Effect of Tuina combined with Chinese herbal compress on primary dysmenorrhea with cold coagulation and blood stasis syndrome, study protocol for a randomized controlled trial

doi:10.21203/rs.3.rs-2721750/v1

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Study protocol

Effect of Tuina combined with Chinese herbal compress on primary dysmenorrhea with cold coagulation and blood stasis syndrome, study protocol for a randomized controlled trial

https://doi.org/10.21203/rs.3.rs-2721750/v1

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Background

Primary dysmenorrhea (PD) is a very common problem in young women, which reduces the quality of women’s lives. Both western medicine and TCM provide several ways to treat PD; however, TCM treatment has fewer side effects for the patient. Tuina and Chinese herbal compresses are considered forms of external TCM therapy, which has been widely used to treat PD, especially in China. Therefore, to provide the most effective and safe treatment for PD, we combined Tuina and Chinese herbal compresses together in this research and observation.

Method/design:

A randomized controlled trial (RCT) consisting of 114 participants from the Shanghai University of Traditional Chinese Medicine who meet inclusion criteria will be divided into 2 groups in a 1:1 allocation ratio. The intervention group will receive Tuina combined with Chinese herbal compress therapy; the control group will only receive Chinese herbal compress therapy. The treatment will be given three days before menstruation (once a day, three times per menstrual cycle). The primary outcome was measured by the visual analog scale (VAS). The secondary outcomes were measured by the dysmenorrhea symptom score, the Chinese medical dysmenorrhea symptom score, the self-rating anxiety scale (SAS), the self-rating depression scale (SDS), and the pain threshold at Guanyuan acupoint (CV4).

Discussion

The study will be the first randomized controlled trial observing the combination of Tuina and Chinese herbal compresses to treat PD in the category of cold coagulation and blood stasis syndrome. If the results demonstrate that Tuina combined with a Chinese herbal compress is effective, this study may provide evidence-based references for a potential alternative treatment to treat PD in the future.

Trial registration:

ChiCTR Registry, ChiCTR2300069527, Registered on 20 March 2023.

Primary dysmenorrhea (PD)

Tuina

Chinese herbal compress

randomized controlled trial

study protocol

Primary dysmenorrhea (PD) usually occurs in adolescents, with symptoms occurring just around the menstrual period. The pain is usually in the lower abdomen and may extend to the lower back area. Systemic symptoms may include headache, dizziness, nausea, vomiting, diarrhea, fever, fatigue, or even fainting [1]. PD can affect the quality of life and mental health. Women with PD often fail to have a normal social life or fail to go to school or work [2]. Moreover, PD also affects being emotional in daily life and being sometimes unable to control oneself [3].

In modern medical treatment, non-steroidal anti-inflammatory drugs (NSAIDs) and a combination of oral contraceptive pills are most commonly used to treat PD [4]. However, NSAIDs also have side effects that may cause gastrointestinal disorders. Besides, it may damage the liver or kidney with long-term treatment [5]. Moreover, oral contraceptive pills could cause headaches, nausea, vomiting, or weight gain [6].

Traditional Chinese Medicine (TCM) believes that dysmenorrhea is located at the uterus and the thoroughfare/conception vessel (Chong-Ren Mai). (Chong and Ren Mai are one of The Eight Extra Meridians, which Chong Mai defined as the sea of the blood and Ren Mai defined as the sea of yin meridians.) The factors causing dysmenorrhea are Qi stagnation and blood stasis; cold congelation and blood stasis; damp-heat stasis; Qi and blood deficiency; liver and kidney deficiency, etc. According to TCM, there are two main types of dysmenorrhea: one is deficiency syndrome, based on the theory of “pain due to malnutrition”, and caused by Qi and blood deficiency, or liver and kidney deficiency. The second one is an excessive syndrome, based on the theory of “pain due to block”, and it’s caused by impeding the circulation of Qi and blood [7].

In China, TCM therapy has been widely used to treat dysmenorrhea for a thousand years. TCM therapy mainly includes Chinese herbal medicine, acupuncture, moxibustion, Tuina (Chinese massage/acupressure), cupping, Chinese herbal compresses, auricular acupuncture, and Qigong.

Tuina is a traditional therapeutic massage in TCM. It works along with energetic meridians and acupoints through the body in order to stimulate the flow of Qi and Blood which are imbalances or blockages that may cause or lead to pain and disease in the future [8–9]. Furthermore, there is research found that Tuina is one of the most recommended due to the fact that it gives an effective outcome and is also a safe non-pharmacologic strategy. Moreover, it is also the greatest way to decrease the severity of PD [10–13].

A Chinese herbal compress is an external treatment based on the theories of TCM. It’s a combination of meridians, acupoints, and Chinese herbal medicines [14]. The treatment relies on the mechanism of percutaneous absorption, which has the ability to dredge meridians, harmonize Yin and Yang, regulate Qi and Blood, strengthen body resistance, and expel pathogenic factors [15]. Herbal compresses have a few side effects, are more practical than internal therapy, and are easily accepted by patients. The study also stated that the effect of Chinese herbal acupoint application on PD with cold coagulation and blood stasis syndrome could increase the level of PGE2, decrease the level of PGF2α, and also significantly improve the whole blood viscosity and platelet adhesion rate [16].

Therefore, to provide the most effective and safe treatment for PD, it can be hypothesized that the combination of Tuina and Chinese herbal compresses will give a better result in relieving pain caused by PD.

Objectives

The purpose of the study is to observe the immediate analgesic effect of Tuina, which is combined with Chinese herbal compresses to cure PD in the category of cold coagulation and blood stasis syndrome, in order to improve the quality of patient life and reduce the effect that may disturb people who have PD in their daily lives.

Hypothesis

Tuina combined with Chinese herbal compress therapy would effectively relieve the pain more than Chinese herbal compress.

Study design

This study is a single-center, analyst-blinded, randomized controlled trial was designed to compare the immediate analgesic effect of Tuina combined with Chinese herbal compress therapy (intervention) vs. Chinese herbal compress therapy (control) in PD with cold coagulation and blood stasis syndrome. This study protocol has been approved by the Shanghai Municipal Hospital of Traditional Chinese Medicine, which is affiliated with the Shanghai University of Traditional Chinese Medicine (approval number: 2022SHL-KY-100-02). In total, 114 participants will be randomly divided into 2 groups in a ratio of 1:1. Written informed consent will be provided by all participants. Independent researchers who are blinded will be assigned to accomplish the outcome assessment and statistical analyses. The study will be conducted at the Shanghai University of Traditional Chinese Medicine. The flowchart of the study designed is shown in Fig. 1.

Participants and recruitment

The recruitment targets are undergraduate and graduate students at the Shanghai University of Traditional Chinese Medicine. Recruitment posters will be put up on notice boards to recruit participants on campus. Participants will be included only if they meet the inclusion criteria and provide written informed consent.

Inclusion criteria

Participants that meet the following criteria will be included:

Diagnostic criteria for PD is based on primary dysmenorrhea consensus guideline (2017) [17]

TCM diagnostic of “cold congelation and blood stasis syndrome” [8]

Main symptoms: cramping pain in the lower abdomen occurring just before or during menstruation; pain relieved by heat

Secondary symptoms: low menstrual flow; dark menstrual color with blood clots; pale face; cold limbs

Tongue and pulse: dark purple tongue or tongue with black spots, cover with white coating, string pulse, or sinking tight pulse

Age between 15–35 years old

Menstrual pain score (VAS) 4

No other relevant treatment has been received within 1 month before entering the study

Able to comply with the intervention and agree not to receive other relevant treatments during the period of treatment

Volunteer for the study and agree to sign an informed consent form

Exclusion criteria

Participants that meet any of the following criteria will be excluded:

Secondary dysmenorrhea is caused by endometriosis, polycystic ovarian syndrome, pelvic inflammation, and other gynecologic diseases

Pregnant, or preparing for pregnant or lactating women

Taking drugs or using products related to the study

The patient has taken painkillers or received other relieving pain therapy in the past 2 weeks before entering the study

Allergic constitution, allergy to Chinese medicines, or skin disorders

Patients with complicated diseases such as cardiovascular, liver, and kidney diseases, or patients with infectious diseases

Involved with mental illness

Patients with poor compliance (e.g. can’t complete a dysmenorrhea questionnaire, can’t understand the purpose of the study, difficult follow-up)

Patients with irregular periods or missed periods

Rejection criteria and Suspension criteria

Reluctance to continue the trial of the study

Non-cooperation of the participants during the trial for any reason

Occurrence of serious illness, no longer suitable for the trial

Occurrence of serious adverse events (SAEs)

Patients willing to quit the trial

Patients’ loss to follow-up

Interventions

The intervention of a Chinese herbal compress, treatment will take 15 minutes and will be given three days before menstruation; treat 3 times (once a day, 3 times per menstrual cycle); the Tuina treatment will be performed by the same registered practitioner and will be given three days before menstruation, treat 3 times (once a day, 3 times per menstrual cycle), each time of the Tuina treatment will take 14 minutes. For 1 course of treatment, continuously treat 3 menstrual cycles.

Control group (Chinese herbal compress)

Chinese herbal compress composed of Fructus evodiae 50g, Motherwort 50g, Mugwort 50g, Fennel seed 50g, and Kosher salt 100g. Place all the herbal mixture into the center of the cloth, folding the edges up and over the herbs, making a firm round ball. Using a steamer, boil water and drop in the poultice. Steam it until it reaches about 35–40 degrees. Prep two herbal compresses for a session, keeping one heated on the steamer while using the other. Check the temperature of the herbal compress on your inner forearm prior to use. Apply the herbal compress to the Guanyuan (CV4) acupoint for 15 minutes.

Intervention group (Tuina combined with Chinese herbal compress)

Basic conditions preparation: a quiet environment, maintain the room temperature at 25°C, patients empty their bladders before treatment.

Acupoint selection: Qihai (CV6), Guanyuan (CV4), Zigongxue (EX-CA1), Diji (SP8), Sanyinjiao (SP6), Baliao (BL31-BL34). A detailed description of these acupoints is provided in Table 1.

In Tuina treatment, the standard operating procedures are listed as follows:

Mo Fa (round rubbing): Place the patient in a supine position, use the palm and fingers to rub the abdomen in a circular motion, applied in a clockwise direction for 5 minutes, and the patient must feel the degree of warmth;

Dian Fa (pressing): Use thumb pressing on Qihai (CV6), Guanyuan (CV4), and both sides of Zigongxue (EX-CA1), Diji (SP8), and Sanyinjiao (SP6), each point for 1 minute, and the patient must feel the degree of sourness;

Ca Fa (scrubbing): Place the patient in a prone position and use the whole palm, scrubbing forwards and backwards in a straight line on Baliao (BL31-BL34) for 1 minute; scrub until the area is hot.

Chinese herbal compress is identical to the control group.

Table 1

Description of acupoints
Acupoints	Location
Qihai (CV6)	On the anterior median line of the lower abdomen, 1.5-cun below the umbilicus
Guanyuan (CV4)	On the anterior median line of the lower abdomen, 3-cun below the umbilicus
Zigongxue (EX-CA1)	On the lower abdomen, 4-cun below the umbilicus, 3-cun away from the midline
Diji (SP8)	On the medial aspect of the lower leg, 3-cun below Yinlingquan (SP9), on the connecting the tip of the medial malleolus and Yinlingquan (SP9)
Sanyinjiao (SP6)	On the medial aspect of the lower leg, 3-cun above the medial malleolus, on the posterior border of the medial aspect of the tibia
Baliao (BL31-34)	In the region of the sacrum, between the posterior superior iliac spine and the midline of the back, in the 1st to 4th sacral foramen

CV = Conception Vessel (Ren Mai); EX = Extraordinary Points; SP = Spleen; BL = Urinary Bladder.

Randomization and blinding

Participants will be randomly assigned to either the Tuina combined with Chinese herbal compress group or the Chinese herbal compress group using a random number generator (SPSS 24.0, SPSS Inc., Chicago, IL, USA) in a 1:1 ratio. In this trial, participants will be informed of the type of treatment they will receive, the therapists know which treatment is being given, so to ensure the treatment is blinding, therapists should learn how to communicate with participants. To reduce the risk of bias, the assessors, data managers, and statisticians will be blinded to the group allocation in the result evaluation procedures and data analysis. The researcher, assessors, data managers, and statisticians are not allowed to share any study information during the data collection and analysis stages.

Outcome measurements

The outcome assessment includes the following items: Visual Analog Scale (VAS); Dysmenorrhea Symptom Scale; Chinese Medical Dysmenorrhea Symptom Scale (cold congelation and blood stasis syndrome); Self-rating Anxiety Scale (SAS); and Self-rating Depression Scale (SDS), will be assessed at the end of each menstrual cycle in the baseline period, treatment period, and follow-up period, a total of seven times. Pain threshold measurement at Guanyuan (CV4) will be measured on the first day of each menstrual cycle in the treatment period and after 1 course of treatment, a total of four times. The detailed outcome assessment time points are provided in Table 2.

Table 2

Trial time points chart
Time points	Baseline	Treatment period			Follow-up period
Visit	1	2	3	4
Menstrual cycle	0	1	2	3	4	5	6
Inclusion criteria	√
Exclusion criteria	√
Informed consent	√
Randomization and allocation	√
Intervention		√	√	√
VAS	√	√	√	√	√	√	√
Dysmenorrhea symptom scale	√	√	√	√	√	√	√
Chinese medical dysmenorrhea symptom scale	√	√	√	√	√	√	√
SAS	√	√	√	√	√	√	√
SDS	√	√	√	√	√	√	√
Guanyuan (CV4) pain threshold		√	√	√	√
Adverse events		√	√	√

Primary outcome measurement

Visual Analog Scale (VAS): score range is from 0 to 10, where 10 signifies “worst pain.” 0 signifies “no pain”, 1–3 signifies “mild pain”, 4–6 signifies “moderate pain”, and 7–10 signifies “severe pain.” The VAS will be assessed using a repeated longitudinal analysis.

Secondary outcome measurements

Dysmenorrhea Symptom Scale: According to the Guiding Principles of Clinical Research on Dysmenorrhea Treated with New Chinese Medicine. This scale comprises 15 items assessing menstrual symptoms; the score range ≤ 8 signifies “mild symptoms”, 8-13.5 signifies “moderate symptoms”, and ≥ 14 signifies “severe symptoms”. The Dysmenorrhea Symptom Scale will be assessed using a repeated longitudinal analysis.

Chinese Medical Dysmenorrhea Symptom Scale (Cold Congelation and Blood Stasis Syndrome): According to the Guiding Principles of Clinical Research on Dysmenorrhea Treated with New Chinese Medicine. It comprises a 10-item questionnaire on the pain and symptoms of menstruation, including a degree of pain, period blood color, period blood volume, period blood texture, low back pain, cold hands and feet, fear of cold, delayed menstruation, tongue, and pulse. The Chinese Medical Dysmenorrhea Symptom Scale will be assessed using a repeated longitudinal analysis.

Self-rating Anxiety Scale (SAS): This scale comprises 20 items assessing a variety of anxiety symptoms, including both positive and negative experiences. SAS scores are classified as normal (< 50), mild anxiety (50–59), moderate to marked major anxiety (60–69), severe to extreme major anxiety (≥ 70). The SAS will be assessed using a repeated longitudinal analysis.

Self-rating Depression Scale (SDS): It is a 20-item self-report questionnaire on the symptoms of depression. SDS scores are classified as normal (< 53), mild depression (53–62), moderate to marked major depression (63–71), severe to extreme major depression (≥ 72). The SDS will be assessed using a repeated longitudinal analysis.

Pain threshold measurement: using the algometer combo equipment (Model OE-220, ITO Co., Ltd., Tokyo, Japan) at Guanyuan acupoint (CV4), according to the method [18]. Measurements will be made on the first day of each menstrual cycle during the treatment period and after 1 course of treatment, a total of four times.

Follow-up period

The purpose of the follow-up assessment is to evaluate the long-term effects of Tuina combined with Chinese herbal compresses on PD patients. After completing 1 course of treatment, there will be a follow-up assessment at the fourth, fifth, and sixth menstrual cycles. However, all of the participants during the follow-up period will be required to complete the VAS, Dysmenorrhea Symptom Scale, Chinese Medical Dysmenorrhea Symptom Scale, SAS, and SDS. WeChat or email will be used for the participant to send all the relevant information to the researchers.

Adverse events (AEs) and safety monitoring

Tuina is a relatively safe approach for various conditions, but some minor side effects were reported. Improper Tuina can probably cause soreness, inflammation, or redness, which may last for two to three days. Patients with poor health, excessive stress, fatigue, or starvation, which may cause dizziness, nausea, cold skin and sweating, or even fainting, basically should immediately stop Tuina, lie down patient, and drink some warm water. Due to the fact that the Chinese herbal compress is for external use, possible adverse events may include redness, itching, burns, and blisters. Stop using the herbal compress if the condition worsens. If the blister is large or painful, puncture the blister with the sterilized needle at its edge, let the fluid drain but leave the overlying skin in place, apply an antibiotic ointment to the blister, and cover the area loosely with a sterile bandage or gauze. If excessive redness or irritation is present, the nearest affiliated Shuguang Hospital doctor will be notified in time, and patients will make judgments and start medical treatment, which will be closely followed up by the research team. The researchers will report all the unexpected responses in the case report form to the corresponding research staff to determine whether the participant needs to withdraw from the study.

Sample size calculation

The total effective rate of Chinese herbal compresses was 85% [16], and the total effective rate of Tuina therapy in PD was 96.7% [19]. With the test level set at α = 0.05, β = 0, considering a 15% dropout rate, two independents sample t-test were used to calculate sample size for further studies:\({{n}_{1}={n}_{2}=1641.4\left[\frac{\left({\mu }_{\alpha }+ {\mu }_{\beta }\right)}{{\text{sin}}^{-1}\sqrt{{\rho }_{1}} - {\text{sin}}^{-1}\sqrt{{\rho }_{2}}}\right]}^{2}\)57 participants will be enrolled in each group, giving a total of 114 participants.

Statistical analysis

The SPSS24.0 program will be used to analyze the data. Continuous data, such as age and disease course, will be expressed as mean ± standard deviation (SD). While categorical data, such as gender and medical history, will be described as numbers and percentages. For comparing the count data between-group differences will be analyzed using the chi-square test. For group comparisons with the normal distribution continuous data will be analyzed using the one-way analysis of variance (ANOVA), and when the data do not follow a normal distribution, the Kruskal-Wallis test will be used. To compare variables before and after treatment in the within-group, the paired t-test will be used. The baseline characteristics between the two groups will be analyzed using the two-sample independent t test, if the baseline characteristics are imbalanced, the covariance analysis (ANCOVA) will be used to control the baseline characteristics. For other variables or if there is some missing data, nonparametric Mann-Whitney U test will be applied. The entire statistical test will use a bilateral examination, and the significance level is set at P < 0.05.

Data collection and management

The CRFs will be used to collect the data, which consists of questionnaire-based assessment of treatment effect, pain threshold measurement, adverse events, and safety evaluations. Then, two data administrators who are beyond the reach of the research team and blinded to group allocation will independently receive the completed CRF and input it into an Excel database (Microsoft, Redmond, WA, USA). To monitor data, they needed to complete extensive training. Finally, the real-time data is entered into the China Clinical Trial Registry (http://www.chictr.org.cn), where the electronic data management system will be utilized to track and monitor test data from the Science and Technology Department of Shanghai Municipal Hospital of Traditional Chinese Medicine in real-time.

Quality control

During the processing of the trial, quality control will be carried out under the direction of the steering committee. Before the researchers take part in the study, they need to receive training in professional trial methods and consistent monitoring methodologies, which can guarantee method consistency. If changes are made to the protocol, they should be communicated to the steering group and ethics committee.

Ethical considerations

Under the guidance of the Declaration of Helsinki’s general guidelines for human medical research and in accordance with regional law, this trial has been approved by the Regional Ethics Review Committee of the Shanghai Municipal Hospital of Traditional Chinese Medicine, which is affiliated with the Shanghai University of Traditional Chinese Medicine (approval number: 2022SHL-KY-100-02) and registered on the China Trial Registry (registration number: ChiCTR2300069527). Protocol changes will be communicated to the Ethics Review Committees and trial registry for approval.

The informed consent form will explain in full detail the purpose of the study, the selection criteria, the treatment procedures, potential risks and benefits, and permission for data recording. Written informed consent will be obtained from all participants before enrollment. Participants can withdraw from the study at any time.

The findings of this study will be published in a peer-reviewed journal or in academic conference proceedings. This study’s data collection can only be used for this research. All members of the research team adhere to ethical confidentiality principles.

PD is the most common gynecologic problem found in women [1]. The symptoms usually begin in adolescence, and they can affect one’s daily life, such as being unable to go to school or work and losing emotional control of oneself. People mostly use western medicine as a first line to cure PD, but it can only relieve symptoms for a short time. Both western medicine and TCM provide several ways to treat PD. However, TCM treatment has fewer side effects for the patient, so this is the reason why Tuina and Chinese herbal compresses, which are part of external TCM therapy, are widely accepted as safe, effective, and easily accepted by the patients.

The purpose of the study is to evaluate the immediate analgesic effect of Tuina combined with Chinese herbal compresses in PD with cold coagulation and blood stasis syndrome. The immediate analgesia result will be determined and evaluated by VAS, SAS, SDS, and the pain threshold at Guanyuan (CV4). The severity of PD and TCM syndromes will be determined by the dysmenorrhea symptom score and the Chinese medical dysmenorrhea symptom score.

Tuina is an external TCM therapy based on the theory of the Zangfu (viscera) and energetic meridians of TCM, combined with the anatomy and pathological diagnosis of modern Western medicine. Tuina involves a lot of massage techniques such as pushing (Tui), grasping (Na), pressing (An), rubbing (Mo), kneading (Rou), scrubbing (Ca), and vibrating (Zhen fa) that are performed on meridians, acupoints, muscles, joints, or around the area of pain or discomfort on the body. Tuina has the ability to dredge the channels and collaterals, promote and invigorate the flow of Qi and Blood, expel pathogenic factors, harmonize Yin and Yang, improve and regulate the functions of the Zangfu, expel the cold-evils, and strengthen the immune system, which is why Tuina can treat many kinds of diseases, including dysmenorrhea [20]. Traditional Tuina massage is one of the most common methods used to treat dysmenorrhea. Most clinical studies have been performed based on Qihai (CV6), Guanyuan(CV4), Shenshu (BL23), and Baliao (BL31-34) acupoints. By using pressing, kneading, and one-finger pushing techniques, discomfort symptoms such as lower abdominal pain and low back pain can significantly improve [21–25].

A Chinese herbal compress uses the warming effect to bring the effective ingredients of Chinese herbs into the meridians and collaterals directly to the location of disease. The herbs in this research contain Fructus evodiae, Motherwort, Mugwort, and Fennel seed. A combination of these Chinese herbs is expected to dispel colds, relieve pain, and treat menstrual cramps. Chinese herbal compresses can heat up local tissues, accelerate blood circulation, expand capillaries, stimulate the lymphatic system, improve local metabolism, and achieve the effects of relieving muscle spasms, being anti-inflammatory, and reducing swelling.

Both Tuina and Chinese herbal compresses have a therapeutic effect of heat, in which the heat from Tuina is generated by friction between the therapist’s hands and the patient’s skin. Heat can improve the blood flow in the uterus and its surrounding veins. A previous study also stated that heat can increase gastrointestinal motility and also have the effect of relaxing the uterus [26].

Acupoint selection and combination play an important role in the effectiveness of PD treatments. Guanyuan (CV4) and Qihai (CV6) belong to Ren Mai. Guanyuan (CV4) is called the Gate of Origin, a meeting point of Ren Mai with the three yin meridians of the foot, and also where Chong Mai converges with the kidney meridian in the abdomen. Qihai is known as the Sea of Qi. These two acupoints can replenish the vital energy (Yuan Qi), disperse Qi, and also relieve local pain by promoting local blood flow [27–28]. Sanyinjiao (SP6), a crossing point of the three yin meridians of the foot, is the most commonly used acupoint for treating PD [29–31]. Diji (SP8) is the Xi-Cleft point of the spleen meridian, clinical trials have shown that Diji (SP8) can activate blood, relieve pain, and control Qi and Blood, thus achieving smooth circulation of Qi and Blood [32]. Zigongxue (EX-CA1) is an extraordinary acupoint, commonly used for treating gynecological diseases. One of the studies showed that the combination of acupoints Guanyuan (CV4), Qihai (CV6), Sanyinjiao (SP6), Diji (SP8), and Ciliao (BL32) was most frequently used to treat PD and might have better therapeutic effects than other acupoint combinations [33]. Also, there is a study states that the effect of multi-acupoint acupuncture is better than single-acupoint acupuncture on treating PD [34].

This research is the first clinical trial observing the combination of Tuina and Chinese herbal compresses for treating PD. The design of the study aimed to provide helpful information for clinicians and patients, and the researcher hopefully will provide reasonable evidence to demonstrate the efficacy and safety of treating PD symptoms.

Strengths and limitation of the study

The strength of this study protocol includes the randomized study design and the predetermined sample size. Tuina and Chinese herbal compresses, two crucial components of TCM's external treatment, are widely used to treat a variety of diseases, including PD. These two treatments do not require expensive equipment and are secure and easily accepted by patients. Moreover, to evaluate the long-term effects on PD patients, this study will observe the changes in PD symptoms at baseline, during the treatment period, and during the follow-up period.

There are some limitations to this study. First, the average menstrual cycle occurs every 287 days. The length of the menstrual cycle varies from woman to woman and might be different from month to month. There are many factors that can affect the menstrual cycle, such as emotional stress, weight, smoking, alcohol use, or even ethnicity [35]. According to our treatment plan, which will begin three days before menstruation, treatment may cause menstruation to occur sooner or later than the usual cycle. Therefore, it is hard to predict the change of the menstrual cycle, and this may affect the duration of the treatment and the therapeutic effect. Second, this trial will be conducted only in Shanghai, and the participants are restricted to the students of a university, whether the results will be generalized to the rest of mainland China or other countries.

The trial protocol has been assessed and approved by the Ethics Committee of the Shanghai Municipal Hospital of Traditional Chinese Medicine, which is affiliated with the Shanghai University of Traditional Chinese Medicine, in November 2022. This study will start recruiting participants in March 2023 and is expected to end in November 2023.

Primary Dysmenorrhea

TCM

Traditional Chinese Medicine

VAS

Visual Analog Scale

SAS

Self-rating Anxiety Scale

SDS

Self-rating Depression Scale

NSAIDs

Non-steroidal anti-inflammatory drugs

PGE2

Prostaglandin E2

PGF2α

Prostaglandin F2α

SAEs

Serious Adverse Events

AEs

Adverse Events

SPSS

Statistical Package for Social Sciences

Standard Deviation.

Ethics approval and consent to participate

This study protocol and consent forms were approved by the Shanghai Municipal Hospital of Traditional Chinese Medicine, which is affiliated with the Shanghai University of Traditional Chinese Medicine (approval number: 2022SHL-KY-100-02). The Regional Ethics Review Committee has the right inspect the conduct of the study at any time. It has been registered to the China Clinical Registration Agency (registration number: ChiCTR2300069527). The informed consent form explains in full detail the purpose of the study, the selection criteria, the treatment procedures, potential risks and benefits, and permission for data recording. Written informed consent will be obtained from all participants before enrollment.

Consent for publication

Not applicable.

Availability of data and materials

The protocol of the study is publicly available on the website of China Registered Clinical Trail Registration Center no. ChiCTR2300069527. After completing the current study, supporting data will be available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was supported by National Natural Science Foundation of China (Grant No. 82105038). The funding organization has no role in study design, analysis, decision to publish, or preparation of the manuscript.

Author’s contributions

The study was conceptualized by FY, PA, and FX. PA planned the study protocol and drafted the manuscript. FX planned the study protocol and revised the manuscript. CX and JM participated in the sample size calculation and statistical analysis. A clinical trial will be conducted by all the investigators collectively. FY final approval of the manuscript of the version to be published. All authors have read and approved the final manuscript.

Acknowledgments

We thank Prof. Min Fang from Shanghai University of Traditional Chinese Medicine (Shanghai, China) for his constructive suggestions and help in manuscript revision.

Author details

¹ School of Acupuncture-Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

² Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine.

³ Department of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China.

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No competing interests reported.

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Effect of Tuina combined with Chinese herbal compress on primary dysmenorrhea with cold coagulation and blood stasis syndrome, study protocol for a randomized controlled trial

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Abstract

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Background

Methods and design

Objectives

Hypothesis

Study design

Participants and recruitment

Inclusion criteria

Exclusion criteria

Interventions

Randomization and blinding

Outcome measurements

Primary outcome measurement

Follow-up period

Adverse events (AEs) and safety monitoring

Sample size calculation

Statistical analysis

Data collection and management

Quality control

Ethical considerations

Discussion

Strengths and limitation of the study

Trial Status

Abbreviations

Declarations

References

Additional Declarations

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