Clinical trial NCT03709849: Effectiveness and Safety of Bushen Culuan Decoction for Anovulatory Infertility
Official title: Effectiveness and Safety of Bushen Culuan Decoction for Anovulatory Infertility：A Clinical Research of "Same Treatment for Different Diseases"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Anovulatory Infertility
Abnormal Uterine Bleeding-Ovulatory Disorders
Polycystic Ovarian Syndrome
Hyperprolactinemia
Luteinized Unruptured Follicle Syndrome
Corpus Luteum Insufficiency
Ovarian Insufficiency
Keywords: Anovulatory Infertility
Bushen Culuan Decoction
Lead sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: Dongzhimen Hospital, Beijing
name: Beijing Obstetrics and Gynecology Hospital
name: Beijing Hospital of Traditional Chinese Medicine
name: Beijing First Hospital of integrated Chinese and Western Medicine
name: Beijing Fengtai Hospital of Integrated Traditional and Western Medicine
First posted: 2018-10-17
Enrollment: 528
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pregnancy Rate
timeFrame: Within 12 menstrual cycles from the first time that patient taking medicines. (Each cycle is 28 days)
Secondary outcomes:
measure: Ovulation Rate
timeFrame: 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)
measure: Basal Body Temperature
timeFrame: 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)
measure: Endocrine Hormone
timeFrame: 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)
measure: Inhibin B
timeFrame: 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)
measure: Anti-Mullerian Hormone (AMH)
timeFrame: 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)
measure: Antral Follicle Count
timeFrame: 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)
measure: Volume of Uterus and Bilateral Ovaries at the Early Follicle Phase
timeFrame: 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)
measure: Thickness of Endometrium at the Early Follicle Phase
timeFrame: 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)
measure: Type of Endometrium at the Early Follicle Phase
timeFrame: 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)
measure: the Size of Dominant Follicle
timeFrame: 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)
measure: Peak-Systolic Flow Velocity of Uterus and Bilateral Ovaries
timeFrame: 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)
measure: Pulsatility Index of Uterus and Bilateral Ovaries
timeFrame: 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)
measure: Resistant Index of Uterus and Bilateral Ovaries
timeFrame: 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)
measure: Coagulation Indicator
timeFrame: 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)
measure: Traditional Chinese Medicine Symptom Score
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
affiliation: Xiyuan Hospital of China Academy of Chinese Medical Sciences
name: Kun Ma, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ma K, Shi Y, He J, Teng X, Wang R, Wang G, Yu Y, Chen Y, Gong L, Yuan Y, Zhang H, Yuan B, Zhang C. The effect of Bushen Culuan Decoction on anovulatory infertile women among 6 different diseases: a study protocol for a randomized, double-blinded, positively controlled, adaptive multicenter clinical trial. Trials. 2022 Jul 8;23(1):563. doi: 10.1186/s13063-022-06289-7.