Polycystic Ovary SyndromePhase 4NCT00679679
Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome
A Phase 4 study testing Metformin in people with Polycystic Ovary Syndrome, run by Hospital Privado de Cordoba, Argentina at 1 site in Argentina.
Trial summary
Polycystic ovary syndrome is a frequent cause of abnormal menses and infertility. It has also been related to cardiovascular disease. The objective of this trial is to evaluate the clinical and metabolic efficacy of metformin plus life style modifications in women with polycystic ovary syndrome compared with life… 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?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteArgentina
- Study dates
- Jan 2003to Dec 2005
- 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
- Women in reproductive age
- With polycystic ovary syndrome defined by hyperandrogenism (elevated serum testosterone concentrations), and oligomenorrhea (cycles of 35 days or longer), or amenorrhea (no menses in the last 6 months) after negative screening pregnancy test
Who cannot join
- Pregnancy
- Cushing' s syndrome
- Late onset congenital adrenal hyperplasia
- Androgen-secreting tumors
- Uncontrolled thyroid disease
- Hyperprolactinemia
Show all 12Show fewer
- Diabetes any
- Cardiovascular diseases (Ischaemic heart disease, uncontrolled hypertension, heart failure)
- Acute or chronic infections at baseline
- Renal disease
- Liver disease
- Had taken any medications for at least 3 months before enrolment in the study.
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Hospital Privado de Córdoba
Córdoba, Córdoba Province, X5016KEH
About this study
Official title: Clinical Metabolic and Endocrine Parameters in Response to Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome: A Phase 4 Randomized, Double- Blind and Placebo Control Trial
Polycystic ovary syndrome is a frequent cause of abnormal menses and infertility. It has also been related to cardiovascular disease.
The objective of this trial is to evaluate the clinical and metabolic efficacy of metformin plus life style modifications in women with polycystic ovary syndrome compared with life style modifications and placebo
Read the detailed description
Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder of women in reproductive age. It is characterized by hyperandrogenism and chronic anovulation. Several studies in diverse populations estimate it's prevalence at 5-10%. Women present, in a high percentage of cases, with obesity, hirsutism, acne, menstrual irregularities and infertility. Although the exact physiopathology of PCOS remains unknown, several studies tend to point to insulinoresistance (IR) as the cause of the syndrome. IR is present in 60 to 70% of patients independently of obesity. Compensatory hyperinsulinism has a pivotal role in the physiopathogenesis of PCOS. In vitro, insulin stimulates androgen synthesis in thecal cells and decrease sex hormone-binding globulin synthesis in the liver, increasing free androgen availability.
Due to the high prevalence of IR, PCOS shares components of metabolic syndrome: abdominal obesity, impaired glucose tolerance, gestational and type 2 diabetes, abnormalities in lipid profile, blood hypertension, endothelial dysfunction and probably cardiovascular disease.
In the past, PCOS treatment was focus on ovulation induction for infertility, oral contraceptives for irregular bleeding, and androgens antagonists for hirsutism or acne. In later years insulin sensitizing agents have been used to reduce hyperinsulinemia, improve ovary function and associated metabolic abnormalities. Metformin (MTF), a biguanide, usually used in obese patients with type 2 diabetes,inhibits glucose hepatic production,decreases insulin secretion and increases peripheral insulin sensitivity.
Some studies have reported an improvement in insulin sensitivity associated with reduction of hyperandrogenism and improvements in reproductive abnormalities with MTF. On the other hand, other authors failed to observe those changes. However, an off label indication for it usage in PCOS for FDA and the lack of large controlled trials, MTF indication to treat PCOS has grown dramatically in later years.
In obese women with PCOS, weight loss effectively ameliorates hyperandrogenism and metabolic disorders by improving insulin resistance.
Some trials have suggested that those effects could be improved with insulin sensitizing agents without changes in body weigh.
The present study was designed to assess, in a randomized, double-blind, placebo-controlled way, the effects of MTF in addition to lifestyle modifications on endocrine and metabolic disturbances in women with PCOS.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Metformin, Placebo
- Keywords
- Polycystic ovary syndrome, Treatment, Metformin
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called D.B.I. 500 mg. 1 1/2 tables BID
Metformin 750 mg BID for 4 months
PlaceboDrug
Diet counseling and exercise
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin Receives: Drug: Metformin |
| Placebo | Placebo comparator | Every patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body mass index,Normalization of menses,Pregnancy,Hirsutism,Waist to hip ratio, Testosterone, Androstenedione, DHEAS,Progesterone, FSH, LH,Glucose, OGTT,Insulinemia,Total HDL and LDL Cholesterol, Triglycerides,Uric acid, Prostate specific antigen
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2008 (estimated)
- Study startJan 2003
- Primary completionSep 2005
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Privado de Cordoba, Argentina
- Sponsor type
- University, hospital or other
- Investigators
- Carolina Fux Otta, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00679679
- Sponsor's protocol ID
- Fux-1
- Status last verified
- May 2008
- First submitted
- 15 May 2008
- Last updated
- 19 May 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.
PubMed 15181052Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8. doi: 10.1210/jcem.85.7.6682.
PubMed 10902790Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006-11. doi: 10.1210/jcem.84.11.6148.
PubMed 10566641Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. doi: 10.1056/NEJMra041536. No abstract available.
PubMed 15788499Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. doi: 10.1210/edrv.18.6.0318.
PubMed 9408743Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
PubMed 2670645Barbieri RL, Makris A, Randall RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986 May;62(5):904-10. doi: 10.1210/jcem-62-5-904.
PubMed 3514651Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1991 Jan;72(1):83-9. doi: 10.1210/jcem-72-1-83.
PubMed 1898744Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.
PubMed 16182882Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999 Jan;84(1):165-9. doi: 10.1210/jcem.84.1.5393.
PubMed 9920077Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun;88(6):2562-8. doi: 10.1210/jc.2003-030334.
PubMed 12788855Wild RA. Long-term health consequences of PCOS. Hum Reprod Update. 2002 May-Jun;8(3):231-41. doi: 10.1093/humupd/8.3.231.
PubMed 12078834Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand. 1992 Dec;71(8):599-604. doi: 10.3109/00016349209006227.
PubMed 1336918Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg RA. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol. 1998 May;51(5):415-22. doi: 10.1016/s0895-4356(98)00010-9.
PubMed 9619969Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001 Mar 13;103(10):1410-5. doi: 10.1161/01.cir.103.10.1410.
PubMed 11245645
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Metabolic and Endocrine Parameters in Response to Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome: A Phase 4 Randomized, Double- Blind and Placebo Control Trial
- ClinicalTrials.gov ID
- NCT00679679
- Acronym / sponsor ID
- Fux-1
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Polycystic ovary syndrome, Treatment, Metformin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Hospital Privado de Cordoba, ArgentinaUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Sep 2005 (actual)
- Study completion
- Dec 2005 (actual)
- First posted
- 19 May 2008 (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.
Polycystic ovary syndrome is a frequent cause of abnormal menses and infertility. It has also been related to cardiovascular disease.
The objective of this trial is to evaluate the clinical and metabolic efficacy of metformin plus life style modifications in women with polycystic ovary syndrome compared with life style modifications and placebo
Detailed description
Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder of women in reproductive age. It is characterized by hyperandrogenism and chronic anovulation. Several studies in diverse populations estimate it's prevalence at 5-10%. Women present, in a high percentage of cases, with obesity, hirsutism, acne, menstrual irregularities and infertility. Although the exact physiopathology of PCOS remains unknown, several studies tend to point to insulinoresistance (IR) as the cause of the syndrome. IR is present in 60 to 70% of patients independently of obesity. Compensatory hyperinsulinism has a pivotal role in the physiopathogenesis of PCOS. In vitro, insulin stimulates androgen synthesis in thecal cells and decrease sex hormone-binding globulin synthesis in the liver, increasing free androgen availability.
Due to the high prevalence of IR, PCOS shares components of metabolic syndrome: abdominal obesity, impaired glucose tolerance, gestational and type 2 diabetes, abnormalities in lipid profile, blood hypertension, endothelial dysfunction and probably cardiovascular disease.
In the past, PCOS treatment was focus on ovulation induction for infertility, oral contraceptives for irregular bleeding, and androgens antagonists for hirsutism or acne. In later years insulin sensitizing agents have been used to reduce hyperinsulinemia, improve ovary function and associated metabolic abnormalities. Metformin (MTF), a biguanide, usually used in obese patients with type 2 diabetes,inhibits glucose hepatic production,decreases insulin secretion and increases peripheral insulin sensitivity.
Some studies have reported an improvement in insulin sensitivity associated with reduction of hyperandrogenism and improvements in reproductive abnormalities with MTF. On the other hand, other authors failed to observe those changes. However, an off label indication for it usage in PCOS for FDA and the lack of large controlled trials, MTF indication to treat PCOS has grown dramatically in later years.
In obese women with PCOS, weight loss effectively ameliorates hyperandrogenism and metabolic disorders by improving insulin resistance.
Some trials have suggested that those effects could be improved with insulin sensitizing agents without changes in body weigh.
The present study was designed to assess, in a randomized, double-blind, placebo-controlled way, the effects of MTF in addition to lifestyle modifications on endocrine and metabolic disturbances in women with PCOS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminEvery patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin |
| Placebo | Placebo comparator | Drug: PlaceboEvery patient will be given diet and exercise counseling in both arms. Intervention arm will receive metformin |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women in reproductive age
- With polycystic ovary syndrome defined by hyperandrogenism (elevated serum testosterone concentrations), and oligomenorrhea (cycles of 35 days or longer), or amenorrhea (no menses in the last 6 months) after negative screening pregnancy test
Key exclusion criteria (12 listed)
- Pregnancy
- Cushing' s syndrome
- Late onset congenital adrenal hyperplasia
- Androgen-secreting tumors
- Uncontrolled thyroid disease
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 |
|---|---|---|
| MetforminAlso: D.B.I. 500 mg. 1 1/2 tables BIDMetformin 750 mg BID for 4 months | Drug | Metformin |
| PlaceboDiet counseling and exercise | Drug | Placebo |
Primary outcome
Body mass index,Normalization of menses,Pregnancy,Hirsutism,Waist to hip ratio, Testosterone, Androstenedione, DHEAS,Progesterone, FSH, LH,Glucose, OGTT,Insulinemia,Total HDL and LDL Cholesterol, Triglycerides,Uric acid, Prostate specific antigen
Time frame: 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2008.
- Background: PubMed 15181052Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.
- Background: PubMed 10902790Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8. doi: 10.1210/jcem.85.7.6682.
- Background: PubMed 10566641Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006-11. doi: 10.1210/jcem.84.11.6148.
- Background: PubMed 15788499Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. doi: 10.1056/NEJMra041536. No abstract available.
- Background: PubMed 9408743Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. doi: 10.1210/edrv.18.6.0318.
- Background: PubMed 2670645Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
- Background: PubMed 3514651Barbieri RL, Makris A, Randall RW, Daniels G, Kistner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986 May;62(5):904-10. doi: 10.1210/jcem-62-5-904.
- Background: PubMed 1898744Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1991 Jan;72(1):83-9. doi: 10.1210/jcem-72-1-83.
- Background: PubMed 16182882Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.
- Background: PubMed 9920077Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999 Jan;84(1):165-9. doi: 10.1210/jcem.84.1.5393.
- Background: PubMed 12788855Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun;88(6):2562-8. doi: 10.1210/jc.2003-030334.
- Background: PubMed 12078834Wild RA. Long-term health consequences of PCOS. Hum Reprod Update. 2002 May-Jun;8(3):231-41. doi: 10.1093/humupd/8.3.231.
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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.
Carolina Fux Otta, MD principal investigator
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 Hospital Privado de Cordoba, Argentina at 1 site in Argentina.
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 2 inclusion and 12 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: finished, as of the sponsor's last update on 19 May 2008. 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 Argentina. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Body mass index,Normalization of menses,Pregnancy,Hirsutism,Waist to hip ratio, Testosterone, Androstenedione, DHEAS,Progesterone, FSH, LH,Glucose, OGTT,Insulinemia,Total HDL and LDL Cholesterol, Triglycerides,Uric acid, Prostate specific antigen (time frame: 4 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 NCT00679679, which also lists 38 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 19 May 2008.