Evaluation of Photodynamic Therapy in Pericoronitis (pdt)

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

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).

Study Overview

• Status: Completed
• Conditions: Pericoronitis
• Intervention / Treatment: Combination product: irrigation /sterile saline; Combination product: Conventional methylene blue as photosensitizer; Combination product: Photodynamic therapy; Combination product: Methylene blue for oral use as photosensitizer

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01504-001
    • Nove de Julho University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group; 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; mechanical removal of bacteria with sterile saline; Combination product: 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; Other Names: photodynamic therapy with conventional methylene blue; Combination product: Photodynamic therapy; 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; Other Names: PDT
Active Comparator: positive control group; 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; mechanical removal of bacteria with sterile saline; Combination product: Photodynamic therapy; 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; Other Names: PDT; Combination product: 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; Other Names: photodynamic therapy with methylene blue for oral use

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Nove de Julho
• Investigators: Principal Investigator: Anna Carolina Ratto T Horliana, phd, Nove de Julho university (UNINOVE)

Publications and helpful links

General Publications

• da Silva T, da Silva FC, Gomes AO, Viana AO, Goncalves MLL, Rodrigues MFSD, Horliana ACRT, da Silva DFT, Chavantes MC, Fragoso YD, Branco LP, Motta LJ, Fernandes KPS, Mesquita-Ferrari RA, Bussadori SK. Effect of photobiomodulation treatment in the sublingual, radial artery region, and along the spinal column in individuals with multiple sclerosis: Protocol for a randomized, controlled, double-blind, clinical trial. Medicine (Baltimore). 2018 May;97(19):e0627. doi: 10.1097/MD.0000000000010627.
• Sobral APT, Godoy CLH, Fernandes KPS, Bussadori SK, Ferrari RAM, Horliana ACRT, Monken SF, Motta LJ. Photomodulation in the treatment of chronic pain in patients with temporomandibular disorder: protocol for cost-effectiveness analysis. BMJ Open. 2018 May 5;8(5):e018326. doi: 10.1136/bmjopen-2017-018326.
• da Cunha Moraes G, Vitoretti LB, de Brito AA, Alves CE, de Oliveira NCR, Dos Santos Dias A, Matos YST, Oliveira-Junior MC, Oliveira LVF, da Palma RK, Candeo LC, Lino-Dos-Santos-Franco A, Horliana ACRT, Gimenes Junior JA, Aimbire F, Vieira RP, Ligeiro-de-Oliveira AP. Low-Level Laser Therapy Reduces Lung Inflammation in an Experimental Model of Chronic Obstructive Pulmonary Disease Involving P2X7 Receptor. Oxid Med Cell Longev. 2018 Mar 4;2018:6798238. doi: 10.1155/2018/6798238. eCollection 2018.
• Okamoto CB, Motta LJ, Prates RA, da Mota ACC, Goncalves MLL, Horliana ACRT, Mesquita Ferrari RA, Fernandes KPS, Bussadori SK. Antimicrobial Photodynamic Therapy as a Co-adjuvant in Endodontic Treatment of Deciduous Teeth: Case Series. Photochem Photobiol. 2018 Jul;94(4):760-764. doi: 10.1111/php.12902. Epub 2018 Apr 30.
• Belotto RA, Chavantes MC, Tardivo JP, Euzebio Dos Santos R, Fernandes RCM, Horliana ACRT, Pavani C, Teixeira da Silva DF. Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial. BMC Womens Health. 2017 Aug 10;17(1):61. doi: 10.1186/s12905-017-0414-y.
• Schalch TO, Palmieri M, Longo PL, Braz-Silva PH, Tortamano IP, Michel-Crosato E, Mayer MPA, Jorge WA, Bussadori SK, Pavani C, Negreiros RM, Horliana ACRT. Evaluation of photodynamic therapy in pericoronitis: Protocol of randomized, controlled, double-blind study. Medicine (Baltimore). 2019 Apr;98(17):e15312. doi: 10.1097/MD.0000000000015312.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2019
• Primary Completion (Actual): April 20, 2024
• Study Completion (Actual): June 15, 2024

Study Registration Dates

• First Submitted: June 6, 2018
• First Submitted That Met QC Criteria: July 1, 2018
• First Posted (Actual): July 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 29, 2026
• Last Update Submitted That Met QC Criteria: July 28, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: laser; third molar; photodynamic therapy; pericoronitis; microbiological analysis; randomized controlled clinical study
• Additional Relevant MeSH Terms: Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Gingival Diseases; Pericoronitis; Dermatologic Agents; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Investigative Techniques; Therapeutics; Drug Therapy; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Physical Therapy Modalities; Rehabilitation; Combined Modality Therapy; Phototherapy; Heterocyclic Compounds, 3-Ring; Phenothiazines; Hydrotherapy; Radiation-Sensitizing Agents; Methylene Blue; Photosensitizing Agents; 1-phenyl-3,3-dimethyltriazene; Photochemotherapy; Therapeutic Irrigation
• Other Study ID Numbers: pericoronitis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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