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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hot Flashes; Acupuncture Therapy; Postmenopausal Symptoms; Perimenopausal Disorder
• Intervention / Treatment: Device: Electro Press Needle; Drug: Gamma-Oryzanol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shudan Yu, Doctor; Phone Number: 15011460149; Email: miaomiao101@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged between 40-60 years old;
2. 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 ;

3. Fulfilling either condition mentioned below:

   1. The last menstrual period was more than 12 months ago (including 12 months);
   2. In the late menopausal transition, and has amenorrhea for more than 60 days;
   3. FSH≥25IU, and has vasomotor symptoms of HF, sweating, insomnia, migraine, or restlessness, etc.
4. Volunteer to participate in this study and sign the informed consent.

Exclusion Criteria:

1. 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;
2. Bilateral salpingo-oophorectomy;
3. Amenorrhea secondary to premature ovarian failure, ovarian cyst or tumor, thyroid disease, hyperprolactinemia, or Cushing's syndrome, etc.;
4. Accepted acupuncture or drugs to treat the symptoms of HF within the previous 3 months;
5. Received radiotherapy or chemotherapy before;
6. Coagulation dysfunction, or taking warfarin, heparin and other anticoagulant drugs at present;
7. Suffering from skin diseases, such as eczema, psoriasis, etc.;
8. Severe hepatic and renal insufficiency;
9. Uncontrolled hypertension, diabetes or thyroid disease;
10. Diabetic neuropathy and mental illness (including depression);
11. Being pregnant, breastfeeding or planning to be pregnant during the trial;
12. Regular usage of sedatives or anti-anxiety drugs;
13. Smoking for more than 5 years (at least twenty cigarettes a day on average) , or with the problem of alcohol abuse;
14. Installation of pacemakers;
15. Poor compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electro Press Needle; 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; 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).; Other Names: Electro Thumb Needle
Active Comparator: Gamma-Oryzanol; 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; The patients in this group were given orally gamma-oryzanol tablets 20mg each time, three times a day, for 6 months.

What is the study measuring?

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 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 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 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants'acceptability towards EPN	Use the 3-point method to evaluate, unacceptable (0 points), acceptable (1 points), easy to accept (2 points), patients who cannot accept should be written the reason clearly.Only patients in electric press needle group will score.	week 1 and 3,at the end of the first and ninth treatments
Participants' belief that EPN might help	Participants in the EPN group will answer the following question before the first intervention: "Do you think acupuncture will be effective for treating the disease?"The participants can answer "Yes", "No", or "Unclear."	Baseline assessmentweek 0
Participants' expectations of improvement to menopausal associated hot flashes	Participants in the EPN group will answer the following question before the first intervention: "Do you think acupuncture will be effective for improving menopausal associated HF?" The participants can answer "Yes", "No", or "Unclear."	Baseline assessment week 0
Safety assessment	Adverse events and severe adverse events will be recorded in case report form, whether related to interventions or not.	Through study completion, an average of 30 weeks

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Estimated): June 19, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 19, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: gamma-oryzanol; Electro-Press Needle
• Additional Relevant MeSH Terms: Hot Flashes; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Ulcer Agents; Gamma-oryzanol
• Other Study ID Numbers: 2023DZMEC-155-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No