Effectiveness and Safety of Bushen Culuan Decoction for Anovulatory Infertility

Polycystic Ovarian Syndrome Clinical Trial

Official title:

Effectiveness and Safety of Bushen Culuan Decoction for Anovulatory Infertility：A Clinical Research of "Same Treatment for Different Diseases"

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03709849
• Other study ID #: Z171100001017104
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 1, 2019
• Est. completion date: August 31, 2020

Study information

• Verified date: August 2018
• Source: Xiyuan Hospital of China Academy of Chinese Medical Sciences
• Contact: Kun Ma, Dr.
• Phone: 86-010-64089750
• Email: makun12348[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the effectiveness and safety of Bushen Culuan Decoction in the treatment of anovulatory infertility, including anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency and ovarian insufficiency, through a randomised, double-blinded, double-dummy, parallel positive controlled, adaptive multicenter clinical trial.

Description:

Anovulation is one of the main causes of female infertility. Anovulatory infertility account for a proportion of 25-30% in whole female infertility.

In western medicine, hormone induced ovulation and assisted reproduction technology are two main ways to solve the problem and Clomiphene citrate is the first-line medication in ovulation induction. There are many side effects being reported in the treatment with modern medicine technique such as ovarian hyperstimulation syndrome, complication with uteroscope and puncture egg retrieval, low pregnancy rate with high ovulation rate, potential cancer occuring risk and offspring healthy risk.

Bushen Culuan Decoction is a traditional Chinese medicine recipe with 10 Chinese herbs including Tusizi, Yinyanghuo, Xianmao, Xuduan, Gouqizi, Nvzhenzi, Zelan, Shengpuhuang, Xiangfu and Chuanshanlong. Previous laboratory and exploratory clinical researches have proved Bushen Culuan Decoction had an exactly efficacy in treating anovulatory infertility safely.

In the first stage, the primary sample size In the study is 528. Half patients will receive Bushen Culuan Decoction and clomiphene citrate placebo, while the other half will receive clomiphene citrate tablets and Bushen Culuan Decoction placebo. When 1/3 of 528 patients complete the treatment, we will analysis the treatment efficacy of 6 diseases separately, and find which of them could be the target diseases of Bushen Culuan Decoction. Then we will modify the sample size depending on the result in first stage, and the research will only be processed in the target diseases being chosen. In the next stage, half patients will receive Bushen Culuan Decoction and clomiphene citrate placebo, while the other half will receive clomiphene citrate tablets and Bushen Culuan Decoction placebo.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 528
• Est. completion date: August 31, 2020
• Est. primary completion date: March 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 21 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Aged 21~40 years old;

2. Diagnosed with infertility;

3. Diagnosed with one of below diseases: anovulatory abnormal uterine bleeding, polycystic ovarian syndrome, hyperprolactinemia, luteinized unruptured follicle syndrome, corpus luteum insufficiency and ovarian insufficiency,

4. Diagnosed with TCM syndrome of kidney deficiency and blood stasis syndrome;

5. Patients who has normal sexual intercourse during treatment;

6. Voluntary to sign the informed consent.

Exclusion Criteria:

1. Infertility due to congenital physiological defect or malformation;

2. Infertility due to hereditary factors;

3. Infertility due to oviduct defect, immune factors, uterine fibroid, adenomyosis, endometriosis or hypoplasia of uterus;

4. Spouse has reproductive defects;

5. Severe abnormity of cardiovascular system, liver function, kidney function or hemopoietic system;

6. Allergy to experimental drugs

Related Conditions & MeSH terms

• Abnormal Uterine Bleeding-Ovulatory Disorders
• Anovulation
• Anovulatory Infertility
• Corpus Luteum Insufficiency
• Hyperprolactinemia
• Infertility
• Luteinized Unruptured Follicle Syndrome
• Ovarian Insufficiency
• Polycystic Ovarian Syndrome
• Polycystic Ovary Syndrome
• Syndrome
• Uterine Hemorrhage

Intervention

Drug:
• experimental group: Bushen Culuan Decoction and Clomiphene Citrate Tablets placebo
the same as group description including dosage, frequency and duration
• control group: Clomiphene Citrate Tablets and Bushen Culuan Decoction placebo
the same as group description including dosage, frequency and duration

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Xiyuan Hospital of China Academy of Chinese Medical Sciences	Beijing Fengtai Hospital of Integrated Traditional and Western Medicine, Beijing First Hospital of integrated Chinese and Western Medicine, Beijing Hospital of Traditional Chinese Medicine, Beijing Obstetrics and Gynecology Hospital, Dongzhimen Hospital, Beijing

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancy Rate		Within 12 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Secondary	Ovulation Rate	If the patient participate 1 treatment cycle, the ovulation will be measured 3 menstrual cycles, and if the patient participate 2 treatment cycle, the ovulation will be measured 6 menstrual cycles.	At every ovulation phase (about day14 in a period cycle) within 3 or 6 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Secondary	Basal Body Temperature		At every morning within 3 or 6 menstrual cycles from the first time that patient taking medicines to the end of the treatment. (Each cycle is 28 days)
Secondary	Endocrine Hormone	Including Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin (PRL), Estradiol (E2), Progesterone(P), Testosterone (T).	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Inhibin B		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Anti-Mullerian Hormone (AMH)		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Antral Follicle Count		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Volume of Uterus and Bilateral Ovaries at the Early Follicle Phase		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Thickness of Endometrium at the Early Follicle Phase		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Type of Endometrium at the Early Follicle Phase	The type of endometrium is measured by ultrasound. The type of endometrium contains type A, B, and C. Type A means the endometrium thickness is about 4-9mm, and there is a "trilaminar patterns" in the image. Type B means the endometrium thickness is about 9-12mm, the image shows moderate homogeneous echo. Type C means the endometrium thickness is about 10-14mm with a strong homogeneous echo. The type only represents different forms of endometrium, but not represents endometrium level or grade.	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	the Size of Dominant Follicle		At every ovulation phase (about day14 in a period cycle) within 3 or 6 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Secondary	Peak-Systolic Flow Velocity of Uterus and Bilateral Ovaries		At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Pulsatility Index of Uterus and Bilateral Ovaries	Pulsatility Index (PI) of Uterus and Bilateral Ovaries is the pulsatility index of uterine arteries and bilateral ovarial arteries. The normal range of uterine PI has no unified standard, but the smaller the index is, the better the endometrial receptivity is. Generally, when uterine PI<2, the endometrial receptivity will be good enough to get zygote implantation, and when uterine PI>3, the endometrial receptivity is too improper to get zygote implantation.	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Resistant Index of Uterus and Bilateral Ovaries	Resistant Index (RI) of Uterus and Bilateral Ovaries is the resistant index of uterine arteries and bilateral ovarial arteries. The normal range of uterine RI has no unified standard, but the smaller the index is, the better the endometrial receptivity is.	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Coagulation Indicator	Including prothrombin time, activated partial thromboplastin time, fibrinogen and thrombin time	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)
Secondary	Traditional Chinese Medicine Symptom Score	Traditional Chinese Medicine Symptom Score (point) including: amenorrhea (0-3); delayed menstruation (0-3); scant menstruation (0-3); weakness in lower back, waist and knees (0-3); dizziness and tinnitus (0-3); sexual apathy (0-3); fatigue (0-3); colorless transparent urination(0-3); frequent urination at night (0-3); feeling obstruction with menstruation (0-3); profuse menstruation with dark color (0-3); clot in menstruation (0-3); stabbing pain in lower abdomen area, may aggravating with sexual intercourse (0-3); dysmenorrhea (0-3) The total score will be measured by summing the subitems' score above, and the total score range is 0-42. The higher the score is, the worse the situation is.	At the early follicle phase (day 3 in a period cycle) before the 1st cycle of the treatment and at the 7th cycle of the treatment. (Each cycle is 28 days)