Administration of L. Paracasei 28.4 as an Adjunct to the Treatment of Periodontitis

Administration of L. Paracasei 28.4 as an Adjunct to the Treatment of Periodontitis: Superiority Placebo-controlled Randomized Clinical Trial

The aim of this study is to evaluate the effects of probiotic administration of L. paracasei 28.4 as an adjunct to the non-surgical periodontal treatment in patients with periodontitis.

Study Overview

• Status: Recruiting
• Conditions: Periodontitis
• Intervention / Treatment: Other: FMUD+Probiotic; Other: FMUD+Placebo

Detailed Description

This is a superiority placebo-controlled randomized clinical trial. The population that will be evaluated in the study will be selected at Institute of Science and Technology (ICT), São José dos Campos, College of Dentistry.

Sixty patients presenting Stage III/IV and Grade B/C periodontitis will be divided into 2 groups:

• FMUD+Placebo (n=30): full-mouth ultrasonic periodontal debridement associated with administration of placebo formulation, twice a day for 30 days;
• FMUD+Probiotic (n=30): full-mouth ultrasonic periodontal debridement associated with administration of probiotic formulation twice a day for 30 days.

The study will consist of two stages of treatment:

• Initial therapy: Before starting treatment, a complete examination of the oral cavity and evaluation of periodontal parameters will be performed. All patients will undergo a prior adjustment of the oral environment and oral hygiene. Thirty days after completion of initial therapy, a new periodontal evaluation will be performed and only patients who present a visible plaque index less than or equal to 25% will undergo subgingival periodontal debridement.
• Non-surgical periodontal therapy: After initial therapy, all patients will receive full-mouth ultrasonic periodontal debridement. Debridement will be performed by a single operator, trained, blind to the allocation of patients and different from the evaluator. If there is any complication that prevents the completion of full-mouth debridement, the procedure will be finished within a maximum period of 24 hours. The randomization envelope will be opened and the probiotic/placebo formulation will be delivered to patients. They will be instructed to consume the samples twice a day during the 30 days following periodontal treatment.

All clinical measurements will be performed by a single researcher, previously calibrated for the measurements. After periodontal therapy, treatment results will be evaluated three and six months after periodontal debridement associated with the use of placebo/probiotic formulation. Indications of adverse oral effects will be verified by visual assessment at 7, 30 and 90 days after the start of consumption of formulations.

To assess patient-centered parameters, the OHIP-14 questionnaire will be applied before and after 6 months of periodontal treatment for each patient. A 30-days diary will be used to assess the adherence to use and occurrence adverse effects.

Microbiological and immunological analyzes will be carried out through subgingival biofilm and gingival crevicular fluid samples collected from sites with moderate pockets and sites with deep pockets at baseline, 3 and 6 months after therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Mauro P Santamaria, PhD; Phone Number: +55 (12) 39479055; Email: mauro.santamaria@unesp.br
• Study Contact Backup: Name: Laís FF Ferraz, MS; Phone Number: +55 (15) 991756747; Email: lais.ferraz@hotmail.com

Study Locations

• Brazil
  • São Paulo
    • São José dos Campos, São Paulo, Brazil, 12245000
      • Recruiting
      • Mauro Pedrine Santamaria
      • Contact: Laís FF Ferraz, MS; Phone Number: +55 (15) 991756747; Email: lais.ferraz@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of stage III/IV and grade B/C generalized periodontitis;
• Presence of at least 20 teeth in the mouth;
• Signing the informed consent form.

Exclusion Criteria:

• Presence of systemic conditions that contraindicate the periodontal procedure or influence the progression of the disease;
• Periodontal treatment history in the last six months;
• Use of antibiotics or probiotics in the last six months;
• Smoke more than 10 cigarettes a day;
• Pregnant or breastfeeding;
• Chronic use of anti-inflammatory drugs or medications that can alter the response of periodontal tissues;
• Need of antibiotic prophylaxis for dental procedures;
• Need of probiotic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMUD+Probiotic; FMUD+Probiotic (n=30): full-mouth ultrasonic periodontal debridement associated with administration of probiotic formulation twice a day for 30 days.	Other: FMUD+Probiotic; Full-mouth ultrasonic periodontal debridement associated with administration of probiotic formulation (Lactobacillus paracasei 28.4) twice a day for 30 days.
Placebo Comparator: FMUD+Placebo; FMUD+Placebo (n=30): full-mouth ultrasonic periodontal debridement associated with administration of placebo formulation, twice a day for 30 days.	Other: FMUD+Placebo; Full-mouth ultrasonic periodontal debridement associated with administration of placebo formulation twice a day for 30 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of pockets with PD ≥ 5 mm	Number of pockets with probing depth ≥ 5 mm	6 months

Collaborators and Investigators

• Sponsor: Universidade Estadual Paulista Júlio de Mesquita Filho
• Investigators: Principal Investigator: Laís F Ferraz, MS, Sao Paulo State University - Brazil; Study Director: Mauro P Santamaria, PhD, Sao Paulo State University - Brazil

Publications and helpful links

General Publications

• Ribeiro FC, Junqueira JC, Dos Santos JD, de Barros PP, Rossoni RD, Shukla S, Fuchs BB, Shukla A, Mylonakis E. Development of Probiotic Formulations for Oral Candidiasis Prevention: Gellan Gum as a Carrier To Deliver Lactobacillus paracasei 28.4. Antimicrob Agents Chemother. 2020 May 21;64(6):e02323-19. doi: 10.1128/AAC.02323-19. Print 2020 May 21.
• Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018 Jun;89 Suppl 1:S159-S172. doi: 10.1002/JPER.18-0006. Erratum In: J Periodontol. 2018 Dec;89(12):1475.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis
• Other Study ID Numbers: Lp + PD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be available at the end of the study after a direct request.
• IPD Sharing Time Frame: After the study completion.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No