Acupuncture or Metformin for Insulin Resistance in Women With PCOS
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18-40
SponsorKarolinska Institutet
About this trial
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 criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
Age >40
Exclusion of other endocrine disorders such as non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone < 3nmol/L), androgen secreting tumors or suspected Cushing's syndrome.
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Lifestyle management
Other interventionAll 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
DeviceDisposable, 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
DrugOral 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).
Treatment groups
303 Participants
are divided into 3 treatment groupsGroup A: Lifestyle managementActive comparator 1 intervention
Group B: Acupuncture + lifestyle managementActive comparator 2 interventions
Group C: Metformin + lifestyle managementActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
4 months2
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.
Time frame
4 months3
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.
Time frame
4 monthsSecondary outcomes
1
Changes from baseline to after 4 months and again 4 months after last treatment in secondary metabolic measures
Changes in secondary metabolic measures with calculation of e.g. HOMA-B
Time frame
8 months2
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.
Changes in mRNA gene expression and DNA methylation expression and biomarkers in whole blood.
Time frame
8 months3
Changes from baseline to after 4 months and again 4 months after last treatment in menstrual pattern.
Changes in menstrual pattern per month.
Time frame
8 months4
Changes from baseline to after 4 months and again 4 months after last treatment in circulating reproductive hormones.
Changes in circulating circulating reproductive hormones.
Time frame
8 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Karolinska Institutet
Lead sponsor
Karolinska University Hospital
Collaborator
Peking University
Collaborator
Source ClinicalTrials.gov