A Randomized Controlled Trial to Evaluate the Effect of a Topical Cream Containing Achillea millefolium and Tanacetum Oils on Musculoskeletal Pain in Adults: Comparison with Placebo

Evaluation of the effect of a cream containing Achillea millefolium (yarrow) and Tanacetum (tansy) oils on reducing musculoskeletal pain, improving motor function, and assessing its safety and anti-inflammatory effects.

This study is a phase2–3randomized, double-blind, parallel-group clinical trial conducted on100patients with mild to moderate musculoskeletal pain. Participants will be randomly assigned to 2 groups: Treatment and, Placebo groups.

This study is conducted in the clinic of a physical medicine specialist and follows a randomized design. Participants are instructed to apply the topical cream once or twice daily for a duration of one to two months, depending on pain severity. The participants, outcome assessor, and data analyst are all blinded to the group assignments.

Inclusion: Stable mild to moderate musculoskeletal pain, written informed consent, no recent use of analgesic drugs or supplements, ability to comply with study procedures, no allergy to herbs or topical products. Exclusion: Allergy to herbs or essential oils, skin disease at the cream application site, recent use of analgesic drugs, systemic disease affecting pain, pregnancy or breastfeeding, use of drugs affecting pain or mood, inability to comply with the study protocol, recent participation in another clinical trial.

1. Treatment group: recipients of a topical cream containing therapeutic oils of Achillea millefolium and Tanacetum. 2. Placebo group: recipients of a cream without active herbal ingredients, with similar appearance and texture.

pain intensity (measured by VAS), motor function (assessed using standard questionnaires), patient satisfaction with treatment, and the occurrence of possible side effects

In this study, randomization will be performed using permuted block randomization with variable block sizes (4 and 6) to maintain balance in the number of participants allocated to the two groups: the intervention group (topical cream containing Achillea millefolium and Melissa officinalis oils) and the control group (placebo cream). Unit of randomization: Individual (each participant will be independently assigned to one of the two groups). Stratification: Randomization will be stratified by sex (male/female) and pain status (acute/chronic) to ensure balanced distribution of these variables between groups. Random sequence generation tool: The allocation sequence will be generated by an independent statistician using statistical software (e.g., R or Stata). Within each stratum, blocks of variable sizes will be randomly arranged. Sequence generation and storage: The final allocation sequence will be stored in an encrypted file and managed by a person not involved in participant recruitment or outcome assessment (statistician or study pharmacist). Allocation concealment: To prevent selection bias, Sequentially Numbered, Opaque, Sealed Envelopes (SNOSE) or a centralized randomization system will be used. The recruiter will open the next envelope or obtain the allocation code from the system only after confirming eligibility of the participant. Blinding: The intervention and placebo creams will be identical in appearance, packaging, labeling, and texture, and will only be distinguished by code. Thus, participants, clinical investigators, and outcome assessors will remain blinded to group allocation. Code breaking (Unblinding): Unblinding will only be permissible in case of a medical emergency and must be fully documented. After data collection is completed and the database is locked, codes will be released by the independent statistician. Quasi-randomization: No quasi-random methods (such as allocation by date of birth or order of recruitment) will be used in this study.

This study will be conducted as a double-blind randomized controlled trial. Both participants and investigators responsible for administering the intervention and assessing outcomes will be blinded to group allocation. The creams for intervention and placebo will be identical in appearance, texture, and packaging to maintain blinding. Data analysts will also be blinded during data analysis to prevent bias. Allocation concealment will be ensured using sealed, opaque envelopes. The Data Safety Monitoring Board, if involved, will have access to unblinded data only when necessary for safety assessments

The study data include de-identified participant information regarding pain intensity (based on the VAS scale), motor function (responses to standardized questionnaires), and other clinical outcome-related data. These data were collected to evaluate the efficacy of the herbal cream in reducing musculoskeletal pain and improving motor function, and will be shared as structured electronic files.

The data will be available from the time of study publication and will remain accessible to researchers for up to 5 years thereafter. Bahar Darou Mehr Company may also request the publication of an article based on the study results.

Researchers affiliated with academic, research, and other recognized scientific institutions who submit a formal request will be granted access to the data and documents. Access for individuals from industry or commercial sectors will be considered only upon ethical and scientific review and approval.

The data and documents may only be used for research, educational, or secondary analysis purposes. Usage must comply with research ethics principles, participant confidentiality, and data protection regulations. Any commercial use or public dissemination without written permission from the research team is strictly prohibited. Applicants must submit a research proposal and sign a data use agreement ensuring responsible and restricted use.

Applicants can contact the principal investigator via email or phone to request access to the study data or documents.

After receiving the request via email or phone, the principal investigator will review the research purpose and the applicant’s affiliation. If the request is deemed appropriate, a data-sharing agreement will be signed. Upon completion of the agreement, the requested de-identified data or documents will be provided within 2 to 4 weeks.