Metformin Administration in Infertile Anovulatory PCOS Patients

Sponsor

University Magna Graecia (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00501787

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Metformin	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tailored Versus Non-tailored Metformin Protocol for Ovulation Induction in Infertile Anovulatory PCOS Patients. A Randomized Controlled Clinical Study

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group B Non-tailoring	Drug: Metformin
Active Comparator: Group A Tailoring	Drug: Metformin

Arm

Intervention/Treatment

Active Comparator: Group B

Non-tailoring

Drug: Metformin

Active Comparator: Group A

Tailoring

Drug: Metformin

Outcome Measures

Primary Outcome Measures

Ovulation rate []

Secondary Outcome Measures

Adverse events []
Adherence rate []
Pregnancy rate []
Abortion rate []
Live-birth rate []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pugliese Hospital	Catanzaro	Catanzaro, CZ	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, Department of Endocrinology, University "Federico II" of Naples
Principal Investigator: Achille Tolino, MD, Department of Obstetrics & Gynecology, University "Federico II" of Naples