Clinical trial NCT03386643: Effect of Bifidobacterium Animalis Subsp. Lactis HN019 on Oral Lichen Planus
Official title: Effect of the Probiotic Bifidobacterium Animalis Subsp. Lactis HN019 on Clinical, Histopathological and Immunophenotypic Features of Oral Lichen Planus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Oral Lichen Planus
Keywords: Oral lichen planus
Probiotics
Immunomodulation.
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2017-12-29
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Symptomatic patients presenting OLP will be randomly assigned to either topical Bifidobacterium animalis subsp lactis HN019 or clobetasol propionate 0.05%, and they 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in symptoms intensity measure
timeFrame: 4 weeks
Secondary outcomes:
measure: Histopathological analysis
timeFrame: Before (baseline) and one month after intensive topical therapy
measure: Immunohistochemical analysis
timeFrame: After 4 weeks of intensive therapy.
measure: Venous blood collection
timeFrame: Before (baseline) and after 4 weeks of topical therapy
Other outcomes:
Locations:
city: Ribeirão Preto
country: Brazil
facility: School of Dentistry of Ribeirão Preto, University of São Paulo
state: São Paulo
Study officials:
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Michel Reis Messora, DDS, PhD
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Sergio L. Souza Salvador, DDS, PhD
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Átila V. Vitor Nobre, DDS
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Cristhiam de J. Hernández Martínez, DDS
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Kleber Tanaka Suzuki, DDS
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Marina C. Gabriel Del Arco
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Lara Maria A Innocentini, DDS,PhD
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil.
name: Gilberto A Silva, MS
role: STUDY_CHAIR
affiliation: University of São Paulo, Ribeirão Preto, SP, Brazil
name: Ellen E Monteiro, Student
role: STUDY_CHAIR
References:
citation: Han X, Zhang J, Tan Y, Zhou G. Probiotics: A non-conventional therapy for oral lichen planus. Arch Oral Biol. 2017 Sep;81:90-96. doi: 10.1016/j.archoralbio.2017.04.026. Epub 2017 Apr 26.
citation: Garcia-Pola MJ, Gonzalez-Alvarez L, Garcia-Martin JM. Treatment of oral lichen planus. Systematic review and therapeutic guide. Med Clin (Barc). 2017 Oct 23;149(8):351-362. doi: 10.1016/j.medcli.2017.06.024. Epub 2017 Jul 28. English, Spanish.
citation: Sivaraman S, Santham K, Nelson A, Laliytha B, Azhalvel P, Deepak JH. A randomized triple-blind clinical trial to compare the effectiveness of topical triamcinolone acetonate (0.1%), clobetasol propionate (0.05%), and tacrolimus orabase (0.03%) in the management of oral lichen planus. J Pharm Bioallied Sci. 2016 Oct;8(Suppl 1):S86-S89. doi: 10.4103/0975-7406.191976.
citation: Ricoldi MST, Furlaneto FAC, Oliveira LFF, Teixeira GC, Pischiotini JP, Moreira ALG, Ervolino E, de Oliveira MN, Bogsan CSB, Salvador SL, Messora MR. Effects of the probiotic Bifidobacterium animalis subsp. lactis on the non-surgical treatment of periodontitis. A histomorphometric, microtomographic and immunohistochemical study in rats. PLoS One. 2017 Jun 29;12(6):e0179946. doi: 10.1371/journal.pone.0179946. eCollection 2017.
citation: Gerhard D, Sousa FJDSS, Andraus RAC, Pardo PE, Nai GA, Neto HB, Messora MR, Maia LP. Probiotic therapy reduces inflammation and improves intestinal morphology in rats with induced oral mucositis. Braz Oral Res. 2017 Jul 3;31:e71. doi: 10.1590/1807-3107BOR-2017.vol31.0071.