Overview
This study is a multi-center 2-arm randomized controlled trial. According to the ratio of 1：1 and block randomization, a total of 108 eligible CM patients will be randomly allocated to either MA(n=54) or SA(n=54). All patients will undergo treatment two weeks before menstruation and treatment will be stopped at the onset of menstruation. Three times a week, six times a menstrual cycle, 3consecutive menstrual cycles for a total of 18 sessions after baseline. The primary outcome will be the change in the average daily breast pain VAS(VAS-BP) scores during the first 2 weeks of menstruation from baseline at weeks 4,8,12. Additionally, VAS-BP scores at weeks 24 and 36 will also be assessed. Secondary outcomes will include the number of nominal days of breast pain (NDBP) 2 weeks before menstruation, WHOQOL-BREF scores, patient global assessment, breast glandular section thickness, and breast duct width three days before menstruation from baseline at weeks 12. This study will evaluate the effectiveness and safety of acupuncture to alleviate cyclic breast pain and to further explore the possible mechanisms underlying the effect.
Description
Sample size Sample size estimation was based on changes in the breast pain VAS(VAS-BP) score. According to the pre-trial, the VAS-BP score significantly decreased by 2.98 ±0.95 in MA group compared to 2.35 ±0.97 in the SM group after treatment from baseline. In the current trial, the investigators assume a significance level α = 0.05 and power (1-β) = 0.90, and providing for a two-sided outcome, at least 42 participants will be required for each group, as calculated by PASS version 11.0 (NCSS, LLC. Kaysville, UT, USA), assuming a two-tailed test with a 20% drop-out rate, a total of 108 patients (54 in each group) will be recruited.
Recruitment Patients are planned to be recruited via outpatient clinic, advertisements on websites and posters from hospitals and a chat group using WeChat (WeChat, Version: 8.0.21, Tencent, Shenzhen, China). Meanwhile, the investigators will cooperate with the gynecology and physical examination departments of the hospital for potential patients to ensure the target sample size is reached. All potentially eligible women with CM will be invited to the trial and be able to contact the researchers with the provided phone number. Patients who meet the inclusion criteria will be introduced to the study in detail and informed about the potential benefits and possible risks of this study, and will sign informed consent agreements.Then personal information including age, marriage, menstrual, and medical history and a series of questionnaire, ultrasound of breast, as recommended by SOGC guideline are cautiously recorded.
Data collection and management Plans for assessment and collection of outcomes The data will be collected using CRF. Questionnaires will be conducted by evaluators. The ultrasound image acquisition tests are performed by the ultrasound physicians. All data obtained during the study will be input into the database and anonymized and stored in the study folder. Only the research team has access to this particular research folder.
Plans to promote participant retention and complete follow-up The patients will receive sufficient information about the study and requirements during the recruitment. All patients will be reminded throughout the study to fill out the questionnaires during study visits.Throughout the follow-up period, the researchers will collect data and contact patients for completion. Patients are allowed to discontinue the study, the data collected up to the withdrawal date will be anonymized and used.
Data management The clinical trial management platform ResMan will be used to manage the data. Repeated input methods will be used to ensure that the entered data is correct. The database will be locked with a password, which will only be known by relevant personnel.
Statistical methods Statistical methods for primary and secondary outcomes The investigators will use SPSS 22.0 software(IBM SPSS Statistics; IBM Corp, Somers, NY)to perform all statistical analyses following the intention-to-treat principle. The CI will be established at 95%, and the significance level at 0.05. For continuous data, the data will be presented as mean±standard deviation when normally distributed or presented as median (IQR) when not normally distributed. Statistical comparisons will be performed by the independent-sample t tests or Wilcoxon rank-sum test for continuous data and by X2-test or Fisher exact test for categorical data, as appropriate. A p-value <0.05 will be considered statistically significant.
The investigators perform statistical analysis on complete case.The researcher will contact participants as much as possible to supplement missing data. The missing data will be assessed using an intention-to-treat analysis.
Oversight and monitoring In order to control the quality of the clinical trial, the study principal investigator and the coinvestigator will be responsible for the coordination, data management of each center monitoring.The study team will meet and discuss the problems in the the study every 3 months.Any decisions needing to be taken modifying the study will be done with the consensus of the entire study team after approval by the ethics committee of Pinggu Hospital of Beijing Traditional Chinese medicine hospital.
Adverse event reporting and harms All adverse events will be documented in the CRF throughout the trial. Adverse events related to acupuncture (such as severe pain, local hematoma, infection and abscess, and broken needles ), including discomfort after treatment, will be recorded in time and detail. A detailed description of the categories, severity and correlation with the treatment of the adverse events will be collected by patients themselves and evaluators. If the adverse event is severe and associated with the trial, the patient will be withdrawn from the study and given appropriate medical care.
Frequency and plans for auditing trial conduct The team will audit every 3 months. Pinggu Hospital of Beijing Traditional Chinese medicine hospital is the Trial Steering Committee and will supervise the trial. Beijing clinical research quality promotion center conducts an annual visit to check the existence and integrity of the investigation documents.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) Any protocol amendments will be reported to the Ethics Committee of Pinggu Hospital of Beijing Traditional Chinese medicine hospital. Online trial registries will be updated accordingly.
Eligibility
Inclusion Criteria:
- Aged 18-45 years old;
- Breast pain starts within 2 weeks before menses, and improves after onset, dull, heavy, or aching, bilateral, poorly localized, and extends into the axilla ;
- Fulfilling all conditions mentioned below: a. Moderate or severe breast pain as indicating 3 or more on scale of 1-10 on the VAS;b. History of CM for at least the past three consecutive cycles;c. Days of premenstrual breast pain≥3 days and≤14 days; d.A history of regular menstrual cycles of 28 plus/minus 3 days;
- Breast X-ray or breast ultrasound examination is excluded from malignant breast lesions;
- The patient signed the informed consent and voluntarily participated in the study.
Exclusion Criteria:
- Accepted acupuncture or drugs to treat breast pain within 1 month before entering the study;
- With breast inflammation, breast fibroma, breast cystic hyperplasia, and other benign breast lesions；
- With severe primary diseases in the cardiovascular system, pulmonary system, liver, kidney, and hematopoietic system;
- History of breast cancer among first-degree relatives;
- Breast pain caused by Costochondritis, chest wall injury, rib fracture, and other extramammary pain diseases;
- The patient is pregnant or lactating;
- with serious mental illness;
- Poor compliance;
- Patient has participated in other clinical trials within 1 month;
- with serious skin disease or infection at the acupuncture site.