Periodontal DiseasesPERIOPRONCT04478643
Lactobacillus Reuteri in the Supportive Therapy of Periodontitis
A study testing Probiotic: Lactobacillus Reuteri in people with Periodontal Diseases, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
Trial summary
Literature shows the potential effectiveness of L. reuteri as an adjunct to non-surgical periodontal therapy in initial treatment of periodontitis, but also underlines the limits of the conclusions, and the heterogeneity and limited sample size of the available studies. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Periodontal Diseases
- What is being tested?
- Probiotic: Lactobacillus Reuteri
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteItaly
- Study dates
- 7 Oct 2020to 12 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form.
- Male and female subjects, aged 18-75 years, inclusive.
- Good general health (free of systemic diseases such as diabetes, HIV infection or genetic disorder, ongoing malignant disease of any type that could influence the outcome of the treatment and might interfere with the evaluation of the study objectives).
- History of periodontitis staging III or IV grading B or C
- At least 2 sites with probing depth ≥6 mm or pockets of 5 mm with bleeding on probing in two different quadrants.
- Previous periodontal non-surgical treatment at least 3 months maximum 6 months.
- Availability for the 6-month duration of the study for an assigned subject.
Who cannot join
- Not willing to follow the agreed protocol.
- Presence of orthodontic appliances.
- Smokers (more than 10 cigarettes per day)
- Chronic obstructive pulmonary disease and asthma.
- Tumors or significant pathology of the soft or hard tissues of the oral cavity.
- Current radiotherapy or chemotherapy.
Show all 11Show fewer
- Pregnant or lactating women.
- Current or past (within 3 months prior to enrolment) administration of medications that may influence periodontal conditions and/or interfere with healing following periodontal treatment (i.e., corticosteroids, calcium channel blockers, systemic antibiotics, ...).
- History of allergy to Erythritol or chlorexidine.
- Restorations on the teeth to be treated which may interfere with treatment administration and/or scoring procedures, at the discretion of the examiner.
- Use of systemically administered antibacterial agents or probiotics 3 months prior to enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical and Microbiological Efficacy of Lactobacillus Reuteri in the Supportive Therapy of Periodontitis: a 6 Months Randomized Controlled Trial
Literature shows the potential effectiveness of L. reuteri as an adjunct to non-surgical periodontal therapy in initial treatment of periodontitis, but also underlines the limits of the conclusions, and the heterogeneity and limited sample size of the available studies. Therefore, there is a need for longer-term, randomized, controlled studies. Moreover, only one study addresses the use of this probiotic during the supportive therapy, in particular in patients with severe forms of periodontitis, and only few patients were included.
Patients meeting the criteria of periodontitis stage III and IV, grade C are considered to be affected by severe and advanced forms of periodontitis with a rapid rate of progression. This group of patients could particularly benefit from supplements for the maintenance of periodontal health.
Read more
The hypothesis of the present randomized controlled trial is that the adjunctive use of probiotic treatment can bring clinical and microbiological advantages during the supportive therapy of periodontal disease, and reduce the number of residual pockets.
To test this hypothesis, the patients, upon initial evaluation, will be divided in 2 study groups and, after a session of professional oral hygiene, will be prescribed one of the therapies below:
- PLACEBO: The patients of the control group will receive control lozenges without live bacteria;
- TEST: The patients of the probiotic group will receive probiotic lozenges containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 (a minimum of 2 × 108 colony-forming units L. reuteri Prodentis/lozenge, BioGaia AB).
The probiotic and control lozenges will be identical in taste, texture and appearance. The lozenges will be given to all patients to consume at home. The patients will be instructed to dissolve them on their tongue twice a day, preferably after brushing, for 3 weeks.
Periodontal and microbiological parameters will be evaluated at 3 and 6 months after the initial therapy, and compared between the two groups.
Read the detailed description
Probiotics are defined as 'live microorganisms which, when administered in adequate amounts, confer a health benefit on the host'. The influence of probiotics on pathogens flora can derive from three principal modes of action: innate and acquired host defense modulation, production of antibacterial substances and competitive exclusion mechanism. In particular, Lactobacillus reuteri has been studied for its antibacterial and anti-inflammatory properties.
It is a heterofermentative bacterium and the distinct strains have different characteristics. In particular it acts as an antibiotic, induces oxidative stress on pathogens, is resistant to proteolytic and lipolytic and present anti-inflammatory properties.
TRIAL DESIGN Parallel-arm, mono-center, statistician operator and examiner blinded RCT. The trial will have 6 months of duration.
STUDY POPULATION Forty-four (44) adults, aged 18-75 years, meeting the criteria of periodontitis stage III and IV, grade C, will be entered into study. It is expected that forty (40) subjects will complete the study.
PRIMARY OUTCOMES
- Change in (Pocket Probing Depth) PPD: change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
SECONDARY OUTCOMES
- Pocket closure
- Risk of progression of periodontitis
- Change in BoP: change in percentage of sites positive to bleeding on probing.
- Change in Plaque Index (PI): change in percentage of sites with presence of plaque. Baseline values will be compared to the values recorded at follow-up visits.
- Change in Periodontal Attachment Level (PAL): change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
- Change in Recession (REC): change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
- Changes in microbial composition and proportion of sequences identified as Lactobacillus reuteri in the deepest residual pockets
- Conditions
- Periodontal Diseases
- Being tested
- Probiotic: Lactobacillus Reuteri, Placebo
- Keywords
- Lactobacillus reuteri, Probiotic, Periodontal diseases, GBT
- Medical subject headings
- Periodontal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic: Lactobacillus ReuteriDietary supplement
Lactobacillus reuteri ATCC PTA 5289 (a minimum of 2 × 108 colony-forming units L. reuteri Prodentis/lozenge, BioGaia AB)
PlaceboDietary supplement
Placebo lozenge. Will be identical in taste, texture and appearance to the Probiotic one.
| Study group | Role | What they receive |
|---|---|---|
| PLACEBO | Placebo comparator | * Collection of microbiological samples from the two deepest sites in two different quadrants.
* All patients receive full periodontal charting, full mouth periodontal treatment and OHI (oral hygiene instruction).
* Study lozenges without live bacteria are administered to consume at home. The patients are instructed to dissolve the lozenges on their tongue twice a day, preferably after brushing, for 3 weeks. Receives: Dietary Supplement: Placebo |
| PROBIOTIC (L. Reuteri) | Experimental | * Collection of microbiological samples from the two deepest sites in two different quadrants.
* All patients receive full periodontal charting, full mouth periodontal treatment and OHI (oral hygiene instruction).
* Study lozenges containing Lactobacillus Reuteri are administered to consume at home. The patients are instructed to dissolve the lozenges on their tongue twice a day, preferably after brushing, for 3 weeks. Receives: Dietary Supplement: Probiotic: Lactobacillus Reuteri |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PD (Periodontal Depth)
Change in mean PD value for each patient measured (from the gingival margin to the bottom of the pocket). Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Secondary outcomes (7)
Risk Progression of the Periodontitis and the Need of Periodontal Surgery
Change in percentage of patient who need periodontal surgery. Periodontal stability is defined as < 10% of sites bleeding on probing, no probing depths of 4 mm or greater that bleed on probing, and lack of progressive periodontal destruction. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: 6 months
Pocket Closure
Change in percentage of site > 4mm. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Microbiological Changes
changes in microbial composition (kind of bacteria) and proportion (% of pathogen) of sequences identified as Lactobacillus reuteri in the deepest residual pockets
Measured: baseline, 3 and 6 months
Change in REC (Clinical Gingival Recession)
Change in mean of REC value for each patient should be calculated. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Change in CAL (Clinical Attachment Level)
Change in mean of CAL value for each patient should be calculated. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Change in BOP (Bleeding on Probing)
Change in percentage of sites positive to bleeding on probing. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Change in PI (Plaque Index)
Change in percentage of site with plaque. Baseline values will be compared to the values recorded in the follow-up visits.
Measured: baseline, 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2020
- Study start7 Oct 2020
- Primary completion12 Feb 2024
- Study completion12 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Periodontal DiseasesStudies 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
- Monocentric, Parallel-Arm, Patient, Statistician, Operator and Examiner are blinded, RCT
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Magda Mensi, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Magda Mensi, Principal investigator, Asst Degli Spedali Civili Di Brescia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04478643
- Sponsor's protocol ID
- PERIOPRO np.: 3965
- Acronym
- PERIOPRO
- Status last verified
- Jun 2025
- First submitted
- 6 Jul 2020
- Last updated
- 14 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Microbiological Efficacy of Lactobacillus Reuteri in the Supportive Therapy of Periodontitis: a 6 Months Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04478643
- Acronym / sponsor ID
- PERIOPRO / PERIOPRO np.: 3965
- Conditions
- Periodontal Diseases
- Keywords
- Lactobacillus reuteri, Probiotic, Periodontal diseases, GBT
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Study start
- 7 Oct 2020 (actual)
- Primary completion
- 12 Feb 2024 (actual)
- Study completion
- 12 Jun 2024 (actual)
- First posted
- 21 Jul 2020 (actual)
- Results
- Posted 14 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Literature shows the potential effectiveness of L. reuteri as an adjunct to non-surgical periodontal therapy in initial treatment of periodontitis, but also underlines the limits of the conclusions, and the heterogeneity and limited sample size of the available studies. Therefore, there is a need for longer-term, randomized, controlled studies. Moreover, only one study addresses the use of this probiotic during the supportive therapy, in particular in patients with severe forms of periodontitis, and only few patients were included.
Patients meeting the criteria of periodontitis stage III and IV, grade C are considered to be affected by severe and advanced forms of periodontitis with a rapid rate of progression. This group of patients could particularly benefit from supplements for the maintenance of periodontal health.
The hypothesis of the present randomized controlled trial is that the adjunctive use of probiotic treatment can bring clinical and microbiological advantages during the supportive therapy of periodontal disease, and reduce the number of residual pockets.
To test this hypothesis, the patients, upon initial evaluation, will be divided in 2 study groups and, after a session of professional oral hygiene, will be prescribed one of the therapies below:
- PLACEBO: The patients of the control group will receive control lozenges without live bacteria;
- TEST: The patients of the probiotic group will receive probiotic lozenges containing Lactobacillus reuteri DSM 17938 and Lactobacillus reuteri ATCC PTA 5289 (a minimum of 2 × 108 colony-forming units L. reuteri Prodentis/lozenge, BioGaia AB).
The probiotic and control lozenges will be identical in taste, texture and appearance. The lozenges will be given to all patients to consume at home. The patients will be instructed to dissolve them on their tongue twice a day, preferably after brushing, for 3 weeks.
Periodontal and microbiological parameters will be evaluated at 3 and 6 months after the initial therapy, and compared between the two groups.
Detailed description
Probiotics are defined as 'live microorganisms which, when administered in adequate amounts, confer a health benefit on the host'. The influence of probiotics on pathogens flora can derive from three principal modes of action: innate and acquired host defense modulation, production of antibacterial substances and competitive exclusion mechanism. In particular, Lactobacillus reuteri has been studied for its antibacterial and anti-inflammatory properties.
It is a heterofermentative bacterium and the distinct strains have different characteristics. In particular it acts as an antibiotic, induces oxidative stress on pathogens, is resistant to proteolytic and lipolytic and present anti-inflammatory properties.
TRIAL DESIGN Parallel-arm, mono-center, statistician operator and examiner blinded RCT. The trial will have 6 months of duration.
STUDY POPULATION Forty-four (44) adults, aged 18-75 years, meeting the criteria of periodontitis stage III and IV, grade C, will be entered into study. It is expected that forty (40) subjects will complete the study.
PRIMARY OUTCOMES
- Change in (Pocket Probing Depth) PPD: change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
SECONDARY OUTCOMES
- Pocket closure
- Risk of progression of periodontitis
- Change in BoP: change in percentage of sites positive to bleeding on probing.
- Change in Plaque Index (PI): change in percentage of sites with presence of plaque. Baseline values will be compared to the values recorded at follow-up visits.
- Change in Periodontal Attachment Level (PAL): change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
- Change in Recession (REC): change in mean value for each patient will be calculated. Baseline values will be compared to the values recorded at follow-up visits.
- Changes in microbial composition and proportion of sequences identified as Lactobacillus reuteri in the deepest residual pockets
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Monocentric, Parallel-Arm, Patient, Statistician, Operator and Examiner are blinded, RCT
| Arm | Type | Receives |
|---|---|---|
| PLACEBO | Placebo comparator | Dietary Supplement: Placebo* Collection of microbiological samples from the two deepest sites in two different quadrants. * All patients receive full periodontal charting, full mouth periodontal treatment and OHI (oral hygiene instruction). * Study lozenges without live bacteria are administered to consume at home. The patients are instructed to dissolve the lozenges on their tongue twice a day, preferably after brushing, for 3 weeks. |
| PROBIOTIC (L. Reuteri) | Experimental | Dietary Supplement: Probiotic: Lactobacillus Reuteri* Collection of microbiological samples from the two deepest sites in two different quadrants. * All patients receive full periodontal charting, full mouth periodontal treatment and OHI (oral hygiene instruction). * Study lozenges containing Lactobacillus Reuteri are administered to consume at home. The patients are instructed to dissolve the lozenges on their tongue twice a day, preferably after brushing, for 3 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed Informed Consent Form.
- Male and female subjects, aged 18-75 years, inclusive.
- Good general health (free of systemic diseases such as diabetes, HIV infection or genetic disorder, ongoing malignant disease of any type that could influence the outcome of the treatment and might interfere with the evaluation of the study objectives).
- History of periodontitis staging III or IV grading B or C
- At least 2 sites with probing depth ≥6 mm or pockets of 5 mm with bleeding on probing in two different quadrants.
Key exclusion criteria (11 listed)
- Not willing to follow the agreed protocol.
- Presence of orthodontic appliances.
- Smokers (more than 10 cigarettes per day)
- Chronic obstructive pulmonary disease and asthma.
- Tumors or significant pathology of the soft or hard tissues of the oral cavity.
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 |
|---|---|---|
| Probiotic: Lactobacillus ReuteriLactobacillus reuteri ATCC PTA 5289 (a minimum of 2 × 108 colony-forming units L. reuteri Prodentis/lozenge, BioGaia AB) | Dietary supplement | PROBIOTIC (L. Reuteri) |
| PlaceboPlacebo lozenge. Will be identical in taste, texture and appearance to the Probiotic one. | Dietary supplement | PLACEBO |
Primary outcome
Change in PD (Periodontal Depth)
Time frame: baseline, 3 and 6 months
Change in mean PD value for each patient measured (from the gingival margin to the bottom of the pocket). Baseline values will be compared to the values recorded in the follow-up visits.
7 secondary outcomes
Risk Progression of the Periodontitis and the Need of Periodontal Surgery
Time frame: 6 months
Pocket Closure
Time frame: baseline, 3 and 6 months
Microbiological Changes
Time frame: baseline, 3 and 6 months
Change in REC (Clinical Gingival Recession)
Time frame: baseline, 3 and 6 months
Change in CAL (Clinical Attachment Level)
Time frame: baseline, 3 and 6 months
Change in BOP (Bleeding on Probing)
Time frame: baseline, 3 and 6 months
Change in PI (Plaque Index)
Time frame: baseline, 3 and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Periodontal Diseases
Not yet recruitingObservational study
Periodontal Status and Biomarkers in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Recruiting
Thermosensitive Hyaluronic Gel With Octenidine as an Adjunctive to Subgingival Instrumentation
Periodontal Disease
Active, not recruitingObservational study
A Retrospective Comparative Evaluation of Omega-3 and Resveratrol Supplementation in Patients With Periodontitis
Periodontitis
Recruiting
Effects of Different Activation Techniques on Antimicrobial Photodynamic Therapy in Apical Periodontitis
Apical Periodontitis, Endodontic Retreatment
Recruiting
Ozone Gel Versus Chlorohexidine Gel as an Adjunct to Non-Surgical Treatment of Stage II Periodontitis Grade B Among Smokers Patients
Ozone Gel, Chlorohexidine Gel
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.
Magda Mensi principal investigator
Asst Degli Spedali Civili Di Brescia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic: Lactobacillus Reuteri in people with Periodontal Diseases, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia at 1 site in Italy.
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 7 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 14 Jul 2025. 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 Italy. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 14 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 in PD (Periodontal Depth) (time frame: baseline, 3 and 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 14 Jul 2025.