Acupuncture and Clomiphene Citrate on Live Birth in Anovulatory Women With Polycystic Ovary Syndrome

Infertility Clinical Trial

— PCOSAct  

Official title:

Effect of Acupuncture and Clomiphene Citrate on Live Birth in Anovulatory Women With Polycystic Ovary Syndrome: A Randomized Controlled Trial (PCOSAct)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01573858
• Other study ID #: PCOSAct
• Status: Completed
• Phase: N/A
• Start date: July 6, 2012
• Est. completion date: October 7, 2015

Study information

• Verified date: August 2021
• Source: Heilongjiang University of Chinese Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of the present trial are to test the following three hypotheses in anovulatory women with PCOS:

1. Acupuncture protocol 1 plus CC (Arm A) is more likely to result in live birth than acupuncture protocol 2 combined with CC (Arm B),

2. Acupuncture protocol 2 plus CC (Arm B) is more likely to result in live birth than acupuncture protocol 1 plus placebo (Arm C),

3. Acupuncture protocol 1 plus placebo (Arm C) is more likely to result in live birth than acupuncture protocol 2 plus placebo (Arm D).

Description:

This is a multicenter, randomized, controlled, 2 by 2 factorial clinical trial for Chinese women with PCOS.

Primary outcomes:

• Live birth rate

Secondary outcomes:

• Ovulation rate

• Ongoing pregnancy rate

• Multiple pregnancy rate

• Miscarriage rate

• Hormonal profile

• Metabolic profile

• Side effect profile

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: October 7, 2015
• Est. primary completion date: November 8, 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

1. Inclusion Criteria:

• Age of women between 20 and 40 years.

• Confirmed diagnosis of PCOS according to the modified Rotterdam criteria and all subjects must have anovulation plus either polycystic ovaries and/or hyperandro-genism.

• Patency of at least one tube and a normal uterine cavity shown by hysterosalpingogram, HyCosi or diagnostic laparoscopy.

• Semen analysis:

1. a. Sperm concentration =15×106/ml and b. total motility (a+b+c) =40% or forward motility (a+b) =32% in the semen analysis of the husband (based on World Health Organization, 2010).

2. Total motile sperm count =9 million [based on WHO (2010) criteria, volume 1.5 ml; conc 15 million; motility 40%. 1.5 x 15 x 0.04=9 million].

2. Exclusion Criteria:

• Exclusion of other endocrine disorders

• Patients with hyperprolactinemia (defined as two prolactin levels at least one week apart 25 ng/mL or greater or as determined by local normative values). The goal of eliminating patients with documented hyperprolactinemia is to decrease the heterogeneity of the PCOS population. These patients may be candidates for ovulation induction with alternate regimens (dopamine agonists). A normal level within the last year or on treatment is adequate for entry.

• Patients with FSH levels > 15 mIU/mL. A normal level within the last year is adequate for entry.

• Patients with uncorrected thyroid disease (defined as TSH < 0.2 mIU/mL or > 5.5 mIU/mL). A normal level within the last year is adequate for entry.

• Patients diagnosed with Type I or Type II diabetes who are poorly controlled (defined as a glycohemoglobin level > 7.0%), or patients receiving antidiabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas likely to confound the effects of study medication; patients currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded.

• Patients with suspected Cushing's syndrome.

• Use of hormonal or other medication including Chinese Herbal prescriptions which may affect the outcome at least in the past 2 months.

• Pregnancy within the past 6 weeks.

• Within 6 weeks post-abortion or postpartum.

• Breastfeeding within the last 6 months.

• Acupuncture within the last 6 months.

• Not willing to give written consent to the study.

• Additional exclusion criteria

• Patients on oral contraceptives, depot progestins, or hormonal implants (including Implanon). A two month washout period will be required prior to screening for patients on these agents. Longer washouts may be necessary for certain depot contraceptive forms or implants, especially where the implants are still in place. A one-month washout will be required for patients on oral cyclic progestins.

• Patients with liver disease defined as AST or ALT > 2 times normal or total bilirubin >2.5 mg/dL. Patients with renal disease defined as BUN > 30 mg/dL or serum creatinine> 1.4 mg/dL.

• Patients with significant anemia (Hemoglobin < 10 g/dL).

• Patients with a history of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident.

• Patients with known heart disease that is likely to be exacerbated by pregnancy.

• Patients with a history of, or suspected cervical carcinoma, endometrial carcinoma, or breast carcinoma. A normal Pap smear result will be required for women 21 and over.

• Patients with a current history of alcohol abuse. Alcohol abuse is defined as > 14 drinks/week or binge drinking.

• Patients enrolled simultaneously into other investigative studies that require medications, proscribe the study medications, limit intercourse, or otherwise prevent compliance with the protocol.

• Patients who anticipate taking longer than a one month break during the protocol should not be enrolled.

• Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, GnRH agonists and antagonists, antiandrogens, gonadotropins, anti-obesity drugs, Chinese herbal formula, anti-diabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, ACE inhibitors, and calcium channel blockers. The washout period on all these medications will be two months.

• Patients with a suspected adrenal or ovarian tumor secreting androgens.

• Couples with previous sterilization procedures (vasectomy, tubal ligation) which have been reversed. The prior procedure may affect study outcomes, and patients with both a reversed sterilization procedure and PCOS are rare enough that exclusion should not adversely affect recruitment.

• Subjects who have undergone a bariatric surgery procedure in the recent past (< 12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon.

• Patients with untreated poorly controlled hypertension defined as a systolic blood pressure 160 mm Hg or a diastolic 100 mm Hg obtained on two measures obtained at least 60 minutes apart.

• Patients with known congenital adrenal hyperplasia.

Related Conditions & MeSH terms

• Infertility
• Polycystic Ovary Syndrome
• Pregnancy
• Syndrome

Intervention

Other:
• Acupuncture treatment 1
Two sets of acupuncture points will be alternated every second treatment. The first set consists of CV3, CV 6, and ST 29 bilaterally,SP 6 and SP 9 bilaterally. Needles will also be placed in LI bilaterally and GV 20. CV 3, CV 6, ST 29, SP 6, and SP 9 will be connected to and electrical stimulator and stimulated with low-frequency EA of 2Hz, 0.3 ms.
• Acupuncture treatment 2
Needles will be inserted to a depth of <5 mm, one in each shoulder and on in each upper arm at non-acupuncture points. Electrodes will be attached to the needles and the stimulator will be turned on at an intensity of zero (no active current) in order to mimic EA in the acupuncture treatment 1. No manual stimulation of the needles will be performed.
• CC
CC 50 mg every day for 5 days (day 3-7 of cycle), for a total of 4 cycles. Non-response will be defined after 4 weeks of CC placebo administration with 3 consecutive weekly negative P4 and hCG levels. Then during the fifth week a higher dose consisting of one more tablet per day (up to 3 tablets per day at third or fourth cycles, if they remain non-responders) will be given 5 days.
• CC placebo
CC placebo 50 mg every day for 5 days (day 3-7 of cycle), for a total of 4 cycles. Non-response will be defined after 4 weeks of CC Placebo administration with 3 consecutive weekly negative P4 and hCG levels. Then during the fifth week a higher dose consisting of one more tablet per day (up to 3 tablets per day at third or fourth cycles, if they remain non-responders) will be given 5 days.

Locations

Country	Name	City	State
China	First Affiliated Hospital,Hunan University of Chinese Medicine	Changsha	Hunan
China	Dalian maternity hospital	Dalian	Liaoning
China	Daqing LongNa Hospital	Daqing	Heilongjiang
China	The Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	First Affiliated Hospital,Guangzhou University of Chinese Medicine	Guangzhou	Guangdong
China	Guangdong Chinese Hospital	Guangzhou	Guangdong
China	Guangzhou Liwan Chinese Hospital	Guangzhou	Guangdong
China	Hangzhou Chinese Medicine Hospital	Hangzhou
China	Integrated Chinese and Western Medicine Hospital of Zhejiang Province	Hangzhou	Zhejiang
China	First Affiliated Hospital,Heilongjiang University of Chinese Medicine	Harbin	Heilongjiang
China	Forth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Second Affiliated Hospital,Heilongjiang University of Chinese Medicine	Harbin	Heilongjiang
China	First Affiliated Hospital,Anhui University of Chinese Medicine	Hefei	Anhui
China	Maternal and Child Health Hospital of Huaian	Huaian	Jiangsu
China	Jiangxi University of Chinese Medicine Affiliated Hospital	Nanchang	Jiangxi
China	Shanxi Chinese Medicine Hospital	Shangxi	Shanxi
China	Liaoning University of Chinese Medicine Affiliated Hospital	Shenyang	Liaoning
China	Suzhou Chinese Medicine Hospital	Suzhou	Jiangsu
China	First Affiliated Hospital,Tianjin University of Chinese Medicine	Tianjin	Tianjin
China	Tianjin Tanggu Maternity and Child Care Center	Tianjin	Tianjin
China	Wenzhou Chinese Medicine Hospital	Wenzhou	Zhejiang
China	Hubei Chinese Medicine Hospital	Wuhan	Hubei
China	Wuhan Tongji Hospital	Wuhan	Hubei
China	Maternal and Child Health Hospital of Xuzhou	Xuzhou	Jiangsu
China	Henan Chinese Medicine Hospital	Zhengzhou	Henan

Sponsors (31)

Lead Sponsor

Collaborator

Heilongjiang University of Chinese Medicine

Beijing University of Chinese Medicine, Dalian maternity hospital, Daqing Longnan Hospital, Daqing Oil Field Hospital, Göteborg University, Guangdong Provincial People's Hospital, Guangzhou Liwan Chinese Hospital, Hangzhou Chinese Medicine Hospital, Harbin Medical University, Henan Chinese Medicine Hospital, Huaian Maternal and Child Health Care Hospital, Hubei Chinese Medicine Hospital, Jiangsu Province Hospital of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Maternal and Child Health Hospital of Xuzhou, Penn State University, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Shanxi Chinese Medicine Hospital, Sichuan University, Suzhou Chinese Medicine Hospital, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, The University of Hong Kong, Tianjin Tanggu Maternity and Child Care Center, Wenzhou Chinese Medicine Hospital, Wuhan TongJi Hospital, Yale University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate		Up to 3 years
Secondary	Ovulation rate		Up to 3 years
Secondary	Ongoing pregnancy rate	Up to 3 years	Aprial 2012 to July 2014 (up to 3 years)
Secondary	Multiple pregnancy rate		Up to 2 years
Secondary	Miscarriage rate	loss of an intrauterine pregnancy before 20 completed weeks of gestation.	Up to 2 years
Secondary	Hormonal profile	Hormonal profile include: Testosterone(T), Sex hormone-binding globulin (SHBG), Follicle stimulating hormone (FSH),Luteinizing hormone(LH),and Dehydroepiandrosterone sulfate (DHEAS).	Up to 2 years
Secondary	Metabolic profile	Metabolic profile includes: Serum glucose concentration, Insulin concentration, cholesterol, Triglycerides (TG), High density lipoprotein cholesterol (HDL-C) and Low density lipoprotein cholesterol (LDL-C)	Up to 2 years
Secondary	Side effect profile	Side effects of CC include hot flashes, mood changes, bloating, formation of ovarian cysts, and pain, extremely rare are pituitary apoplexy and deep venous thrombosis. The major side effects of acupuncture are local skin irritation, discomfort, and vasovagal reactions during the procedure. All above mentioned side effects will be recorded weekly.	Up to 2 years