A Trial of Personalized Acupuncture, Fixed Acupuncture, Letrozole and Placebo on Live Birth in Women With PCOS

Polycystic Ovary Syndrome Clinical Trial

Official title:

A Multicenter Randomized Trial of Personalized Acupuncture, Fixed Acupuncture, Letrozole and Placebo on Live Birth for Infertility in Women With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03625531
• Other study ID #: PPCOSAct
• Status: Recruiting
• Phase: Phase 3
• Start date: August 13, 2018
• Est. completion date: January 31, 2024

Study information

• Verified date: March 2022
• Source: The First Affiliated Hospital of Guangzhou Medical University
• Contact: Hongxia Ma, Dorctor
• Phone: 18928868335
• Email: doctorhongxia[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized assessor-blind controlled trial. A total of 1,100 women with PCOS will be recruited from 28 hospitals and randomly allocated into four groups: personalized acupuncture, fixed acupuncture, letrozole or placebo letrozole. Patients will receive treatment for 16 weeks and the primary outcome is live birth.

Description:

Traditional Chinese Medicine (TCM) usually involves syndrome and disease differentiation, and for acupuncture selection of appropriate points and skillful needling techniques. Many clinical trials on acupuncture used fixed acupuncture protocols without accounting for individual differences. We here design a multicenter randomized controlled trial to evaluate whether personalized or fixed acupuncture increases the likelihood of live births for infertility in women with polycystic ovary syndrome (PCOS) compared with letrozole or placebo letrozole. We hypothesis that letrozole is more effective than personalized acupuncture and that personalized acupuncture is more effective than standardized acupuncture, which is more effective than placebo letrozole.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: January 31, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

Inclusion criteria

1. Age of women between 20 and 40 years.

2. Chronic oligomenorrhea or amenorrhea: oligomenorrhea is defined as an intermenstrual interval > 35 days or < 8 menstrual bleedings in the past year. Amenorrhea is defined as an intermenstrual interval >90 days.

3. Hyperandrogenism (either hirsutism or hyperandrogenemia) or polycystic ovaries on ultrasound. Hirsutism is determined by a modified Ferriman-Gallwey Score = 5 at screening examination, and biochemical hyperandrogenism is defined as total testosterone (T) > 2.6 nmol/L and free testosterone = 6.0 pg/mL. Polycystic ovaries are present when there are = 12 antral follicles (2 - 9 mm) or ovarian volume > 10 mL on transvaginal scanning.

4. At least one patent tube shown by hysterosalpingogram or diagnostic laparoscopy within 3 years if the patient does not have a history of abortion or pelvic operation. If the patient has a history of pregnancy and no history of pelvic operation within the past 5 years, she is not required to undergo a tubal patency test.

5. Sperm concentration ? 15 × 106/mL and total motility ? 40% or total motile sperm count ? 9 million in the semen analysis of the husband. Agree to have regular intercourse i.e. 2-3 times per week during the study period.

Exclusion criteria

1. Exclusion of other endocrine disorders: a. patients with hyperprolactinemia (defined as two prolactin levels at least one week apart = 25 ng/mL); b. Patients with FSH levels > 15 mIU/mL. A normal level within the last year is adequate for entry; c. 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. d. Patients diagnosed with Type I or Type II diabetes who are poorly controlled (defined as HbA1c level > 7.0%), or patients receiving antidiabetic medications such as metformin, insulin, thiazolidinediones, acarbose, or sulfonylureas. e. Patients with suspected Cushing's syndrome.

2. Use of other TCM treatments including Chinese herbal prescriptions and acupuncture in the past 3 months.

3. Use of other western medications known to affect reproductive function or metabolism in the past 2 months.

4. Pregnancy within the past 6 weeks.

5. Within 6 weeks postabortion or postpartum.

6. Breastfeeding within the last 6 months.

7. Not willing to give written consent to the study.

8. Additional exclusion criteria are as follows.

1. Patients taking other medications known to affect reproductive function or metabolism. These medications include oral contraceptives, depot progestins, hormonal implants (including Implanon), GnRH agonists and antagonists, antiandrogens, gonadotropins, antiobesity drugs, antidiabetic drugs such as metformin and thiazolidinediones, somatostatin, diazoxide, angiotensin-converting-enzyme (ACE) inhibitors, and calcium channel blockers. The washout period on these medicationswill be two months, 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 depot progestins.

2. 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.

3. Patients with hemoglobin < 10 g/dL.

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

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

6. 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.

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

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

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

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

11. 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.

12. 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.

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

14. Patients with known congenital adrenal hyperplasia.

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Other:
• Acupuncture
Women in both personalized and fixed acupuncture groups will receive acupuncture treatment three times a week. Acupuncture treatment will start on day 3 after a spontaneous period or after a withdrawal bleeding following progestin. Each treatment session will last for 30-60 minutes, with a maximum of 48 treatment sessions over 16 weeks. If they become pregnant, the acupuncture treatment will be stopped. For personalized and fixed acupuncture group, credibility and expectancy questionnaires will be completed on the third acupuncture treatment and the last acupuncture treatment.

Drug:
• Letrozole
Letrozole will be started on day 3 to day 7 of the spontaneous period or a withdrawal bleeding following progestin. If there is response with ovulation, this dose will be maintained. In those with no ovulatory response, letrozole tablets of the next ovulation cycle will be take on the day 28 of the menstrual cycle and the letrozole dose will be increased to 5 mg (2 pills) a day for 5 days. If there is still no response, the dose will be increased to 7.5 mg per day for 5 days in the next cycle. The maximum daily dose of letrozole will be 7.5 mg (3 pills) daily for five days.
• Placebo letrozole
Placebo letrozole will be given in the same way as letrozole. Women will receive 1 tablet a day of placebo letrozole from the day 3 to day 7 of the menstrual cycle and placebo letrozole dose will be increased 2 tablets a day in the next cycle if there is no response. The maximum daily dose of placebo letrozole will be 3 tablets daily for five days.

Locations

Country	Name	City	State
China	The first affiliated hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Hongxia Ma

Country where clinical trial is conducted

China, 

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate	Live birth rate defined as a delivery after =20 weeks gestation.	Up to 14 months
Secondary	Ovulation rate	Ovulation defined as a serum progesterone level >3 ng/mL on day 21 or day 28 of the cycle.	Up to 4 months
Secondary	Conception rate	Conception defined as positive serum hCG.	Up to 4 months
Secondary	Pregnancy rate	Around 8-10 weeks gestation.	Up to 6.5 months
Secondary	Pregnancy loss rate	Pregnancy loss defined as pregnancy loss occurring from conception to 27 completed weeks of gestational age.	Up to 9 months
Secondary	Follicle stimulating hormone (FSH)	Hormonal profile	Up to 4 months
Secondary	Luteinizing hormone(LH)	Hormonal profile	Up to 4 months
Secondary	Testosterone(T)	Hormonal profile	Up to 4 months
Secondary	Sex hormone-binding globulin (SHBG)	Hormonal profile	Up to 4 months
Secondary	Serum glucose concentration	Metabolic profile	Up to 4 months
Secondary	Insulin concentration	Metabolic profile	Up to 4 months
Secondary	Cholesterol	Metabolic profile	Up to 4 months
Secondary	Triglycerides (TG)	Metabolic profile	Up to 4 months
Secondary	High density lipoprotein cholesterol (HDL-C)	Metabolic profile	Up to 4 months
Secondary	Low density lipoprotein cholesterol (LDL-C)	Metabolic profile	Up to 4 months
Secondary	The scores of short form 36 (SF 36)	SF-36 is one of questionnaires for assessments of health-related quality of life. It includes 36 items, the scores for each domain range from 0 to 100, with high scores indicating a better status.	Up to 4 months
Secondary	The scores of polycystic ovary syndrome questionnaire (PCOSQ)	PCOSQ is one of questionnaires for assessments of health-related quality of life. It concludes 26 items. Each question is associated with a 7-point scale in which 7 represents optimal function and 1 represents the poorest function.	Up to 4 months
Secondary	The scores of Chinese quality of life (ChQOL) questionnaire	ChQOL is one of questionnaires for assessments of health-related quality of life. The ChQOL is unique in that it is a health-related quality of life (HRQOL) measure specific to Traditional Chinese Medicine (TCM). ChQOL consists of 50 items ,each item is rated on a five-point Likert scale with higher scores indicating better HRQOL.	Up to 4 months
Secondary	The scores of Zung Self-Rating Anxiety Scale (SAS)	Zung SAS is one of questionnaires for symptoms of anxiety and depression. For the SAS, index score of 50 is a cut-off point for clinically significant anxiety, with higher score suggesting more serious depression.	Up to 4 months
Secondary	The scores of Zung Self-reported Depression Scale (SDS)	Zung SDS is one of questionnaires for symptoms of anxiety and depression. Index scores of 25 to 49 indicate nil depression, 50-59 indicate mild to moderate depression, 60-69 indicate moderate to severe depression, and scores over 70 indicate severe depression.	Up to 4 months
Secondary	Side effect profile	Adverse events will be categorized and percentage of patients experiencing. adverse events and serious adverse events during the treatment period will be documented.	Up to 14 months