Materials and methods
MAY
This study was a prospective, parallel-arm, 4-arm, multicenter, triple-blind randomized, placebo-controlled clinical trial performed from 2020 to 2022 on 729 participants in a private clinic and a hospital in Tehran, Iran with a treatment/placebo allocation ratio of about 1:2. All participants were briefed completely before the study and signed written informed consent. The ethics of this study was approved by two independent bodies: the research committee of the Islamic Azad University (ethics code: IR.IAU.DENTAL.REC.1399.301, date: 07/03/2021) as well as an international organization responsible for examining, approving, and registering randomized clinical trials (IRCT.ir) following the Helsinki declaration (RCT code: IRCT20210401050804N1, date: 26/04/2021). After the registration of the study, the sample size was augmented to 729 from an original size of 96 individuals, per more conservative criteria to ensure high power, reliability, and generalizability (given that the treatment was harmless; detailed below). The experiments began on 25/04/2021 and continued until May 2022.