Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy

Not Applicable

Completed

• Conditions: Periodontitis

• Registration Number: NCT05608564
• Lead Sponsor: University of Belgrade

Brief Summary

The main treatment of every patient with periodontitis is non-surgical periodontal treatment (NSPT) with the ultimate goal to arrest inflammation. Given the biofilm microorganisms associated etiology of the periodontitis, NSPT can be combined with adjunctive antimicrobial therapy. Hence, this randomized clinical trial aims to compare the clinical and microbiological effectiveness and relative expression levels (REL) of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) between local and systemic antibiotics as adjunctive therapy to NSPT in patents with periodontitis stage 3.

Detailed Description

Study protocol:

This randomized clinical study will include 40 patients diagnosed with periodontitis stage 3. The investigation will be conducted at the Department of Periodontology and Oral Medicine, at the School of Dental Medicine, University of Belgrade. The laboratory part of the research will be carried out at the Department of Human genetics, at the School of Dental Medicine, University of Belgrade. Patients will be divided into two groups. The test group will consist of 20 patients who will be prescribed a local antibiotic (LA group), while the control group will consist of 20 patients who will be prescribed systemic antibiotic therapy (SA group). The division of patients into groups will be done with randomization envelopes after the diagnostic procedure.

Upon clinical examination, clinical periodontal parameters such as periodontal probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI) will be recorded for each patient around every tooth. Previous to treatment, subgingival crevicular fluid will be sampled with paper points from periodontal pockets for laboratory analysis.

Sampling will be performed as follows: first, a relatively dry working field will be established using paper water rollers and air jets, and then 3 paper points (number 30 - marked in blue) will be applied for 30 seconds in the periodontal pocket area of the selected premolar/molar tooth with a depth of more than 5mm. The procedure will be repeated immediately in the same region, to obtain duplicate samples. After that, the paper points will be placed in Eppendorf tubes and immediately transported to the basic research laboratory, where they will be stored at a temperature of -80 degrees Celsius and where microbiological and molecular analyses will be carried out.

After sampling, all patients will undergo a non-surgical phase of periodontal therapy, following a Full-mouth disinfection protocol. Six months after the NSPT, at the follow-up, clinical examination, detection of clinical parameters, and sampling procedure will be repeated. In the LA group, antibiotics will be applied after the NSPT, while in the SA group therapy will be prescribed at the beginning of the treatment. Locally will be applied a combination of piperacillin and tazobactam in gel form (Gelcide ®, Italmed MedTechDental, Florence, Italy) designed for use in the subgingival region. The local antibiotic will be applied into the periodontal pockets, using a syringe and a flexible blunt needle, 24 hours after the NSPT. The administration will be done by quadrants, following the principles of a dry work field, and after application, the dry field should be maintained for 5 minutes. After this procedure, the patient should not rinse the oral cavity for 15 minutes. For systemic use in the SA group, patients will receive a combination of Amoxicillin (Amoxicillin ®, 500mg, 3 times a day, 7 days) and Metronidazole (Orvagyl ®, 400mg, 3 times a day, 7 days) for oral use.

Total bacterial count (TBC) and REL of proinflammatory cytokines TNF-α and IL-17 will be detected using the quantitative real-time polymerase chain reaction (qPCR) in a basic research laboratory at the Department of Human genetics, at the School of Dental Medicine, University of Belgrade.

Study Timeline

• Study First Submitted: 2022-10-24
• Study First Submitted QC: 2022-10-31
• Study First Posted: 2022-11-08
• Study Start: 2023-01-17
• Primary Completion: 2023-08-10
• Study Completion: 2024-03-11
• Results First Submitted: 2024-03-27
• Results First Submitted QC: 2025-04-28
• Results First Posted: 2025-05-14
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-08
• Last Update Posted: 2025-07-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

1. Both sexes, 18 - 45 years old
2. Willingness to participate in the research, comply with all the study protocols, and sign an informed consent;
3. Active periodontitis stage II and III according to the criteria of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions;
4. Non-smokers and light smokers (up to 10 cigarettes per day).

Exclusion Criteria

1. Presence of systemic diseases known to affect the tooth-supporting apparatus and bone metabolism (such as uncontrolled diabetes mellitus, cancer, immunodeficiency, metabolic bone diseases);
2. Patients receiving an immunosuppressive, anti-resorptive, or anti-inflammatory therapy;
3. Allergy to penicillin;
4. Patients who had undergone periodontal therapy within the last 6 months;
5. Use of local and/or systemic antimicrobial agents within the last 6 months;
6. Use of oral anti-plaque mouthwash at least one month prior to the study;
7. Alcohol or drug abuse;
8. Pregnancy or lactation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Bleeding On Probing (BOP)	baseline and 6 months follow up	Bleeding on probing (BOP) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
Change in Plaque Index (PI)	baseline and 6 months follow up	Plaque Index (PI) was assessed using a periodontal probe at 6 sites around each present tooth during baseline and 6-month follow-up clinical examinations. BOP was recorded as present (1) or absent (0) at each site, and expressed as a percentage (%).
Change in Pocket Probing Depth (PPD)	baseline and 6 months follow up	Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.
Change in Clinical Attachment Level (CAL)	baseline and 6 months follow up	Pocket probing depth (PPD) was measured using a periodontal probe at 6 sites per tooth, recorded in millimeters (mm), at baseline and at 6-month follow-up. This measure was used to compare outcomes between local and systemic antimicrobial therapies.

Secondary Outcome Measures

Name	Time	Method
Changes in Relative Expression Levels of Tumor Necrois Factor Alpha (TNF-α)	baseline and 6 months follow up	Relative expression levels (REL) of TNF-α were assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and 6-month follow-up. GCF was obtained using sterile paper strips, and TNF-α levels were quantified using the real-time polymerase chain reaction (qPCR) method. Results were expressed in nanograms per milliliter (ng/mL) to compare local and systemic antimicrobial therapy groups.
Change in Total Bacterial Load (TBL)	baseline and 6 months follow up	Total bacterial load (TBL) was assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and at the 6-month follow-up. GCF was obtained using sterile paper strips, and bacterial quantification was performed using the real-time polymerase chain reaction (qPCR) method. Results were expressed in colony-forming units per milliliter (CFU/mL) to evaluate differences between local and systemic antimicrobial therapies.
Changes in Relative Expression Levels of IL-17	baseline and 6 months follow up	Relative expression levels (REL) of interleukin-17 (IL-17) were assessed in gingival crevicular fluid (GCF) samples collected from periodontal pockets at baseline and at the 6-month follow-up. GCF was obtained using sterile paper strips, and REL of IL-17 was quantified using the real-time polymerase chain reaction (qPCR) method. Results were expressed in nanograms per milliliter (ng/mL) to compare local and systemic antimicrobial therapies.

Trial Locations

Locations (1)

Department of Periodontology, School of Dental Medicine, University of Belgrade; 🇷🇸 Belgrade, Serbia