PeriodontitisNCT07598656
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 study testing Lactobacillus reuteri DSM 17938 and Distilled water in people with Periodontitis and Diabetes, run by Mahsa University at 1 site in Malaysia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Periodontitis, Diabetes
- What is being tested?
- Lactobacillus reuteri DSM 17938 and Distilled water
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteMalaysia
- Study dates
- 1 Jul 2024to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.);
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
- Oral hygiene instructions (OHI) + Professional mechanical plaque removal
- Root surface debridement (RSD)
- (a) Test group: L. reuteri probiotic subgingival applications on all pockets of ≥ 5mm
- (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:
- 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.
- 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.
- 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.
- 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.
- Infection; While rare, there is a potential risk of infection, particularly if proper hygiene practices are not followed after the procedure.
- 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.
- Conditions
- Periodontitis, Diabetes
- Being tested
- Lactobacillus reuteri DSM 17938, Distilled water
- Medical subject headings
- Periodontitis, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus reuteri DSM 17938Procedure or surgery
Applied with a syringe and blunt needle until overflowing from the periodontal pocket.
Distilled waterProcedure or surgery
Applied with a syringe and blunt needle until overflowing from the periodontal pocket.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Procedure: Lactobacillus reuteri DSM 17938 |
| Distilled Water Control group | Active comparator | Sterile distilled water was administered subgingivally at the control sites Receives: Procedure: Distilled water |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From enrollment to the end of treatment at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2026
- Study start1 Jul 2024
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PeriodontitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mahsa University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yeu Kai Zhe, Mahsa University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07598656
- Sponsor's protocol ID
- RMC/MAR/2024/EC18
- Status last verified
- Apr 2026
- First submitted
- 15 Apr 2026
- Last updated
- 20 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07598656
- Acronym / sponsor ID
- RMC/MAR/2024/EC18
- Conditions
- Periodontitis, Diabetes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Mahsa UniversityUniversity, hospital or other
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 20 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- Oral hygiene instructions (OHI) + Professional mechanical plaque removal
- Root surface debridement (RSD)
- (a) Test group: L. reuteri probiotic subgingival applications on all pockets of ≥ 5mm
- (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:
- 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.
- 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.
- 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.
- 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.
- Infection; While rare, there is a potential risk of infection, particularly if proper hygiene practices are not followed after the procedure.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Probiotic Test group | Experimental | Procedure: Lactobacillus reuteri DSM 17938Lactobacillus 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 |
| Distilled Water Control group | Active comparator | Procedure: Distilled waterSterile distilled water was administered subgingivally at the control sites |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus reuteri DSM 17938Applied with a syringe and blunt needle until overflowing from the periodontal pocket. | Procedure or surgery | Probiotic Test group |
| Distilled waterApplied with a syringe and blunt needle until overflowing from the periodontal pocket. | Procedure or surgery | Distilled Water Control group |
Primary outcome
Change from baseline in the periodontal probing depth at 3 months and 6 months
Time frame: From enrollment to the end of treatment at 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.
4 secondary outcomes
Change from baseline in the plaque index at 3 months and 6 months
Time frame: From enrollment to the end of treatment at 6 months
Change from baseline in the gingival index at 3 months and 6 months
Time frame: From enrollment to the end of treatment at 6 months
Change from baseline in the bleeding on probing at 3 months and 6 months
Time frame: From enrollment to the end of treatment at 6 months
Change from baseline in the clinical attachment level at 3 months and 6 months
Time frame: From enrollment to the end of treatment at 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus reuteri DSM 17938 and Distilled water in people with Periodontitis and Diabetes, run by Mahsa University at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the periodontal probing depth at 3 months and 6 months (time frame: From enrollment to the end of treatment at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2026.