Effect and Safety of Electroacupuncture for Symptoms of Menopausal Transition

Study Overview
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Brief Summary
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The primary object is to evaluate the efficacy and safety of electroacupuncture for symptoms of women during menopausal transition .

Detailed Description
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Menopause transition is called perimenopause in the past time. 40-80% women aged 40 to 65 have symptoms during this period. Hormone therapy is the recommended therapy for menopause and there is not enough evidence in favor of alternative medicine's effect. Our pilot trial showed that electroacupuncture had better effect for menopause transition symptoms than sham electroacupuncture. We are going to conduct a phase Ⅱ clinical trial to further evaluate the safety and effect of electroacupuncture for menopause transition symptoms.

Official Title
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Effect and Safety of Electroacupuncture for Symptoms of Menopausal Transition -a Multicenter Randomized Controlled Trial

Conditions
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Menopausal Syndrome

Intervention / Treatment
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* Other: electroacupuncture
* Other: sham electroacupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cycle irregularity (periods occur 7 days or over earlier or later ) in the past 12 months (early menopausal transition); subjects with the last menstruation at least 2 but no longer than 12 months in the past 12 months (late menopausal transition). Menopausal transition symptoms such as hot flushes, sweating, sleep disturbance, migraine, anxiety, vaginal dryness and sexual problems. 40 to 55 years old. Volunteer to join in the trial and sign the informed consent. Patients conformed with the 4 items at the same time will be included. - Exclusion Criteria: Regular cycles during the past 3 months before enrollment. use of estrogen, SSRIs, soybean isoflavone, progestin, vitamin E or black sesame in the past 4 weeks. Patients with ovarian cyst, uterine myoma (diameter≥4cm) or after hysterectomy/ ovariectomy. Patients with radiochemotherapy history or undergoing radiochemotherapy. Cryptogenic vaginal bleeding Coagulation disorder or use of anticoagulants like warfarin and heparin sodium. Existing skin diseases like eczema or psoriasis. Severe hepatic/renal insufficiency. Insufficiently controlled hypertension, diabetes or thyroid diseases. Existing diabetic neuropathy, malignant tumor and psychiatric disorders. Wish to become pregnant or is pregnant or breast-feeding. Regular use of sedative or anxiolytic. Smoking or alcohol intake. Subjects with mandatory indication for HT (e.g. postsurgical menopause or active osteoporosis). With cardiac pacemaker or artificial joint.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 55 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: electroacupuncture<br>Electroacupuncture at RN4, EX-CA1，ST25, SP6 (double sides). One session will be given every two days, 3 sessions per week (24 sessions in all) and each session lasts for 30 minutes. | Other: electroacupuncture<br>* Stick adhesive tapes to all points. For ST25, EX-CA1 and RN4, insert the needle vertically through the pads and the skin, and then slowly and vertically penetrate through the layer of fatty tissue, into the muscles of the abdominal wall .For RN4, manipulate the needle with an even lifting, thrusting and twisting method slightly for 3 times. Insert the needle vertically at SP6 to a depth of 1 cm. Manipulate the needle with an even lifting, thrusting and twisting method slightly for 3 times to reach de-qi. Put the electric stimulator on the pair of EX-CA1 and ST25 points with a dilatational wave, 10/50 Hz, 0.5-1.0mA. To turn on the current intensity till the abdomen shivers. The same manipulation methods for RN4 and SP6 will be given every 10 minutes (3 times in all).<br>|
| Sham Comparator: sham electroacupuncture<br>Sham electroacupuncture at non-points proximate to RN4 (P1), EX-CA1(P2)，ST25 (P3) and SP6 (P4) (double sides).Specially constructed EA apparatus were used with no skin penetration, electricity output, or de qi requirement for needle manipulation One session will be given every two days, 3 sessions per week (24 sessions in all) and each session lasts for 30 minutes. | Other: sham electroacupuncture<br>* Non-points proximate to RN4 (P1), EX-CA1(P2)，ST25 (P3) and SP6 (P4) (double sides) are used.P1 and P3 are at the sites 1 cm (outward in horizontal direction) proximate to RN4 and ST25 respectively. P2 is 2 cm (outward in horizontal direction) proximate to EX-CA1. P4 is at the middle site of the spleen meridian and the kidney meridian (backward in horizontal direction proximate to SP6). Stick adhesive tapes to all points. Blunt needles will be used to be inserted to but not piercing the skin. Even lifting, thrusting and twisting manipulation methods will be given for each non-point for 3 times. Put the sham electric stimulator on the pair of P2 and P3 with the same parameters as the acupuncture group. But there is no current intensity actually.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Menopause Rating Scale Total Score | The change in menopause rating scale (MRS) total score compared with baseline at week 8 equals MRS total score at week 8 minus MRS total score at baseline. MRS is a self-report questionnaire for evaluating the severity of menopausal symptoms in women, which contains 11 items. Each of the 11 symptoms contained a scoring scale from 0 (no complaints) to 4 (very severe symptoms). The total score will be calculated as the all items ranging from 0 to 44, with higher scores indicating worse symptoms. The MRS including 3 dimensions: psychological, somatic-vegetative, and urogenital. | at baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Menopause Rating Scale Total Score | The change in Menopause Rating Scale (MRS）total score compared with baseline at weeks 4, 20 and 32 equals MRS total score at weeks 4, 20 and 32 minus MRS total score at baseline,respectively. MRS is a self-report questionnaire for evaluating the severity of menopausal symptoms in women, which contains 11 items. Each of the 11 symptoms contained a scoring scale from 0 (no complaints) to 4 (very severe symptoms). The total score will be calculated as the all items ranging from 0 to 44, with higher scores indicating worse symptoms. The MRS including 3 dimensions: psychological, somatic-vegetative, and urogenital. | at baseline，and weeks 4, 20 and 32 | 
| Change From Baseline in Somatic-vegetative Domain of Menopause Rating Scale | The change from baseline in somatic-vegetative domain of Menopause Rating Scale(MRS) at weeks 4, 8, 20 and 32 equals the somatic-vegetative domain of MRS at weeks 4, 8, 20 and 32 minus the somatic-vegetative domain of MRS at baseline, respectively. The somatic-vegetative domain contains 4 items (items 1-3 and 11). Each of the item scores ranges from 0 to 4. The somatic-vegetative domain score will be calculated as the all somatic-vegetative items ranging from 0 to 16, with higher scores indicating worse symptoms. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in Psychological Domain of Menopause Rating Scale | The change from baseline in psychological domain of Menopause Rating Scale(MRS) at weeks 4, 8, 20 and 32 equals the psychological domain of MRS at weeks 4, 8, 20 and 32 minus the psychological domain of MRS at baseline, respectively. The psychological domain contains 4 items (items 4-7). Each of the item scores ranges from 0 to 4. The psychological domain score will be calculated as the all psychological items ranging from 0 to 16, with higher scores indicating worse symptoms. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in Urogenital Domain of Menopause Rating Scale | The change from baseline in urogenital domain of Menopause Rating Scale(MRS) at weeks 4, 8, 20 and 32 equals the urogenital domain of MRS at weeks 4, 8, 20 and 32 minus the urogenital domain of MRS at baseline, respectively. The urogenital domain contains 3 items (items 8-10). Each of the item scores ranges from 0 to 4. The psychological domain score will be calculated as the all urogenital items ranging from 0 to 12, with higher scores indicating worse symptoms. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in Mean 24-h Hot Flash Score | The 24-h hot flash score was daily hot flash episodes multiplied by the corresponding severities. The change from baseline in mean 24-h HF score at weeks 4, 8, 20 and 32 equals the mean 24-h HF score at weeks 4 , 8, 20 and 32 minus the mean 24-h HF score at baseline, respectively. Hot flashes score consisted the number and the degree of hot flashes. The hot flashes score is the sum of the scores of all the hot flashes occurring in a whole day, with a higher score indicating worse symptoms. A 3-point rating scale allows the women to describe the perceived severity of hot flash. 1 point = mild hot flash, 2 point = moderate hot flash, 3 point = severe hot flash. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in Menopause-Specific Quality of Life Questionnaire Total Score | The change from baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) total score at weeks 4, 8, 20 and 32 equals the MENQOL total score at weeks 4, 8, 20 and 32 minus the MENQOL score at baseline, respectively. It composed of 29 items and was divided into four domains: vasomotor (items 1-3), psychosocial (items 4-10), physical (items 11-26), and sexual (items 27-29). Each of the item scores ranges from 0 to 6. The total score will be calculated as the all items ranging from 0 to 174, with lower scores indicating a better quality of life. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in the Vasomotor Domain of Menopause-Specific Quality of Life Questionnaire | The change from baseline in the vasomotor domain of Menopause-Specific Quality of Life Questionnaire (MENQOL) at weeks 4, 8, 20 and 32 equals the vasomotor domain of MENQOL at weeks 4, 8, 20 and 32 minus the vasomotor domain of MENQOL at baseline, respectively. The vasomotor domain contains 3 items (items 1-3). Each of the item scores ranges from 0 to 6. The vasomotor domain score will be calculated as the all vasomotor items ranging from 0 to 18, with lower scores indicating a better quality of life. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in the Psychosocial Domain of Menopause-Specific Quality of Life Questionnaire | The change from baseline in the psychosocial domain of Menopause-Specific Quality of Life Questionnaire (MENQOL) at weeks 4, 8, 20 and 32 equals the psychosocial domain of MENQOL at weeks 4, 8, 20 and 32 minus the psychosocial domain of MENQOL at baseline, respectively. The psychosocial domain contains 7 items (items 4-10). Each of the item scores ranges from 0 to 6. The vasomotor domain score will be calculated as the all psychosocial items ranging from 0 to 42, with lower scores indicating a better quality of life. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in the Physical Domain of Menopause-Specific Quality of Life Questionnaire | The change from baseline in the physical domain of Menopause-Specific Quality of Life Questionnaire (MENQOL) at weeks 4, 8, 20 and 32 equals the physical domain of MENQOL at weeks 4, 8, 20 and 32 minus the physical domain of MENQOL at baseline, respectively. The physical domain contains 16 items (items 11-26). Each of the item scores ranges from 0 to 6. The vasomotor domain score will be calculated as the all physical items ranging from 0 to 96, with lower scores indicating a better quality of life. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in the Sexual Functioning Domain of Menopause-Specific Quality of Life Questionnaire | The change from baseline in the sexual functioning domain of Menopause-Specific Quality of Life Questionnaire (MENQOL) at weeks 4, 8, 20 and 32 equals the sexual functioning domain of MENQOL at weeks 4, 8, 20 and 32 minus the sexual functioning domain of MENQOL at baseline, respectively. The sexual functioning domain contains 3 items (items 27-29). Each of the item scores ranges from 0 to 6. The vasomotor domain score will be calculated as the all sexual functioning items ranging from 0 to 18, with lower scores indicating a better quality of life. | at baseline, and weeks 4, 8, 20 and 32 | 
| Change From Baseline in Serum FSH Level | The change from baseline in serum FSH level at weeks 8 and 20 equals FSH at weeks 8 and 20 minus FSH at baseline, respectively. | at baseline, and weeks 8 and 20 | 
| Change From Baseline in Serum E2 Level | The change from baseline in serum E2 level at weeks 8 and 20 equals E2 at weeks 8 and 20 minus E2 at baseline, respectively. | at baseline, and weeks 8 and 20 | 
| Change From Baseline in Serum LH Level | The change from baseline in serum LH level at weeks 8 and 20 equals LH at weeks 8 and 20 minus LH at baseline, respectively. | at baseline, and weeks 8 and 20 | 
| Change From Baseline in Serum FSH/LH Level | The change from baseline in serum FSH/LH at weeks 8 and 20 equals FSH/LH at weeks 8 and 20 minus FSH/LH at baseline, respectively. | at baseline, weeks 8 and 20 | 
| Number of Participants Who Used Other Treatment During Study | The number and percentage of patients who used other treatments will be compared between groups during weeks 1-8 and 9-32. | weeks 1-8; weeks 9-32 |