Metformin and Gestational Diabetes in High-risk Patients: a RCTs

Study Overview
=================
Brief Summary
-----------------
Gestational diabetes mellitus (DM) is one of the most frequent complications in pregnant patients with polycystic ovary syndrome (PCOS) in 20-40% of cases and  40% of patients with gestational DM are likely to have underlying polycystic ovarian morphology. A recent meta-analysis demonstrated a significantly higher risk of developing gestational DM [odds ratio (OR) 2.94; 95% confidence interval (CI): 1.70-5.08] in the PCOS population. Metformin is an oral biguanide insulin sensitizer used for treating type-2 DM and recently introduced to treat PCOS. At the moment, preliminary data seem to reassure regarding the use of metformin in PCOS patients showing benefits for maternal and fetal outcomes, without serious adverse events. Furthermore, well-designed randomized, controlled trials (RCTs) on this issue are lacking, thus it is not possible to either suggest or advice against the use of metformin during pregnancy for reducing gestational DM risk. To this regard, PCOS represents an intriguing model of high-risk patients to evaluate the efficacy of metformin for preventing DM development. The present protocol firstly will evaluate the effects of metformin administration in reducing incidence of gestational DM in high-risk patients, such as pregnant PCOS patients.

Detailed Description
-----------------
Obese pregnant PCOS patients with previous diagnosis of gestational DM will be enrolled and allocated into two treatment arms (experimental and placebo groups). Subjects in the experimental group will receive metformin at dosage of 850 mg twice daily, whereas subjects in the control group will receive placebo tablets (microcristallyne cellulose) twice daily. At baseline, all subjects will undergo clinical evaluation, serial ultrasound examinations, and venous blood drawing to evaluate complete hormonal assays and serum fasting glucose and insulin levels. The homeostasis model of assessment-insulin resistance, the fasting glucose-to-insulin ratio, and the free androgen index will be also calculated. Monthly follow-up visits will be performed for assessing maternal and fetal wellbeing. The primary endpoint of the study will be the incidence of gestational DM. The power analysis and the sample size calculation, performed using SamplePower release 2.0, showed that we will need to enroll at least 40 patients for each group to yield a statistically significant result with a power study of 90%. For categorical variables, the Pearson chi-square test will be performed. Continuous data will be expressed either as mean and standard deviation or median and inter-quartile range with min-max values, according to their normal distribution, and analysed using the Student t test or Mann-Whitney U test, respectively. Statistical significance will be set at P<0.05. The Statistics Package for Social Science (SPSS 14.0.1; Chicago, IL, USA) will be used for statistical analysis.

Official Title
-----------------
Metformin Treatment for Preventing Gestational Diabetes in High-risk Patients

Conditions
-----------------
Obesity, Polycystic Ovary Syndrome, Gestational Diabetes

Intervention / Treatment
-----------------
* Drug: Metformin
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with Polycystic Ovary Syndrome (using ASRM/ESHRE criteria) BMI > 30 Previous diagnosis of gestational DM Exclusion Criteria: Major medical conditions Organic pelvic diseases Previous pelvic surgery

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Metformin treatment | Drug: Metformin<br>* 850 mg twice daily<br>|
| Placebo Comparator: Placebo<br>Placebo tablets | Other: Placebo<br>* Microcristallyne cellulose 1 table twice daily<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of gestational DM in high-risk patients |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abortion |  | 36 months | 
| Pregnancy-induced hypertension |  | 36 months | 
| Pre-eclampsia |  | 36 months | 
| Macrosomia |  | 36 months | 
| Fetal malformations |  | 36 months | 
| Premature deliveries |  | 36 months | 
| Intrauterine deaths |  | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
High-risk patients, Metformin, PCOS, Pregnancy complications, Previous gestational DM