Clinical trial NCT04478643: Lactobacillus Reuteri in the Supportive Therapy of Periodontitis
Official title: Clinical and Microbiological Efficacy of Lactobacillus Reuteri in the Supportive Therapy of Periodontitis: a 6 Months Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Periodontal Diseases
Keywords: Lactobacillus reuteri
Probiotic
Periodontal diseases
GBT
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2020-07-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric, Parallel-Arm, Patient, Statistician, Operator and Examiner are blinded, RCT
Primary purpose: TREATMENT

Brief 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. 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

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Change in PD (periodontal depth)
timeFrame: baseline, 3 and 6 months
Secondary outcomes:
measure: Risk progression of the periodontitis and the need of periodontal surgery
timeFrame: 6 months
measure: Pocket closure
timeFrame: baseline, 3 and 6 months
measure: Microbiological changes
timeFrame: baseline, 3 and 6 months
measure: change in REC (Clinical Gingival Recession)
timeFrame: baseline, 3 and 6 months
measure: change in CAL (Clinical Attachment Level)
timeFrame: baseline, 3 and 6 months
measure: Change in BOP (Bleeding on Probing)
timeFrame: baseline, 3 and 6 months
measure: Change in PI (Plaque Index)
timeFrame: baseline, 3 and 6 months
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: Magda Mensi
state: Lombardia
Study officials:
affiliation: ASST Spedali Civili di Brescia
name: Magda Mensi
role: PRINCIPAL_INVESTIGATOR
References: