Evaluation of Acupuncture and Metformin Hydrochloride on Insulin Sensitivity in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial

The primary objective of this randomized controlled trial is to determine the clinical effectiveness of a 4-month intervention involving either **acupuncture** combined with lifestyle management or **metformin** combined with lifestyle management, compared to lifestyle management alone, in improving insulin sensitivity in women with **Polycystic Ovary Syndrome** (PCOS). This will be assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), the insulin response to glucose calculated by the area under the curve (AUC_insulin) during the oral glucose tolerance test (OGTT), and glucose regulation evaluated by analyzing HbA1c levels. The clinical relevance of this study lies in its potential to identify effective treatment strategies for enhancing insulin sensitivity in women with PCOS, a condition often associated with insulin resistance.

Secondary objectives include evaluating changes in secondary metabolic measures such as fasting insulin, c-peptide, glucose, and adipokines, as well as assessing the Islet β-cell function (HOMA-B) and the c-peptide index. The study also aims to determine changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle, and endometrial tissue biopsies, and biomarkers in whole blood. Additionally, it will evaluate endocrine measures including menstrual pattern and ovulation frequency, circulating hormones, and excretion of metabolites of sex steroids in urine. Further objectives are to assess changes in women's health-related quality of life (HRQL), symptoms of anxiety and depression, and negative side-effects, as well as to evaluate the cost-effectiveness of the different treatments.

The clinical trial focuses on evaluating the effectiveness of different treatment modalities for **polycystic ovary syndrome** (PCOS). The study population comprises women aged 18 to 40 years, with a body mass index (BMI) ranging from 25 to 45. Participants are exclusively female, and the trial does not include any vulnerable populations. The selection criteria for the trial include women diagnosed with PCOS according to the Rotterdam criteria 2003, which requires the presence of at least two of the following symptoms: clinical signs of hyperandrogenism, oligo/amenorrhea, or polycystic ovaries. The trial also includes a control group with women having a BMI over 25 and under 45, regular menstrual cycles, and no signs of hyperandrogenism. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are integral to the trial, as the study aims to assess the impact of acupuncture and metformin combined with lifestyle management on insulin sensitivity and glucose regulation.

The clinical trial is designed to evaluate the **clinical effectiveness** of acupuncture and **metformin** in improving insulin sensitivity in women diagnosed with **polycystic ovary syndrome** (PCOS). This is a randomized, controlled trial with a double-blind design, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial will span a total duration of 16 weeks, with the primary endpoint being changes in insulin sensitivity as measured by HOMA-IR, insulin response to glucose, and glucose regulation. Secondary endpoints include changes in metabolic measures, gene expression, and DNA methylation profiles.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, BMI, and PCOS diagnosis according to the Rotterdam criteria. Follow-up visits will occur at regular intervals to monitor progress and collect data on insulin sensitivity and other metabolic parameters. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the outcomes of the interventions.

The expected length of participant involvement is 16 weeks, corresponding to the trial's duration. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent by the participant. The trial is categorized as a low-intervention study, as it involves standard interventions and is designed to minimize additional risk to participants. The trial phase is identified as Phase III, focusing on the effectiveness and safety of the interventions in a larger population.

The clinical trial involves the administration of **Metformin Actavis 500 mg** film-coated tablets as an experimental treatment. The active substance in this medication is **metformin hydrochloride**, a chemical compound. The pharmaceutical form of the medication is a film-coated tablet, designed for oral administration. Participants in the trial will receive a maximum daily dose of 1500 mg, with a total maximum dose of 2550 mg over the course of the treatment. The treatment period is set for a maximum of 16 weeks. The medication is not a pediatric formulation and is not classified as an orphan drug. The trial aims to assess the effectiveness of metformin in improving insulin sensitivity in women with polycystic ovary syndrome.

In addition to the experimental treatment, the study includes non-experimental treatments such as lifestyle management, which serves as a standard-of-care therapy. The trial also compares the effects of acupuncture combined with lifestyle management against metformin combined with lifestyle management, and lifestyle management alone. The primary objective is to evaluate the improvement in insulin sensitivity, measured by HOMA-IR, the insulin response to glucose, and glucose regulation through HbA1c levels. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the improvement of insulin sensitivity in women with **Polycystic Ovary Syndrome (PCOS)**. The primary endpoint focuses on changes in insulin sensitivity after 16 weeks of intervention. This will be measured using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), the insulin response to glucose assessed by calculating the area under the curve (AUC_insulin) during the oral glucose tolerance test (OGTT), and glucose regulation assessed by analyzing HbA1c levels.

Secondary endpoints will be evaluated after 4 months of intervention and include changes in secondary metabolic measures such as fasting insulin, c-peptide, glucose, and adipokines. The assessment will also involve the calculation of HOMA-B (Islet β-cell function) and the c-peptide index, as well as the evaluation of adipokines and lipid profiles, body size and proportions, and body fat distribution. Additionally, changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle, and endometrial tissue biopsies, along with biomarkers in whole blood, will be analyzed.