Evaluation of Photodynamic Therapy in Pericoronitis

Study Overview
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Brief Summary
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In order to reduce the chances of systemic dissemination of the infection and the use of antibiotics, it is mandatory to test effective treatments in the initial phase of pericoronitis aiming to avoid the evolution of the infectious disease. Photodynamic therapy (PDT) is an interesting alternative because it is an effective antimicrobial treatment that is easy to perform and does not cause bacterial resistance. The aim of this study is to evaluate the effectiveness of photodynamic therapy (PDT) with methylene blue in a surfactant vehicle in pericoronitis in the initial phase in healthy youngsters through microbiological, clinical and immunoregulatory response. The impact of pericoronitis on oral health-related quality of life (OHRQoL) of these patients will also be evaluated. 34 healthy young patients with pericoronitis will be evaluated. Microbiological analysis will be performed by RT-PCR for the bacterium Tannarella forsithia (Tf).Gingival crevicular fluid will be collected to evaluate TNF-α, IL1-β, IL-6 and IL-8 and IL-10 by the Luminex assay. The variables will be pain (visual analogue scale), edema, trismus (digital caliper) and oral health-related quality of life (OHRQoL) will also be evaluated through the OHIP-14 questionnaire. The variables will be assessed at T1 (baseline)and T2 (4th day after PDT).

Detailed Description
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Pericoronitis is a common disease in the eruption phase of third molars, sometimes debilitating, with an impact on the quality of life. The most indicated treatment in the initial phase is the irrigation for cleanliness of the region. If there is no adequate treatment at this stage, there may be evolution of the infectious condition so that antibiotic therapy is indicated. In order to reduce the chances of systemic dissemination of the infection and the use of antibiotics, it is mandatory to test effective treatments in the initial phase of pericoronitis aiming to avoid the evolution of the infectious disease. Photodynamic therapy (PDT) is an interesting alternative because it is an effective antimicrobial treatment that is easy to perform and does not cause bacterial resistance. The methylene blue used in PDT has been studied in a surfactant vehicle, which optimizes the formation of monomers increasing its antimicrobial action. Objective: The aim of this study is to evaluate the effectiveness of photodynamic therapy (PDT) with methylene blue in an surfactant vehicle in pericoronitis in the initial phase in healthy youngsters through microbiological, clinical and immunoregulatory response. The impact of pericoronitis on oral health-related quality of life (OHRQoL) of these patients will also be evaluated. Method: In this randomized, controlled, double-blind clinical bioequivalence trial, 34 healthy young patients with pericoronitis will be evaluated. Patients will be randomized into the positive control group (G1) (n = 17): irrigation with sterile saline and photodynamic therapy (conventional methylene blue at 0.005% concentration and irradiation with low intensity laser λ = 660 nm, 9J per point and radiant exposure of 318 J / cm2), and the experimental group (G2) (n = 17): treatment identical to G1, however methylene blue will be delivered in a new formulation for oral use. Microbiological analysis will be performed by RT-PCR for the bacterium Tannerella forsithia (Tf).Non-stimulated saliva will be collected to evaluate TNF-α, IL1-β, IL-6 and IL-8 and IL-10 by Luminex assay. The pain (visual analogue scale), edema and buccal opening (digital caliper) and oral health-related quality of life (OHRQoL) will also be evaluated through the OHIP-14 questionnaire. The variables will be evaluated in T1 (baseline), and T2 (4th day after PDT).

Official Title
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Evaluation of Photodynamic Therapy in Pericoronitis: a Randomized, Controlled, Double-blind Clinical Study

Conditions
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Pericoronitis

Intervention / Treatment
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* Combination Product: irrigation /sterile saline
* Combination Product: Conventional methylene blue as photosensitizer
* Combination Product: Methylene blue for oral use as photosensitizer
* Combination Product: Photodynamic therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should have at least one lower third partially visible molar in the oral cavity to be examined (Lower third molar erupted or partially erupted, with pericoronitis) All patients, regardless of age, gender, cultural level or socioeconomic status may participate in the research. Exclusion Criteria: patients allergic to methylene blue pregnant or breastfeeding women, those with local infection (e.g., pericoronitis or periodontal abscess) presence of purulent exudate, those with fever (temperature above 37.8 C) Patients who have used anti-inflammatory drugs or antibiotic medications in the last three months will also be excluded.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Endpoint Classification: Bio-equivalence Study Enrollment: 34 [Anticipated]
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>G1 - 17 patients Photodynamic therapy with convention methylene blue as photosesintizer irrigation /sterile saline Conventional methylene blue as photosensitizer -Irrigation with 0,04mL of photosensitizer (0,005%) inside the gingival sulcus around the third molar with pericoronarite for 3 minutes Photodynamic therapy -Device irradiation with low intensity laser λ = 660 nm, 9J per point and radiant 90 seconds | Combination Product: irrigation /sterile saline<br>* mechanical removal of bacteria with sterile saline<br>Combination Product: Conventional methylene blue as photosensitizer<br>* Irrigation with 0,04mL of photosensitizer (0,005%) inside the gingival sulcus around the third molar with pericoronarite for 3 minutes<br>* Other names: photodynamic therapy with conventional methylene blue;Combination Product: Photodynamic therapy<br>* Red laser for photodynamic therapy (Therapy XT,DMC,Sao Carlos,Sao Paulo,Brazil) Device irradiation with low intensity laser λ = 660 nm, 9J per point and radiant 90 seconds<br>* Other names: PDT;|
| Active Comparator: positive control group<br>G2 - 17 patients Photodynamic therapy with oral formula of methylene blue as photosesintizer, treatment identical to G1, however methylene blue will be delivered in a new formulation for oral use (patent aplicattion INPI BR1020170253902) irrigation /sterile saline Photodynamic therapy -Methylene blue for oral use as photosensitizer-Irrigation with 0,04mL of photosensitizer (0,005%) inside the gingival sulcus around the third molar with pericoronarite for 3 minutes Device irradiation with low intensity laser λ = 660 nm, 9J per point and radiant 90 seconds | Combination Product: irrigation /sterile saline<br>* mechanical removal of bacteria with sterile saline<br>Combination Product: Methylene blue for oral use as photosensitizer<br>* Irrigation with 0,04mL of photosensitizer(0,005%) inside the gingival sulcus around the third molar with pericoronarite for 3 minutes<br>* Other names: photodynamic therapy with methylene blue for oral use;Combination Product: Photodynamic therapy<br>* Red laser for photodynamic therapy (Therapy XT,DMC,Sao Carlos,Sao Paulo,Brazil) Device irradiation with low intensity laser λ = 660 nm, 9J per point and radiant 90 seconds<br>* Other names: PDT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological analysis will be performed by RT-PCR for the bacterium Tannarella forsithia (Tf) | Sample collection for microbiological analysis Biofilm collection will be done at two points of the vestibular gingival sulcus of the lower third molar using minifive curettes. The collected material will be maintained in TE (Tris-EDTA), conditioned in microtubes and later transported for laboratory analysis in the Microbiology Laboratory of ICB-USP Prof. Marcia Mayer | change from baseline, immediately after PDT and on fourth day after PDT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Profile of cytokines Gingival crevicular fluid will be collected | gingival crevicular fluid sample will be obtained. Samples will be kept in ice cube tubes. The saliva will be centrifuged at 4000 rpm for 10 minutes at -4 ° C and stored at -80 ° C for further analysis. Determination of plasma levels of the inflammatory markers TNF-α, IL1-β, IL-6 and IL-8 by Luminex assay | change from baseline and on fourth day after PDT | 
| pain assessed by Vas | The pain will be assessed by applying a VAS visual analogic 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 with the point that best matches the intensity of pain during the evaluation. Instructions on marking will always be given to the patient by the same operator | change from baseline, immediately after PDT and on fourth day after PDT | 
| edema assessed by measuring facial distance | The criteria for the determination of edema will follow pre-established measurements: (I) Corner of the eye to angle of the jaw (II) Tragus to the labial commissure and (III) Tragus to pogonion as described by Ustun, 2003. Edema will be the sum of three pre-established facial measures (using a digital caliper). | change from baseline, immediately after PDT and on fourth day after PDT | 
| trismus assessed by measuring bucal opening | For evaluation of the presence of trismus the inter-incisor measurement (distance between the incisal edge of the maxillary central incisor and lower) will be used with a digital caliper (Mitutoyo Digimatic Caliper model, Japan). | change from baseline, immediately after PDT and on fourth day after PDT | 
| OHRQoL assessed by ohip-14 | Oral health related quality of life: using OHIP-14 questionnaire we will assess the impact on HRQOL will be measured. This instrument consists of 14 items arranged in 7 factors: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability, and handicap. The answers are given in a 5-point Likert scale (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = always). | change from baseline, immediately after PDT and on fourth day after PDT | 
| position and classification of third molar | Position and classification of the lower third molars: the position of the teeth will be assessed by panoramic radiography, according to the classification of Pell and Gregory and Winter (1942), performed only by an evaluator, following the criteria of imaginary lines as proposed by Almendros-Marques , (2008). | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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third molar, pericoronitis, photodynamic therapy, microbiological analysis, laser, randomized controlled clinical study