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

This study is not yet open for participant recruitment.
Verified April 2013 by University Magna Graecia
Sponsor:
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT00883259
First received: April 16, 2009
Last updated: April 5, 2013
Last verified: April 2013
History of Changes
  Purpose

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 Intervention Phase
Obesity
Polycystic Ovary Syndrome
Gestational Diabetes
 Drug: Metformin
Other: Placebo
 Phase 4

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Magna Graecia:

Primary Outcome Measures:
  • Incidence of gestational DM in high-risk patients [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental
Metformin treatment
 Drug: Metformin
850 mg twice daily
Placebo Comparator: Placebo
Placebo tablets
 Other: Placebo
Microcristallyne cellulose 1 table twice daily

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00883259

Contacts
Contact: Stefano Palomba, MD +39-0961-883234 stefanopalomba@tin.it

Locations
Italy
Pugliese Hospital
Catanzaro, Catanzaro, CZ, Italy, 88100
University of Catanzaro, Italy
Catanzaro, Italy, 88100
"Pugliese" Hospital Not yet recruiting
Catanzaro, Italy, 88100
Contact: Ingrid Tomaino, MD     +39-0961-883234     angela.falbo@libero.it    
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
  More Information

No publications provided

Responsible Party: Stefano Palomba, Associate Professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT00883259     History of Changes
Other Study ID Numbers: 12/2008
Study First Received: April 16, 2009
Last Updated: April 5, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:
High-risk patients
Metformin
PCOS
Pregnancy complications
Previous gestational DM

Additional relevant MeSH terms:
Diabetes Mellitus
Obesity
Polycystic Ovary Syndrome
Diabetes, Gestational
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
 Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Pregnancy Complications
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013