Evaluation of the efficacy of C-phycocyanin oral spray compared to placebo on healing of recurrent aphthous stomatitis

To evaluate and compare the efficacy of a C-phycocyanin-containing oral spray versus placebo in reducing pain intensity, the size of the erythematous halo, and the healing time of recurrent aphthous stomatitis lesions.

A phase II, randomized, double-blind, placebo-controlled, parallel-group clinical trial with an internal pilot involving at least 30 patients. Randomization will be performed using permuted blocks with a fixed block size of two generated by Random Allocation Software 2

The study will be conducted at Tooba Clinic, on at least 30 patients with recurrent aphthous stomatitis. Participants will be randomly assigned to receive either C-phycocyanin oral spray or placebo and will be assessed over seven days. Participants and outcome assessors will remain blinded to group allocation.

Eligible participants will be aged 16–45 years, have specialist-confirmed recurrent aphthous stomatitis within 24 hours of lesion onset, and provide informed consent. Exclusion criteria include relevant systemic conditions, pregnancy, poor oral hygiene, specified medication use, concurrent aphthous ulcer treatment, and inability to complete follow-up.

Intervention group: Fifteen participants will receive an oral spray containing 8% C-phycocyanin. The product will be administered three times daily for seven days. Control group: Fifteen participants will receive a placebo spray containing the same vehicle formulation but without C-phycocyanin. The placebo will be similar to the intervention product in appearance, color, odor, taste, volume, and packaging and will be administered at the same dose, frequency, and duration.

Change in the diameter of the inflammatory halo surrounding the aphthous lesion, measured in millimeters.

Randomization will be performed at the individual level using permuted-block randomization with a fixed block size of two. The allocation sequence will be generated using Random Allocation Software 2, with a 1:1 allocation ratio between the intervention and control groups. Given the initial sample size of 30 participants, the sequence will consist of 15 blocks of two, with one participant assigned to the intervention group and one to the control group within each block. Stratified randomization will not be used in this study. The random allocation sequence will be generated by an independent individual who is not involved in participant enrollment, implementation of the intervention, or outcome assessment. To ensure allocation concealment, the intervention product and placebo will be prepared in identical containers labeled with sequential, non-identifying codes. Each participant will receive the container bearing the corresponding number according to their order of enrollment.

This study will be conducted in a double-blind manner. The participants, principal investigator, healthcare personnel involved in conducting the study, data collector, and outcome assessors will remain unaware of the assigned study product. The C-phycocyanin-containing spray and the placebo will be prepared in identical containers with equal volumes and labeled with sequential, non-identifying codes. The placebo will be made as similar as possible to the intervention product in terms of appearance, color, odor, and taste so that participants cannot identify their assigned group. The code key linking the study codes to the intervention and control groups will be held by an independent individual who has no role in participant enrollment, administration of the intervention, data collection, or outcome assessment. The dental student responsible for measuring the lesion diameter and the surrounding erythematous area and recording data on days 0, 3, 5, and 7 will also have no access to the allocation list.