Optimizing Metformin Use in Polycystic Ovary Syndrome - A Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 184
- 试验地点
- 1
- 主要终点
- Weight
研究概览
简要总结
The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
Participants will:
- Be randomized to take metformin at a dose of either 1500mg or 2250mg every day for 6 months
- Visit the clinic three times during the trial for checkups and tests
- Answer questionnaires on menstrual cyclicity, mental health, quality of life and side-effects
详细描述
INTRODUCTION Polycystic ovary syndrome (PCOS) remains a key public health burden as it is one of the most common endocrine and metabolic disorders affecting up to 13% of women globally. The Rotterdam diagnostic criteria were updated and internationally endorsed in the 2023 International PCOS guideline and include a) ovulatory and menstrual dysfunction, b) biochemical and/or clinical hyperandrogenism and c) polycystic ovary morphology (PCOM) at ultra-sound. For a diagnosis in adults two of three criteria are required, with PCOM remaining nonspecific for PCOS in adolescents.
Women with PCOS present with diverse features; metabolic (weight gain, obesity, insulin resistance and diabetes) reproductive (infertility and pregnancy complications), endocrine (hyperandrogenism, hirsutism and acne) and psychosocial (depression, anxiety and poor quality of life).
While lifestyle management is strongly recommended for weight management, for those with higher body mass index (BMI), sustainable efficacy for weight loss can be limited and additional pharmacological treatment may be needed. The 2023 Updated International PCOS Guideline recommends that metformin, in addition to lifestyle, should be considered in adults with PCOS and BMI ≥ 25 kg/m2 for prevention of weight gain and management of weight and metabolic disorders. Metformin may be considered in adults with BMI < 25 kg/m2 and adolescents with PCOS, acknowledging more limited evidence.
The aim of this randomized controlled trial (RCT) is to evaluate whether a metformin dose of 1500 mg is inferior compared to a dose of 2250 mg per day for females 18-37 years of age with PCOS in:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 37 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Diagnosed PCOS (According to the International evidence-based Guideline for PCOS 2023)
- •Age: 18-37 years
- •BMI: ≥ 25 and <40 kg/m2
- •Signed informed consent and willingness to comply with the trial procedures
- •Sufficient skills in the Finnish or Swedish language
排除标准
- •Not meeting the criteria according to the International evidence-based Guideline for PCOS 2023)
- •Use of hormonal contraceptive during the last 3 months
- •Pregnancy
- •Breastfeeding
- •Untreated diabetes
- •Hypothyroidism
- •Hyperprolactinemia
- •Use of medications for diabetes,
- •Use of medications for high cholesterol
- •Use of medications for obesity
- •Use of medications for cortisone (per oral)
- •Hypersensitivity to metformin
- •Acute metabolic acidosis
- •Renal impairment
- •Hepatic insufficiency
- •Heart- or respiratory failure
- •Serious mental illness
- •Alcoholism
- •Investigator site staff directly involved in the conduct of the study and their family members
研究组 & 干预措施
Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 2250mg per day
metformin tablets 2250 mg per day
干预措施: Metformin 2250 mg daily (Drug)
Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 1500mg per day
metformin tablets 1500 mg per day
干预措施: Metformin 1500 mg daily (Drug)
结局指标
主要结局
Weight
时间窗: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Weight will be measured by a standard scale to an accuracy of +/- 0,1kg.
Homeostatic model assessment for insulin resistance (HOMA-IR)
时间窗: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
HOMA-IR will be calculated with the formula: fasting plasma glucose (mmol/L) × fasting serum insulin (mU/L) divided by 22.5 (9)
Hirsutism
时间窗: The investigators will report change from baseline to 14 and 26 weeks.
Modified Ferriman Gallwey score (mFG) will be measured and a score of 4 or more will be regarded as hirsutism in Caucasian women, whereas a score of 6 or more will be regarded hirsutism for other ethnicities
Total testosterone
时间窗: The investigators will measure change from baseline to 14 and 26 weeks
Testosterone nmol/l (liquid chromatography with tandem mass spectrometry (LC-MS/MS). All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Appearance of severe of adverse effects
时间窗: The investigators will measure change from baseline to 14 and 26 weeks
In our questionnaire the investigators will ask the participants whether they have experienced abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks and grade the symptoms from 1-5 (1 being never and 5 being all the time). The investigators will count the scores and give each participant a score between 5-25. A severe adverse effect is defined as a score of 4 or more in one of the questions (indicating a daily experience of abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks).
Anti-Mullerian hormone (AMH)
时间窗: The investigators will measure change from baseline to 14 and 26 weeks
AMH will be measured in ug/l. All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
次要结局
- Body mass index (BMI)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Waist circumference (WC)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Waist-hip-ratio (WHR)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Body adiposity index (BAI)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Body composition(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Blood pressure (BP)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Pulse(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Fasting glucose(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Fasting insulin(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- HbA1C(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Lipids (cholesterol and its subclasses, triglycerides)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- C-reactive protein (CRP)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- 2-hour oral glucose tolerance test (OGTT)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Alanine Aminotransferase (ALAT)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Gamma-glutamyl transferase (G-GT)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Fatty Liver Index (FLI)(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Matsuda Index(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Triglyceride-Glucose (TyG) index(The investigators will measure change in outcomes from baseline to 14 and 26 weeks)
- Acne(The investigators will report change from baseline to 14 and 26 weeks)
- Weight stigma(The investigators will measure change from baseline to 14 and 26 weeks)
- Alopecia(The investigators will report change from baseline to 14 and 26 weeks)
- Sex hormone binding globulin (SHBG)(The investigators will measure change from baseline to 14 and 26 weeks)
- Free androgen index (FAI)(The investigators will measure change from baseline to 14 and 26 weeks)
- Quality of life (QoL)(The investigators will measure change from baseline to 14 and 26 weeks)
- Dehydroepiandrosterone sulfate (DHEAS)(The investigators will measure change from baseline to 14 and 26 weeks)
- Androstenedione(The investigators will measure change from baseline to 14 and 26 weeks)
- Free testosterone(The investigators will measure change from baseline to 14 and 26 weeks)
- Menstrual regularity(The investigators will measure change from baseline to 14 and 26 weeks)
- Menstrual cycle length(The investigators will measure change from baseline to 14 and 26 weeks)
- Appearance of gastrointestinal adverse effects (GI AE)(The investigators will measure change from baseline to 14 and 26 weeks)
- Follicle number per ovary (FNPO) and antral follicle count (AFC)(The investigators will measure change from baseline to 14 and 26 weeks.)
- Ovarian volume(The investigators will measure change from baseline to 14 and 26 weeks.)
研究者
Johanna Melin
MD, PhD, specialist in obstetrics & gynecology
Helsinki University Central Hospital