Minor Recurrent Aphthous Ulcer Management with Hyaluronic Acid Gel in an Italian Cohort: A Double-Blind Randomized Clinical Trial

Background. Recurrent aphthous ulcer is a common mucosal disease and encompasses diverse interventions for its management of symptoms like pain and discomfort. Since new therapies keep evolving with better outcomes as compared to traditional interventions, one such therapy using hyaluronic acid has been recently explored using clinical studies based on advances in dental therapeutics. Therefore, we designed this clinical study which is double blinded and randomized using minor recurrent aphthous cases. Objective. To evaluate the efficacy of hyaluronic acid topical oral gel in the treatment of minor RAS ulcers, with regard to pain relief and reduction in ulcer size. Design. A double-blind randomized controlled clinical trial was designed to conduct an experimental research at IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan. The participants were recruited from the unit of oral maxillofacial surgery and randomly assigned to test (hyaluronic acid gel) and control groups (placebo gel). 1: 1 computer-generated random sequence was prepared, and opaque closed envelopes were used for allocation concealment. Participants and clinical investigators were blinded. The outcome measures included ulcer size (mm) and the visual analogue scale for pain and healing as a secondary outcome measure (efficacy index). Results. The mean baseline score for ulcer size for the test group was 1.85±1 and the placebo group was 1.85±1.2. At day 7, the test group was 1±1.5 and the placebo group was 2±1.5 (p<0.001). There was significant reduction in ulcer size as compared to the placebo group. In addition, there was significant improvement in pain levels (p<0.01) in the test group as compared to the control group. Conclusion. In conclusion, there was significant decrease in the size of the ulcer in the test group as compared to the placebo group. Hyaluronic acid seems to have promising effects on the ulcer size and pain relief associated with minor aphthous ulcers. Trial Registration. The protocol of this clinical trial was registered with the Clinical Trial Registry of ISRCTN with study ID ISRCTN16509838, registered 30 June 2020. It can be accessed on this URL: 10.1186/ISRCTN16509838