Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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%.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Placebo Comparator | 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. |
|
| Probiotic | Experimental | 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. |
|
| Antibiotic | Experimental | 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. |
|
| Antibiotic + probiotic | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Scaling and root planing | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm at 12 months | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of sites with PD ≥ 5 mm. | Baseline, 3, 6 and 12 months | |
| Number of sites with PD ≥ 6 mm. | Baseline, 3, 6 and 12 months | |
| Number of sites with PD ≥ 7 mm. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Belén Retamal-Valdes, Professor | Contact | +55 (11) 942801064 | belenretamalvaldes@gmail.com | |
| Magda Feres, Professor | Contact | mferes@ung.br |
| Name | Affiliation | Role |
|---|---|---|
| Magda Feres, Professor | University of Guarulhos | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Federal University of Paraná | Recruiting | Curitiba | Paraná | 80210170 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25494600 | Background | Feres M, Figueiredo LC, Soares GM, Faveri M. Systemic antibiotics in the treatment of periodontitis. Periodontol 2000. 2015 Feb;67(1):131-86. doi: 10.1111/prd.12075. | |
| 23016867 | Result | Feres M, Soares GM, Mendes JA, Silva MP, Faveri M, Teles R, Socransky SS, Figueiredo LC. Metronidazole alone or with amoxicillin as adjuncts to non-surgical treatment of chronic periodontitis: a 1-year double-blinded, placebo-controlled, randomized clinical trial. J Clin Periodontol. 2012 Dec;39(12):1149-58. doi: 10.1111/jcpe.12004. Epub 2012 Sep 27. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010518 | Periodontitis |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D014080 | Tooth Exfoliation |
| D016745 | Root Planing |
| D008795 | Metronidazole |
| D000658 | Amoxicillin |
| D019936 | Probiotics |
| ID | Term |
|---|---|
| D009063 | Dental Physiological Phenomena |
| D055688 | Digestive System and Oral Physiological Phenomena |
| D012534 | Dental Scaling |
| D003777 | Dental Prophylaxis |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Metronidazole and Amoxicillin placebos | Drug | Amoxicillin and metronidazole placebos thrice a day for 14 days (beginning with the first SRP session). |
|
| Metronidazole | Drug | Metronidazole 400 mg thrice a day for 14 days (beginning with the first SRP session). |
|
| Amoxicillin | Drug | Amoxicillin 500 mg thrice a day for 14 days (beginning with the first SRP session). |
|
| Probiotic | Dietary Supplement | 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. |
|
| Probiotic placebo | Dietary Supplement | 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. |
|
| Baseline, 3, 6 and 12 months |
| Change in the number of sites with PD ≥ 5 mm. | Baseline, 3, 6 and 12 months |
| Change in the number of sites with PD ≥ 6 mm | Baseline, 3, 6 and 12 months |
| Change in the number of sites with PD ≥ 7 mm | Baseline, 3, 6 and 12 months |
| Mean PD changes in sites with initial PD between 4-6 mm | Baseline - 12 months |
| Mean PD changes in sites with initial PD ≥ 7 mm. | Baseline - 12 months |
| Mean CAL changes in sites with initial CAL between 4-6 mm | Baseline - 12 months |
| Mean CAL changes in sites with initial CAL ≥ 7 mm. | Baseline - 12 months |
| Full-mouth Probing Depth (mm). | Baseline, 3, 6 and 12 months |
| Full-mouth Clinical Attachment Level (mm) | Baseline, 3, 6 and 12 months |
| Percentage of sites with bleeding on probing | Baseline, 3, 6 and 12 months |
| Percentage of sites with plaque accumulation | Baseline, 3, 6 and 12 months |
| Percentage of sites with marginal bleeding | Baseline, 3, 6 and 12 months |
| Occurrence of headache obtained through a questionnaire of adverse effects | 14 days after taking antibiotic |
| Occurrence of headache obtained through a questionnaire of adverse effects | 90 days after taking probiotic |
| Occurrence of vomiting obtained through a questionnaire of adverse effects | 14 days after taking antibiotic |
| Occurrence of vomiting obtained through a questionnaire of adverse effects | 90 days after taking probiotic |
| Occurrence of diarrhea obtained through a questionnaire of adverse effects. | 14 days after taking antibiotic |
| Occurrence of diarrhea obtained through a questionnaire of adverse effects. | 90 days after taking probiotic |
| Occurrence of nausea obtained through a questionnaire of adverse effects. | 14 days after taking antibiotic |
| Occurrence of nausea obtained through a questionnaire of adverse effects. | 90 days after taking probiotic |
| Proportions of periodontal pathogenic bacterial species. | Baseline, 3, 6 and 12 months |
| Counts of periodontal pathogenic bacterial species. | Baseline, 3, 6 and 12 months |
| Counts of chemokines in the crevicular gingival fluid. | Baseline and 12 months |
| Counts of chemokines in the peripheral blood samples | Baseline and 12 months |
| University of Guarulhos | Not yet recruiting | Guarulhos | São Paulo | 07023-070 | Brazil |
|
| 28303587 | Result | Borges I, Faveri M, Figueiredo LC, Duarte PM, Retamal-Valdes B, Montenegro SCL, Feres M. Different antibiotic protocols in the treatment of severe chronic periodontitis: A 1-year randomized trial. J Clin Periodontol. 2017 Aug;44(8):822-832. doi: 10.1111/jcpe.12721. Epub 2017 Jul 26. |
| 26427036 | Result | Laleman I, Yilmaz E, Ozcelik O, Haytac C, Pauwels M, Herrero ER, Slomka V, Quirynen M, Alkaya B, Teughels W. The effect of a streptococci containing probiotic in periodontal therapy: a randomized controlled trial. J Clin Periodontol. 2015 Nov;42(11):1032-41. doi: 10.1111/jcpe.12464. Epub 2015 Nov 29. |
| 33858486 | Derived | Retamal-Valdes B, Teughels W, Oliveira LM, da Silva RN, Fritoli A, Gomes P, Soares GMS, Temporao N, Furquim CP, Duarte PM, Doyle H, Faveri M, Figueiredo LC, Feres M. Clinical, microbiological, and immunological effects of systemic probiotics in periodontal treatment: study protocol for a randomized controlled trial. Trials. 2021 Apr 15;22(1):283. doi: 10.1186/s13063-021-05246-0. |
| D010517 | Periodontics |
| D003813 | Dentistry |
| D013357 | Subgingival Curettage |
| D011313 | Preventive Dentistry |
| D009593 | Nitroimidazoles |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 | Amides |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D019587 | Dietary Supplements |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |