Immune modulation, associated or not with systemic antibiotics, in the treatment of periodontitis; and repercussions of different periodontal treatments on immune signaling networks

Abstract

Immune modulation therapy with omega-3 polyunsaturated fatty acids and low-dose aspirin (ASA) as adjunct to Periodontal Debridement (PD) has shown superior results than PD alone for the treatment of Periodontitis in two Randomized Clinical Trials (RCTs) with follow-up of 6 months. However, to date no placebo-controlled RCT has evaluated the effects of this therapy has compared to/associated with systemic antibiotics. Therefore, the objective of this multicenter RCT is to compare the periodontal and systemic effects of immunomodulation with omega-3 + ASA adjunct to PD, associated or not with metronidazole (MTZ)+ amoxicillin (AMX) in the treatment of stages III and IV, grades B and C Periodontitis. Additionally, this translational study aims to analyze the immune profiling and the impact of periodontal treatment on immune signaling networks in peripheral blood and gingival tissue in order to evaluate systemic immunological aspects that could be associated with different responses to periodontal therapy. Thus, 200 volunteers with Periodontitis will be randomly assigned to 4 therapeutic groups (n = 50/group) that will receive PD alone (control group), PD in combination with 400mg MTZ +500mg AMX (test group 1), PD in combination with 3g omega-3 +100mg ASA (test group 2), or PD in combination with 400mg MTZ +500mg AMX associated with 3g omega-3 +100mg ASA (test group 3). Antibiotics will be administered for 14 days and omega-3+ASA for 6 months. All volunteers will receive clinical assessment at baseline, 3, and 6 months post-therapy. Peripheral blood and gingival tissue will be collected at baseline and 6 months for the analysis of C-reactive protein and immune signaling networks through a high-dimensional mass cytometry immunoassay. The results of the proposed study may contribute to the understanding of the etiopathogenesis of periodontal diseases, and provide scientific basis for the development of new therapeutic agents for the treatment of Periodontitis. (AU)