will be taken for stent fabrication.

One day before NSPT clinical measurements of the related sites with the stent will be repeated. NSPT will be completed in three sessions within two weeks.

Before starting NSPT, baseline pooled gingival crevicular fluid (GCF) then pooled subgingival microbiological samples will be collected sequentially from the related sites of the selected jaw. Then oral hygiene instructions will be provided, followed by full-mouth supragingival and subgingival scaling using ultrasonic and hand instruments in two weeks time.

At the last session of NSPT, test sites (non adjacent sites with ≥6mm pocket depth) for adjunctive use of HA gel will be randomly determined by a toss of a coin from the selected jaw, and HA will be applied subgingivally.

All patients will be followed up at the 1-, 3-, and 6-month intervals.

Periodontal Clinical Measurements

At baseline, 1-, 3-, and 6-month, full mouth clinical measurement will be performed.

Periodontal clinical measurements will be recorded at six sites per tooth-mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual-using a Williams periodontal probe (Hu-Friedy).

Plaque Index (PI): Dental plaque accumulation will be assessed after air drying the teeth using a periodontal probe and visual inspection, according to the PI system developed by Silness and Löe.

Gingival Index (GI): The gingival inflammatory status will be assessed using the GI developed by Löe and Silness.

Probing Depth (PD): PD will be measured as the distance from the free gingival margin to the base of the periodontal pocket by inserting the periodontal probe to the pocket base.

Clinical Attachment Level (CAL): CAL will be recorded by measuring the distance from the cemento-enamel junction to the base of the pocket.

Bleeding on Probing (BOP) (%): BOP will be assessed 25-30 seconds after pocket probing. Sites showing bleeding will be recorded as positive (+), while those without bleeding will be recorded as negative (-).

Collection of GCF and Subgingival Microbiological Samples

At baseline, both GCF and pooled subgingival microbiological samples will be collected after clinical measurements from test and control sites, but at follow-up visits (1st, 3rd, and 6th months) prior to clinical measurements. Before sampling, supragingival plaque will be carefully removed, then the test (n=2) and control (n=2) sites isolated from saliva using cotton rolls and dried.

First, GCF samples will be collected. Periopaper strips will be inserted 1-2 mm into the periodontal pocket and left in place for 30 seconds at the selected sites. GCF volume will be measured.

Following GCF sampling, subgingival microbiological sampling will be carried out by inserting sterile paper points (#30) to the base of the periodontal pockets and kept in place for 10 seconds.

All GCF and the subgingival microbiological samples will be stored at -80°C until analysis day.

GCF samples will be analyzed by using commercially available Enzyme-Linked Immunosorbent Assay kits for metallothionein (MT) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels.

Quantification of A. actinomycetemcomitans, F. nucleatum, P. gingivalis, T. forsythia, and P. intermedia in subgingival microbiological samples will be performed using Real-Time Polymerase Chain Reaction.

Statistical Analysis

Statistical analyses will be performed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). A confidence level of 95% will be adopted for all analyses, and a p value of less than 0.05 will be considered statistically significant.

Due to the split-mouth study design, test and control sites within the same individual will be treated as paired samples.

Descriptive statistics for clinical parameters ( PI, GI, BOP, PD, and CAL) and biochemical markers (MT and 8-OHdG) will be expressed as mean ± standard deviation, median, and minimum-maximum values.

The normality of data distribution will be assessed using the Shapiro-Wilk test. For normally distributed variables, within-group comparisons over time (baseline, 1 month, and 3 months) will be analyzed using one-way repeated measures analysis of variance (ANOVA). When a statistically significant difference is detected, pairwise comparisons will be performed using the Tukey post hoc test.

Comparisons between test and control sites will be conducted using the paired samples t-test.

For variables that do not follow a normal distribution, within-group comparisons over time will be analyzed using the Friedman two-way analysis of variance. When significant differences are observed, pairwise comparisons will be performed using the Wilcoxon signed-rank test.

Between-group comparisons for non-normally distributed variables will be performed using the Mann-Whitney U test.

Correlations between clinical, biochemical, and microbiological variables will be evaluated using Spearman's correlation analysis. Variables found to be significant will be further analyzed using multiple linear regression to assess their independent effects.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Basak Dogan; Phone Number: +905332621170; Email: basakdogan@marmara.edu.tr
• Study Contact Backup: Name: Onur Akova; Phone Number: +905318926492; Email: onur.akova@marmara.edu.tr

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Department of Periodontology, Faculty of Dentistry, Marmara University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Individuals who sign the informed consent form
2. Participants who are systemically healthy
3. Participants who smoke (for >5 years and ≥10 cigarettes per day)
4. Participants diagnosed with Stage III or Stage IV periodontitis
5. Participants with at least 20 natural teeth present in the mouth (excluding third molars)
6. Participants in either of the jaws, in both quadrants, having two non-adjacent interproximal sites with probing depth (PD) and clinical attachment level (CAL) ≥6 mm with no caries, restorations or furcation involvement

Exclusion Criteria:

1. Individuals who do not sign the informed consent form
2. Individuals having any systemic disease
3. Participants who have used antibiotics within the last 3 months
4. Participants have received any periodontal treatment within 6 months prior to the study
5. Participants who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Test; Non-surgical periodontal treatment and Hyaluronic Acid gel	Procedure: Scaling and Root Planing; Scaling and root planing is a conventional gold-standard treatment for periodontitis. As part of this procedure, subgingival plaque and tartar are removed and root surfaces are planed.; Device: Hyaluronic Acid (HYADENT BG); Hyaluronic acid will be locally applied to periodontal pockets as an adjunct to non-surgical periodontal treatment, aiming to support periodontal healing. After completion of scaling and root planing, the material will be delivered subgingivally to designated test sites.
Other: Control; Non-surgical periodontal treatment alone	Procedure: Scaling and Root Planing; Scaling and root planing is a conventional gold-standard treatment for periodontitis. As part of this procedure, subgingival plaque and tartar are removed and root surfaces are planed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Probing Depth (PD)	PD will be measured around each tooth by recording the distance in milimeters from the gingival margin to the bottom of the pocket at 6 locations (mesiobuccal, mid-buccal, distobuccal, mesiopalatal, mid-palatal, distopalatal)	Baseline to 1, 3 and 6 months after NSPT.
Change in Clinical Attachment Level	Clinical attachment level will be measured in millimeters using a periodontal probe. The change in CAL will be calculated as the difference between baseline and follow-up measurements. A decrease in CAL indicates an improvement in periodontal attachment.	Baseline to 1, 3 and 6 months after NSPT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bleeding on Probing (%)	Possible score for BOP range from %0 (no sites with bleeding on probing) to %100 (all sites with bleeding on probing). Higher scores mean worse outcome.	Baseline to 1, 3 and 6 months after NSPT.
Change in Plaque Index	Possible scores for Plaque Index range from 0 (no plaque) to 3 (visible plaque all around the tooth). Higher scores mean a worse outcome	Baseline to 1, 3 and 6 months after NSPT.
Change in Gingival Index	Possible score for Gingival Index range from 0 (healthy gingiva) to 3 (severe gingivitis with bleeding). Higher scores mean worse outcome	Baseline to 1, 3 and 6 months after NSPT.
Change in GCF Metallothionein Levels	Change in metallothionein levels from baseline to 1, 3 and 6 months after NSPT	Baseline to 1, 3 and 6 months after NSPT
Change in GCF 8-OHdG levels	Change in 8-OHdG levels from baseline to 1, 3 and 6 months after NSPT	Baseline to 1, 3 and 6 months after NSPT
Change in Porphyromonas gingivalis levels	Change in Porphyromonas gingivalis levels in subgingival microbiological samples from baseline to 1, 3 and 6 months after NSPT.	Baseline to 1, 3 and 6 months after NSPT.
Change in Fusobacterium nucleatum levels	Change in Fusobacterium nucleatum levels in subgingival microbiological samples from baseline to 1, 3 and 6 months after NSPT.	Baseline to 1, 3 and 6 months after NSPT.
Change in Aggregatibacter actinomycetemcomitans levels	Change in A. actinomycetemcomitans levels in subgingival microbiological samples from baseline to 1, 3 and 6 months after NSPT.	Baseline to 1, 3 and 6 months after NSPT.
Change in Tanerella forsythia levels	Change in Tanerella forsythia levels in subgingival microbiological samples from baseline to 1, 3 and 6 months after NSPT.	Baseline to 1, 3 and 6 months after NSPT.
Change in Prevotella intermedia levels	Change in Prevotella intermedia levels in subgingival microbiological samples from baseline to 1, 3 and 6 months after NSPT.	Baseline to 1, 3 and 6 months after NSPT.

Collaborators and Investigators

• Sponsor: Marmara University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 13, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: periodontitis; periodontal pathogens; hyaluronic acid; 8-OHdG; Non-surgical periodontal treatment; split-mouth study; metallothionein
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Periodontitis; Digestive System and Oral Physiological Phenomena; Dentistry; Dental Physiological Phenomena; Dental Scaling; Dental Prophylaxis; Periodontics; Subgingival Curettage; Preventive Dentistry; Root Planing; Tooth Exfoliation
• Other Study ID Numbers: 09.2025.544; TDH-2026-12418 (Other Grant/Funding Number: Marmara University Scientific Research Projects Coordination Unit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No