Recruiting
Phase 2
Acupuncture or Metformin for Insulin Resistance in Women With PCOS
Condition(s) studied
Polycystic Ovary SyndromeInsulin ResistanceHyperandrogenism
Investigational drug(s) / intervention(s)
Lifestyle managementAcupunctureMetformin
Lifestyle management: All women will receive lifestyle management instructions at the baseline visit, before randomization. The lifestyle management involves one initial counselling session in connection with the baseline visit, which includes information about the importance of weight management, healthy diet and physical activity.
Acupuncture: Disposable, single-use, sterilized CE marked needles made of stainless steel, 0.25 x 30 mm and 0.30 x 40/50 mm will be inserted to a depth of 15-40 mm in segmental acupuncture points located in abdominal and leg muscles, with innervations corresponding to the ovaries and the pancreas. Two sets of acupuncture points will be alternated every second treatment.
Metformin: Oral metformin 500 mg three times daily, in total 1500 mg per day. To reduce gastrointestinal side-effects of metformin, the dose will be slowly escalated starting with 500 mg daily during the first week, increasing to 500 mg twice per day during the second the week, and 500 mg three times daily, morning, lunch and dinner from the third week in total 16 weeks including the 3 weeks step-up phase (i.e. 4 months).
Study summary
The hypothesis is that acupuncture is equally effective as metformin (both treatments combined with lifestyle management) in improving whole body glucose homeostasis in insulin resistant women with polycystic ovary syndrome (PCOS), and that both are superior to lifestyle management alone. The investigators hypothesize that acupuncture and metformin induce ovulation and improve hyperandrogenism, as well as health related quality of life (HRQoL) and symptoms of anxiety and depression. Although equally effective (acupuncture and metformin), the investigators hypothesize that acupuncture is associated with less negative side-effects. The investigators also hypothesize that these treatments have the potential to restore epigenetic and molecular alterations in target tissues (endometrial-, adipose-, and skeletal muscle tissue) and thus have the potential to prevent the development of type 2 diabetes (T2D).
Eligibility
Inclusion criteria - women with PCOS:
1. Age 18 to 40 years
2. Body mass index (BMI) ≥25 to ≤40 given that 95% of all women with PCOS with a BMI ≥25 are insulin resistant (71,72).
3. PCOS diagnosis according to Rotterdam criteria 2003 (73), with at least two of the following three symptoms: Clinical signs of hyperandrogenism (hirsutism or acne); oligo/amenorrhea; and/or polycystic ovaries (PCOS). Hirsutism is defined as a self-reported Ferriman-Gallwey (FG) score ≥8 (≥5 Asian) (74,75). Acne is defined by a positive response to the question Do you have acne? Oligomenorrhea is defined as an intermenstrual interval \>35 days and \<8 menstrual bleedings in the past year. Amenorrhea as \<3 cycles per year. PCO is defined by transvaginal ultrasound with ≥12 follicles 2-9 mm and/or ovarian volume ≥10 ml in one or both ovaries.
4. Willing to sign the consent form.
Inclusion criteria - controls:
Controls should have BMI \>25 to \<40, regular cycles with 28 days ± 2 days, and no signs of hyperandrogenism. They are excluded if they have menstrual irregularities, signs of hyperandrogenism (FG \>4), or evidence of PCO morphology on ultrasound.
Exclusion criteria for all women
1. Age \>40
2. Exclusion of other endocrine disorders such as non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone \< 3nmol/L), androgen secreting tumors or suspected Cushing's syndrome.
3. Having known renal disease (creatinine clearance \< 60 mL/min), hepatic insufficiency, autoimmune disorders or cancer.
4. Any acute condition with potential to alter renal function or cause tissue hypoxia.
5. Type I diabetes.
6. Pharmacological treatment (cortizon, 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.
7. Hypersensitivity to metformin hydrochloride or to any of the excipients.
8. Blood pressure \>160 / 100 mmHg
9. Pregnancy or breastfeeding the last 6 months
10. Acupuncture the last 2 months
11. Daily smoking and alcoholic intake
12. Language barrier or disabled person with reduced ability to understand the information given.
In total 50 controls will be matched at baseline (age, weight and BMI) to women with PCOS. Controls will undergo screening and baseline visit, but will not be randomized to any treatment.
Primary outcome measure(s)
- Changes from baseline to after 4 months in HOMA-IR [fasting insulin (μU/mL) × fasting glucose (mmol/L)] / 22.5) — 4 months
Changes from baseline to after 4 months of treatment in HOMA-IR \[fasting insulin (μU/mL) × fasting glucose (mmol/L)\] / 22.5) between 1) acupuncture + lifestyle management and 2) metformin + lifestyle management compared to 3) lifestyle management only.
- Changes from baseline to after 4 months of treatment in HbA1c — 4 months
Changes from baseline to after 4 months of treatment in HbA1c between 1) acupuncture + lifestyle management and 2) metformin + lifestyle management compared to 3) lifestyle management only.
- Changes from baseline to after 4 months of treatment in insulin response to glucose during the oral glucose tolerance test (OGTT) — 4 months
Changes from baseline to after 4 months of treatment in insulin response to glucose during the OGTT (AUC using the trapezoidal rule) between 1) acupuncture + lifestyle management and 2) metformin + lifestyle management compared to 3) lifestyle management only.
Trial sites (2)
| Facility | City | Region | Status |
|---|
| Peking University |
Beijing |
China |
Recruiting |
| Karolinska University Hospital |
Stockholm |
Sweden |
Recruiting |
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