Clinical trial NCT05608564: Local and Systemic Antimicrobials in Non-surgical Periodontal Therapy
Official title: The Impact of Local vs. Systemic Adjuvant Antibiotics During Non-surgical Periodontitis Therapy on Clinical Parameters, Bacterial Count and Cytokine Levels - a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Periodontitis
Keywords: local antibiotics
systemic antibiotics
Lead sponsor: University of Belgrade
Sponsor class: OTHER
First posted: 2022-11-08
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After the non-surgical periodontal treatment, the test group will be treated with local antibiotics, while the control group will be treated with systemic antibiotics. Randomization will be performed using randomization envelopes.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Pocket Probing Depth (PPD)
timeFrame: baseline and 6 months follow up
measure: Change in Clinical Attachment Level (CAL)
timeFrame: baseline and 6 months follow up
measure: Change in Bleeding On Probing (BOP)
timeFrame: baseline and 6 months follow up
measure: Change in Plaque Index (PI)
timeFrame: baseline and 6 months follow up
Secondary outcomes:
measure: Changes in Relative Expression Levels of Tumor Necrois Factor Alpha (TNF-α)
timeFrame: baseline and 6 months follow up
measure: Change in Total Bacterial Load (TBL)
timeFrame: baseline and 6 months follow up
measure: Changes in Relative Expression Levels of IL-17
timeFrame: baseline and 6 months follow up
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Department of Periodontology, School of Dental Medicine, University of Belgrade
Study officials:
affiliation: School of Dental Medicine, University of Belgrade, Department of Periodontology and Oral Medicine
name: Iva Z Milinkovic, DDS, PhD
role: PRINCIPAL_INVESTIGATOR
References: