Non Surgical Therapy of Periodontitis in Diabetes Patients: the Adjunctive Use of Probiotics (ProDiabet)

The aim of this study is to evaluate the clinical and microbiological performance of a probiotic formulation (Sunstar GUM Periobalance) as adjunctive to non-surgical periodontal therapy in patients with diabetes. The null hypothesis is that the adjunctive use of this probiotic formulation would not have any additional benefit over scaling and root planning in the number of residual pockets or in the microbiological impact of the treatment. Conversely, the alternative hypothesis is that the adjunctive use of this formulation would improve the clinical results of non-surgical periodontal therapy when compared to scaling and root planing alone, through a modification of the subgingival biofilm composition.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Periodontitis
• Intervention / Treatment: Other: Probiotic; Procedure: Scaling and root planing; Other: Placebo

Detailed Description

Diabetes patients will be consecutively selected among those attending the Faculty of Odontology, University Complutense (Madrid, Spain). Patients fulfilling the required criteria will be invited to participate in the study, will be informed on the study purposes, and will be invited to sign and IRB approved informed consent.The study will be designed as a doubled-blind, placebo controlled, parallel, randomized clinical trial with a 6-month follow-up. The patients will be examined for clinical parameters and microbiological sampling, and randomised into two different groups.The following study visits will be scheduled:

Screening visit Potential patient eligibility will be based on the inclusion/exclusion criteria already presented. Patients will be informed about their periodontal condition and treatment needs. Patients willing to participate in the study will be given additional information about the study and upon signing a consent form, they will be appointed for the graduate clinic of Periodontology.

Baseline visit Patients will undergo a comprehensive oral and periodontal examination. Full-mouth clinical measurements of PPD and clinical attachment level (CAL) will be taken at 6 sites per tooth, excluding third molars, and will be rounded to the nearest millimetre using a UNC-15 probe (Hu-Friedy, Chicago, IL, USA). Panoramic radiographs and/or full-mouth periapical radiographs will also be taken, as standard procedures of the postgraduate clinic. Microbiological samples will be taken. The patient smoking history will be recorded and participants will be categorized as: current smokers (those who smoked at least one cigarette per day); never smokers (those who had never smoked in their life); and former smokers (those who had stopped smoking at least 1 year previously). Other relevant aspects of the medical history will be also collected, including the evaluation of the glycated haemoglobin (HbA1c) levels by means of standard laboratory procedures.

Treatment visits Subjects will receive non-surgical periodontal therapy in the form of full-mouth SRP, in two consecutive days, in combination with 0.12% chlorhexidine (Gum Chlorhexidine Oral Rinse, Etoy, Switzerland) application by means of rinsing prior to and at the end of each SRP session. All patients will receive standardized oral hygiene instructions, including the use of a manual toothbrush (GUM® Activital Toothbrush), and interdental brushers (GUM® Trav-ler and GUM® Soft Picks). Instructions will be periodically reinforced.

Immediately after oral hygiene instructions, patients will be randomly allocated to the test or control groups. One investigator before patient recruitment will generate the randomization sequence by blocks. Random assignment into two groups will be carried out with the use of a computer program. Containers will be designed to maintain examiner blinding. The patients will be randomly allocated, with the help of a computer, in two groups:

• Test group: Subjects in the test group will take two probiotic lozenges per day for 3 months (one in the morning and one in the afternoon after brushing their teeth), starting after the last session of SRP. Lozenges will contain L. reuteri (2 x 108 colony forming units/tablet of strains ATCC 55730 and ATCC PTA 5289; Sunstar GUM Periobalance).
• Placebo group: Subjects assigned to the placebo group will take lozenges exactly like the test ones but without bacteria.

Follow up visits after 3 and 6 months Follow up visits will have the objective to monitor the clinical and microbiological changes in the periodontal condition and to evaluate the bacterial re-colonization pattern in the subgingival niche. This phase will include two recall visits, at which clinical measurements will be repeated and microbiological samples will be collected. Oral hygiene will be reinforced. Glycated haemoglobin levels will be assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eduardo Montero, MSc; Phone Number: +34 630138408; Email: eduardomonterosolis@ucm.es

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Faculty of Odontology
    • Contact: Eduardo Montero, MSc; Phone Number: +34 630138408; Email: eduardomonterosolis@ucm.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with diagnosed diabetes, for at least 1 year.
• Presence of a minimum of 18 teeth.
• Untreated stages II and III periodontitis with radiographic evidence of generalized alveolar bone loss higher than 30%, and presence of at least one pocket with probing pocket depth (PPD) higher than 5 mm per quadrant with bleeding on probing (BOP).

Exclusion Criteria:

• Subgingival instrumentation within 12 months before baseline examination.
• Use of antibiotics in the three months prior to the study.
• Use of other probiotic products in the month prior the study.
• Systemic diseases that could affect the course of periodontitis or its treatment such as immunological disorders, excluding diabetes.
• Ongoing drug therapy influencing the evaluated clinical parameters (non-steroid inflammatory drugs, etc.).
• Compromised medical conditions requiring prophylactic antibiotic therapy (e.g. patients with valvular prostheses, patients with previous history of bacterial endocarditis, congenital heart diseases like shunts or heart transplant recipients who developed valvular heart disease)
• Pregnancy.
• Stage IV periodontitis, or acute periodontal conditions.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Group; Subjects in the test group will receive scaling and root planing, plus the take two probiotic lozenges per day for 3 months (one in the morning and one in the afternoon after brushing their teeth), starting after the last session of SRP. Lozenges will contain L. reuteri (2 x 108 colony forming units/tablet of strains ATCC 55730 and ATCC PTA 5289; Sunstar GUM Periobalance).	Other: Probiotic; Subjects in the test group will take two probiotic lozenges per day for 3 months (one in the morning and one in the afternoon after brushing their teeth), starting after the last session of SRP. Lozenges will contain L. reuteri (2 x 108 colony forming units/tablet of strains ATCC 55730 and ATCC PTA 5289; Sunstar GUM Periobalance).; Procedure: Scaling and root planing; Mechanical debridement with US and curettes of hard and soft plaque deposits; Other Names: SRP
Placebo Comparator: Control Group; Subjects assigned to the placebo group will receive scaling and root planing, and will take lozenges exactly like the test ones but without bacteria.	Procedure: Scaling and root planing; Mechanical debridement with US and curettes of hard and soft plaque deposits; Other Names: SRP; Other: Placebo; Subjects assigned to the placebo group will take lozenges exactly like the test ones but without bacteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Probing Pocket Depth (PPD)	Change in Probing Pocket Depth (PPD)	Baseline, 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Pockets (PPD>4m )	Percentage of residual pockets	Baseline, 3 and 6 months
Bleeding on Probing (BOP)	Changes in bleeding on probing	Baseline, 3 and 6 months
Patient Satisfaction	Patient satisfaction as determined by visual analogue scales (min:0; max:10; 0 indicates worst patient satisfaction, while 10 indicates maximum satisfaction)	Baseline, 3 and 6 months

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Collaborators: Sunstar, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2020
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Diabetes Mellitus; Periodontitis
• Other Study ID Numbers: 19/101-R_X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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