Metformin Administration in Infertile Anovulatory PCOS Patients

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT00501787
First received: July 12, 2007
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Polycystic Ovary Syndrome
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Magna Graecia:

Primary Outcome Measures:
  • Ovulation rate

Secondary Outcome Measures:
  • Adverse events
  • Adherence rate
  • Pregnancy rate
  • Abortion rate
  • Live-birth rate

Enrollment: 0
Study Start Date: January 2008
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group B
Non-tailoring
Drug: Metformin
Active Comparator: Group A
Tailoring
Drug: Metformin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501787

Locations
Italy
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
  More Information

No publications provided

Responsible Party: Stefano Palomba, Associate Professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT00501787     History of Changes
Other Study ID Numbers: 05/2006d
Study First Received: July 12, 2007
Last Updated: April 5, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:
Anovulation
metformin
PCOS
treatment

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Adnexal Diseases
Cysts
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014