Metformin and Gestational Diabetes in High-risk Patients: a RCTs
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.
Polycystic Ovary Syndrome
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Metformin Treatment for Preventing Gestational Diabetes in High-risk Patients|
- Incidence of gestational DM in high-risk patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Abortion [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Pregnancy-induced hypertension [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Pre-eclampsia [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Macrosomia [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Fetal malformations [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
- Premature deliveries [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Intrauterine deaths [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
850 mg twice daily
Placebo Comparator: Placebo
Microcristallyne cellulose 1 table twice daily
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00883259
|Contact: Stefano Palomba, MDfirstname.lastname@example.org|
|Catanzaro, Catanzaro, CZ, Italy, 88100|
|"Pugliese" Hospital||Not yet recruiting|
|Catanzaro, Italy, 88100|
|Contact: Ingrid Tomaino, MD +39-0961-883234 email@example.com|
|University of Catanzaro, Italy|
|Catanzaro, Italy, 88100|
|Principal Investigator:||Stefano Palomba, MD||Department of Obstetrics & Gynecology - University Magna Graecia of Catanzaro|
|Principal Investigator:||Francesco Orio, MD||Endocrinology - University " Parthenope" of Naples|
|Principal Investigator:||Achille Tolino, MD||Department of Obstetrics & Gynecology, University of Naples|
|Principal Investigator:||Tommaso Simoncini, MD||Department of Obstetrics & Gynecology - University of Pisa|
|Principal Investigator:||Fulvio Zullo, MD||Gynecologic Unit, Cancer Center of Excellence "Tommaso Campanella" of Catanzaro|