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.

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.