Effect of Bifidobacterium Animalis Subsp. Lactis HN019 on Oral Lichen Planus

March 25, 2020 updated by: Ana Carolina Fragoso Motta, DDS, PhD, University of Sao Paulo

Effect of the Probiotic Bifidobacterium Animalis Subsp. Lactis HN019 on Clinical, Histopathological and Immunophenotypic Features of Oral Lichen Planus

Lichen planus is a chronic inflammatory mucocutaneous disease, which often results in oral manifestations, receiving the name of oral lichen planus (OLP). Its frequency varies from 0,1 to 4% of the general population, with a higher incidence in women, around the 4th and 5th decades of life. Although the pathogenesis of OLP is related to a immune-cellular response, mainly mediated by T lymphocytes, its cause remains unknown. Considering its chronic nature, control of OLP aims to reduce symptoms and improve function, and agents with anti-inflammatory action, especially topical corticosteroids result in some degree of success in most patients, depending on the clinical presentation. However, some cases are resistant to the use of corticosteroids, thus justifying the search for new therapeutic options. The immunomodulation proved to be one of the main functions of probiotic bacteria, and recent studies have shown effect of probiotics on decreasing the expression of inflammatory markers, which enables the study of this therapy as an alternative to the control of OLP. Thus, this project aims to evaluate the effects of therapy with Bifidobacterium animalis subsp. lactis HN019 comparing with clobetasol propionate 0.05% in symptomatic patients with OLP referred for diagnosis and treatment of School of Dentistry of Ribeirão Preto - University of São Paulo (USP). The impact of the topical therapy (probiotic or corticosteroid) on the clinical, histopathological and immunopathological features will be evaluated. This project was previously submitted and approved by the Institutional Review Board of the School of Dentistry of Ribeirão Preto/USP, and all patients must give informed consent to participate in this study.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized double-blind clinical trial with symptomatic patients presenting OLP, which will be randomly assigned to either topical Bifidobacterium animalis subsp lactis HN019 or clobetasol propionate 0.05%. The selected patients will receive capsules to be diluted in 15 ml of water containing 6 x 109 CFUs of Bifidobacterium subsp. lactis HN019 (experimental group) or 0.05% clobetasol propionate (control group) for mouth washing, twice a day for 4 weeks. Patients will be instructed to maintain normal brushing and not to use or consume another corticosteroid and /or probiotic during the study. Outcomes measures will be symptoms (VAS and Likert-like scale), quality of life (SF-36 form), and clinical changes (erythema, reticulation, erosion/ulcer based on clinical photographs), which will be performed at baseline, 15 days (only VAS, Likert-like scale and photographs) and and at one month of treatment. All patients will undergo biopsies for the diagnosis of OLP, and those who consent will be submitted to an optional biopsy at the end of the topical treatment for histopathological and immunopathological characterization.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
22

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14040-904
        • School of Dentistry of Ribeirão Preto, University of Sao Paulo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical inclusion

    • Adults ≥ 18 years old, both genres, who consent to participate of the study;
    • Presence of symptomatic reticular lesion and/or white-gray papules. In afro-descendent individuals, reticular lesions may be associated with hyperpigmented lesions;
    • Additional clinical features such as ulcerative, erythematous, plaque and bullous lesions will be accepted in the presence of bilateral and symmetrical reticular lesions.

  • Histopathological inclusion criteria

    • Presence of subepithelial infiltrate predominantly lymphocytic, in band and confined to the subepithelial area.
    • Liquefaction degeneration of the basal cells layer.

Exclusion Criteria:

  • Clinical exclusion criteria

    • Exclusion of contact lichenoid lesions: the pattern of reticular lesion and / or papules should not be present only in areas of physical contact with restorative materials;
    • Exclusion of lichenoid reaction to the drug: difficult to differentiate from OLP, however it is necessary to report all drugs in use by the patient; the comparison between patients on medication, and those who do not use medication is important to establish subgroups of OLP;
    • Exclusion of chronic graft versus host disease (GVHD): differentiation between OLP and GVHD is established in most cases by medical history;
    • Exclusion of immunocompromised patients or patients with systemic diseases of high complexity.
    • Exclusion of patients who have previously used probiotic bacteria in the last 4 weeks prior to the study.
  • Histopathological criteria for exclusion • Presence of epithelial dysplasia, absence of the lymphocytic inflammatory infiltrate band and liquefaction degeneration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Bifidobacterium animalis subsp. lactis

Intervention:

Bifidobacterium animalis subsp. lactis HN019
Drug: Bifidobacterium animalis subsp. lactis HN019
The selected patients will receive capsules to be diluted in 15 ml of water containing 6 x 109 CFUs of Bifidobacterium subsp. lactis HN019 for mouthwash twice a day for 4 weeks.
Other Names:
  • Probiotic
Active Comparator: Clobetasol propionate 0.05%

Intervention:

Clobetasol propionate 0.05%
Drug: Clobetasol propionate 0.05%
The selected patients will receive capsules to be diluted in 15ml of water containing clobetasol propionate 0.05% for mouthwash twice a day for 4 weeks.
Other Names:
  • Topical corticosteroid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in symptoms intensity measure
Time Frame: 4 weeks
Self reported symptoms at baseline, 15 and 30 days after therapy through an visual analogue scale (VAS). It consists of a subjective scale scoring the symptoms from 0 to 10 (0 = no symptoms and 10 = as bad as can be).
4 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Histopathological analysis
Time Frame: Before (baseline) and one month after intensive topical therapy
Biopsies will be collected at the baseline stage or at the time of the diagnosis of OLP (optional), consisting of a 5mm x 5mm fragment or a 4mm punch of reticular lesions. The second biopsy will be optional, with patient consent, close to the area of the first biopsy for comparative purposes. The histological findings will be determined quantitatively and qualitatively regarding the presence of epithelial hyperplasia, degeneration by liquefaction of the basal cells layer, lymphocytic infiltrate in the subepithelial connective tissue, and apoptotic cells. Photographs will be used at 400x and quantification using the Image J. program.
Before (baseline) and one month after intensive topical therapy
Immunohistochemical analysis
Time Frame: After 4 weeks of intensive therapy.
The population of inflammatory cells will be characterized by analysis of oral mucosa samples, with emphasis on the T cell line (CD3, CD4, CD8, CD25, CD103, perforin, granzyme B and Foxp3), B cells (CD20 / CD20), dendritic cells (CD123 and CD303), submucosal dendritic cells (CD209 and factor XIIIa), Langerhans cells (CD1a and CD207), endothelial activity (e-selectin and CD31), mast cells ), macrophages (CD68 and CD163), myeloid dendritic cells (S100 and CD11c), cell proliferation markers (Ki-67, MCM-2, MCM-5, cyclin D1) and extracellular matrix (laminin-5). For immunohistochemical reactions, histological sections of 3μm thickness will be performed, which will be placed on slides coated with organosilane (Sigma-Aldrich, St Louis, MO, USA).
After 4 weeks of intensive therapy.
Venous blood collection
Time Frame: Before (baseline) and after 4 weeks of topical therapy
10 ml of venous blood to evaluate the probiotic systemic effect, by means of the research of pro-inflammatory, anti-inflammatory and regulatory cytokines.
Before (baseline) and after 4 weeks of topical therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Sao Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Michel Reis Messora, DDS, PhD, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Sergio L. Souza Salvador, DDS, PhD, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Átila V. Vitor Nobre, DDS, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Cristhiam de J. Hernández Martínez, DDS, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Kleber Tanaka Suzuki, DDS, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Marina C. Gabriel Del Arco, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Lara Maria A Innocentini, DDS,PhD, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Gilberto A Silva, MS, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Study Chair: Ellen E Monteiro, Student, University of São Paulo, Ribeirão Preto, SP, Brazil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 5, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 6, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 29, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CAAE: 63003716.2.0000.5419

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

No plan to make individual participant data available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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