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

Sponsor

University Magna Graecia (Other)

Overall Status

Unknown status

CT.gov ID

NCT00883259

Collaborator

(none)

Enrollment

Locations

Arms

26.7

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity Polycystic Ovary Syndrome Gestational Diabetes	Drug: Metformin Other: Placebo	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Metformin Treatment for Preventing Gestational Diabetes in High-risk Patients

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Metformin treatment	Drug: Metformin 850 mg twice daily
Placebo Comparator: Placebo Placebo tablets	Other: Placebo Microcristallyne cellulose 1 table twice daily

Arm

Intervention/Treatment

Experimental: Experimental

Metformin treatment

Drug: Metformin

850 mg twice daily

Placebo Comparator: Placebo

Placebo tablets

Other: Placebo

Microcristallyne cellulose 1 table twice daily

Outcome Measures

Primary Outcome Measures

Incidence of gestational DM in high-risk patients [36 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pugliese Hospital	Catanzaro	Catanzaro, CZ	Italy	88100
2	"Pugliese" Hospital	Catanzaro		Italy	88100
3	University of Catanzaro, Italy	Catanzaro		Italy	88100

Sponsors and Collaborators

University Magna Graecia

Investigators

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