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

NCT ID: NCT03625531

Last Updated: 2022-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-13

Study Completion Date

2024-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Polycystic Ovary Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Personalized acupuncture

Two sets of acupoints will be selected for the two types. The basic acupoint-prescription includes CV 4, CV 6, CV 12 and SP 6 bilaterally, ST 25 bilaterally, EX-CA 1 bilaterally, ST 40 bilaterally and SP 9 bilaterally. Additional point ST 36 bilaterally and moxibustion as adjuvant therapy will be added for the type of yang deficiency of spleen and kidney, while additional points K 13, LR 3 for the type of yin deficiency of liver and kidney. Besides, flexible modifications of 2-3 acupoints will be performed according to patients special symptoms.

Group Type EXPERIMENTAL

Acupuncture

Intervention Type OTHER

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.

Fixed acupuncture

Two sets of acupuncture points will be alternated every second treatment. The first set consists of CV 3, CV 6, ST 29 bilaterally, SP 6 bilaterally, SP 9 bilaterally, GV 20 and LI 4 bilaterally. The second set consists of 13 needles: ST 25 bilaterally, ST 29 bilaterally, CV 3, CV 6, SP 6 bilaterally, LR 3 bilaterally, PC 6 bilaterally and GV 20. The following points will be connected to an electrical stimulator: ST 25 bilaterally, ST 29 bilaterally, SP 6 bilaterally, LR 3 bilaterally.

Group Type EXPERIMENTAL

Acupuncture

Intervention Type OTHER

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.

Letrozole

Women in the letrozole group will be given letrozole (Femara, Novartis Pharmaceuticals, Basel, Switzerland) from day 3 to day 7 of the spontaneous menstrual cycle or after a withdrawal bleeding following progestin. The maximum daily dose of letrozole will be 7.5 mg (3 pills) daily for five days.

Group Type ACTIVE_COMPARATOR

Letrozole

Intervention Type DRUG

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

Women will receive placebo letrozole with no acupuncture from day 3 to day 7 of the spontaneous menstrual cycle or after a withdrawal bleeding following progestin. Placebo letrozole will be given in the same way as letrozole.

Group Type PLACEBO_COMPARATOR

Placebo letrozole

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type OTHER

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Femara, Novartis Pharmaceuticals Placebo

Eligibility Criteria

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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.

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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hongxia Ma

OTHER

Sponsor Role lead

Responsible Party

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Hongxia Ma

professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Hongxia HX Ma, Dorctor

Role: STUDY_CHAIR

The First Affiliated Hospital of Guangzhou Medical University

Locations

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The first affiliated hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Hongxia Ma, Dorctor

Role: CONTACT

18928868335

Facility Contacts

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Hongxia HX Ma, Dorctor

Role: primary

18928868335

References

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Reference Type BACKGROUND
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Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008 Mar;23(3):462-77. doi: 10.1093/humrep/dem426.

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Huang S, Hu M, Ng EHY, Stener-Victorin E, Zheng Y, Wen Q, Wang C, Lai M, Li J, Gao X, Wang X, Hu Z, Xia T, Hu R, Liu J, Wen X, Li S, Quan K, Liang X, Shang H, Ma H, Qiao J. A multicenter randomized trial of personalized acupuncture, fixed acupuncture, letrozole, and placebo letrozole on live birth in infertile women with polycystic ovary syndrome. Trials. 2020 Mar 4;21(1):239. doi: 10.1186/s13063-020-4154-1.

Reference Type DERIVED
PMID: 32131886 (View on PubMed)

Other Identifiers

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PPCOSAct

Identifier Type: -

Identifier Source: org_study_id

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