Systemic Probiotics in the Periodontal Treatment

January 8, 2020 updated by: Belén Retamal-Valdes

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
176

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Brazil
    • Paraná
      • Curitiba, Paraná, Brazil, 80210170
        • Recruiting
        • Federal University of Parana
        • Contact:
        • Contact:
    • São Paulo
      • Guarulhos, São Paulo, Brazil, 07023-070
        • Not yet recruiting
        • University of Guarulhos
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Luciene Figueiredo, Professor
        • Sub-Investigator:
          • Marcelo Faveri, Professor
        • Sub-Investigator:
          • Poliana Duarte, Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Control
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.
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.
Other Names:
  • SRP
Drug: Metronidazole and Amoxicillin placebos
Amoxicillin and metronidazole placebos thrice a day for 14 days (beginning with the first SRP session).
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.
Experimental: Probiotic
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.
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.
Other Names:
  • SRP
Drug: Metronidazole and Amoxicillin placebos
Amoxicillin and metronidazole placebos 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.
Experimental: Antibiotic
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.
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.
Other Names:
  • SRP
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).
Experimental: Antibiotic + probiotic
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.
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.
Other Names:
  • SRP
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.
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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of subjects reaching ≤ 4 periodontal sites with probing depth (PD) ≥ 5 mm at 12 months
Time Frame: 12 months
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Number of sites with PD ≥ 5 mm.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Number of sites with PD ≥ 6 mm.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Number of sites with PD ≥ 7 mm.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Change in the number of sites with PD ≥ 5 mm.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Change in the number of sites with PD ≥ 6 mm
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Change in the number of sites with PD ≥ 7 mm
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Mean PD changes in sites with initial PD between 4-6 mm
Time Frame: Baseline - 12 months
Baseline - 12 months
Mean PD changes in sites with initial PD ≥ 7 mm.
Time Frame: Baseline - 12 months
Baseline - 12 months
Mean CAL changes in sites with initial CAL between 4-6 mm
Time Frame: Baseline - 12 months
Baseline - 12 months
Mean CAL changes in sites with initial CAL ≥ 7 mm.
Time Frame: Baseline - 12 months
Baseline - 12 months
Full-mouth Probing Depth (mm).
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Full-mouth Clinical Attachment Level (mm)
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Percentage of sites with bleeding on probing
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Percentage of sites with plaque accumulation
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Percentage of sites with marginal bleeding
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Occurrence of headache obtained through a questionnaire of adverse effects
Time Frame: 14 days after taking antibiotic
14 days after taking antibiotic
Occurrence of headache obtained through a questionnaire of adverse effects
Time Frame: 90 days after taking probiotic
90 days after taking probiotic
Occurrence of vomiting obtained through a questionnaire of adverse effects
Time Frame: 14 days after taking antibiotic
14 days after taking antibiotic
Occurrence of vomiting obtained through a questionnaire of adverse effects
Time Frame: 90 days after taking probiotic
90 days after taking probiotic
Occurrence of diarrhea obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic
14 days after taking antibiotic
Occurrence of diarrhea obtained through a questionnaire of adverse effects.
Time Frame: 90 days after taking probiotic
90 days after taking probiotic
Occurrence of nausea obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic
14 days after taking antibiotic
Occurrence of nausea obtained through a questionnaire of adverse effects.
Time Frame: 90 days after taking probiotic
90 days after taking probiotic
Proportions of periodontal pathogenic bacterial species.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Counts of periodontal pathogenic bacterial species.
Time Frame: Baseline, 3, 6 and 12 months
Baseline, 3, 6 and 12 months
Counts of chemokines in the crevicular gingival fluid.
Time Frame: Baseline and 12 months
Baseline and 12 months
Counts of chemokines in the peripheral blood samples
Time Frame: Baseline and 12 months
Baseline and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Belén Retamal-Valdes

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Magda Feres, Professor, University of Guarulhos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 5, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAAE: 74049717.7.1001.5506

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings