Systemic Probiotics in the Periodontal Treatment

Belén Retamal-Valdes

Status and phase: Unknown; Phase 3

Conditions: Periodontitis

Treatments: Dietary Supplement: Probiotic placebo; Drug: Metronidazole and Amoxicillin placebos; Drug: Metronidazole; Procedure: Scaling and root planing; Drug: Amoxicillin; Dietary Supplement: Probiotic

Study type: Interventional

Funder types: Other

Identifiers

NCT03733379

CAAE: 74049717.7.1001.5506

Details and patient eligibility

About

The aim of this multicenter randomized clinical trial is to evaluate the clinical, microbiological and immunological effects of probiotics as an adjunct to Scaling and Root Planing alone or in combination with Metronidazole and Amoxicillin in the treatment of periodontitis.

Full description

The association of scaling and root planing (SRP) with systemic metronidazole (MTZ) and amoxicillin (AMX) has been advocated as one of the most promising therapeutic protocol for the treatment of advanced periodontitis, since the early 2000's. More recently, probiotics has also been suggested as a promising adjunctive treatment for periodontitis due to their antimicrobial and anti-inflammatory properties. Therefore, the aim of this study is to evaluate the clinical, microbiological and immunological effects of probiotics as an adjunct to SRP alone or in combination with MTZ and AMX in the treatment of periodontitis. In this randomized, double-blind, placebo-controlled trial, subjects with periodontitis will be randomly assigned to receive (i) SRP alone, or combined with: (ii) two probiotics lozenges a day for 90 days (Prob), (iii) 400 of MTZ, plus AMX (500 mg) thrice a day (TID) for 14 days (MTZ+AMX), or (iv) Prob and MTZ+AMX. Subjects will be monitored up to 1 year post-therapy. Nine subgingival plaque samples will be collected at baseline and at 3, 6 and 12 months post-therapy; three samples in each of the following pockets categories: shallow (probing depth [PD]≤3 mm), moderate (PD=4-6 mm) and deep (PD≥7 mm). The microbiological samples will be analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species. Two non-contiguous diseased sites (i.e PD and CAL ≥ 5mm, bleeding and probing [BOP] and no furcation involvement) and two non-contiguous healthy sites (i.e. PD and clinical attachment level [CAL] ≤ 4 mm without BoP and/or marginal bleeding) will be randomly chosen per patient for gingival crevicular fluid (GCF) sampling, from the same sites selected for the microbiological monitoring. Peripheral blood samples will also be collected one week after clinical examination. The GCF and blood samples will be analyzed using a multi-analyte method by means of a 17-multiplex fluorescent bead-based immunoassay for 17 cyto/chemokines. The significance of differences over the course of the study will be sought using repeated measures ANOVA and Tukey multiple comparison tests, and at each time point (among groups) using either ANOVA and Tukey multiple comparison tests or ANCOVA with adjustments for the baseline values. The Chi-square test will be used to compare the differences in the frequency of gender, and to compare the differences in the frequency of subjects achieving the clinical endpoint at 1 year and of self-perceived adverse effects. A stepwise forward logistic regression analysis will be performed in order to investigate the impact of predictor variables on the clinical endpoint for treatment, i.e., "presence of ≤4 sites with PD≥5 mm at 12 months post-therapy (yes/no)". The Number Needed to Treat (NNT) with adjunctive antibiotic in order to obtain treatment success (≤4 sites with PD ≥5 mm) will be calculated. The level of significance will be set at 5%.

Enrollment: 176 estimated patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥30 years of age;
• at least 15 teeth (excluding third molars and teeth with advanced decay indicated for extraction);
• a minimum of 6 teeth with at least one site each with probing depth (PD) and clinical attachment level (CAL) ≥5 mm;
• at least 30% of the sites with probing depth (PD) and clinical attachment level (CAL) ≥4 mm and bleeding on probing (BOP);

Exclusion criteria

• pregnancy;
• breastfeeding;
• current smoking and former smoking within the past 5 years;
• systemic diseases that could affect the progression of periodontitis (e.g. diabetes, immunological disorders, osteoporosis);
• scaling and root planing an in the previous 12 months;
• antibiotic therapy in the previous 6 months;
• long-term intake of anti-inflammatory medications;
• need for antibiotic pre-medication for routine dental therapy;
• use of orthodontic appliances;
• extensive dental prosthetic rehabilitation;
• allergy to metronidazole and/or amoxicillin.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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176 participants in 4 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

Scaling and root planing + Placebos of Metronidazole and Amoxicillin three times a day (TID) for 14 days + placebo lozenges of probiotics two times a day for 90 days.

Treatment:

Procedure: Scaling and root planing

Drug: Metronidazole and Amoxicillin placebos

Dietary Supplement: Probiotic placebo

Probiotic

Experimental group

Description:

Scaling and root planing + Placebos of Metronidazole and Amoxicillin three times a day (TID) for 14 days + lozenges of probiotics two times a day for 90 days.

Treatment:

Dietary Supplement: Probiotic

Procedure: Scaling and root planing

Drug: Metronidazole and Amoxicillin placebos

Antibiotic

Experimental group

Description:

Scaling and root planing + Metronidazole (400 mg/thrice a day,TID) and Amoxicillin (500 mg/ TID) for 14 days + placebo lozenges of probiotics two times a day for 90 days.

Treatment:

Drug: Amoxicillin

Procedure: Scaling and root planing

Drug: Metronidazole

Antibiotic + probiotic

Experimental group

Description:

Scaling and root planing + Metronidazole (400 mg/thrice a day,TID) and Amoxicillin (500 mg/ TID) for 14 days + lozenges of probiotics two times a day for 90 days.

Treatment:

Drug: Amoxicillin

Procedure: Scaling and root planing

Drug: Metronidazole

Dietary Supplement: Probiotic placebo