Metformin Administration in Infertile Anovulatory PCOS Patients

NCT ID: NCT00501787

Last Updated: 2013-04-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31

Brief Summary

In a recent prospective study evaluating the efficacy of 1700 mg/day metformin as first-line approach for infertile anovulatory patients with PCOS, we identified predictors for metformin efficacy. Our analysis demonstrated that body mass index (BMI) and insulin resistance were the strongest predictors for both ovulation and pregnancy. In particular, adjusting the data for insulin resistance, a trend in reduced effectiveness was observed with increasing BMI. On the other hand, adjusting the data for BMI, a trend in improved efficacy was detected for higher insulin resistance degrees.

To date, no dose-finding study is currently available in literature evaluating the best dose of metformin to administer. In addition, very few data regarding the best protocol for metformin treatment also are available. However, in order to reduce drug-related side effects incidence due to start-up syndrome, metformin is generally administrated with meals at incremental weekly doses until the maximum dosage ranging from 500 to 2550 mg daily; the doses are reduced if side effects appear. This commonly accepted protocol has not been supported by scientific evidences.

The aim of the present study will be to evaluate in a clinical setting the compliance, the safety and the effectiveness of two schedules for metformin administration in infertile anovulatory PCOS patients.

Detailed Description

Infertile anovulatory PCOS eligible patients will be enrolled and randomly allocated to receive tailored (tailored group) or non-tailored metformin treatment (non-tailored group).

Tailored metformin treatment will consist of incremental doses regimen starting from a dosage of 850 mg daily (one tablet daily) with a weekly increase up to 2550 mg daily (three tablets daily). The dosage of metformin will be reduced according to the appearance of serous or affecting compliance drug-related side effects. Conversely, non-tailored metformin treatment consisted of fixed doses regimen of 850 mg twice daily. For both groups, the treatment will be of six months.

All patients eligible will undergo baseline assessment consisting of anthropometric, hormonal, and ultrasonographic evaluations. During the study, the clinical and reproductive outcomes, and the adverse experience will be evaluated in each patient.

Data will be analyzed using the intention-to-treat principle and a P value of 0.05 or less will be considered significant. Continuous variables will be analyzed with the unpaired t test and general linear model for repeated measures analysis with Bonferroni test for the post-hoc analysis as required. For categorical variables, the Pearson chi-square and Fisher's exact tests will be used.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group B

Non-tailoring

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Group A

Tailoring

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Interventions

Metformin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Polycystic ovary syndrome (using NIH criteria)
• Anovulatory infertility (using WHO criteria)

Exclusion Criteria

• Age <18 or >35 years
• Severe obesity (BMI >35)
• Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses
• Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugs
• Previous use of ovulation induction agents
• Intention to start a diet or a specific program of physical activity
• Organic pelvic diseases
• Previous pelvic surgery
• Suspected peritoneal factor infertility
• Tubal or male factor infertility or sub-fertility

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Magna Graecia

OTHER

Sponsor Role: lead

Responsible Party

Stefano Palomba

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefano Palomba, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro

Francesco Orio, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Endocrinology, University "Federico II" of Naples

Achille Tolino, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Obstetrics & Gynecology, University "Federico II" of Naples

Locations

Pugliese Hospital

Catanzaro, Catanzaro, CZ, Italy

Countries

Italy

Other Identifiers

05/2006d

Identifier Type: -

Identifier Source: org_study_id