This study is a prospective, two-arm, multicenter, randomized controlled trial. A total of 180 patients with chronic migraine will be allocated in a 2:1 ratio to a treatment or control group. The trial will consist of 6 weeks of acupuncture or sham acupuncture treatment, followed by an 8-week follow-up period. The study centers are the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Yantai Traditional Chinese Medicine Hospital, and Shandong Provincial Third Hospital. Patient recruitment has been ongoing since May 2024, and the timeline for all patients to complete the assessment is shown in Figure 1. The study flowchart is shown in Figure 2. The protocol adheres to the principles of the Declaration of Helsinki and will be reported in accordance with the Standard Protocol Items: Recommendations for Interventional Trials guidelines (Supplementary File S1).

Participants are being recruited from individuals diagnosed with chronic migraine according to the criteria established by the International Headache Society (IHS). Recruitment is taking place across the three previously designated medical centers. Recruitment advertisements have been published through posters and social media to attract potential participants. Clinicians will determine in person whether patients meet the strict inclusion and exclusion criteria for the study. Patients who meet the criteria and volunteer to participate will sign a written informed consent form before the start of the study. They will be fully informed of the study details, including procedures, potential benefits, and risks, with the exception of specific information regarding the needling site. Participants will be free to withdraw from the study at any time without any negative impact on their future medical treatment. In addition, measures will be taken to ensure the confidentiality of participants’ data.

Participants in this study are strictly being screened according to the diagnostic, inclusion, and exclusion criteria. A random number list was generated using SPSS 25.0 software and converted into random number cards. Participants will be randomly allocated into two groups in a 2:1 ratio: 120 participants in the acupuncture treatment group and 60 of them in the control group. The allocation process will be kept confidential using sealed, opaque envelopes. The random number cards will be placed inside these envelopes, which will be numbered sequentially. The envelopes will be opened in the order in which the participants enter the study, and the participants will be assigned to their respective groups based on the number inside the envelope, ensuring a 2:1 allocation ratio between the groups.

Due to the specific nature of acupuncture, it is not feasible to blind practitioners. Therefore, blinding will be implemented for the participants, evaluators, and statisticians. Practitioners adhere to strict confidentiality protocols to avoid disclosing group allocation to the participants and evaluators. Evaluators are responsible for collecting and analyzing the data unrelated to the treatment process and are not exposed to any information about group allocation throughout the study. Statisticians are solely responsible for data analysis and are not involved in the treatment process, thereby ensuring the objectivity and impartiality of the results.

To evaluate participant blinding integrity, Bang’s Blinding Index (BI) will be calculated at the completion of the treatment phase (17). After the final treatment session, the participants will be asked to guess their group allocation (real acupuncture, sham acupuncture, or unsure) and to rate their confidence in this guess.

The Credibility/Expectancy Questionnaire (CEQ) (18) will be administered after the first treatment session. Group differences in the CEQ scores will be examined to verify that expectancy was balanced between the groups.

After the completion of statistical analysis, the unblinding procedure will be initiated. Researchers responsible for unblinding will disclose group information to the data analysts as necessary to finalize comparisons and interpret the study results.

The intervention measures will be in accordance with the Uniform Standard for Trial Reporting (19) and the Standard for Reporting Interventions in Clinical Trials of Acupuncture and Moxibustion (20).

To maximize participant safety and proactively minimize risks, all participants will undergo a careful anamnesis and baseline assessment before the first treatment. During the study, the participants undergoing acupuncture treatment may experience adverse events (AEs), including but not limited to pain, subcutaneous congestion, hematoma, local infection, and, in rare cases, severe events such as syncope. Safety assessments will encompass vital sign measurements (blood pressure, heart rate, respiration rate, body temperature) and physical examinations. These vital sign measurements will be performed before the start of the protocol (at baseline assessment) and at key points during the treatment period (before and after treatment). Their primary purpose will be to monitor participant safety and ensure early detection of potential adverse reactions, rather than to serve as clinical indicators of acupuncture efficacy. Detailed documentation of AEs will include the time of occurrence, duration, classification, severity, remedial actions, and final resolution. Participants will be instructed to report any abnormal reactions or discomfort, which will be carefully documented, including the time, severity, and potential causes. Regardless of their relationship to the treatment, all AEs will be promptly and appropriately managed, recorded in the Case Report Forms (CRFs), and reported to the study director and the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine.

Mild and moderate AEs will be managed symptomatically and monitored, while severe AEs, such as death, life-threatening disability, or hospitalization, will receive emergency treatment and will be reported to the Research Ethics Committee within 24 h, which will provide guidance on whether the trial should be terminated. To minimize the risk of severe adverse events, all practitioners have received specific training on recognizing and managing autonomic adverse responses to acupuncture, consistent with safety guidelines outlined in recent systematic reviews (29, 30).

The sample size was calculated using the PASS 11.0 software. Based on published literature (12), the number of migraine attack days was estimated as the outcome indicator for long-term efficacy observation. The number of migraine attack days in the acupuncture treatment group was reduced by 3.9 ± 3.0 days, while the number of migraine attack days in the sham acupuncture control group was reduced by 2.2 ± 3.2 days. The level of statistical significance was set at α = 0.05, and test efficacy was defined as (1-β) = 0.90. The ratio of the sample size between the treatment and control groups was set at 2:1, resulting in an estimated requirement of 107 participants in the treatment group and 54 in the control group. Considering potential dropout during the trial, with a predicted shedding rate of 10%, the initial number of participants was set at 120 in the treatment group and 60 in the control group, totaling 180 participants.

All personnel involved in data management, including data collectors, data managers, and statisticians, will receive training to ensure adherence to the study’s data management protocols. Each participant’s CRF will be meticulously completed by the investigator based on the participant’s hospital records and original observation notes. Data entry will be conducted using the EpiData 3.1 software with a double-entry system by independent data entry personnel. The data manager, in collaboration with the principal investigator, will define the range and logical checks for the data and program these into the system to prevent errors. Any discrepancies found during data entry or validation will be documented and corrected, with records of the errors and corrections maintained.

All data, including paper CRFs and electronic files, will be securely stored. Paper records will be archived in a designated order and stored in a secure location, and electronic documents will be securely stored on a passwordprotected computer. These records will be preserved for at least 5 years following publication, in accordance with national regulations on clinical trial data management.

The Ethics Committee will periodically review the trial’s progress, monitoring data collection, allocation, and security. A formal data monitoring committee (DMC) will not be established. This decision is justified by the low-risk nature of the interventions (acupuncture and sham acupuncture) when performed by certified practitioners, the relatively short duration of the treatment phase (6 weeks), and the fact that no formal interim analyses for efficacy are planned. Instead, safety monitoring responsibilities will be jointly handled by the principal investigators and the Ethics Committee, which will conduct periodic reviews of safety data (including all AEs and SAEs) in addition to its standard oversight of trial conduct.

Statistical analysis will be performed using SPSS 25.0 and the R software package. The primary analysis will be based on the full analysis set (FAS), which will include all participants who receive at least one acupuncture treatment and have primary outcome data. Missing baseline data for primary outcomes will lead to exclusion from the FAS. Sensitivity analysis will be conducted using the per-protocol set (PPS), comprising participants who meet all inclusion and exclusion criteria, have valid baseline data, demonstrate good compliance, and have not violated the study protocol. Safety analysis will be performed based on the safety set (SS), which will include all participants who receive at least one acupuncture treatment.

Descriptive statistics will be used to summarize demographic and baseline characteristics. Categorical data will be presented as counts (n) and percentages (%), with differences between the groups analyzed using the chi-squared test or Fisher’s exact test. Continuous variables will undergo normality testing. Normally distributed data will be expressed as mean±standard deviation (X¯ ± S) and compared between the groups using independent samples t-tests. Non-normally distributed data will be presented as medians and interquartile ranges [M, (P25, P75)] and analyzed using the Mann–Whitney U test. Repeated measures data that meet the assumptions of normality, homogeneity of variance, and sphericity will be analyzed using repeated measures ANOVA, with corrections applied as necessary for violations of sphericity. To ensure the study’s scientific reliability and rigor, we will work to keep missing data under 20% and will use multiple imputation to handle missing data for the primary outcome.

Bang’s Blinding Index will be calculated for each group with 95% confidence intervals using the Wilson score method. Blinding will be considered successful if BI values are close to zero (|BI| < 0.3). Group differences in the CEQ scores will be compared using independent samples t-tests (or the Mann–Whitney U test if data are non-normally distributed). If the CEQ scores differ significantly between the groups, sensitivity analyses will include the CEQ as a covariate in primary outcome models (ANCOVA or mixed models) to adjust for potential expectancy effects. Correlation analyses will explore associations between the CEQ scores, acupuncture sensation scores, and primary outcomes to identify potential mediators of treatment effects.

Safety analysis will include the incidence of adverse events (AEs) during the study, with group comparisons of treatment-related adverse events conducted using a chi-squared test or Fisher’s exact test. Additional analyses may be conducted as deemed appropriate, with further details provided in the statistical analysis plan. Statistical significance will be set at a p-value of <0.05 for all analyses.

The acupuncture procedure will primarily be carried out by acupuncture specialists with more than 10 years of clinical experience. A launch meeting has been convened before the formal initiation of the trial to provide training on the purpose and design of the trial, treatment strategies, and quality control for all staff. The clinical participants will be required to complete the CRFs according to the design requirements, filling them in carefully and in detail. The study medical records and the CRFs shall be the original records and shall not be altered. All data in the clinical trial should be recorded, and the original report (or copy) should be attached to the case report form. Data that are significantly high or outside the clinically acceptable range will be verified, and necessary explanations will be provided by the physicians participating in the clinical trial. Clinical supervisors make regular on-site visits to research centers, check original information on a sample basis, hold regular meetings on specific issues, and provide timely feedback in the form of supervision reports and subject briefings to improve the quality of supervision.

Patients and the public are not involved in the planning, design, recruitment, or conduct of the study. The results of the study will be disseminated to the participants and the broader public through various channels, including educational talks, booklets, and publication in open-access peer-reviewed journals.

This study was approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine on 6 March 2024 (2024–014-01-KY) and conforms to the principles of the Declaration of Helsinki. The trial is registered in the Chinese Clinical Trial Registry (Registration No: ChiCTR2400084720; Register date: May 23, 2024). Written informed consent will be obtained from all participants prior to their inclusion in the trial. Data will be handled anonymously, and only participant codes will be available in the central database to protect confidentiality. All personal information outside the scope of this trial will not be collected, shared, or maintained. Participants retain the right to withdraw from the study at any time. The results of this study will be disseminated through publications in peer-reviewed journals and presentations at academic conferences.

Recruitment for this study began on 23 May 2024 and is scheduled to continue until 31 December 2026. The trial is currently in the participant recruitment phase.