Evaluating the Efficacy of Royal Jelly Compared to Placebo in Improving Tinnitus in Affected Patients: Randomized controlled trial

To evaluate the efficacy of oral royal jelly in reducing tinnitus severity in patients diagnosed with subjective tinnitus.

This is a randomized, double-blind, placebo-controlled, parallel-group phase II clinical trial. A total of 60 participants (30 per group) will be enrolled. Randomization will be performed using block randomization (blocks of four) with the Rand function in Microsoft Excel.

The study will be conducted in 2025 at Al-Zahra Hospital in Isfahan and Ayatollah Kashani Hospital in Kashan. Both participants and assessors will be blinded. Syrups will be packaged identically and labeled with anonymized codes. Participants will be assessed at baseline and at 3, 6, and 12 weeks after the intervention.

Inclusion criteria: confirmed diagnosis of tinnitus by an ENT specialist, no prior history of hypersensitivity to royal jelly, absence of psychiatric disorders, and no history of hearing aid use or ototoxic medications. Exclusion criteria: unwillingness to continue participation, hypersensitivity to royal jelly, irregular medication use, concurrent use of other therapeutic strategies, and presence of acoustic neuroma or other organic auditory nerve lesions.

The intervention group will receive oral royal jelly syrup daily for 30 days. The control group will receive a placebo syrup matched in color, taste, and viscosity without the active ingredient.

Tinnitus severity measured using the Tinnitus Handicap Inventory (THI) at weeks 0, 3, 6, and 12; changes in THI score from baseline.

To ensure equal distribution of patients to the treatment and placebo groups and to maintain balance during the randomization process, a block randomization method will be used. The block size is chosen as 4, which is a multiple of the number of groups. For a block of four, the combinations AABB, ABAB, ABBA, BBAA, BABA, BAAB will be defined. The order of the blocks will be randomized using Excel software. Fifteen blocks will be required to allocate 60 patients (30 in each group).These 15 blocks are randomly selected and will be repeated as needed. Patients are then assigned sequentially based on the random order of the blocks. For example, the first four patients are assigned according to the first block allocation, the next four patients according to the second block, and so on until all 60 patients are assigned.

To ensure a double-blind study, both patients and investigators will be unaware of group assignments (royal jelly or placebo). Group A will receive 10 cc of royal jelly syrup daily for 30 days. Group B will receive 10 cc of placebo syrup following the same schedule. The placebo syrup is formulated to match the active drug in color, odor, and viscosity, and contains distilled water as the base, sucrose as a sweetener, flavoring, food coloring, and, if necessary, an approved preservative (e.g., sodium benzoate). The placebo formulation and preparation will be conducted by a specialized pharmacist in compliance with Good Manufacturing Practice (GMP) standards. The placebo syrup will be packaged and labeled in containers and boxes identical to those of the active drug and coded by an independent pharmacist. The code key will remain with the pharmacist until the study’s completion to prevent bias.

Study Protocol: Full study design and methodology document. Statistical Analysis Plan: Detailed plan of pre-specified statistical methods. Clinical Study Report: Structured summary of trial results and findings. Statistical Code: Scripts used for data analysis (e.g., SPSS, R). Data Dictionary: Descriptions of dataset variables, formats, and coding. All shared documents will exclude personally identifiable information. No individual-level data will be shared.

Access will be granted 6 months after publication of study results and will remain available for 5 years thereafter.

Qualified researchers affiliated with academic institutions, public health organizations, or regulatory agencies may submit requests.

Data and documents may be used for non-commercial, academic purposes such as secondary analysis or meta-analysis. All applicants must provide a brief proposal outlining the intended use. Data sharing is conditional on the signing of a data use agreement ensuring ethical and legal compliance.

Requests should be directed to: Dr. Afrooz Eshagh Principal Investigator Email: afroozeshaghian@med.mui.ac.ir Affiliation: Isfahan University of Medical Sciences

Applicants should submit a formal request including a research proposal, institutional affiliation, and intended analysis. The review process will take approximately 2 to 4 weeks, and decisions will be communicated via email. If approved, documents will be shared via secure cloud storage or institutional email.

The research team reserves the right to deny requests that do not meet ethical or scientific standards. No financial charge will be applied for access to documents.