Acupuncture or Metformin for Insulin Resistance in Women With PCOS

NCT02647827 | Recruiting Phase 2 DMC

• 2 other identifiers: EudraCT: 2015-004250-182015-004250-18
• Study Type: interventional
• Target: 303
• Locations: 2 countries
• Sites: 2

Brief 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).

Conditions

Polycystic Ovary Syndrome; Insulin Resistance; Hyperandrogenism

Keywords

Acupuncture; Metformin; Glucose metabolism; Hba1c

Outcome Measures

Primary Outcomes (3)

• Changes from baseline to after 4 months in HOMA-IR [fasting insulin (μU/mL) × fasting glucose (mmol/L)] / 22.5)

  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.

  4 months

• Changes from baseline to after 4 months of treatment in HbA1c

  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.

  4 months

• Changes from baseline to after 4 months of treatment in insulin response to glucose during the oral glucose tolerance test (OGTT)

  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.

  4 months

Secondary Outcomes (8)

• Changes from baseline to after 4 months and again 4 months after last treatment in secondary metabolic measures

  8 months

• Changes from baseline to after 4 months and again 4 months after last treatment gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood.

  8 months

• Changes from baseline to after 4 months and again 4 months after last treatment in menstrual pattern.

  8 months

• Changes from baseline to after 4 months and again 4 months after last treatment in circulating reproductive hormones.

  8 months

• Changes from baseline to after 4 months and again 4 months after last treatment in women's HRQoL.

  8 months

Study Arms (3)

Lifestyle management

ACTIVE COMPARATOR

All women will receive lifestyle management instructions at the baseline visit, before randomization.

Other: Lifestyle management

Acupuncture + lifestyle management

ACTIVE COMPARATOR

Three treatment per week (4 weeks) and thereafter 2 times per week during 12 weeks.

Other: Lifestyle management; Device: Acupuncture

Metformin + lifestyle management

ACTIVE COMPARATOR

Oral metformin 500 mg three times daily, in total 1500 mg per day.

Other: Lifestyle management; Drug: Metformin

Interventions

Lifestyle management OTHER

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 + lifestyle management; Lifestyle management; Metformin + lifestyle management

Acupuncture DEVICE

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.

Acupuncture + lifestyle management

Metformin DRUG

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).

Metformin + lifestyle management

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 40 years
• Body mass index (BMI) ≥25 to ≤40 given that 95% of all women with PCOS with a BMI ≥25 are insulin resistant (71,72).
• 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.
• Willing to sign the consent form.
• 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.

You may not qualify if:

• Age \>40
• Having known renal disease (creatinine clearance \< 60 mL/min), hepatic insufficiency, autoimmune disorders or cancer.
• Any acute condition with potential to alter renal function or cause tissue hypoxia.
• Type I diabetes.
• 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.
• Hypersensitivity to metformin hydrochloride or to any of the excipients.
• Blood pressure \>160 / 100 mmHg
• Pregnancy or breastfeeding the last 6 months
• Acupuncture the last 2 months
• Daily smoking and alcoholic intake
• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator
• Peking University: collaborator

Study Sites (2)

Peking University

Beijing, 100871, China

RECRUITING

Karolinska University Hospital

Stockholm, 17176, Sweden

RECRUITING

Related Publications (1)

• Stener-Victorin E, Zhang H, Li R, Friden C, Li D, Wang W, Wang H, Chang C, Li S, Huo Z, Zhang H, Ji X, Linden-Hirschberg A, Qiao J. Acupuncture or metformin to improve insulin resistance in women with polycystic ovary syndrome: study protocol of a combined multinational cross sectional case-control study and a randomised controlled trial. BMJ Open. 2019 Jan 4;9(1):e024733. doi: 10.1136/bmjopen-2018-024733.

  PMID: 30612112 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance; Hyperandrogenism

Interventions

Acupuncture Therapy; Metformin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Complementary Therapies; Therapeutics; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Elisabet Stener-Victorin, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisabet Stener-Victorin, PhD

CONTACT

+46705643655; elisabet.stener-victorin@ki.se

Berit Legerstam, Study nurse

CONTACT

+46851773782; berit.legerstam@karolinska.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, Associate Professor

Study Record Dates

• First Submitted: December 23, 2015
• First Posted: January 6, 2016
• Study Start: December 1, 2015
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 9, 2024

Record last verified: 2024-10

Locations

SE (1); CN (1)