NCT03733379

Systemic Probiotics in the Periodontal Treatment

Clinical, Microbiological and Immunological Evaluation of the Effects of Systemic Probiotics in the Periodontal Treatment

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 176 (estimated)
• Sponsor: Belén Retamal-Valdes · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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%.

Conditions

• Periodontitis

Interventions

Type	Name	Description
PROCEDURE	Scaling and root planing	SRP will be performed in four to six appointments lasting approximately 1 h each, using manual curettes (Hu-Friedy, Chicago, IL, USA) and ultrasonic device (Cavitron Select SPC, Dentsply professional, York, PA, USA) under local anesthesia. The deep sites will be scaled throughout the first week and treatment of the entire oral cavity will be completed in 14 days.
DRUG	Metronidazole and Amoxicillin placebos	Amoxicillin and metronidazole placebos thrice a day for 14 days (beginning with the first SRP session).
DRUG	Metronidazole	Metronidazole 400 mg thrice a day for 14 days (beginning with the first SRP session).
DRUG	Amoxicillin	Amoxicillin 500 mg thrice a day for 14 days (beginning with the first SRP session).
DIETARY_SUPPLEMENT	Probiotic	The probiotic contains 2 different strains of Lactobacillus reuteri: L.reuteri DSM 17938 and L. reuteri ATCC PTA 5289 each at a concentration of 1 x 108 CFU per tablet. It will be used 2 times per day by 90 days.
DIETARY_SUPPLEMENT	Probiotic placebo	The placebo is identical to the active but without L. reuteri. The two Study Products are identical in taste, texture and shape. It will be used 2 times per day by 90 days.

Timeline

• Start date: 2018-11-05
• Primary completion: 2020-12-30
• Completion: 2021-12-30
• First posted: 2018-11-07
• Last updated: 2020-01-13

Locations

2 sites across 1 country: Brazil