Traditional Chinese Medicine, Western Medicine and Low-level Light Therapy（LLLT） for Primary Dysmenorrhea（PD）

Study Overview
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Brief Summary
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To observe the clinical efficacy and safety of three methods for the treatment of primary dysmenorrhea. Establish an integrated biomarker index system for the evaluation of the efficacy of traditional Chinese medicine, western medicine and Low-level Light Therapy for the treatment of primary dysmenorrhea, and further explore the mechanism and therapeutic material basis of the three treatment methods for the treatment of primary dysmenorrhea

Detailed Description
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480 women clinically diagnosed of primary dysmenorrhea will be enrolled from nationwide multi-centers. Blood samples were collected from 480 patients before and after treatment (1 experimental group, 3 control groups, treatment cycle of 3 menstrual cycles, follow-up cycle of 5 menstrual cycles), Metabonomics study, and integration of clinical sample information (Serum biochemical indicators, imaging indicators, etc.), through bioinformatics to establish a comprehensive biomarker index system for the evaluation of the efficacy of traditional Chinese medicine, Western medicine and Low-level Light Therapy instrument Methods for the treatment of primary dysmenorrhea and its therapeutic basis.

Official Title
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Clinical and Systematic Biology Study of Traditional Chinese Medicine, Western Medicine and Low-level Light Therapy for Primary

Conditions
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Primary Dysmenorrhea, Traditional Chinese Medicine, Light

Intervention / Treatment
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* Device: low level light therapy
* Drug: DING KUN DAN
* Drug: Simulated drug of DING KUN DAN
* Drug: Marvelon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female (16-35 years old); regular Menstruation (cycle 21-35 days, menstrual period 3-7 days); Be clinically diagnosed with primary dysmenorrhea; Be willing to participate in the whole process of the research in 5 consecutive menstrual cycles. Exclusion Criteria: irregular menstruation affecting the treatment and efficacy judgment; Patients with secondary dysmenorrhea; Those who have used related drugs in the past 3 months; Abuse or dependence on substances (alcohol or medicine) in the past 3 months; heavy smokers (smokers who smoke 20 or more cigarettes per day); Those who have severe or unstable physical illnesses, related to liver, kidney, gastrointestinal tract, cardiovascular, respiratory, endocrine, nervous, immune or blood systems, neuropsychiatric systems and so on; Lactating or pregnant women, or women within 1 year after delivery; Those who are allergic to the test drug or light, have contraindications for Marvelon and Ding kun dan; Have a history of thromboembolic disease or a tendency to thrombosis; one month before joining in this study (first interview), Who participated in another clinical trial; Those who meet the inclusion criteria, fail to follow the doctor's advice so that we cannot judge the curative effect ,the incomplete data cannot be evaluated.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: One fourth of participants will receive Ding Kun Dan Pills, one fourth of participants will receive Simulated drug of DING KUN DAN Pills, one fourth of participants will receive MARVELON ,and the another fourth will receive low level light therapy
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DING KUN DAN<br>DING KUN DAN,3.5g BID for 10 days (starting 3-5 days before menstruation) *3 menstrual cycle | Drug: DING KUN DAN<br>* DING KUN DAN,3.5g BID for 10 days (starting 3-5 days before menstruation) *3 menstrual cycle<br>|
| Placebo Comparator: Simulated drug of DING KUN DAN<br>Simulated drug of DING KUN DAN，3.5g BID for 10 days (starting 3-5 days before menstruation) *3 menstrual cycle | Drug: Simulated drug of DING KUN DAN<br>* Simulated drug of DING KUN DAN，3.5g BID for 10 days (starting 3-5 days before menstruation) *3 menstrual cycle<br>|
| Experimental: low level light therapy<br>Start using low level light therapy after the menstrual period, once a day, every 20 minutes * 5 days ( one treatment cycle), start the next course at intervals of 2 days until the next menstruation | Device: low level light therapy<br>* Start using low level light therapy after the menstrual period, once a day, every 20 minutes * 5 days ( one treatment cycle), start the next course at intervals of 2 days until the next menstruation<br>|
| Active Comparator: Marvelon<br>1 pill QD*21 days (starting on the 5th day of menstruation, continuing the next cycle after 1 week of withdrawal) *3 menstrual cycle | Drug: Marvelon<br>* Marvelon 1 pill QD*21 days (starting on the 5th day of menstruation, continuing the next cycle after 1 week of withdrawal) *3 menstrual cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale,VAS | Visual Analogue Scale/Score (VAS): Draw a 10 cm horizontal line on the paper. The degree of pain is indicated by the line segment，One end of the horizontal line is 0, indicating no pain; the other end is 10, indicating severe pain; the middle part indicates different degrees of pain（the mild pain is 1-3, the moderate is 4-6, the severity is 7-9），The patient chooses the value that can represent the degree of pain. | about 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-form McGill Pain Questionnaire-2, SF-MPQ-2 | Short-form McGill Pain Questionnaire-2(SF-MPQ-2), By this scale, we can evaluate the different types of pain and the emotional effects of PD. It has 22 entries. These 22 entries include: Jumping pain, shooting pain, knife-like pain, sharp pain, cramping and dragging pain, constant biting pain, hot burning pain, sore pain, falling pain, slightly pressing pain, tearing pain, exhaustion - weakness, disgusting, fear, Torture - punishment, electric shock, cold pain, puncture pain, pain caused by gentle touch, itching, pin and needles pain, numbness. Each entry scored 0 10 points, the minimum score is 0,the maximum score is 10,a total of 11 levels. 0 indicates that never have this pain or symptom, 10 represents that this pain or feel is severe,1-9 indicates different degrees of this type of pain or symptom. At last, Calculate the total score of all 22 items. | about 30 days | 
| the COX menstrual symptom scale，CMSS | the COX menstrual symptom scale (CMSS), this score evaluate the level of PD from the two aspects of dysmenorrhea symptoms: the duration and severity , It has 17 entries including: cramps , nausea, vomiting, loss of appetite, headaches, backaches, leg aches, dizziness, weakness, diarrhea, facial blemishes, abdominal pain, flushing, general aching, depression, irritability, nervousness. Each entry scored 0 4 points, different score represents different duration or severity of corresponding symptoms : for the duration, 0 indicates never have this symptom, 1 means lasting less 3 hours, 2 means lasting 3 7 hours, 3 means 7 24 hours, 4 means more than 24 hours. as for the severity,0 indicates no pain; the mild is 1, the moderate is 2, the severity is 3, the extreme severity is 4. Then, Calculate the score of the duration and severity of all 17 items respectively, lastly, sum the total score of the duration and severity. | about 30 days | 
| Menstrual flow graph analysis table | Through this form, we can know about the menstrual period and menstrual flow before and after treatment: Mild: blood stained area ≤ 1/3 of the entire sanitary napkin area; Moderate: blood stained area accounts for 1/3-3/5 of the entire sanitary napkin area; Severe: The blood stained area is basically the entire sanitary napkin. Blood clot area <1 dollar coin, which is a small blood clot; The blood clot area is ≥1 yuan coin, which is a large blood clot. fill in the number of sanitary napkins used in the appropriate space according to the degree of blood stain or the amount of the blood clot on each sanitary napkin discarded. | about 30 days | 
| Uterine artery Pulsation index | Determination of uterine artery hemodynamics, can reflect the state of uterine blood circulation, the higher the uterine artery pulsation index, the decrease of blood flow, the lower the uterine artery pulsation index, the increase of blood flow or neo-vascularization | 3 months | 
| Uterine artery Resistance index | Determination of uterine artery hemodynamics, can reflect the state of uterine blood circulation, the higher the uterine artery resistance index, indicating less blood supply to uterine, the lower the uterine artery resistance index, the increased blood supply to uterine. | 3 months | 
| Uterine artery Systolic peak and diastolic peak ratio | The greater the ratio of uterine artery systolic peak to diastolic peak, indicating that the end-diastolic blood flow velocity is small and the peripheral resistance is large; conversely, the blood flow velocity is large and the peripheral resistance is small. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Dysmenorrhea, traditional Chinese medicine, low-level light therapy