Polycystic Ovary SyndromePhase 4NCT00501904
Metformin in Infertile PCOS Patients
A Phase 4 study testing Metformin in people with Polycystic Ovary Syndrome, run by University Magna Graecia at 1 site in Italy.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2012to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Polycystic ovary syndrome (using NIH criteria)
- Anovulatory infertility (using WHO criteria)
- Ovulatory cycles under metformin (three cycles)
Who cannot join
- 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
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- Organic pelvic diseases
- Previous pelvic surgery
- Suspected peritoneal factor infertility
- Tubal or male factor infertility or sub-fertility
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Pugliese Hospital
Catanzaro, Catanzaro, CZ, Italy, 88100
Ingrid Tomaino, MD, +39-0961965097, angela.falbo@libero.it
Stefano Palomba, MD
About this study
Official title: Efficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients
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.
Read the detailed description
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
- Polycystic Ovary Syndrome
- Being tested
- Metformin
- Keywords
- Anovulation, Infertility, Metformin, PCOS, Treatment
- Medical subject headings
- Polycystic Ovary Syndrome, Anovulation, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Short protocol Receives: Drug: Metformin |
| Group B | Active comparator | Long protocol Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy rate
Measured: 12 months
Secondary outcomes (1)
Ovulation rate Abortion rate Live-birth rate Adverse events
Measured: 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2007 (estimated)
- Study startApr 2012
- Primary completionJun 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefano Palomba, University Magna Graecia
- Investigators
- Stefano Palomba, MD, Principal investigator, Department of Obstetrics & Gynecology, University "Magna Graecia" of CatanzaroFrancesco Orio, MD, Principal investigator, Department of Endocrinology, University "Federico II" of NaplesAchille Tolino, MD, Principal investigator, Department of Obstetrics & Gynecology, University "Federico II" of Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00501904
- Sponsor's protocol ID
- 05/2006b
- Status last verified
- Dec 2015
- First submitted
- 12 Jul 2007
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17595241Palomba 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.
PubMed 15840746
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Long- Versus Short-term Metformin Protocol in Infertile Anovulatory PCOS Patients
- ClinicalTrials.gov ID
- NCT00501904
- Acronym / sponsor ID
- 05/2006b
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Anovulation, Infertility, Metformin, PCOS, Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 16 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: MetforminShort protocol |
| Group B | Active comparator | Drug: MetforminLong protocol |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Polycystic ovary syndrome (using NIH criteria)
- Anovulatory infertility (using WHO criteria)
- Ovulatory cycles under metformin (three cycles)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin | Drug | Group A, Group B |
Primary outcome
Pregnancy rate
Time frame: 12 months
1 secondary outcome
Ovulation rate Abortion rate Live-birth rate Adverse events
Time frame: 21 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
- Background: PubMed 17595241Palomba 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.
- Background: PubMed 15840746Palomba 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Palomba, MD principal investigator
Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro
Francesco Orio, MD principal investigator
Department of Endocrinology, University "Federico II" of Naples
Achille Tolino, MD principal investigator
Department of Obstetrics & Gynecology, University "Federico II" of Naples
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin in people with Polycystic Ovary Syndrome, run by University Magna Graecia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stefano Palomba, MD (+39-0961-883234, stefanopalomba@tin.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancy rate (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00501904, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2015.