Clinical trial NCT05743218: Clinical Efficacy of Acupuncture on the Liver Meridian in Women With Diminished Ovarian Reserve
Official title: Clinical Study of Liver Meridian in the Treatment of Male Impotence and Female Premature Ovarian Failure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ovarian Reserve
Acupuncture Therapy
Meridian
Lead sponsor: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2023-02-24
Enrollment: 198
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The subjects were randomly assigned to the liver meridian group, the stomach meridian group and the non-acupoint acupuncture groups group at a ratio of 1:1:1.
Primary purpose: TREATMENT

Brief summary: Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes in the ovary, which results in impaired ovarian function and decreased fertility. Meanwhile, levels of the anti-Müllerian hormone (AMH), antral follicle count (AFC), and Follicle-Stimulating Hormone (FSH) also decrease in patients with DOR. In general, there is a decline in fertility and premature menopause. Some patients will have low menstrual volume, oligomenorrhea or even amenorrhea, abnormal uterine bleeding, ovulation disorders, infertility and perimenopausal performance before the age of 40, and eventually develop into premature ovarian failure. In recent years, with the changes of social culture, living environment, work pressure and other factors, the incidence of this disease has increased year by year, which has a great impact on women's fertility, mental health, quality of life, family relations and other aspects.

As a green and safe complementary and alternative therapy, acupuncture has been proved to be effective. According to the statistics, 904 (33.54%) of the 2695 syndromes indicated by acupoints of the liver meridian recorded in 93 ancient medical books are reproductive disorders, ranking first in the diseases indicated by the liver meridian and the 14 meridians. The body surface course of the liver meridian is closely related to the genitals, and there is a close relationship between the liver meridian and the genitals in physiology and pathology. According to the theory of the relationship between meridians and zangfu organs, the study aims to verify the efficacy and safety of acupuncture of the liver meridian and provide high-level research evidence for meridian syndrome differentiation of reproductive system diseases via "treatment from the liver."

Detailed description: This is an exploratory multicenter randomized controlled trial involving four clinical research centers, including the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Hubei Hospital of Traditional Chinese Medicine, Shaanxi Hospital of Traditional Chinese Medicine, and Guizhou Hospital of Traditional Chinese Medicine. Each clinical research center strictly screened cases according to the diagnostic criteria, inclusion criteria and exclusion criteria. After confirmation of enrollment, random numbers were obtained according to the application for random coding process until the total number of observation was completed. According to the sample size, a total of 198 patients with DOR need to be enrolled. The 29-week study period consists of a 4-week screening period, 1-week baseline period, 12-week treatment period, 12-week follow-up period, and assessments at baseline. He patients were randomly divided into three groups: the liver meridian, stomach meridian, and non-acupoint acupuncture groups. Due to the particularity of acupuncture research, it is impossible to blind acupuncture operators. Blinded evaluation will be adopted in the trial, and the third party who does not know the grouping will evaluate the efficacy. Blind statistical analysis was used in the data summary stage, and the researchers, operators and statisticians were separated. In the experimental group (liver meridian group), EA was applied to Taichong, Li gou, Ququan and Jimai. In the control group 1 (gastric meridian group), EA was applied to Chongyang, Fenglong, Zusanli and Biguan. In the control group 2 (the non-meridian non-acupoint group), 4 non-meridian non-acupoints were selected from the lateral thigh, the lateral calf and the lateral calcaneus, respectively (see the treatment methods of the non-meridian non-acupoint group for details) and stimulated with EA.

The main evaluation index will be Anti-Müllerian hormone(AMH), The secondary evaluation index include serum sex hormones (bFSH, bE2, bLH, bFSH/bLH), antral follicle count(AFC),, menstrual status, the modified Kupperman Index(KI), perimenopausal quality of life score (MENQOL) ,Self-Rating Anxiety Scale( SAS ), self-rating depression scale(SDS), Menstrual conditions. The patients were evaluated at different time points during the baseline period, treatment period and follow-up period, and the incidence of adverse events will be recorded. Double data entry will be used in this trial to ensure the accuracy of data entry. A three-level quality control system (self-inspection by each center, supervision by project management team, and third-party audit) was implemented to ensure that the implementation, recording and reporting of clinical trials were in accordance with the trial protocol, standard operating procedures, and relevant laws and regulations. The statistical analysis plan was developed by the statistical analysis principal and the principal investigators in accordance with the protocol and was finalized before the database was locked. The tables for the statistical analysis were developed. Statistical analysis will be calculated by SPSS25.0 statistical analysis software, P\<0.05 (i.e., =0.05) will be considered statistically significant, in order to clarify the efficacy and safety of acupuncture on DOR.

Eligibility criteria: Inclusion Criteria:

- The inclusion criteria are as follows:

1. patients with the detection indicators within 3 months before enrollment met the diagnostic criteria of DOR.
2. patients aged between 18 and 40 years old.
3. patients who have received no other treatment in the 2 months before enrollment. (4) patients who voluntarily participate in this study and can actively cooperate with the study process.

(5) patients who have signed an informed consent form. Patients who meet all five criteria will be eligible for this study.

Exclusion Criteria:

* (1) Patients with polycystic ovarian syndrome, hyperprolactinemia, pituitary or hypothalamic amenorrhea, thyroid dysfunction, congenital malformations, and organic lesions in the reproductive organs.

  (2) Patients with a history of local ovarian surgery, such as oophorectomy and ovarian tumor surgery.

  (3) Patients with a history of chemotherapy or pelvic radiotherapy and a history of therapy with immunosuppressive agents.

  (4) Patients with comorbidities in the cardiovascular system, liver, kidney, hematopoietic system, nervous and mental system, diabetes, hypertension, and other diseases.

  (5) Patients being administered estrogen, progesterone, or dehydroepiandrosterone (DHEA) within 2 months before enrollment.

  (6) Patients who cannot tolerate blood or ultrasound testing. (vii) Patients who are also participating in other clinical trials.

  (7) Patients who refuse to sign the informed consent form. Patients who meet any of the above criteria will be excluded.

Primary outcomes:
measure: The value of anti-mullerian hormone(AMH)
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
Secondary outcomes:
measure: The number of antral follicle count (AFC)
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: Sex hormone: follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2）
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: The total score of the modified Kupperman scale
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: The total score of the perimenopausal quality of life score
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: The total score of the self-rating anxiety Scale
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: The total score of the self-rating Depression Scale
timeFrame: 3 checkpoints. Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks) and enrollment 24 weeks(Changes at 12 weeks of treatment and 12 weeks of follow-up).
measure: Menstrual assessment
timeFrame: Enrollment 1、4、8、12、16、20、24 weeks.
Other outcomes:
measure: White blood cell (WBC)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks).
measure: Red blood cell (RBC)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Blood platelet
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Hemoglobin
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Alanine aminotransferase(ALT)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Aspartate aminotransferase (AST)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Blood - urea nitrogen (UREA)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Creatinine (CREA)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Prothrombin time (PT)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Activated partial thromboplastin time(ATPP)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Thrombin time(TT)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
measure: Fibrinogen concentration(FBI)
timeFrame: Baseline period(1 week before enrollment), enrollment 12 weeks (Change from Baseline at 12weeks)
Locations:
city: Changsha
country: China
facility: The First Affiliated Hospital of Hunan University of Chinese Medicine
state: Hunan
Study officials:
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