Non-Thermal Plasma vs. Low-Level Laser Therapy for Recurrent Oral Ulcers: A Randomized Controlled Pilot Study

Background/Objectives: Recurrent oral ulcers (ROUs) are a common condition that significantly impacts patients’ quality of life. This pilot study was conducted to evaluate the feasibility and preliminary results of using non-thermal plasma (NTP) compared to low-level laser therapy (LLLT) and placebo to treat these ulcers. Methods: A prospective, controlled, randomised, parallel-group pilot study was conducted using a convenience sample of 50 patients with ROUs. Patients were randomly assigned (2:2:1) to one of three groups: NTP (n = 20), LLLT (n = 20), and placebo (n = 10). Feasibility and preliminary data acquisition were the primary goals. Exploratory outcomes included ulcer size reduction and safety profile. This was a single-blinded trial, where participants and outcome assessors were masked to group assignment. Ulcer size, pain perception, and time to complete healing were measured. For statistical analysis, ANOVA was used, with a p-value ≤ 0.05. Results: The groups were comparable at baseline. Exploratory results suggest that NTP demonstrated a promising trend in accelerating healing, with a mean healing time difference of 5.5 days compared to LLLT (2.5 ± 1.9 days vs. 8.0 ± 4.3 days) and 7.1 days compared to placebo (2.5 ± 1.9 days vs. 9.6 ± 5.3 days) (p < 0.001). Regarding pain, NTP provided significant and sustained relief. Patients in the NTP group were asymptomatic on day 2, unlike the LLLT and placebo groups, where pain persisted significantly (NTP VAS score at 1 h: 1.1 ± 2.1 vs. LLLT/Placebo VAS score at 1 h: 3.4 ± 2.4 and 7.3 ± 1.9, respectively) (p < 0.001). NTP was well tolerated, and no adverse events were reported. Conclusions: This pilot study suggests that NTP is a potentially safe and effective therapy for recurrent oral ulcers. Preliminary results indicate that it may accelerate healing and offer superior pain relief, warranting a large-scale clinical trial to confirm these findings.