Omega-3 and aspirin associated with systemic antibiotics in the treatment of periodontitis in patients with Type 2 Diabetes Mellitus: local and systemic effects, immunological actions, and impact on oral and gut microbiota

• Grant number: 21/14439-0
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2022 - September 30, 2024
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Nidia Cristina Castro dos Santos
• Grantee: Nidia Cristina Castro dos Santos
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated researchers: Giuseppe Alexandre Romito ; Magda Feres Figueiredo ; Sergio Atala Dib

Abstract

Immune modulation therapy with omega-3 polyunsaturated fatty acids (É-3) 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 associated with systemic antibiotics. Therefore, the objective of this multicenter study is to evaluate local and systemic effects of É-3+ASA associated with metronidazole (MTZ) + amoxicillin (AMX) as adjuncts to PD compared to MTZ+AMX+PD in the treatment of Stages III and IV, generalized, Grades B and C periodontitis in patients with type 2 diabetes mellitus. Additionally, this study aims to analyze immunological and microbiological effects of these therapeutic approaches. Thus, 123 patients with periodontitis and diabetes will be randomly assigned to 3 groups (n=41/group) that will receive: (i) immunomodulators (IM) (3g É-3+100mg ASA) associated with systemic antibiotics (SA) (400mg MTZ+500mg AMX) as adjuncts to PD (IM+SA Group), (ii) SA (400mg MTZ+500mg AMX) and placebo of IM as adjuncts to PD (SA Group) or (iii) Placebo + PD (Control Group). The IM will be administered for 6 months and the SA, for 14 days. All volunteers will receive clinical assessment at baseline (BL), 3, and 6 months post-therapy. Peripheral blood will be collected at BL, 3, and 6 months for the analysis of bioclinical variables, including glycated hemoglobin, HOMA-IR, lipidic profile, C-reactive protein and interleukin-6. Gingival crevicular fluid samples will be collected and analyzed using ELISA Multiplex at BL, 3, and 6 months. Additionally, subgingival biofilm and faecal samples will be collected for the analysis of oral and intestinal microbiota using 16S rRNA gene sequencing at BL and 6 months. The results of the proposed study may contribute to the understanding of the important aspects related to host response to periodontal treatment, and demonstrate systemic repercussions and host-microbial interactions in different levels after periodontal treatment in patients with type 2 diabetes mellitus. (AU)