Metformin and Gestational Diabetes in High-risk Patients: a RCTs
Overview[ - collapse ][ - ]
| 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 | Obesity Polycystic Ovary Syndrome Gestational Diabetes |
| Intervention | Drug: Metformin Other: Placebo |
| Phase | Phase 4 |
| Sponsor | University Magna Graecia |
| Responsible Party | University Magna Graecia |
| ClinicalTrials.gov Identifier | NCT00883259 |
| First Received | April 16, 2009 |
| Last Updated | April 5, 2013 |
| Last verified | April 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | April 16, 2009 |
|---|---|
| Last Updated Date | April 5, 2013 |
| Start Date | September 2013 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Incidence of gestational DM in high-risk patients [Time Frame: 36 months] [Designated as safety issue: No] |
| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Metformin and Gestational Diabetes in High-risk Patients: a RCTs |
|---|---|
| Official Title | Metformin Treatment for Preventing Gestational Diabetes in High-risk Patients |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention |
| Condition |
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| Intervention | Drug: Metformin 850 mg twice daily Other: Placebo Microcristallyne cellulose 1 table twice daily |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Not yet recruiting |
|---|---|
| Estimated Enrollment | 80 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | December 2013 |
| 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 |
| Gender | Female |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Stefano Palomba, MD +39-0961-883234 stefanopalomba@tin.it |
| Location Countries | Italy |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00883259 |
|---|---|
| Other Study ID Numbers | 12/2008 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University Magna Graecia |
| Study Sponsor | University Magna Graecia |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Stefano Palomba, MD Department of Obstetrics & Gynecology - University Magna Graecia of CatanzaroPrincipal Investigator: Francesco Orio, MD Endocrinology - University " Parthenope" of NaplesPrincipal Investigator: Achille Tolino, MD Department of Obstetrics & Gynecology, University of NaplesPrincipal Investigator: Tommaso Simoncini, MD Department of Obstetrics & Gynecology - University of PisaPrincipal Investigator: Fulvio Zullo, MD Gynecologic Unit, Cancer Center of Excellence "Tommaso Campanella" of Catanzaro |
| Verification Date | April 2013 |
Locations[ + expand ][ + ]
| Pugliese Hospital | Catanzaro, Catanzaro, CZ, Italy, 88100 |
|---|---|
| University of Catanzaro, Italy | Catanzaro, Italy, 88100 |
| "Pugliese" Hospital | Catanzaro, Italy, 88100 Contact: Ingrid Tomaino, MD | +39-0961-883234 | angela.falbo@libero.itNot yet recruiting |