Effectiveness of Electro-Press Needle and Gamma-Oryzanol for Menopause-associated Hot Flashes

Study Overview
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Brief Summary
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The investigators plan to conduct the randomized controlled trial to evaluate the effectiveness of electro-press needle (EPN), a novel acupuncture needle combining shallow and gentle insertion with transdermal electrical stimulation, on menopause-associated hot flash in comparison with gamma-oryzanol group among women during menopausal transition and postmenopausal periods.

Detailed Description
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As the most common type of menopause-associated symptoms, hot flashes affect up to 85% of women aging between 40 and 65 years . In China, women suffer from hot flushes as long as 4 to 5 years on average, some of whom may bear the symptoms for 12 years.Hormone replacement therapy (HRT) is generally recommended to relieve menopause-associated hot flashes.However, long-term usage of HRT may increase the incidence of endometrial, breast and ovarian cancer, thrombosis and strokes.Results of previous studies indicated that acupuncture might help to relieve the symptoms.There is insufficient evidence supporting its effectiveness for relieving the hot flash symptom.

Official Title
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Effectiveness and Safety of Electro-press Needle and Gamma-oryzanol for Menopause-associated Hot Flashes: Protocol of a Randomized Controlled Trial

Conditions
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Hot Flashes, Acupuncture Therapy, Perimenopausal Disorder, Postmenopausal Symptoms

Intervention / Treatment
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* Device: Electro Press Needle
* Drug: Gamma-Oryzanol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 40-60 years old; Scoring 14 points or more in at least one day during the one-week baseline assessment, or having an average of ≥ 7 moderate or severe heating per 24 hours recorded in HF Dairy ; Fulfilling either condition mentioned below: The last menstrual period was more than 12 months ago (including 12 months); In the late menopausal transition, and has amenorrhea for more than 60 days; FSH≥25IU, and has vasomotor symptoms of HF, sweating, insomnia, migraine, or restlessness, etc. Volunteer to participate in this study and sign the informed consent. Exclusion Criteria: Usage of HRT via transdermal administration in the previous one month, or via oral or intrauterine administration in the previous two months; usage of phytoestrogens therapy, transvaginal estrogen administration, or estrogen or progesterone injections in the previous three months; Bilateral salpingo-oophorectomy; Amenorrhea secondary to premature ovarian failure, ovarian cyst or tumor, thyroid disease, hyperprolactinemia, or Cushing's syndrome, etc.; Accepted acupuncture or drugs to treat the symptoms of HF within the previous 3 months; Received radiotherapy or chemotherapy before; Coagulation dysfunction, or taking warfarin, heparin and other anticoagulant drugs at present; Suffering from skin diseases, such as eczema, psoriasis, etc.; Severe hepatic and renal insufficiency; Uncontrolled hypertension, diabetes or thyroid disease; Diabetic neuropathy and mental illness (including depression); Being pregnant, breastfeeding or planning to be pregnant during the trial; Regular usage of sedatives or anti-anxiety drugs; Smoking for more than 5 years (at least twenty cigarettes a day on average) , or with the problem of alcohol abuse; Installation of pacemakers; Poor compliance.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 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: Electro Press Needle<br>Body acupoints of Yintang (GV29), Dazhui (GV14), Guanyuan (CV4), bilateral Zigong (EX-CA1), and bilateral Sanyinjiao (SP6) and auricular acupoints of Heart (CO15), Chuiqian (LO4) and Shenmen (TF4) will be selected for treatment. Auricular acupoints on right and left ear will be stimulated alternatively, one side on each time.The treatment will last 40mins for each session, 3 sessions a week (ideally every other day) for a succession of 6 weeks. | Device: Electro Press Needle<br>* Body acupoints will be stimulated by the press needles 0.25mm in diameter and 2mm in length and ear acupoints will be stimulated by the press needles 0.25mm in diameter and 0.9mm in length (all from ZhenXing Brand, Hangzhou Yuanli Medical Appliance Factory, China). After sterilization of the local skin, the needle will be pressed to the acupoints and the tape will be sticked to the skin. Then, the electric device (φ44×15.8mm Type ZXHPAMDZB-02C) together with the electrode patch will be sticked to the surface of skin (on top of the sticky tapes of the press needle) in the area of CV4 and bilateral EX-CA1, and bilateral SP6 respectively. The electric device will be switch to the mode of dense intermittent wave, and the current intensity will be increased gradually till the muscles around jumps slightly.All the needles on the body acupoints will be removed after each session, while those on the auricular acupoints can be kept for as long as 6 hours (removed before going to bed).<br>* Other names: Electro Thumb Needle;|
| Active Comparator: Gamma-Oryzanol<br>The patients in this group were given 10mgx100 tablets/bottle of gamma-oryzanol tablets (Tianjin Lishen Pharmaceutical), 20mg each time, three times a day, for 6 months. | Drug: Gamma-Oryzanol<br>* The patients in this group were given orally gamma-oryzanol tablets 20mg each time, three times a day, for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with a reduction of 50% or more on the mean 24-hour HF score from baseline | The mean 24-hour HF score = (1 × number of mild HF + 2 × number of moderate HF + 3 × number of severe HF + 4 × number of very severe HF)/Number of days reported. | week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of participants with a reduction of 50% or more on the mean 24-hour HF score from baseline | The mean 24-hour HF score = (1 × number of mild HF + 2 × number of moderate HF + 3 × number of severe HF + 4 × number of very severe HF)/Number of days reported. | week 3,18,30 | 
| The proportion of participants with a reduction of 50% or more in the mean 24-hour HF frequency from baseline24-hour HF score from baseline | The mean 24-hour HF frequency = total number of HF reported/Number of days reported. | week 3,6,18,30 | 
| The proportion of patients with at least a 50% reduction in the mean 24-hour HF severity from baselineHF frequency from baseline24-hour HF score from baseline | The mean 24-hour HF severity = (1 × number of mild HF + 2 × number of moderate HF + 3 × number of severe HF + 4 × number of very severe HF)/ Number of HF reported. | week 3,6,18,30 | 
| The changes in the mean 24-h HF score from baseline | The mean 24-hour HF score = (1 × number of mild HF + 2 × number of moderate HF + 3 × number of severe HF + 4 × number of very severe HF)/Number of days reported. | week 3,6,18,30 | 
| The change of Menopause rating scale (MRS) score from baseline | MRS is a common menopause specific subscale, including 11 items from psychological, somatic to urogenital, with 5 as minimal clinically important differences(MCID). | week 6,18 and 30 | 
| The change of Menopause-Specific Quality of Life Questionnaire (MENQOL) score from baseline | MENQOL consists of 29 items assessing four domains: VMS, physical symptoms, psychological symptoms, and urogenital/sexual symptoms,with 4 as minimal clinically important differences(MCID). | week 6,18 and 30 | 
| Time domain analysis of 24-hour heart rate variability(HRV) | The indexes included total autonomic energy (SDNN) and sympathetic sensation Nerve tone (SDANN) and vagal tone (rMSSD) | week 6,30 | 
| Frequency domain analysis of 24-hour heart rate variability(HRV) | the indexes included total power spectrum (TP) reflecting the total energy of autonomic nerve, The low frequency power (LF, 0.04 0.15Hz) reflects the sympathetic nerve activity and the high vagus nerve activity.Frequency power (HF, 0.15 0.4Hz), LF/HF reflecting the balance between sympathetic and vagal tension. | week 6,30 | 
| The proportion of participants reporting significantly reduced or moderately reduced based on Global Response Assessment (GRA) | The response of participants to the treatments are divided into seven grades by GRA: significantly reduced, moderately reduced, slightly reduced, no change, slightly aggravated, moderately aggravated and significantly aggravated. The proportion of participants reporting significantly reduced or moderately reduced are recorded as the response rate of the overall efficacy. | week 3,6,18,30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gamma-oryzanol, Electro-Press Needle