Clinical and Microbiological Aspects of Probiotics in Non-surgical Periodontal Therapy.

Periodontitis Clinical Trial

Official title:

Clinical and Microbiological Aspects of Probiotics in Non-surgical Periodontal Therapy: a Randomized Controlled Trial.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06063226
• Other study ID #: PARO
• Status: Not yet recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: June 1, 2024

Study information

• Verified date: September 2023
• Source: G. d'Annunzio University
• Contact: Marco Dolci, MD DDS PHD
• Phone: +393281665925
• Email: marco.dolci[@]unich.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this randomized clinical trial is to test the effect orally administration of Probiotics based on Lactobacillus rhamnosus LR04 and Lactobacillus plantarum LP14 as adjuvant in people suffering from periodontitis stage II-III. The main questions it aims to answer are:

• QUESTION 1: orally administered probiotics based on the previous strains could represent a useful tool in support of non-surgical periodontal therapy in reducing clinical periodontal indexes?

• QUESTION 2: orally administered probiotics based on the previous strains could represent a useful tool in support of non-surgical periodontal therapy in reduce the amount of periodontal pathogens in periodontal pockets?

Partecipants in the test group will take the test probiotic for 90 days in adjunction of the routinary oral hygiene procedures.

Partecipants in the positive controlled group will take the placebo for 90 days in adjunction of the routinary oral hygiene procedures.

Partecipants in the negative control group will perform only the routinary oral hygiene procedures.

Researchers will compare 3 groups to see if orally administered probiotics based on L. rhamnosus and L. plantarum may hel in the reduction of periodontal indexes and of the periodontal pathogen bacteria.

Description:

The diagnosis of periodontitis passes through the recording of periodontal probing values on 6 sites for each periodontal element, the recording of clinical indices such as the percentage of bleeding sites and those with plaque, finally through the execution of a full-x-ray consisting of intraoral films that guarantee staging through the calculation of the loss of clinical attachment, corresponding to the loss of alveolar bone caused by the disease. The therapy of periodontitis is composed of several steps and begins with the control of the biofilm. This control is carried out with professional supragingival hygiene sessions followed by subgingival instrumentation of the periodontal pockets in order to remove the hard and soft deposits below the gingival margin, which would not otherwise be eliminated with the supragingival strategy alone. The response to mechanical therapy and the risk of relapses go hand in hand with the patient's response, his ability to maintain a good level of oral hygiene at home and to keep return appointments. In this sense, dental research has worked hard to develop additional aids to mechanical therapy to try to improve its performance. In the last decade in particular, the use of probiotics has found an increasingly wider field in periodontology, as they are based on the idea of enhancing the eubiosis ratios of the non-pathogenic flora in order to make the environment unfavorable for the proliferation of a pathogenic flora.

The present study aims to evaluate whether the quarterly oral administration of probiotics based on Lactobacillus plantarum LP14 and Lactobacillus rhamnosus LR04 can improve the response to non-surgical periodontal therapy of subgingival instrumentation in patients suffering from stage II-III periodontitis and complexity of grade A-B.

Primary objective To evaluate the adjuvant effect of probiotics based on Lactobacillus plantarum LP14 and Lactobacillus rhamnosus LR04 in non-surgical periodontal therapy.

Secondary objective Characterize the microbiological picture of patients with periodontitis with and without the aid of probiotics.

MATERIALS AND METHODS Three groups of volunteers of both sexes will be enrolled for the study without age restrictions.

Inclusion criteria Patients in the absence of other systemic pathologies reported in the medical history, smokers and non-smokers, non-drinkers, in the absence of previous or current administration of other sources of probiotics, capable of providing informed consent.

Exclusion criteria Subjects with a history of systemic diseases (diabetes, autoimmune diseases, inflammatory bowel diseases, neurodegenerative diseases), drinkers, who take or have taken probiotics in the last 3 months, unable to provide informed consent.

Minimum sample size Sample size calculation (Alpha = 0.05; Power = 95%) for 3 independent study groups, and a continuous primary endpoint. Sample size = Z2 (1-alpha/2) p (1-p) / d2 Where Z(1-alpha/2) is the standard variate corresponding to 1.96 at 5% type 1 error, p is the expected proportion in the population expressed in decimals based on previous studies and d is the confidence level decided by the researcher expressed in decimal. Regarding the primary outcome of Bleeding On Probing (BOP), the expected difference between the means was assumed to be 20%, therefore 20 patients per group are required, for a total of 60 patients. To these patients, the dropout percentage of 10% must be added, so the total is 70 patients.

T0 - BASELINE The first dental visit and the treatment plan will be carried out by Prof. Marco Dolci. The periodontal visit with the registration of the indices and the full-rx will be carried out by Prof. Marco Dolci.

Clinical indixes

• Bleeding On Probing - BOP, percentage value on 6 sites for each tooth

• Pocket Probing Depth - PPD on 6 sites for each tooth

• Clinical Attachment Loss - CAL on intraoral radiographs of pathological sites

• Plaque Index - PI, rated from 0 to 4 for each site

• Percentage of pathological sites out of total sites. The recording of BOP, PPD, PI will be carried out through periodontal probing using the PCP-15 UNC periodontal probe (HuFriedi) in a completely atraumatic and non-invasive manner.

The operational session will be organized as follows:

• Supragingival instrumentation with piezoelectric ultrasonic scaler handpiece;

• BPA microbiological test (Bacterial Periodontal Assessment - Biomolecular Diagnostic, Via Nicola Porpora, 550144 - Florence) through sampling of the gingival crevicular fluid with a thin cone of sterile paper with a diameter of 0.3 mm positioned in the pocket for 60 seconds, in an atraumatic and non-traumatic manner invasive. After sampling, the cones will be inserted into a single test tube;

• Subgingival instrumentation of periodontal pockets using Gracey curettes. The treatment is to be considered as Full Mouth Treatment (FMT). The samples will be transported to the laboratory located on the third floor of Building A, taken into custody by Prof. Marco Dolci and stored at + 4° C until the arrival of the dedicated courier.

The same Biomolecular Diagnostic company will take care of collecting the samples via dedicated biological courier and will carry out the PCR analyzes in its laboratories.

At the end of the analyses, a copy of a unique identification code will be sent to the Experimenters so that they can access the report.

Placement of the patient in the test, positive and negative control groups

TEST: home oral hygiene 2/day with soft bristle toothbrush + standard fluoride toothpaste + probiotic in buccal sachet to be consumed once a day until the quarterly check-up.

POSITIVE CONTROL: home oral hygiene 2/day with soft bristle toothbrush + standard fluoride toothpaste + industrial placebo in buccal sachet to be consumed once a day until the quarterly check-up.

NEGATIVE CONTROL: home oral hygiene 2/day with soft bristle toothbrush + standard fluoride toothpaste.

The products (test and placebo) will be delivered to the patient at the end of the session in order to cover 3 months of administration.

T1 - AFTER 3 MONTHS FROM T0

• Recording of periodontal indices.

• Microbiological samples.

Randomization The treatment that is due to the individual patient is kept in sequentially numbered, opaque and sealed envelopes (SNOSE Sequentially Numbered, Opaque, Sealed Envelopes). The products used for both the test and the controls will be supplied in anonymous tubes so that neither the patient nor the investigator will be aware of them.

Statistical analysis Proper statistical analysiswill be perfomed by the trusted statistical group.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: June 1, 2024
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients in the absence of other systemic pathologies reported in the medical history

• smokers and non-smokers, non-drinkers,

• subjects in the absence of previous or current administration of other sources of probiotics,

• subjects capable of providing informed consent.

Exclusion Criteria:

• Subjects with a history of systemic diseases (diabetes, autoimmune diseases, inflammatory bowel diseases, neurodegenerative diseases),

• drinkers,

• subjects who take or have taken probiotics in the last 3 months,

• subjects unable to provide informed consent.

Related Conditions & MeSH terms

• Non Surgical Periodontal Therapy
• Periodontitis
• Probiotics

Intervention

Other:
• Experimental
Orally administred probiotics with L. plantarum and L. rhamnosus
• Negative control
Only routinary oral hygiene procedures
• Positive control
Orally administred placebo without probiotics

Locations

Country	Name	City	State
Italy	University G. d'Annunzio	Chieti

Sponsors (2)

Lead Sponsor	Collaborator
G. d'Annunzio University	Probiotical S.p.A.

Country where clinical trial is conducted

Italy, 

References & Publications (17)

Bustamante M, Oomah BD, Mosi-Roa Y, Rubilar M, Burgos-Diaz C. Probiotics as an Adjunct Therapy for the Treatment of Halitosis, Dental Caries and Periodontitis. Probiotics Antimicrob Proteins. 2020 Jun;12(2):325-334. doi: 10.1007/s12602-019-9521-4. — View Citation

Etebarian A, Sheshpari T, Kabir K, Sadeghi H, Moradi A, Hafedi A. Oral Lactobacillus species and their probiotic capabilities in patients with periodontitis and periodontally healthy individuals. Clin Exp Dent Res. 2023 Apr 20. doi: 10.1002/cre2.740. Online ahead of print. — View Citation

Fu J, Jia L, Wu L, Jiang Y, Zhao R, Du J, Guo L, Zhang C, Xu J, Liu Y. Lactobacillus rhamnosus inhibits osteoclast differentiation by suppressing the TLR2/NF-kappaB pathway. Oral Dis. 2023 Aug 21. doi: 10.1111/odi.14712. Online ahead of print. — View Citation

Furlaneto F, Ishikawa KH, Messora MR, Mayer MPA. Probiotics During the Therapeutic Management of Periodontitis. Adv Exp Med Biol. 2022;1373:353-375. doi: 10.1007/978-3-030-96881-6_19. — View Citation

Gatej SM, Marino V, Bright R, Fitzsimmons TR, Gully N, Zilm P, Gibson RJ, Edwards S, Bartold PM. Probiotic Lactobacillus rhamnosus GG prevents alveolar bone loss in a mouse model of experimental periodontitis. J Clin Periodontol. 2018 Feb;45(2):204-212. doi: 10.1111/jcpe.12838. Epub 2017 Dec 11. — View Citation

Gruner D, Paris S, Schwendicke F. Probiotics for managing caries and periodontitis: Systematic review and meta-analysis. J Dent. 2016 May;48:16-25. doi: 10.1016/j.jdent.2016.03.002. Epub 2016 Mar 8. — View Citation

Iwasaki K, Maeda K, Hidaka K, Nemoto K, Hirose Y, Deguchi S. Daily Intake of Heat-killed Lactobacillus plantarum L-137 Decreases the Probing Depth in Patients Undergoing Supportive Periodontal Therapy. Oral Health Prev Dent. 2016;14(3):207-14. doi: 10.3290/j.ohpd.a36099. — View Citation

Lee Y, Yoon Y, Choi KH. Probiotics-Mediated Bioconversion and Periodontitis. Food Sci Anim Resour. 2021 Nov;41(6):905-922. doi: 10.5851/kosfa.2021.e57. Epub 2021 Nov 1. — View Citation

Mendi A, Kose S, Uckan D, Akca G, Yilmaz D, Aral L, Gultekin SE, Eroglu T, Kilic E, Uckan S. Lactobacillus rhamnosus could inhibit Porphyromonas gingivalis derived CXCL8 attenuation. J Appl Oral Sci. 2016 Jan-Feb;24(1):67-75. doi: 10.1590/1678-775720150145. — View Citation

Morales A, Carvajal P, Silva N, Hernandez M, Godoy C, Rodriguez G, Cabello R, Garcia-Sesnich J, Hoare A, Diaz PI, Gamonal J. Clinical Effects of Lactobacillus rhamnosus in Non-Surgical Treatment of Chronic Periodontitis: A Randomized Placebo-Controlled Trial With 1-Year Follow-Up. J Periodontol. 2016 Aug;87(8):944-52. doi: 10.1902/jop.2016.150665. Epub 2016 Mar 4. — View Citation

Morales A, Gandolfo A, Bravo J, Carvajal P, Silva N, Godoy C, Garcia-Sesnich J, Hoare A, Diaz P, Gamonal J. Microbiological and clinical effects of probiotics and antibiotics on nonsurgical treatment of chronic periodontitis: a randomized placebo- controlled trial with 9-month follow-up. J Appl Oral Sci. 2018 Jan 18;26:e20170075. doi: 10.1590/1678-7757-2017-0075. — View Citation

Nguyen T, Brody H, Radaic A, Kapila Y. Probiotics for periodontal health-Current molecular findings. Periodontol 2000. 2021 Oct;87(1):254-267. doi: 10.1111/prd.12382. — View Citation

Pudgar P, Povsic K, Cuk K, Seme K, Petelin M, Gaspersic R. Probiotic strains of Lactobacillus brevis and Lactobacillus plantarum as adjunct to non-surgical periodontal therapy: 3-month results of a randomized controlled clinical trial. Clin Oral Investig. 2021 Mar;25(3):1411-1422. doi: 10.1007/s00784-020-03449-4. Epub 2020 Jul 14. — View Citation

Routier A, Blaizot A, Agossa K, Dubar M. What do we know about the mechanisms of action of probiotics on factors involved in the pathogenesis of periodontitis? A scoping review of in vitro studies. Arch Oral Biol. 2021 Sep;129:105196. doi: 10.1016/j.archoralbio.2021.105196. Epub 2021 Jun 10. — View Citation

Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F, Herrera D, Jepsen S, Lione L, Madianos P, Mathur M, Montanya E, Shapira L, Tonetti M, Vegh D. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International diabetes Federation and the European Federation of Periodontology. Diabetes Res Clin Pract. 2018 Mar;137:231-241. doi: 10.1016/j.diabres.2017.12.001. Epub 2017 Dec 5. — View Citation

Sulijaya B, Takahashi N, Yamazaki K. Lactobacillus-Derived Bioactive Metabolites for the Regulation of Periodontal Health: Evidences to Clinical Setting. Molecules. 2020 Apr 29;25(9):2088. doi: 10.3390/molecules25092088. — View Citation

Teughels W, Durukan A, Ozcelik O, Pauwels M, Quirynen M, Haytac MC. Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol. 2013 Nov;40(11):1025-35. doi: 10.1111/jcpe.12155. Epub 2013 Sep 15. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction of clinical periodontal indexes	Evaluation of clinical periodontal indexes, such as: bleeding on probing (BOP), periodontal pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), total number of pathological sites in %.	From enrollement to the end of treatment at 3 months.
Secondary	Reduction of periodontal pathogen bacteria amount.	Evaluation of the amount of periodontal pathogen bacteria such as: A. actinomycetemcomitans, P. gingivalis, P. intermedia and F. nucleatum	From enrollement to the end of treatment at 3 months.

External Links

•   New Classification of periodontal and peri-implant diseases