Effect of Metformin and Probiotics in Reproductive-aged Patients With Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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The purpose of this clinical trial is to evaluate the safety and effectiveness on the clinical and biological parameters of reproductive-aged PCOS women after a 12-week metformin and/or probiotics administration.

Detailed Description
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Probiotics are live bacteria that offer a health benefit to the host when administered in adequate amounts. Probiotic supplementation is safe for use and has demonstrated beneficial effects for metabolic diseases such as obesity and diabetes. In this study, about 90 reproductive-aged women with PCOS will be enrolled. Participants will be randomly assigned into one of the following three groups: Metformin tablets (0.5g tid po), ProMetS probiotics powder (4g qN po), Metformin tablets (0.5g tid po) and ProMetS probiotics powder (4g qN po), for 12 weeks. Blood and stool samples will be collected before and after treatment. Fasting glucose levels, fasting insulin levels, sex hormone levels, serum lipid profiles, inflammation markers, other metabolic related parameters and change of gut microbiota and immune cells will be evaluated.

Official Title
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Effect of Metformin and Probiotics in Reproductive-aged Patients With Polycystic Ovary Syndrome: a Randomized, Parallel Study

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin tablets
* Drug: ProMetS probiotics powder
* Drug: 1. Metformin tablets; 2. ProMetS probiotics powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal between 18-40 years of age. Diagnosed PCOS defined as 2003 Rotterdam diagnostic criteria. Exclusion Criteria: During the pregnancy and lactation period. Significant impaired liver function, impaired renal function, mental disease, severe infection, severe anemia, severe heart disease and neutropenia disease. Use of antibiotics within 3 months. Symptoms of any infection at screening. Immunodeficient or use of immunosuppressive drugs. Use of products containing prebiotics or probiotics within the last 3 months. Previous history of gastrointestinal surgery or disease (such as peptic ulcer, irritable bowel syndrome, inflammatory bowel disease or other gastrointestinal disorder). Medical conditions or diseases that may affect subject safety or confound study results in the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br> | Drug: Metformin tablets<br>* 0.5g (1 pill) of Metformin tablets administered three times a day orally before meal<br>|
| Experimental: Probiotics<br> | Drug: ProMetS probiotics powder<br>* 4g (2 strips) of ProMetS probiotics powder administered orally every night<br>|
| Experimental: Metformin and Probiotics<br> | Drug: 1. Metformin tablets; 2. ProMetS probiotics powder<br>* 0.5g (1 pill) of Metformin tablets administered three times a day orally before meal; 4g (2 strips) of ProMetS probiotics powder administered orally every night<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in menstrual cycle | Patients will be required to maintain a menstrual calendar and record their basal body temperature for the duration of the study and asked to fill a questionnaire before and after study. The questionnaire will cover menstrual cycle dates, duration and amount. | 12 weeks | 
| Improvement in hirsutism | Modified Ferriman and Gallwey score (m-FG scores) will be measured before and after study. M-FG score > 8 is considered hirsutism and when the score is higher, the symptom is more serious. | 12 weeks | 
| Improvement in acne score | Visual assessment of acne using mild/moderate/severe grades will be assessed before and after study. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota |  | 12 weeks | 
| Fasting glucose levels |  | 12 weeks | 
| Fasting insulin levels |  | 12 weeks | 
| Serum follicle-stimulating hormone levels |  | 12 weeks | 
| Serum luteinizing hormone levels |  | 12 weeks | 
| Serum estradiol levels |  | 12 weeks | 
| Serum testosterone levels |  | 12 weeks | 
| Serum lipid profiles | including triglycerides (mmol/L), total cholesterol (mmol/L), low density lipoprotein cholesterol (mmol/L), and high density lipoprotein cholesterol (mmol/L) | 12 weeks | 
| Inflammation markers | including C-reactive protein (mg/L) | 12 weeks | 
| Immune cells | including count and frequency of T-cell subpopulations like T-regulatory (Treg) cells (/ml), T-helper (Th) cells (/ml) | 12 weeks |