Photobiomodulation in Oral Lichen Planus

Study Overview
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Brief Summary
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The aim of this study was to compare the efficacy of PBM (660nm) and corticosteroid therapy with clobetasol propionate 0.05% in the treatment of OLP. This is a protocol for a randomized, controlled, double blind clinical trial. Fourty-four patients will be randomized in two experimental groups. Control group will be treated with clobetasol propionate 0.05% for 30 consecutive days and with placebo PBM twice a week. The experimental group will be treated with placebo gel for 30 consecutive days to mask the treatment and patients will receive PBM twice a week during 1 month (laser λ = 660±10 nm; power 100mW; radiant energy 177J/cm2; 5-s exposure time per point and 0.5J of energy per point. The primary variable (pain) and the secondary variables including clinical scores and functional scores as well as patient anxiety and depression (The Hospital Anxiety and Depression Scale-HADS), will be evaluated at the baseline, once a week during treatment and after 30 and 60 days of follow up. Evaluation of clinical resolution will be performed at the end of the treatment (30 days). Evaluation of recurrence will be performed after 30 and 60 days of follow up. Serum and salivary levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated at baseline and at the end of treatment (30 days). Quality of life will be evaluated by OHIP-14 questionnaire at baseline, at the end of treatment and after 30 and 60 days of follow up. The chi-square test, Student's t-test and ANOVA will be used and the level of significance of 5% will be considered (p < 0.05).

Detailed Description
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Oral lichen planus is an idiopathic chronic mucocutaneous disease with a ride range of clinical manifestations, including white reticular patches, erosive/ulcerative and atrophic lesions, both associated with intense symptomatology. CD4+ and CD8+ T lymphocytes cells play an important role in the pathogenesis of OLP and are responsible for the production of different cytokines, including IL-6, IL-10, IL-1β, INF-γ and TNF-α. Treatment is symptomatic and topical corticosteroids are commonly used as standard therapy. However, patients frequently present relapses after treatment's discontinuation, develop resistance to corticosteroids therapy as well as secondary candidiasis. Photobiomodulation (PBM) has shown to be a potential therapeutic tool to treat inflammatory disorders, including OLP. Some studies have demonstrated that PBM improves the clinical presentation of OLP (erosive/ulcerative or atrophic lesions to reticular lesions), reduces pain and recurrence. However, it remains controversy if PBM is more effective than corticosteroid in the treatment of OLP. The aim of this study is to evaluate the efficacy of PBM in the treatment of OLP in relation to the standard therapy with corticosteroids. This is a protocol for a randomized, controlled, doubled blind clinical trial, with two months of follow up. Patients with symptomatic OLP and with histopathological diagnosis of OLP based on WHO criteria will be included in this study. Fourty-four patients will be randomized in two experimental groups. Control group will be treated with clobetasol propionate 0.05% gel for 30 consecutive days and the laser device will be positioned over the lesion but will be switched off to mask the treatment. The experimental group will be treated with placebo gel for 30 consecutive days to mask the treatment and patients will receive laser treatment twice a week during 1 month for PBM (laser λ = 660±10 nm; power 100mW; radiant energy; 177J/cm2; 5-s exposure time per point and 0.5J of energy per point). The primary variable (pain by VAS scale) and the secondary variables (clinical scores, functional scores and Patient anxiety and depression) will be evaluated at the baseline, once a week during treatment and after 30 and 60 days of follow up. Evaluation of clinical resolution will be performed at the end of the treatment (30 days). Evaluation of recurrence will be performed after 30 and 60 days of follow up. Serum and salivary levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated at baseline and at the end of treatment (30 days). Quality of life will be evaluated by OHIP-14 questionnaire at baseline, at the end of treatment and after 30 and 60 days of follow up. The findings will be computed and submitted to statistical analysis. Interval estimates will be used for the variables of interest to determine the prevision of the estimates and perform comparisons. If necessary, transformation methods or non-parametric tests will be applied. The chi-square test, Student's t-test and ANOVA will be used and the level of significance of 5% will be considered (p < 0.05).

Official Title
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Efficacy of Photobiomodulation for Oral Lichen Planus Treatment

Conditions
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Lichen Planus, Oral, Low-Level Light Therapy

Intervention / Treatment
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* Drug: Propionate clobetasol gel 0.05%
* Device: Photobiomodulation
* Other: Placebo gel
* Other: Placebo Photobiomodulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participants in this study will be male and female (aged over 18 years) diagnosed with symptomatic oral lichen planus, based on the clinical and histopathological criteria of the World Health Organization (WHO). Exclusion Criteria: Patients with ongoing cancer; pregnant or breastfeeding women; patients with history of corticosteroids and nonsteroidal anti-inflammatory treatment in the last one months, patients with uncontrolled systemic disease; consumption of illicit drugs; use of medication associated with oral lichenoid reactions; amalgam restoration near to OLP lesions; epithelial dysplasia in the histopathological examination.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Control group Experimental Group
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Photobiomodulation<br>Patients will be treated with localized PBM with a diode laser with continuous wave (laser λ =660 nm; power 100mW;radiant energy: 177J/cm2; 5-s exposure time per point and 0.5J of energy per point) applied directly to the surrounding oral mucosa and to the center of OLP, always by the same operator, twice a week for 4 weeks, totaling 8 session. The number of points will be variable according to the lesion size. The output power of the laser equipment will be evaluated using a power meter (Laser Check; MMOptics LTDA, São Paulo, Brazil) before treatment to confirm the effective mean power as well as the doses applied during the procedure. | Device: Photobiomodulation<br>* Patients will be treated with localized PBM with a diode laser with continuous wave (laser λ = 660 nm; power 100mW;radiant energy: 177J/cm2; 5-s exposure time per point and 0.5J of energy per point) applied directly to the surrounding oral mucosa and to the center of OLP, always by the same operator, twice a week for 4 weeks, totaling 8 session. The number of points will be variable according to the lesion size. The output power of the laser equipment will be evaluated using a power meter (Laser Check; MMOptics LTDA, São Paulo, Brazil) before treatment to confirm the effective mean power as well as the doses applied during the procedure.<br>* Other names: Low level laser therapy;Other: Placebo gel<br>* Placebo gel for 30 consecutive days to mask the treatment<br>* Other names: inative gel;|
| Active Comparator: Propionate clobetasol gel 0.05%<br>Patients will be treated with Propionate clobetasol gel 0.05% for 30 consecutive days. Laser device will be positioned over the lesion but will be switched off to mask the treatment. Patients will be instructed to apply the propionate clobetasol gel 0.05% in the entire lesion three times/days. To prevent oral candidiasis, patients will use micostatin solution (Nystatin oral suspension 100,000 USP/ml) once a day during 4 weeks. | Drug: Propionate clobetasol gel 0.05%<br>* Patients will be treated with Propionate clobetasol gel 0.05% for 30 consecutive days and with placebo laser twice a week. Patients will be instructed to apply the propionate clobetasol gel 0.05% in the entire lesion three times/days. To prevent oral candidiasis, patients will use micostatin solution (Nystatin oral suspension 100,000 USP/ml) once a day during 4 weeks.<br>* Other names: Clobetasol;Other: Placebo Photobiomodulation<br>* Laser device will be positioned over the lesion but will be switched off to mask the treatment.<br>* Other names: Laser off;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | Participants will be evaluated at baseline (Day 0) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | Participants will be evaluated after 1 week of treatment (Day 7) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | Participants will be evaluated after 2 weeks of treatment (Day 14) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | Participants will be evaluated after 3 weeks of treatment (Day 21) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | Participants will be evaluated after 4 weeks of treatment (Day 30) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | 30 days after the discontinuation of treatment (follow-up period) | 
| Assessment of Pain of OLP | The pain will be assessed by applying a Visual Analog Scale, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled 0 and the other 100, meaning no pain and terrible pain, respectively. Each patient will be instructed to mark a vertical line according to the best value that matches the intensity of pain during the evaluation. | 60 days after the discontinuation of treatment (follow-up period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | Participants will be evaluated at baseline (Day 0) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | Participants will be evaluated after 1 week of treatment (Day 7) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | Participants will be evaluated after 2 weeks of treatment (Day 14) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated scores according to Thongprasom et al | Participants will be evaluated after 3 weeks of treatment (Day 21) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | Participants will be evaluated after 4 weeks of treatment (Day 30) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | 30 days after the discontinuation of treatment (follow-up period) | 
| Assessment of clinical presentation of OLP | Clinical data will be evaluated by scores according to Thongprasom et al | 60 days after the discontinuation of treatment (follow-up period) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | Participants will be evaluated at baseline (Day 0) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | Participants will be evaluated after 1 week of treatment (Day 7) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | Participants will be evaluated after 2 weeks of treatment (Day 14) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | Participants will be evaluated after 3 weeks of treatment (Day 21) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | Participants will be evaluated after 4 weeks of treatment (Day 30) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | 30 days after the discontinuation of treatment (follow-up period) | 
| Function | The functional scores will be applied to evaluate chewing function, swallowing, fluid intake and altered sense of taste, according to Libelly et al (2006). Each function evaluated will receive the follow scores: 0 ( no difficulty) , 1 ( mild difficulty) , 2, ( moderate difficulty), 3, (severe difficulty), and 4 ( impossibility to perform certain function). | 60 days after the discontinuation of treatment (follow-up period) | 
| Clinical Resolution | The clinical resolution will be evaluated at the end of treatment (day 30) according to Corozzo et al. (1999). Complete resolution will be considered when patients present absence of symptoms and remission of atrophic/erosive lesions regardless the presence of any persisting hyperkeratotic lesions. Partial resolution will be considered when a decrease but not the complete remission of atrophic/erosive areas and symptoms were observed. No response to treatment will be considered when OLP lesions present the same clinical or worse presentation in relation to the baseline condition. | Participants will be evaluated after 4 weeks of treatment (Day 30) | 
| Recurrence rate | No recurrence will be considered when the patient presents the same clinical aspect of lesion at the end of treatment and recurrence, when the patient present new atrophic/erosive lesion at the same site during the follow-up period. | The recurrence rate will be evaluated 30 days after the discontinuation of treatment (follow-up period) | 
| Recurrence rate | No recurrence will be considered when the patient presents the same clinical aspect of lesion at the end of treatment and recurrence, when the patient present new atrophic/erosive lesion at the same site during the follow-up period. | The recurrence rate will be evaluated 60 days after the discontinuation of treatment (follow-up period) | 
| Salivary levels of IL-1β, IL-6, IL-8, IL-10 and TNFα | The samples will be centrifuged and stored at -80°C. Salivary levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated by Enzyme Linked Immune Sorbent Assay (ELISA), according to manufacturer's instructions. | Baseline (day 0) | 
| Salivary levels of IL-1β, IL-6, IL-8, IL-10 and TNFα | The samples will be centrifuged and stored at -80°C. Salivary levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated by Enzyme Linked Immune Sorbent Assay (ELISA), according to manufacturer's instructions. | After 4 weeks of treatment (Day 30) | 
| Serum levels of IL-1β, IL-6, IL-8, IL-10 and TNFα | Peripheral blood will be centrifuged at 400xg for 10 min at 4°C. Serum will be collected and stored at -80°C. Serum levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated by Enzyme Linked Immune Sorbent Assay (ELISA), according to manufacturer's instructions. | Baseline (Day 0) | 
| Serum levels of IL-1β, IL-6, IL-8, IL-10 and TNFα | Peripheral blood will be centrifuged at 400xg for 10 min at 4°C. Serum will be collected and stored at -80°C. Serum levels of IL-6, IL-10, IL-1β, INF-γ and TNF-α will be evaluated by Enzyme Linked Immune Sorbent Assay (ELISA), according to manufacturer's instructions. | After 4 weeks of treatment (Day 30) | 
| Assessment of Quality of life in OLP patients | Patient quality of life will be measured by means of the Oral Health Impact Profile (OHIP 14) | Baseline (Day 0) | 
| Assessment of Quality of life in OLP patients | Patient quality of life will be measured by means of the Oral Health Impact Profile (OHIP 14) | After 4 weeks of treatment (Day 30) | 
| Assessment of Quality of life in OLP patients | Patient quality of life will be measured by means of the Oral Health Impact Profile (OHIP 14) | 30 days after the discontinuation of treatment (follow-up period) | 
| Assessment of Quality of lifein OLP patients | Patient quality of life will be measured by means of the Oral Health Impact Profile (OHIP 14) | 60 days after the discontinuation of treatment (follow-up period) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | Baseline (Day 0) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | Participants will be evaluated after 1 week of treatment (Day 7) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | Participants will be evaluated after 2 weeks of treatment (Day 14) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | Participants will be evaluated after 3 weeks of treatment (Day 21) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | Participants will be evaluated after 4 weeks of treatment (Day 30) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | 30 days after the discontinuation of treatment (follow-up period) | 
| Anxiety and Depression | Patient anxiety and depression will be measured by means of The Hospital Anxiety and Depression Scale (HADS) | 60 days after the discontinuation of treatment (follow-up period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oral lichen planus; photobiomodulation; inflammation