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IRCT20260912071020N1 IRCT 2026-09-17 Kerman University of Medical Sciences Evaluation of the Effect of Myrtus communis Mucoadhesive Buccal Tablet in the Treatment of Recurrent Aphthous Stomatitis Development and clinical evaluation of a Myrtus communis mucoadhesive buccal tablet for minor recurrent aphthous stomatitis: a randomized controlled trial 2026-04-04 anticipated 75 Complete https://irct.ir/trial/93208 interventional Randomization: Randomized, Blinding: Not blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: This study had a two-phase design: Phase 1 involved the development and physicochemical characterization of a mucoadhesive buccal tablet containing Myrtus communis essential oil; Phase 2 was a randomized, parallel-group, active-controlled, three-arm clinical trial. In the clinical phase, patients were allocated in a 1:1:1 ratio to receive either 2% amitriptyline gel, the Myrtus communis mucoadhesive tablet, or 0.01% dexamethasone mouthwash. The study had no placebo group and used active comparators. Participant blinding was not feasible because of the distinct dosage forms (tablet, gel, and mouthwash); however, outcome assessors and the statistician were blinded. Randomization was performed using block randomization with a block size of 6, and allocation concealment was achieved with sequentially numbered, opaque, sealed envelopes. The primary outcome was change in ulcer diameter, and secondary outcomes included pain intensity (VAS), erythema, and exudate, assessed at baseline and on days 1, 4, 6, and 10. Due to baseline imbalance in erythema and exudate scores among the groups, analyses were conducted using mixed-effects models adjusted for baseline values. The study was single-center and limited to patients with minor recurrent aphthous stomatitis (RAS), Randomization description: 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. 3 Minor recurrent aphthous stomatitis (MiRAS). Intervention 1: Intervention group: Dexamethasone sodium phosphate mouthwash was prepared at a concentration of 0.01% w/v (equivalent to 0.5 mg per 5 mL). The solution was prepared by dissolving dexamethasone sodium phosphate with sodium monophosphate and sodium diphosphate in distilled water. Patients rinsed with 5 mL of the mouthwash for 30 seconds and then spat it out, three times daily for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. Intervention 2: Intervention group: Topical amitriptyline hydrochloride gel was prepared at a concentration of 2% w/w. The gel was formulated using hydroxypropyl methylcellulose as the gelling agent and preserved with methylparaben (0.1%) and propylparaben (0.01%). Patients applied a small amount of the gel sufficient to cover the ulcer three times daily for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. Intervention 3: Intervention group: A mucoadhesive buccal tablet containing 25 mg of Myrtus communis essential oil (equivalent to 12.5% w/w) per 200 mg tablet. The essential oil was extracted by hydrodistillation from dried, authenticated Myrtus communis leaves. Each tablet was formulated with polymeric excipients including carbomer, alginate, microcrystalline cellulose (Avicel), polyethylene glycol 6000, and magnesium stearate (Formulation F2). Patients placed one tablet directly onto the ulcer three times daily (every 8 hours), allowing it to adhere and dissolve in situ, for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. Yes - There is a plan to make this available What will be shared: 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. When: Access will begin 6 months after publication of the study results and will remain available for 5 years. To whom: 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. Conditions: 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. Where to obtain: Requests for access to de-identified data and study documents should be directed primarily to the corresponding author. How to obtain: 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. Comments:
public Morteza Barkam
Kerman, Hooshang Moradi St., Alley 11
Kerman Iran (Islamic Republic of) 7616911319 0098343621856501 mortezabarkam@outlook.com Kerman University of Medical Sciences scientific Morteza Barkam
Kerman, Hooshang Moradi St., Alley 11
Kerman Iran (Islamic Republic of) 7616911319 009834621856501 mortezabarkam@outlook.com Kerman University of Medical Sciences Iran (Islamic Republic of) Age between 18 and 65 years Presence of an active minor recurrent aphthous stomatitis lesion on non-keratinized oral mucosa (labial or buccal mucosa) History of at least three recurrent aphthous stomatitis episodes per year Provision of written informed consent 18 years 65 years Both Known hypersensitivity to study components Acute infectious disease Pregnancy or lactation Systemic use of corticosteroids or immunosuppressants within the past 3 months Oral lesions secondary to systemic conditions (e.g., ulcerative colitis, Crohn's disease, Behçet's syndrome, or severe anemia) Systemic antibiotic use within the past 14 days Topical oral ulcer treatment within the past 72 hours Diagnosis of active cancer Orthodontic appliances or removable partial dentures Concurrent participation in another clinical trial Inability or unwillingness to comply with study protocols K12.0 Recurrent oral aphthae Treatment - Drugs Treatment - Drugs Treatment - Drugs Intervention group: Dexamethasone sodium phosphate mouthwash was prepared at a concentration of 0.01% w/v (equivalent to 0.5 mg per 5 mL). The solution was prepared by dissolving dexamethasone sodium phosphate with sodium monophosphate and sodium diphosphate in distilled water. Patients rinsed with 5 mL of the mouthwash for 30 seconds and then spat it out, three times daily for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. Intervention group: Topical amitriptyline hydrochloride gel was prepared at a concentration of 2% w/w. The gel was formulated using hydroxypropyl methylcellulose as the gelling agent and preserved with methylparaben (0.1%) and propylparaben (0.01%). Patients applied a small amount of the gel sufficient to cover the ulcer three times daily for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. Intervention group: A mucoadhesive buccal tablet containing 25 mg of Myrtus communis essential oil (equivalent to 12.5% w/w) per 200 mg tablet. The essential oil was extracted by hydrodistillation from dried, authenticated Myrtus communis leaves. Each tablet was formulated with polymeric excipients including carbomer, alginate, microcrystalline cellulose (Avicel), polyethylene glycol 6000, and magnesium stearate (Formulation F2). Patients placed one tablet directly onto the ulcer three times daily (every 8 hours), allowing it to adhere and dissolve in situ, for 10 consecutive days. Participants were advised to refrain from eating, drinking, or rinsing for 30 minutes after application. The primary outcome variable was the change in minor recurrent aphthous ulcer diameter (mm) from baseline (day 0) to day 10. Ulcer diameter was measured using a calibrated UNC-15 periodontal probe; the largest and perpendicular diameters were recorded, and their mean was used as the ulcer diameter. Measurements were performed on days 0, 1, 4, 6, and 10. The primary endpoint was the difference in ulcer diameter at day 10 compared with day 0. The sample size was calculated to detect a 2.0 mm difference in ulcer diameter with SD = 2.5 mm, 80% power, and α = 0.05. Timepoint: Ulcer diameter was measured at baseline (Day 0, before intervention) and on Days 1, 4, 6, and 10 after treatment initiation. The primary outcome was the change in ulcer diameter from Day 0 to Day 10. Method of measurement: Ulcer diameter was measured using a calibrated UNC-15 periodontal probe. The largest diameter of the ulcer and its perpendicular diameter were recorded, and the mean of the two was considered as the ulcer diameter. Oral pain intensity experienced by the patient was measured using a Visual Analogue Scale from 0 to 10, where 0 indicated no pain and 10 indicated the worst imaginable pain. Timepoint: At baseline (Day 0, before intervention) and on Days 1, 4, 6, and 10 after treatment initiation. Method of measurement: Visual Analogue Scale with a range of 0 to 10; patient-reported. The degree of redness (erythema) of the oral mucosa surrounding the aphthous ulcer was assessed by a clinician using a 4-point scale: 0 = none (normal mucosal color), 1 = mild (faint or light pink halo), 2 = moderate (distinct red halo), 3 = severe (intense, deep red or violaceous halo). Timepoint: Erythema score was measured at baseline (Day 0, before intervention) and on Days 1, 4, 6, and 10 after treatment initiation. Method of measurement: Erythema score was measured using a standardized 4-point scale through clinical examination by the assessing clinician. The amount of fibrinous coating (exudate) on the ulcer base was assessed by a clinician using a 4-point scale: 0 = none (clean ulcer base), 1 = mild (thin, patchy white/yellow layer covering less than 25% of the ulcer base), 2 = moderate (moderate fibrinous layer covering 25% to 75% of the ulcer base), 3 = severe (thick, continuous layer covering more than 75% of the ulcer base). Timepoint: Exudate score was measured at baseline (Day 0, before intervention) and on Days 1, 4, 6, and 10 after treatment initiation. Method of measurement: Exudate score was measured using a standardized 4-point scale through clinical examination by the assessing clinician. Kerman University of Medical Sciences Approved 2026-08-29 Ethics committee of Kerman University of Medical Sciences Kerman University of Medical Sciences Campus, Beginning of Haft Bagh Alavi Road, Kerman Kerman Kerman Iran (Islamic Republic of)