Berberine and Polycystic Ovary Syndrome

Study Overview
=================
Brief Summary
-----------------
Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disease in female reproductive-age. Recently, increasing evidence has shown that natural plant-based products may play a role in PCOS management. Previous study in PCOS preclinical model and in humans demonstrated that berberine is an effective insulin sensitizer and improves homeostasis of metabolic, inflammatory and hormonal disorders. However, to date there is no clinical study that considers globally all the activities carried out by berberine in PCOS clinical features. Given this background, aim of this study was to evaluate in normal-overweight PCOS women with normal menses the berberine effectiveness on: insulin resistance by Homeostasis Model Assessment (HOMA); inflammation by C-Reactive Protein (CRP), TNF-alpha; lipid metabolism; sex hormone profile and symptoms correlated to hyperandrogenism, such as acne, by Global Acne Grading System (GAGS) and Cardiff Acne Disability Index (CADI); body composition by dual-energy X-ray absorptiometry. All these parameters were collected at baseline and 60 days after supplementation with a new bioavailable and safe berberine formulation. Finally, adverse effects were assessed by liver and kidney functions. To evaluate statistically significant pre- post-supplementation changes, fitted a linear mixed model for each investigated endpoint was performed.

Official Title
-----------------
Berberine is an Effective Insulin Sensitizer and Improves Homeostasis of Metabolic and Hormonal Disorders in Women With Polycystic Ovary Syndrome: a Novel Treatment Strategy for PCOS

Conditions
-----------------
Berberine, Polycystic Ovary Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Berberine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: normal and overweight women (Body Mass Index (BMI) 25-30 kg/m2) newly detected Polycystic Ovary Syndrome Exclusion Criteria: any concomitant medication presence of liver, renal and thyroid disease smoking drinking more than two standard alcoholic beverages/day (20 g of alcohol/day)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berberine<br>2 daily oral doses (one before lunch and one dinner) of 550 mg of berberine tablets | Dietary Supplement: Berberine<br>* 2 daily oral doses (one before lunch and one dinner) of 550 mg of berberine tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on insulin resistance | Homeostasis Model Assessment (pt), for evaluate insulin resistance if > 2.4 | Changes from baseline insulin resistance at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on inflammation | C-Reactive Protein (mg/dl) | Changes from baseline inflammation at 8 weeks | 
| Changes on inflammation | Tumor Necrosis Factor alpha (pg/ml) | Changes from baseline inflammation at 8 weeks | 
| Changes on lipid profile | Total Cholesterol (mg/dl), High Density Lipoprotein Cholesterol (mg/dl), Low Density Lipoprotein Cholesterol (mg/dl), Very Low Density Lipoprotein (mg/dl),Triglycerides (mg/dl) | Changes from baseline lipid profile at 8 weeks | 
| Changes on Carbohydrate profile | Glycemia (mg/dl) | Changes from baseline Carbohydrate profile at 8 weeks | 
| Changes on Carbohydrate profile | Insulin (mcU/ml) | Changes from baseline Carbohydrate profile at 8 weeks | 
| Changes on Hormonal profile | Sex Hormone Binding Globulin (nmol/l) | Changes from baseline Hormonal profile at 8 weeks | 
| Changes on Hormonal profile | Testosterone (ng/ml) | Changes from baseline Hormonal profile at 8 weeks | 
| Changes on Hormonal profile | Free Androgen Index (ratio) | Changes from baseline Hormonal profile at 8 weeks | 
| Changes on safety | Aspartate aminotransferase (IU/l), alanine aminotransferase (IU/l) | Changes from baseline safety at 8 weeks | 
| Changes on safety | Total bilirubin (mg/dl) | Changes from baseline safety at 8 weeks | 
| Changes on safety | Gamma Glutamyl Transferase (U/I), Creatine Phosphokinase (U/I) | Changes from baseline safety at 8 weeks | 
| Changes on anthropometry | waist circumference (cm), hip circumference (cm) | Changes from baseline anthropometry at 8 weeks | 
| Changes on anthropometry | Weight (kg) | Changes from baseline anthropometry at 8 weeks | 
| Changes on anthropometry | Body Mass Index (Kg/m2) | Changes from baseline anthropometry at 8 weeks | 
| Changes on body composition | Fat mass (g), lean mass (g), visceral adipose tissue (g) | Changes from baseline body composition at 8 weeks | 
| Changes on acne assessment | Global Acne Grading System (scale): each type of acne lesion is given a value depending on severity: no lesions = 0, comedones = 1, papules = 2, pustules = 3, and nodules = 4. Each of the location was graded separately on 0-4 scale, with the most severe lesion within that location determining the local score. The severity was then graded according to the global score which is the summation of all local scores. A score of 1-6 was considered mild; 7-18, moderate; 19- 26, severe; and 27-32, very severe. The maximum score was 32 | Changes from baseline acne assessment at 8 weeks | 
| Changes on acne assessment | Cardiff Acne Disability Index (scale): the Cardiff Acne Disability Index consists of five questions with a Likert scale, four response categories (0-3). The five questions relate to feeling of aggression, frustration, interference with social life, avoidance of public changing facilities and appearance of the skin-all over the last month-and an indication of how bad the acne was now. The CADI score was calculated by summing the score of each question resulting in a possible maximum of 15 and minimum of 0. CADI scores were graded as low (0-4), medium (5-9), and high (10-15) | Changes from baseline acne assessment at 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
berberine, Polycystic Ovary Syndrome