Development and clinical evaluation of a Myrtus communis mucoadhesive buccal tablet for minor recurrent aphthous stomatitis: a randomized controlled trial

Comparison of the efficacy and safety of a Myrtus communis mucoadhesive buccal tablet versus 2% amitriptyline gel and 0.01% dexamethasone mouthwash in treating minor recurrent aphthous stomatitis.

In this single-center, randomized, active-controlled phase 2/3 trial, 81 patients were allocated to three parallel arms (27/28/26) using computer-generated blocks of 6 with sealed, opaque allocation concealment. Outcome assessors and the statistician were blinded; participants were not, due to different dosage forms (tablet, gel, mouthwash). No placebo group was included.

Single-center study at Kerman University of Medical Sciences. Block randomization; allocation concealment with sealed envelopes. Outcome assessor and statistician blinded; participants not blinded. No placebo. Treatment for 10 days; assessments on days 0, 1, 4, 6, and 10.

Inclusion criteria: Age 18–65 years; active minor aphthous lesion; ≥3 recurrent aphthous stomatitis episodes per year; written informed consent. Exclusion criteria: Hypersensitivity to study components; acute infectious disease; pregnancy or lactation; systemic corticosteroids or immunosuppressants within 3 months; oral lesions due to systemic conditions; systemic antibiotics within 14 days; topical oral ulcer treatment within 72 hours; active cancer; orthodontic appliances or removable partial dentures; participation in another clinical trial; inability or unwillingness to comply with the protocol.

Three parallel active-treatment groups (all three times daily for 10 days; no eating, drinking, or rinsing for 30 minutes afterward): Group A: Topical 2% amitriptyline gel Group B: Myrtus communis mucoadhesive buccal tablet Group C: 0.01% dexamethasone mouthwash

Change in aphthous ulcer diameter (mm) from baseline to day 10

This study used block randomization with a block size of 6. The unit of randomization was individual patients. The random sequence was generated in a 1:1:1 ratio for the three groups (2% amitriptyline gel, Myrtus communis mucoadhesive tablet, and dexamethasone mouthwash) by an independent statistician using computer-generated random numbers. No stratification was applied. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes, so allocation was revealed only after patient enrollment. Treatments were dispensed in identical coded containers. Outcome assessors and the statistician were blinded to group assignment. Complete participant blinding was not feasible due to the distinct physical forms of the interventions (tablet, gel, mouthwash). No quasi-random methods (e.g., day of visit, odd/even) were used.

De-identified individual participant data (without any identifying information) and the study protocol are available upon reasonable request from the corresponding author. Access will be granted to researchers with a clearly defined and approved research objective. The raw data include demographic information, ulcer diameter, pain scores, erythema, and exudate scores at different time points. No sensitive or personally identifiable data will be publicly released.

Access will begin 6 months after publication of the study results and will remain available for 5 years.

Researchers affiliated with academic and scientific institutions are permitted to access the de-identified data and study documents after submitting a written request with a clearly defined research objective and obtaining approval from the corresponding author and the ethics committee. Access for commercial or industrial purposes is not permitted without a separate agreement.

Data and documents may be used solely for academic and scientific research purposes, including re-analysis, meta-analysis, verification of results, and secondary research related to minor recurrent aphthous stomatitis and topical therapies. Commercial, legal, or patent-related use is not permitted.

Requests for access to de-identified data and study documents should be directed primarily to the corresponding author.

The applicant must complete the following steps: Submit a written request Ethics committee approval Sign a data sharing agreement Data preparation Data/document delivery Estimated total process time: 6 to 8 weeks from initial request submission to data receipt.