Evaluation of the Systemic Burden of Non-surgical Periodontal Therapy: A Randomized Clinical Trial on Five Different Treatment Protocols

Overview

Periodontitis is a chronic inflammatory disease of the periodontal tissues leading to the destruction of the tooth supporting structures. Despite the fact that periodontal bacteria are etiological agents, host susceptibility related to the inflammatory response to plaque bacteria is the main determinant of the development of periodontitis. Non-surgical periodontal therapy (NSPT) represents the base of any therapeutic approach. Its main component is the removal of bacterial deposits, i.e. soft biofilm or mineralized calculus, from the tooth surface via mechanical debridement. It is well established that patients suffering from periodontitis present with a low-grade systemic inflammatory state when compared to healthy subjects. Increased concentrations of inflammatory biomarkers in systemic circulation, such as, C-reactive protein (CRP) and interleukin (IL)-6, have already been reported. A significant amount of evidence derived from epidemiological as well as experimental studies has implicated periodontitis as a putative risk factor for a number of systemic diseases, such as, cardiovascular diseases, diabetes and respiratory diseases having systemic low-grade inflammation as their underlying pathogenic mechanism. Furthermore, several intervention studies provide evidence that periodontal treatment may improve systemic inflammatory markers and potentially reduce the risk for cardio-metabolic diseases. However, periodontal therapy may pose a transient, short-term health hazard immediately after instrumentation of the root surface presumably due to the spill of bacteria and their products in the systemic circulation and the subsequent acute inflammatory response. Positive bacteremia in NSPT ranges from 13% to 80.9% after mechanical debridement depending primarily on the periodontal status of the patient, but also on the study design and the microbiological methodology. Finally, an important aspect concerning NSPT is method and duration of delivery. NSPT may be carried out with either hand instruments, power driven instruments, such as, ultrasonic and sonic or a "blended approach" using both. Besides these instruments, the adjunctive use of lasers or/and air powder technology has been proposed. Regarding duration, treatment may be staged over several visits with a quadrant approach, or with a full-mouth debridement approach, also referred to as an intensive treatment approach, which delivers complete debridement within 24 hours. The aim of this clinical trial is to assess the immediate systemic burden of five different treatment protocols for the NSPT on: 1. bacteremia 2. serum inflammatory responses. Additionally, saliva CRP levels will be assessed and compared to serum. Moreover, the effectiveness of the treatment protocols on clinical periodontal parameters will be assessed.

Interventions

• Procedure Scaling and Root Planing
  Mechanical debridement of tooth surfaces using hand and ultrasonic instruments
• Drug antibiotic prophylaxis
  2g Amoxicillin given 1 hour prior to instrumentation
• Device 810nm Diode Laser
  Laser applied at base of gingival pockets prior to mechanical debridement.
• Procedure Air Polishing
  air flow-based mechanical debridement with erythritol powder

Primary outcome measures

• Change in serum high-sensitivity C-reactive protein (hs-CRP) levels [Time frame: Baseline-7 days after the last periodontal session]

Secondary outcome measures (12)

• Changes in serum Interleukin 6 (IL-6) [Time frame: Baseline-7 days after the last periodontal session]
• Presence and load of bacteremia [Time frame: Baseline-15 minutes after the last periodontal session]
• Changes in mean Clinical Attachment Level (CAL) [Time frame: Baseline-8 weeks after the last periodontal session]
• Salivary CRP correlation with serum CRP [Time frame: Baseline-7 days after the last periodontal session]
• Changes in serum Tumor Necrosis Factor a (TNF-a) levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in Serum amyloid A (SAA) levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in Serum cystatin c levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in Matrix metalloproteinase-8 (MMP-8) levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in serum D-dimers levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in serum Lipopolysaccharide (LPS) levels [Time frame: Baseline-7 days after the last periodontal session]
• Changes in mean Pocket Depth (PD) [Time frame: Baseline-8 weeks after the last periodontal session]
• Changes in mean Gingival Recession (GR) [Time frame: Baseline-8 weeks after the last periodontal session]

Eligibility criteria

Inclusion criteria

• Periodontitis stage III or IV
• Non-smokers or light smokers (<10 cigarettes/day)
• No NSAIDs in regular basis or antibiotics 3 months before
• No previous periodontal treatment 12 months before
• No presence of other acute or chronic infections
• No systemic disease or medication known to affect the serum level of inflammatory markers (cyclooxygenase inhibitors, platelet aggregation inhibitors, lipid lowering agents, â-adrenoreceptor antagonists, angiotensin converting enzyme inhibitors, antidiabetic agents, estrogen-based medications, medication for autoimmune disease, magnesium or vitamin E supplements)
• No pregnancy or lactation
• Written informed consent.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Greece · 1 center

• Department of Periodontology, Dental School of Athens — Athens

Publications

• Sanz M, Marco Del Castillo A, Jepsen S, Gonzalez-Juanatey JR, D'Aiuto F, Bouchard P, Chapple I, Dietrich T, Gotsman I, Graziani F, Herrera D, Loos B, Madianos P, Michel JB, Perel P, Pieske B, Shapira L, Shechter M, Tonetti M, Vlachopoulos C, Wimmer G. Periodontitis and cardiovascular diseases: Consensus report. J Clin Periodontol. 2020 Mar;47(3):268-288. doi: 10.1111/jcpe.13189. Epub 2020 Feb 3. PMID 32011025
• Sanz M, Herrera D, Kebschull M, Chapple I, Jepsen S, Beglundh T, Sculean A, Tonetti MS; EFP Workshop Participants and Methodological Consultants. Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline. J Clin Periodontol. 2020 Jul;47 Suppl 22(Suppl 22):4-60. doi: 10.1111/jcpe.13290. PMID 32383274
• Kinane DF, Riggio MP, Walker KF, MacKenzie D, Shearer B. Bacteraemia following periodontal procedures. J Clin Periodontol. 2005 Jul;32(7):708-13. doi: 10.1111/j.1600-051X.2005.00741.x. PMID 15966875

Identifiers

NCT: NCT07077122 · 688/11.02.2025 · Ethics committee

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗