Metformin in Infertile PCOS Patients

NCT ID: NCT00501904

Last Updated: 2015-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-04-30

Study Completion Date

2016-12-31

Brief Summary

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Metformin, an oral biguanide administrated for treating type-2 diabetes mellitus, is a safe and effective drug recently experimented also in patients with polycystic ovary syndrome (PCOS). The administration of metformin induces ovulatory cycles in CC-resistant or -nonresistant patients with PCOS, and improves the ovulation rate as an additional treatment in women who received CC.

To date, it is unknown the best protocol for metformin administration. In particular, it is not known how long patients who ovulate under metformin should continue treatment before switching to second-line ovulation induction therapy. In this regard, in a recent study by the Kaplan-Meier survival analysis we demonstrated that the first pregnancy occurred late after metformin with an estimated median of seven months.

Based on these considerations, the aim of the present study will be to evaluate the clinical efficacy of metformin according to its duration of administration in infertile PCOS patients ovulating under treatment.

Detailed Description

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Infertile PCOS patients having three ovulatory cycles under metformin, administered using tailored protocol, will be enrolled and randomized in two groups (groups A and B). Patients of group A will continue metformin administration for further three cycles followed by six months of progestogens cyclically administered, whereas patients of group B will continue metformin therapy for further nine cycles.

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. Cumulative pregnancy rate, our primary end-point, will be calculated by the Kaplan-Maier method, and the differences between the two groups will be assessed with the log-rank test. Cox proportional-hazards model will be used to calculate the hazard ratio for new pregnancy in both groups.

Conditions

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Polycystic Ovary Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Group A

Short protocol

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

Group B

Long protocol

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

Interventions

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Metformin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Polycystic ovary syndrome (using NIH criteria)
* Anovulatory infertility (using WHO criteria)
* Ovulatory cycles under metformin (three cycles)

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 drugsPrevious 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

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University Magna Graecia

OTHER

Sponsor Role lead

Responsible Party

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Stefano Palomba

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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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

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Pugliese Hospital

Catanzaro, Catanzaro, CZ, Italy, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Stefano Palomba, MD

Role: CONTACT

+39-0961-883234

Facility Contacts

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Ingrid Tomaino, MD

Role: primary

+39-0961965097

References

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Palomba S, Orio F Jr, Falbo A, Russo T, Tolino A, Zullo F. Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Sep;92(9):3498-503. doi: 10.1210/jc.2007-1009. Epub 2007 Jun 26.

Reference Type BACKGROUND
PMID: 17595241 (View on PubMed)

Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.

Reference Type BACKGROUND
PMID: 15840746 (View on PubMed)

Other Identifiers

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05/2006b

Identifier Type: -

Identifier Source: org_study_id