Local Delivery of Lactobacillus Reuteri Probiotic as An Adjunct to Non-surgical Periodontal Therapy in Patients With Stage II, III, and IV Periodontitis and Type 2 Diabetes Mellitus

NCT07598656 | Completed

• 1 other identifier: RMC/MAR/2024/EC18
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the effectiveness of local delivery of Lactobacillus reuteri probiotic on periodontitis patients with type 2 diabetes mellitus, as an adjunct to non-surgical periodontal treatment. To date, the efficacy of local drug delivery as an adjunct has been established, whereas research on the effectiveness of probiotics as an adjunct remains limited. Specifically, there is a lack of studies focusing on the clinical effectiveness of Lactobacillus reuteri probiotic as an adjunct in subgingival debridement for patients with type 2 diabetes mellitus. Over the past decade, there has been a growing interest in using probiotics to enhance periodontal health. Subsequent studies investigated the application of probiotics in individuals with periodontal disease, concluding that the depth of periodontal pockets in humans also decreases with probiotic use as part of periodontal treatment. Positive effects of probiotics have been reported at both the microbiological and immunological levels. Lactobacillus reuteri probiotic has also shown a notable decrease in pro-inflammatory markers and an increase in anti-inflammatory markers. Despite these findings, the clinical application of Lactobacillus reuteri probiotics in patients with type 2 diabetes mellitus has not yet been explored. Your participation will be about 6months duration. If you agree to participate in the study, the doctor (YKZ) may need to perform some tests and examinations to determine if you are suitable for the study. If you are deemed suitable, you will be assigned to both of the treatment groups below (split-mouth study design). Both right (quadrant 1 and 4) and left (quadrant 2 and 3) halves will be assigned randomly to one of the two treatment modalities. The study products do not contain porcine, bovine or animal components.

1. 1.Oral hygiene instructions (OHI) + Professional mechanical plaque removal
2. 2.Root surface debridement (RSD)
3. 3.(a) Test group: L. reuteri probiotic subgingival applications on all pockets of ≥ 5mm
4. 4.Temporary discomfort; Some individuals may experience temporary discomfort or pain following non-surgical periodontal procedures, such as scaling and root surface debridement. This discomfort typically subsides within a few days.
5. 5.Gingival and/ or root sensitivity; Some individuals may experience increased sensitivity in the gums or teeth, particularly to hot or cold temperatures, after non-surgical periodontal therapy.
6. 6.Bleeding gums; Individuals might notice temporary bleeding from the gums, especially during and immediately after the procedure. This is usually minor and resolves with proper post-operative care.
7. 7.Recession of gums; In rare instances, there may be a risk of gingival recession, where the gums pull away from the teeth. This is more likely in individuals with thin or fragile gum tissue.
8. 8.Infection; While rare, there is a potential risk of infection, particularly if proper hygiene practices are not followed after the procedure.
9. 9.Allergic reactions; Some individuals may be allergic to probiotic used during adjunctive non-surgical periodontal therapy, leading to allergic reactions (skin rashes or itchiness).

Conditions

Periodontitis; Diabetes

Outcome Measures

Primary Outcomes (1)

• Change from baseline in the periodontal probing depth at 3 months and 6 months

  Probing pocket depth was measured as the distance from the free gingival margin (FGM) to the base of the periodontal pocket. All measurements were recorded to the nearest millimeter using a standardized and graduated UNC-15 periodontal probe. Six sites per tooth were examined, namely mesio-buccal, mid-buccal, disto-buccal, mesio-lingual, mid-lingual, and disto-lingual.

  From enrollment to the end of treatment at 6 months

Secondary Outcomes (4)

• Change from baseline in the plaque index at 3 months and 6 months

  From enrollment to the end of treatment at 6 months

• Change from baseline in the gingival index at 3 months and 6 months

  From enrollment to the end of treatment at 6 months

• Change from baseline in the bleeding on probing at 3 months and 6 months

  From enrollment to the end of treatment at 6 months

• Change from baseline in the clinical attachment level at 3 months and 6 months

  From enrollment to the end of treatment at 6 months

Study Arms (2)

Probiotic Test group

EXPERIMENTAL

Lactobacillus reuteri probiotic drops (a minimum of 100 colony forming units Lactobacillus reuteri DSM 17938 Protectis drops, BioGaia AB, Turnhout, Belgium) were administered subgingivally at the test sites

Procedure: Lactobacillus reuteri DSM 17938

Distilled Water Control group

ACTIVE COMPARATOR

Sterile distilled water was administered subgingivally at the control sites

Procedure: Distilled water

Interventions

Lactobacillus reuteri DSM 17938 PROCEDURE

Applied with a syringe and blunt needle until overflowing from the periodontal pocket.

Probiotic Test group

Distilled water PROCEDURE

Applied with a syringe and blunt needle until overflowing from the periodontal pocket.

Distilled Water Control group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals aged between 18 and 65 years;
• Diagnosed with controlled type 2 diabetes mellitus (HbA1c \< 7%);
• Presence of a minimum of 20 natural teeth;
• Untreated stage II, III, or IV periodontitis (Tonetti et al., 2018), with radiographic evidence of generalized alveolar bone loss;
• At least one periodontal pocket per quadrant with a probing pocket depth of 5 mm and bleeding on probing.

You may not qualify if:

• Participation in another clinical trial;
• Pregnancy or lactation;
• Smoker;
• Individuals with autoimmune diseases;
• Individuals with compromized medical conditions requiring prophylactic antibiotic therapy (e.g., patients with valvular prosthesis, patients with history of infective endocarditis, heart transplant recipients, etc.);
• Individuals currently receiving ongoing drug therapy (corticosteroid, bisphosphonates, nonsteroidal anti-inflammatory drugs, etc.);
• Use of systemic antibiotics within the 3 months prior to the study;
• Use of probiotic products within the 3 months prior to the study;
• History of subgingival instrumentation within the previous 6 months;
• Presence of acute periodontal lesions and/or endo-periodontal lesions (Herrera et al., 2018);
• Physical limitations that may interfere proper oral hygiene practices.

Sponsors & Collaborators

• Mahsa University: lead

Study Sites (1)

Mahsa University

Hulu Langat, Selangor, 42610, Malaysia

Location

MeSH Terms

Conditions

Periodontitis; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: For each participant, the right (quadrants 1 and 4) and left (quadrants 2 and 3) halves of the mouth were randomly assigned to one of two treatment modalities. All participants were allocated into two groups using a simple randomization method: Group 1 (right halves: test; left halves: control) and Group 2 (right halves: control; left halves: test).

Study Record Dates

• First Submitted: April 15, 2026
• First Posted: May 20, 2026
• Study Start: July 1, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 20, 2026

Record last verified: 2026-04

Locations

MY (1)