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

Obesity Clinical Trial

Official title:

Metformin Treatment for Preventing Gestational Diabetes in High-risk Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00883259
• Other study ID #: 12/2008
• Status: Not yet recruiting
• Phase: Phase 4
• First received: April 16, 2009
• Last updated: April 5, 2013
• Start date: September 2013

Study information

• Verified date: April 2013
• Source: University Magna Graecia
• Contact: Stefano Palomba, MD
• Phone: +39-0961-883234
• Email: stefanopalomba[@]tin.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes, Gestational
• Gestational Diabetes
• Obesity
• Polycystic Ovary Syndrome

Intervention

Drug:
• Metformin
850 mg twice daily

Other:
• Placebo
Microcristallyne cellulose 1 table twice daily

Locations

Country	Name	City	State
Italy	"Pugliese" Hospital	Catanzaro
Italy	Pugliese Hospital	Catanzaro	Catanzaro, CZ
Italy	University of Catanzaro, Italy	Catanzaro

Sponsors (1)

Lead Sponsor	Collaborator
University Magna Graecia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of gestational DM in high-risk patients		36 months	No
Secondary	Abortion		36 months	No
Secondary	Pregnancy-induced hypertension		36 months	No
Secondary	Pre-eclampsia		36 months	No
Secondary	Macrosomia		36 months	No
Secondary	Fetal malformations		36 months	Yes
Secondary	Premature deliveries		36 months	No
Secondary	Intrauterine deaths		36 months	Yes