Non-Thermal Plasma vs. Low-Level Laser Therapy for Recurrent Oral Ulcers

Tissue Repair of Incisions for Biopsy and Mouth Ulcers Using Non-Thermal Plasma

The goal of this clinical trial (pilot study) is to evaluate the feasibility and preliminary effectiveness of Non-Thermal Plasma (NTP) in treating pain and accelerating healing in 50 patients with Recurrent Oral Ulcers (ROUs). The main questions it aims to answer are:

Is the study design feasible for a future large-scale trial?

Does NTP show promising preliminary results in reducing ulcer size and healing time compared to standard laser therapy and placebo?

Does NTP provide superior pain relief compared to standard laser therapy and placebo?

Researchers will compare the NTP group (n=20) to the Low-Level Laser Therapy (LLLT) group (n=20) and the placebo group (n=10) to see if NTP is more effective in accelerating healing and reducing pain.

Participants will:

Be randomly assigned to one of three treatment groups (NTP, LLLT, or placebo).

Receive their assigned treatment for their oral ulcers.

Undergo measurements of their ulcer size, report their pain perception using a visual analog scale (VAS), and have their time to complete healing recorded.

Study Overview

• Status: Completed
• Conditions: Stomatitis; Aphthous Ulcer
• Intervention / Treatment: Device: Non-Thermal Plasma (NTP); Device: Low-Level Laser Therapy (LLLT); Procedure: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • State of Mexico
    • Ocoyoacac, State of Mexico, Mexico, 52750
      • Plasma Physics Laboratory, National Institute of Nuclear Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 years of age
• Patients of both sexes
• Patients with recurrent oral ulcers (ROU)
• Patients without oral soft tissue diseases
• Patients with at least one recurrent ulcer

Exclusion Criteria:

• Patients under 18 years of age
• Patients with ROU of more than 48 hours' duration
• Patients with gingivitis and/or periodontitis
• Patients undergoing maxillofacial orthopedic and/or orthodontic treatment
• Patients with ill-fitting dentures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with Non-Thermal Plasma (NTP)	Device: Non-Thermal Plasma (NTP); Topical application of cold (non-thermal) plasma to the oral ulcer using a plasma generator, with specific time and power parameters.
Active Comparator: Treatment with Low-Level Laser Therapy (LLLT)	Device: Low-Level Laser Therapy (LLLT); Topical application of low-power laser radiation (low-level laser therapy) to the oral ulcer, following a standardized time and wavelength protocol.
Placebo Comparator: Treatment with Placebo	Procedure: Placebo; Simulation of the application procedure (e.g., turning on a device without active plasma or laser emission, or application with the device turned off) to mask group assignment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Patient recruitment rate	Proportion of the target sample size successfully recruited within the recruitment period. Unit of Measure: Percentage (%)	From the start of enrollment to the end of the recruitment period, an average of 1 month.
Feasibility - Patient adherence to the intervention protocol	Proportion of prescribed treatment sessions completed by enrolled participants. Unit of Measure: Percentage (%)	From the first intervention to the last planned session for each participant.
Preliminary efficacy - Time to complete ulcer re-epithelialization	Number of days required for the ulcer to achieve complete re-epithelialization (visual absence of ulcer crater) confirmed by clinical examination. Unit of Measure: Days	From baseline (day of intervention) until complete healing, assessed daily up to 30 days.
Preliminary efficacy - Change in pain intensity measured by a Visual Analogue Scale (VAS)	The Visual Analogue Scale (VAS) is a 0 to 10 scale, where "0" represents "no pain" and "10" represents "the worst pain". A higher score indicates worse pain. The change score (post-intervention minus baseline) will be calculated. Unit of Measure: 0-10 VAS	From baseline (pre-intervention) to 48 hours post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ulcer surface area	Ulcer size will be measured by calculating the surface area from perpendicular diameters (length and width in millimeters) using a standard periodontal probe or digital caliper. Unit of Measure: Square millimeters (mm²)	From baseline (day of intervention) to days 1, 2, 3, 5, and 7 post-intervention
Safety - Incidence and severity of treatment-related adverse events	All adverse events and local reactions (e.g., erythema, edema, pain exacerbation) will be recorded and graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or a similar standardized scale. The relationship to the intervention will be assessed. Unit of Measure: Number of participants with adverse events, and severity grade.	From the first intervention until the end of the follow-up period (up to 7 days post-intervention)
Cumulative use of rescue analgesic medication	The total amount of rescue analgesic medication (e.g., acetaminophen/paracetamol) consumed by each participant, recorded in a daily diary. Unit of Measure: Milligrams (mg) of medication	From baseline to complete healing or up to 30 days, whichever comes first

Collaborators and Investigators

• Sponsor: National Institute of Nuclear Research - Mexico
• Collaborators: Autonomous University of the State of Mexico

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2019
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Actual): January 7, 2026

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pain; Placebo; Healing; Low-Level Laser Therapy; Oral Ulcers; Non-Thermal Plasma
• Additional Relevant MeSH Terms: Neurologic Manifestations; Mouth Diseases; Stomatognathic Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Stomatitis; Oral Ulcer; Stomatitis, Aphthous; Therapeutics; Laser Therapy; Phototherapy; Low-Level Light Therapy
• Other Study ID Numbers: CEICIEAO-2018-001

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