This clinical study investigates two different non-surgical periodontal therapy approaches in patients with advanced periodontitis and compares them with periodontally healthy individuals. Participants with Stage III/IV Grade C periodontitis are randomly assigned to either a single-session or a three-session scaling and root planing (SRP) protocol. Clinical parameters, gingival crevicular fluid inflammatory markers, and subgingival microbial profiles are assessed at baseline and during a 6-month follow-up period. The study aims to determine whether performing non-surgical periodontal therapy in multiple sessions influences clinical, biochemical, and microbiological responses.

This randomized, single-blinded, controlled clinical trial is conducted at the Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey. The purpose of the study is to evaluate whether a three-session non-surgical periodontal therapy protocol provides different clinical, biochemical, and microbiological responses compared to a single-session protocol in patients with Stage III/IV Grade C periodontitis.

Participants with periodontitis are randomly assigned to one of two intervention groups:

Single-Session Therapy Group (SSTG): full-mouth scaling and root planing (SRP) performed in one visit.

Three-Session Therapy Group (TSTG): quadrant-wise SRP delivered over three sessions within the same week.

All procedures are carried out by a single calibrated clinician. Clinical periodontal parameters-probing depth, clinical attachment level, plaque index, and bleeding on probing-are recorded at baseline and at predetermined follow-up visits at 1, 3, and 6 months.

Gingival crevicular fluid samples are collected to quantify inflammatory biomarkers, including interleukin-1β (IL-1β), interleukin-6 (IL-6), clusterin, cystatin C, and osteocalcin, using multiplex immunoassays. Subgingival microbial profiles are evaluated using checkerboard DNA-DNA hybridization targeting a panel of selected bacterial species.

The study protocol has received ethics approval from the Ege University School of Medicine Ethics Committee, and written informed consent is obtained from all participants. The research is supported by the Scientific Research Projects Coordination Unit of Ege University.

Inclusion Criteria:

• Systemically healthy, non-smoking individuals aged 18-65 years
• Diagnosis of Stage III or IV Grade C periodontitis according to the 2018 classification of periodontal diseases
• Presence of at least 20 teeth
• No periodontal treatment within the previous 6 months
• Willingness to participate and provide written informed consent

Exclusion Criteria:

• Presence of systemic diseases or conditions affecting the periodontium (e.g., diabetes mellitus, cardiovascular diseases, immunological disorders)
• Pregnancy or lactation
• Use of antibiotics, anti-inflammatory, or immunosuppressive drugs within the past 3 months
• History of periodontal therapy or surgery within the last 6 months
• Smoking or use of any tobacco products

The individual participant data (IPD) underlying this article will not be shared because anonymized patient-level data were analyzed only in aggregate form, and no separate data repository was created for public access. Summary results are fully presented in the published article.

Single-blinded design: Outcome assessors were blinded to treatment allocation, while participants and care providers were aware of the assigned intervention.