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Acupuncture or Metformin for Insulin Resistance in Women With PCOS

Phase 2
Recruiting
Conditions
Hyperandrogenism
Insulin Resistance
Polycystic Ovary Syndrome
Interventions
Other: Lifestyle management
Device: Acupuncture
Drug: Metformin
Registration Number
NCT02647827
Lead Sponsor
Karolinska Institutet
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).

Detailed Description

Specific Aims The purpose of the study is to perform a randomized controlled trial of women with PCOS, comparing the effectiveness of lifestyle management alone, and in combination with acupuncture or metformin treatment on whole body glucose homeostasis, with the ultimate goal to prevent the development of type 2 diabetes.

Primary aim

1. To determine the clinical effectiveness of 4 months of 1) electroacupuncture + lifestyle management and 2) metformin + lifestyle management, compared to 3) lifestyle management only, for improvement of insulin sensitivity as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels).

Secondary aims

1. To evaluate changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet β-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution.

2. To determine changes in genome-wide gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood.

3. To evaluate endocrine measures including menstrual pattern and ovulation frequency, circulating hormones (sex steroids, AMH, gonadotropins), and excretion of metabolites of sex steroids in urine.

4. To determine changes in women's HRQoL, symptoms of anxiety and depression, dieting and eating patterns, and negative side-effects.

5. To evaluate the cost-effectiveness of the different treatments.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
303
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lifestyle managementLifestyle managementAll women will receive lifestyle management instructions at the baseline visit, before randomization.
Acupuncture + lifestyle managementAcupunctureThree treatment per week (4 weeks) and thereafter 2 times per week during 12 weeks.
Metformin + lifestyle managementLifestyle managementOral metformin 500 mg three times daily, in total 1500 mg per day.
Acupuncture + lifestyle managementLifestyle managementThree treatment per week (4 weeks) and thereafter 2 times per week during 12 weeks.
Metformin + lifestyle managementMetforminOral metformin 500 mg three times daily, in total 1500 mg per day.
Primary Outcome Measures
NameTimeMethod
Changes from baseline to after 4 months of treatment in HbA1c4 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 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 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.

Secondary Outcome Measures
NameTimeMethod
Changes from baseline to after 4 months and again 4 months after last treatment in secondary metabolic measures8 months

Changes in secondary metabolic measures with calculation of e.g. HOMA-B

Changes from baseline to after 4 months and again 4 months after last treatment in circulating reproductive hormones.8 months

Changes in circulating circulating reproductive hormones.

Changes from baseline to after 4 months and again 4 months after last treatment in women's HRQoL.8 months

Changes in women's HRQoL measured with polycystic ovary syndrome questionnaire (PCOSQ) and short form-36 (SF36) two validated questionnairs.

Changes from baseline to after 4 months and again 4 months after last treatment in women's symptoms of anxiety and depression.8 months

Changes in women's symptoms of anxiety and depression measured with the self-reported version of the Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A).

Cost-effectiveness of the different treatments throughout the study.8 months

Cost-effectiveness of the different treatments by calculation of e.g. treatment visits, time for patient and with EuroQol-5 dimension (EQ-5D).

Changes from baseline to after 4 months and again 4 months after last treatment in menstrual pattern.8 months

Changes in menstrual pattern per month.

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 in mRNA gene expression and DNA methylation expression and biomarkers in whole blood.

Changes from baseline to after 4 months and again 4 months after last treatment in women's dieting and eating patterns.8 months

Changes in women's dieting and eating patterns assessed with Three-Factor Eating Questionnaire (TFEQ-R21), and Questionnaire of Eating and Weight Patterns-Revised (QEWP-R).

Trial Locations

Locations (2)

Peking University

🇨🇳

Beijing, China

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

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