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

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.

Study Overview

• Status: Recruiting
• Conditions: Periodontitis
• Intervention / Treatment: Procedure: Scaling and Root Planing; Drug: antibiotic prophylaxis; Device: 810nm Diode Laser; Procedure: Air Polishing

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zampa Evangelia; Phone Number: 00306987027896; Email: elina_zampa@windowslive.com

Study Locations

• Greece
  • Athens, Greece
    • Recruiting
    • Department of Periodontology, Dental School of Athens
    • Contact: Prof. Madianos P., DDS, PhD; Phone Number: 00302107461181; Email: pmadian@dent.uoa.gr

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Full-Mouth SRP; oral hygiene instructions and full mouth scaling and root planing in 24 hours. Clinical re-evaluation in 8 weeks.	Procedure: Scaling and Root Planing; Mechanical debridement of tooth surfaces using hand and ultrasonic instruments
Experimental: SRP + Antibiotics; oral hygiene instructions and full mouth scaling and root planing in 24 hours along with antibiotic prophylaxis. Clinical re-evaluation in 8 weeks.	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
Experimental: SRP + Laser; oral hygiene instructions and 810nm diode laser at the base of the gingival sulcus/pocket following by full mouth scaling and root planing in 24 hours. Clinical re-evaluation in 8 weeks.	Procedure: Scaling and Root Planing; Mechanical debridement of tooth surfaces using hand and ultrasonic instruments; Device: 810nm Diode Laser; Laser applied at base of gingival pockets prior to mechanical debridement.
Experimental: SRP + Air Polishing; oral hygiene instructions and air polishing following by full mouth scaling and root planing in 24 hours. Clinical re-evaluation in 8 weeks.	Procedure: Scaling and Root Planing; Mechanical debridement of tooth surfaces using hand and ultrasonic instruments; Procedure: Air Polishing; air flow-based mechanical debridement with erythritol powder
Active Comparator: Quadrant SRP (Control); Oral hygiene instructions, scaling and root planing per quadrant with an interval of 7 days per session. Clinical re-evaluation in 8 weeks after last session.	Procedure: Scaling and Root Planing; Mechanical debridement of tooth surfaces using hand and ultrasonic instruments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum high-sensitivity C-reactive protein (hs-CRP) levels	For hs-CRP, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in serum Interleukin 6 (IL-6)	For IL-6, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Presence and load of bacteremia	culture, PCR, 16S rRNA sequencing	Baseline-15 minutes after the last periodontal session
Changes in mean Clinical Attachment Level (CAL)	CAL would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. CAL would be recorded at six sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session
Salivary CRP correlation with serum CRP	saliva CRP levels will be assessed and compared to serum	Baseline-7 days after the last periodontal session
Changes in serum Tumor Necrosis Factor a (TNF-a) levels	For changes in TNF-a levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in Serum amyloid A (SAA) levels	For changes in SAA levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in Serum cystatin c levels	For changes in serum cystatin c levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in Matrix metalloproteinase-8 (MMP-8) levels	For changes in MMP-8 levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in serum D-dimers levels	For changes in serum D-dimers levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in serum Lipopolysaccharide (LPS) levels	For changes in serum LPS levels, blood would be collected: Before each periodontal session; 24 hours after each periodontal session; 7 days after each periodontal session	Baseline-7 days after the last periodontal session
Changes in mean Pocket Depth (PD)	PD would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. PD would be recorded at six sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session
Changes in mean Gingival Recession (GR)	GR would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. GR would be recorded at six sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session
Changes in Full-Mouth Plaque Score (FMPS)	FMPS would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. FMPS would be recorded at six sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session
Changes in Full-Mouth Bleeding Score (FMBS)	FMBS would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. FMBS would be recorded at six sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session
Changes in simplified gingival index (s-GI)	s-GI would be assessed before treatment initiation and would then be recorded at 8 weeks after the last periodontal session. All clinical measurements would be taken using a manual probe. s-GI would be recorded at four sites per tooth. Third molars would be excluded from the measurements.	Baseline-8 weeks after the last periodontal session

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Investigators: Study Chair: Madianos Phoebus, Professor

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2025
• Primary Completion (Estimated): July 15, 2027
• Study Completion (Estimated): December 15, 2027

Study Registration Dates

• First Submitted: June 30, 2025
• First Submitted That Met QC Criteria: July 11, 2025
• First Posted (Actual): July 22, 2025

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: periodontitis; inflammatory markers; bacteremia; non-surgical periodontal therapy
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections; Bacterial Infections and Mycoses; Pathological Conditions, Signs and Symptoms; Periodontitis; Bacteremia; Investigative Techniques; Therapeutics; Drug Therapy; Equipment and Supplies; Lasers; Optical Devices; Radiation Equipment and Supplies; Dentistry; Dental Scaling; Dental Prophylaxis; Periodontics; Subgingival Curettage; Preventive Dentistry; Chemoprevention; Premedication; Weights and Measures; Lasers, Semiconductor; Root Planing; Antibiotic Prophylaxis
• Other Study ID Numbers: 688/11.02.2025; Ethics Committee (Registry Identifier: Ethics Committee for Clinical Trials of the Provinces of Verona and Rovigo)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD used in the results publication
• IPD Sharing Time Frame: After publication of the main study results.
• IPD Sharing Access Criteria: Data will be available upon reasonable request to qualified researchers for academic purposes.

Drug and device information, study documents

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