Efficacy of Photobiomodulation in the Treatment and Relief of Pain in Recurrent Aphthous Stomatitis

Efficacy of Photobiomodulation in the Treatment and Relief of Pain in Recurrent Aphthous Stomatitis: a Randomized, Triple-blind, Controlled Clinical Trial

Photobiomodulation (PBM) is a therapy that stimulates repair, pain relief, and reduces inflammation. The aim of this study is to evaluate the effectiveness of a new PBM protocol in the treatment and pain relief of RAS lesions.

Study Overview

• Status: Not yet recruiting
• Conditions: Stomatitis, Aphthous; Photobiomodulation
• Intervention / Treatment: Device: Gemini laser; Other: Placebo

Detailed Description

Recurrent aphthous stomatitis (RAS) is the most common chronic ulcerative inflammatory disorder of the oral cavity, affecting approximately 20% of the general population, with no gender predilection. Its etiopathogenesis remains undefined, although factors such as local trauma and syndromes like Behcet's syndrome are implicated in predisposition. RAS manifests in three distinct clinical presentations, with the smallest being the most common, accounting for 80% of cases. Minor RAS present as round or oval ulcers, smaller than 1 cm, covered by a grayish-white pseudomembrane, commonly occurring on non-keratinized mucosa such as lips, buccal mucosa, and floor of the mouth. Photobiomodulation (PBM) is a therapy that stimulates repair, pain relief, and reduces inflammation. The aim of this study is to evaluate the effectiveness of a new PBM protocol in the treatment and pain relief of RAS lesions. The study is a randomized, triple-blind, placebo-controlled clinical trial to be conducted at the Hospital de Clinicas de Porto Alegre (HCPA) in Rio Grande do Sul, from March 2023 to December 2025. Thirty-four patients of both genders will be selected and randomly allocated into three groups: 17 patients in the PBM treatment group with 4.5J and 17 patients in the control group. Inclusion criteria are patients over 18 years old with at least one painful ulcer in the mouth. If the patient has more than one ulcer, all will be treated. Exclusion criteria include patients who have undergone previous treatment for RAS, patients with asymptomatic ulcers, and patients with any systemic condition related to RAS - for example, Behçet's Syndrome, Periodic Fever Syndrome, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis, HIV infection. The study outcome is lesion healing, and the independent variables analyzed in the study will be: pain, lesion size, and difficulty in eating, drinking, and brushing teeth due to the presence of RAS. These variables will be collected through questionnaires administered during all patient visits. Analyses will be performed using PASW 18.0 software. Initially, data distribution will be assessed using Shapiro-Wilk and Kolmogorov-Smirnov tests. If the data show normal distribution (p>0.05), the t-test will be used. If the distribution is non-normal (p<0.05), the Wilcoxon test will be employed. The significance level (p-value) will be set at 5%.

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

Contacts and Locations

• Study Contact: Name: Manoela Martins, PhD; Phone Number: 555133085011; Email: manomartins@gmail.com
• Study Contact Backup: Name: Liliana Braun; Phone Number: 5551996664438; Email: lili.wolfb@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patients over the age of 18
• Patients presenting at least one painful mouth ulcer (minor ulcer), located on the tongue, jugal mucosa or labial mucosa, starting on the same day or the day before.

Exclusion Criteria:

• Patients who have already undergone other treatment for RAS;
• Patients with asymptomatic ulcers;
• Patient must not be undergoing or have undergone any treatment for RAS;
• Patients with any systemic condition related to RAS - e.g. Behcet's Syndrome, Periodic Fever Syndrome, Pharyngitis and Cervical Adenitis, HIV infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intraoral photobiomodulation (PBM); A gallium-aluminum arsenide diode laser (Gemini® manufactured by Azena Medical, LLC, distributed by Ultradent Products, Inc.) with double wavelength 810 + 980 nm. The equipment will be programmed with 0,3W of power. The application of PBM will be carried out for at least 03 alternate days within 01 week by a trained professional. Patients who still have an ulcerated lesion on the 7th day will be assessed every 2 days until complete healing. During each irradiation, the applicator and patients will wear specific protective goggles and the instruments will be disinfected with an antiseptic solution (Chlorhexidine 2%). Points of application: Equidistant points (0.5cm) along the length of the lesion and in contact with the lesion.	Device: Gemini laser; Photobiomodulation (810 + 980 nm, 15s/point, 11.8J/cm²) to evaluate healing and pain relief in recurrent aphthous stomatitis. A 0.7mm intraoral tip will be used - spot 0.38cm2 on the extent of the lesion.
Placebo Comparator: Placebo; The application of placebo will be carried out for at least 03 alternate days within 01 week (3x within 07 days) by a trained professional. Patients who still have an ulcerated lesion on the 7th day will be assessed every 2 days until complete healing. The device will not be activated and the applicator and patients will wear specific protective goggles and the instruments will be disinfected with antiseptic solution (Chlorhexidine 2%).	Other: Placebo; Examination and follow-up until the lesion heals spontaneously. The laser will not be activated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain assessment	Pain will be assessed at all appointments using the Visual Analog Scale (VAS), which will be represented by a 10 cm straight line, where 0 corresponds to the best situation and 10 to the worst situation. The research subjects will be instructed by the evaluator to mark a point on the 10 cm line.	1 week
Assessment of ulcer size	Ulcer size will be assessed at every appointment using the tip of a millimeter-sized periodontal probe.	1 week
Functional assessment	The functional assessment will be carried out at all appointments, evaluating the patient's subjective experience of difficulty in eating, drinking and brushing their teeth due to the presence of RAS. The answers will be scored from 0 (no difficulty) to 4 (a lot of difficulty) according to the questionnaire given to the patients	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time measurement	The time of all the sessions carried out will be timed with the aid of a stopwatch, starting at the beginning of the device's activation until its deactivation. The time in seconds will be recorded on the daily evaluation form.	1 week
Saliva collection	Saliva samples will be collected from participants at two clinical assessment points. Patients must abstain from eating or drinking for 30 minutes prior. Saliva is collected unstimulated, with patients seated, eyes open, head slightly tilted down, and refraining from speaking, swallowing, or mouth opening for 5 minutes. Samples are collected in sterile Falcon tubes, immediately placed on ice, and stored at -80°C for later inflammatory marker analysis. Samples are stored in HCPA's Biobank per regulations and analyzed at CPE, then discarded post-analysis.	1 week

Collaborators and Investigators

• Sponsor: Federal University of Rio Grande do Sul
• Investigators: Study Director: Manoela Martins, PhD, Federal University of Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Stomatitis; Stomatitis, Aphthous
• Other Study ID Numbers: PMB and RAS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected IPD
• IPD Sharing Time Frame: After publication of the outcomes, for one year
• IPD Sharing Access Criteria: If formally requested and referenced by the interested researcher
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes