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

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: A Prospective Split-Mouth Clinical Trial

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. Oral hygiene instructions (OHI) + Professional mechanical plaque removal
2. Root surface debridement (RSD)
3. (a) Test group: L. reuteri probiotic subgingival applications on all pockets of ≥ 5mm

3. (b) Control group: Sterilised distilled water subgingival applications on all pockets of ≥ 5mm 4. The applications will be repeated again in both groups after initial applications on every 7, 14, 21 and 28 day.

Participating in this study, you will receive a complete set of oral hygiene kit. While participating, you may or may not experience direct benefits.

The risks for probiotic adjunctive non-surgical periodontal therapy, while generally considered safe, may pose some potential risk factors. Some potential risk factors may include:

1. 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.
2. 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.
3. 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.
4. 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.
5. Infection; While rare, there is a potential risk of infection, particularly if proper hygiene practices are not followed after the procedure.
6. Allergic reactions; Some individuals may be allergic to probiotic used during adjunctive non-surgical periodontal therapy, leading to allergic reactions (skin rashes or itchiness).

If you require additional information regarding risks and side effects, please consult your study doctor (YKZ). The trial staff will promptly update you on any new discoveries or modifications to the study product that may impact your health or willingness to continue in this study. If needed, you may be requested to provide your consent to participate again.

Nonetheless, the data and information collected will contribute to advancing the treatment or management of individuals with the same disease or condition.

Yes, you have the right to refuse to take part in the study at any time. You do not have to participate in this study to get treatment for your periodontal disease. Your participation in the research is entirely voluntary, and you can choose not to participate without any obligation or negative consequences.

Study Overview

• Status: Completed
• Conditions: Diabetes; Periodontitis
• Intervention / Treatment: Procedure: Lactobacillus reuteri DSM 17938; Procedure: Distilled water

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Selangor
    • Hulu Langat, Selangor, Malaysia, 42610
      • Mahsa University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic Test group; 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; Applied with a syringe and blunt needle until overflowing from the periodontal pocket.
Active Comparator: Distilled Water Control group; Sterile distilled water was administered subgingivally at the control sites	Procedure: Distilled water; Applied with a syringe and blunt needle until overflowing from the periodontal pocket.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the plaque index at 3 months and 6 months	Score 0 = No plaque in the gingival area. Score 1 = A film of plaque adhering to the free gingival margin and adjacent area of the tooth. The plaque may only be recognized by running a probe across the tooth surface. Score 2 = Moderate accumulation of soft deposits within the gingival pocket, on the gingival margin and/or adjacent tooth surface, which can be seen by the naked eye. Score 3 = Abundance of soft matter within the gingival pocket and/ or on the gingival margin and adjacent tooth surface.	From enrollment to the end of treatment at 6 months
Change from baseline in the gingival index at 3 months and 6 months	Score 0 = Normal gingiva. Score 1 = Mild inflammation - slight change in color, slight oedema. No bleeding on probing. Score 2 = Moderate inflammation - redness, oedema and glazing. Bleeding on probing. Score 3 = Severe inflammation - marked redness and oedema. Ulceration. Tendency to spontaneous bleeding.	From enrollment to the end of treatment at 6 months
Change from baseline in the bleeding on probing at 3 months and 6 months	Score 0 = Healthy looking papillary and marginal gingiva. No bleeding on probing. Score 1 = Healthy looking gingiva. Bleeding on probing. Score 2 = Bleeding on probing. Change in color, no oedema. Score 3 = Bleeding on probing. Change in color, slight oedema. Score 4 = Bleeding on probing. Change in color, obvious oedema. Score 5 = Spontaneous bleeding. Change in color, marked oedema.	From enrollment to the end of treatment at 6 months
Change from baseline in the clinical attachment level at 3 months and 6 months	Clinical attachment level was measured as the distance from the cemento-enamel junction (CEJ) of the tooth 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

Collaborators and Investigators

• Sponsor: Mahsa University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Actual): December 31, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: May 16, 2026
• First Posted (Actual): May 20, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Periodontitis; Diabetes Mellitus
• Other Study ID Numbers: RMC/MAR/2024/EC18

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