Effects of Acupuncture on Body Mass Index in Overweight and Obese Women With Polycystic Ovary Syndrome (PCOS )

Study Overview
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Brief Summary
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This is a cross-sectional case-control study combined with a randomised controlled trial (RCT) study. This study aims to compare the effect of acupuncture, with usual care (lifestyle management) for weight control, with BMI (Body Mass index) as main outcome along with improvement of reproductive and metabolic dysfunction in overweight and obese women with PCOS, and further exploring the alteration of lipidomics, bile acid omics, proteomics and branched-chain amino acids between PCOS and the normal controls, and before and after the acupuncture treatment in different gourps.

Detailed Description
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Polycystic ovary syndrome (PCOS) affects 6 to 18% of all women and is the most common female endocrine and metabolic disorder during the reproductive years. PCOS is characterized by anovulation, hyperandrogenism and metabolic dysfunction.Obesity is  40% higher in women with PCOS than in healthy women. Overweight results in irregular cycles, insulin resistance and infertility. Acupuncture is assumed to reduce weight The overall hypothesis is that if the Body mass index (BMI) decreased, ovulation can be induced, hyperandrogenism decreased, and insulin sensitivity improved in these women. Although several treatment strategies have shown efficacy, importantly, there is a need for Comparative Effectiveness Research (CER) to strengthen the evidence base for clinical and policy decision-making. Therefore, the investigators aim to compare the effect of acupuncture, with usual care (lifestyle management) for weight loss, and improvement and prevention of reproductive and metabolic dysfunction in overweight and obese women with PCOS. We further compare the differences of PCOS and the controls with the methods of lipidomics, bile acid omics, proteomics and branched-chain amino acids, exploring the mechanisms of acupuncture on PCOS with this kind of methods.

Official Title
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Department of Traditional Chinese Medicine (TCM), Peking University Third Hospital, Beijing, China

Conditions
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PCOS, Overweight, Obesity

Intervention / Treatment
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* Other: Active acupuncture
* Other: Sham acupuncture
* Other: Lifestyle management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCOS Age 20 to 40 years BMI≥ 24 to <40 PCOS diagnosis according to Rotterdam criteria 2003 with at least two of the following three symptoms: (1) infrequent ovulation or anovulation; (2) hyperandrogenism or clinical manifestations of high blood androgen; (3) ultrasound findings of polycystic ovaries in 1 or 2 ovaries, or ≥12 follicles measuring 2 to 9 mm in diameter, and/or ovarian volume ≥10 mL. Inclusion criteria: Controls Controls should have BMI>25to<40, regular cycles with 28 days±2 days and no signs of hyperandrogenism and PCO morphology on ultrasound Exclusion Criteria: Exclusion of other endocrine disorders such as androgen secreting tumors, suspected Cushing's syndrome and non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone < 3nmol/L) thyroid dysfunction and hyperprolactinemia. Type I diabetes or not well controlled type II diabetes Pharmacological treatment (cortizone, antidepressant, other antidiabetic treatment such as insulin and acarbose, hormonal contraceptives, hormonal ovulation induction or other drugs judged by discretion of investigator) within 12 weeks. Depo Provera or similar within 6 months. Pregnancy or breastfeeding the last 6 months Acupuncture last 3 months Daily smoking and alcoholic intake

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a cross-sectional case-control part and an open-labelled RCT with a comparative effectiveness design. The inter-ventions to be tested are (1) acupuncture during 4 months+lifestylemanagement; (3) sham acupuncture+lifestyle management
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active acupuncture + lifestyle management<br>Participants in this group are treated by active acupuncture and lifestyle management for 4 months and follow up 4 months after the last treatment. | Other: Active acupuncture<br>* The rationale of the active acupuncture protocol is based on Western Medical Acupuncture theories and follows CONSORT and STRICTA protocols. All patients received acupuncture treatment for 30 minutes three times a week, with a maximum of 48 acupuncture treatments.<br>Other: Lifestyle management<br>* All women will receive lifestyle management before randomization after baseline measurements. The lifestyle management assisted by a PCOS lifestyle management system (Invention patent, ZL 2015 1 0500978.9). All participants will get a step-counter for daily use and physical exercise diary for daily reporting of exercise: number of steps, type of activity, intensity and time (minutes). Once a week each participant receive a SMS in which they report the activity during the week.<br>|
| Sham Comparator: control acupuncture + lifestyle management<br>Participants in this group are treated by control acupuncture and lifestyle management for four months and follow up 4 months after the last treatment. | Other: Sham acupuncture<br>* In the sham acupuncture protocol, 2 needles were inserted superficially to a depth of less than 5 mm, 1 in each shoulder and 1 in each upper arm at nonacupuncture and non-meridian points, and then, 4 needles were attached to electrodes and the stimulator was turned on to mimic the active acupuncture but with zero intensity, no electrical stimulation. They also received the treatment for 30 minutes three times a week and a maximum of 48 treatments.<br>Other: Lifestyle management<br>* All women will receive lifestyle management before randomization after baseline measurements. The lifestyle management assisted by a PCOS lifestyle management system (Invention patent, ZL 2015 1 0500978.9). All participants will get a step-counter for daily use and physical exercise diary for daily reporting of exercise: number of steps, type of activity, intensity and time (minutes). Once a week each participant receive a SMS in which they report the activity during the week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body mass index (BMI) | PCOS's weight in kilograms divided by the square of her height in meters, reported in kg/m2 | After 4 months of intervention; | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total body fat | examined with a body composition analyzer (Tanita Corporation, model MC-180, Japan) . | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| body fat and lean ratio | examined with a body composition analyzer (Tanita Corporation, model MC-180, Japan) . | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| visceral fat | examined with a body composition analyzer (Tanita Corporation, model MC-180, Japan) . | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| basal metabolic rate | examined with a body composition analyzer (Tanita Corporation, model MC-180, Japan) . | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| antral follicle count | examined the ovarian morphology with the B-ultrasound | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| sex hormone binding globulin (SHBG) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| anti-mullerian hormone (AMH) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| follicle stimulating hormone (FSH) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| luteinizing hormone (LH) | examined with the blood sample | After 4 months of intervention Follow-up 4 months after last treatment.， | 
| Progestin (P) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Estrogen (E2) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Androgen(T) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Androstenedione (A2) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| HOMA-IR | will be assessed during the oral glucose tolerance test (OGTT) , calculation of HOMA-IR: [fasting insulin (μU/mL) × fasting glucose (mmol/L)] / 22.5) | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| HOMA- β | will be assessed during the oral glucose tolerance test (OGTT) ,calculation of HOMA-β: 20 × fasting insulin (mU/mL) / (fasting plasma glucose (mmol/L) - 3.5 | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| glycated hemoglobin ( HbA1c) | The insulin and glucose response in blood | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| total cholesterol | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| triglycerides | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| high density lipoprotein (HDL) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| low density lipoprotein (LDL) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| lipometabonomic/lipidomics | Detection with the method of metabonomic in blood, the sample size is about 20 participants in each group. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| bile acid omics | Detection with the method of metabonomic in blood, the sample size is about 20 participants in each group | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| β-endorphin | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| 5- hydroxytryptamine (5-HT) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| FerrimanGallwey (FG )value | To determine changes in women's hairy with FG rating scale (0-36 score), the higher, the worse. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| short form-36 (SF36) | determine the health quality of life by the questionnaire of SF36 (0-100 score), the higher, the better. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| EuroQol health index scale (EQ-5D) | determine the health quality of life by the questionnaire of EQ-5D (0-100 score), the higher, the better. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| polycystic ovary syndrome questionnaire (PCOSQ); | determine the Effects of PCOS specific symptoms on the participants by the questionnaire of and polycystic ovary syndrome questionnaire (PCOSQ)(26-182 score); the higher, the better. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Self-Rating Anxiety Scale (SAS) | determine the anxiety level with the questionnaire of SAS (20-100 score), the higher, the worse. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Self-Rating Depress Scale (SDS) | determine the depress level with the questionnaire of SDS (20-100 score), the higher, the worse. | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Body mass index (BMI) | Weight in kilograms divided by the square of her height in meters, reported in kg/m2 | Follow-up 4 months after last treatment. | 
| Fibroblast growth factor 19(FGF-19) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Ghrelin | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Interleukin 6( IL-6 ) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Interleukin 8( IL-8 ) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Interleukin 22( IL-22 ) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Tumor Necrosis Factor-Alpha (TNF-α) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Gamma-Amino Butyric Acid(GABA) | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| dopamine（DA） | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| Glutamate | examined with the blood sample | After 4 months of intervention， Follow-up 4 months after last treatment. | 
| proteomics | Detection with the Proteomic techniques in blood, the sample size is about 30 participants in each group. | After 4 months of intervention | 
| branched-chain amino acids | examined with the blood sample, the sample size is about 30 participants in each group. | After 4 months of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Overweight, Obesity, Acupuncture, Lifestyle management