Effects of Metformin and Oral Hormonal Contraceptive in Adolescents With Polycystic Ovary Syndrome
Overview[ - collapse ][ - ]
| Purpose | The polycystic ovary syndrome is the most common endocrinopathy in reproductive age women. The pathophysiology of this syndrome remains unclear, but there are evidences that a decreased in insulin sensitivity may be related in this syndrome. There are studies that showed the action of factors on the sensitivity of the insulin receptor, such as melatonin. It is a hormone produced by the pineal gland, whose role is still uncertain in human reproduction, although many studies have found that it may relate sex hormone effect. Many patients with polycystic ovary syndrome (PCOS) may have hyperinsulinemia, and that pinealectomized rats determined hypoglycemia and hyperinsulinemia, with reduced release of insulin in response to glucose. Therefore, it is supposed that blood levels of melatonin might correlate with the blood insulin concentration in patients with the syndrome. Moreover, the insulin sensitizing agents have been used in the treatment of patients with insulin resistance and PCOS, based on its main pathophysiological substrate which is the hyperinsulinemia. In fact, the metformin is the most used in the literature. However, there are few studies on the use of metformin in adolescents. The evidences of this drugs in this group of patients have showed good therapeutic response with few side effects. The objective of the study is to evaluate the effects of metformin on insulin resistance and levels of melatonin in adolescents with PCOS. It will be performed a prospective, randomized, double-blind and placebo-controlled study with 90 adolescents with PCOS. It will be evaluated clinical and laboratory parameters (TSH, free T4, prolactin, FSH, LH, estradiol, total testosterone, androstenedione, DHEA-s, 17-OH progesterone, SHBG, free androgen index, index of HOMA-IR and QUICKI from fasting glucose and insulin, total cholesterol and fractions, triglycerides, creatinine, AST and ALT and creatinkinase, fibrinogen and PAI-1, and melatonin for 6 months of treatment. |
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| Condition | Polycystic Ovary Syndrome |
| Intervention | Drug: Placebo Drug: Metformin |
| Phase | N/A |
| Sponsor | Federal University of São Paulo |
| Responsible Party | Federal University of São Paulo |
| ClinicalTrials.gov Identifier | NCT00988078 |
| First Received | September 30, 2009 |
| Last Updated | June 24, 2012 |
| Last verified | October 2009 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 30, 2009 |
|---|---|
| Last Updated Date | June 24, 2012 |
| Start Date | July 2011 |
| Estimated Primary Completion Date | December 2013 |
| Current Primary Outcome Measures | serum melatonin [Time Frame: 0 and 6 months] [Designated as safety issue: Yes] |
| Current Secondary Outcome Measures | hormonal and metabolic measurements, clinical assessment [Time Frame: 0, 3 and 6 months] [Designated as safety issue: Yes] |
Descriptive Information[ + expand ][ + ]
| Brief Title | Effects of Metformin and Oral Hormonal Contraceptive in Adolescents With Polycystic Ovary Syndrome |
|---|---|
| Official Title | Effect of Metformin Therapy on Insulin Resistance and Melatonin in Adolescents With Polycystic Ovary Syndrome. |
| Brief Summary | The polycystic ovary syndrome is the most common endocrinopathy in reproductive age women. The pathophysiology of this syndrome remains unclear, but there are evidences that a decreased in insulin sensitivity may be related in this syndrome. There are studies that showed the action of factors on the sensitivity of the insulin receptor, such as melatonin. It is a hormone produced by the pineal gland, whose role is still uncertain in human reproduction, although many studies have found that it may relate sex hormone effect. Many patients with polycystic ovary syndrome (PCOS) may have hyperinsulinemia, and that pinealectomized rats determined hypoglycemia and hyperinsulinemia, with reduced release of insulin in response to glucose. Therefore, it is supposed that blood levels of melatonin might correlate with the blood insulin concentration in patients with the syndrome. Moreover, the insulin sensitizing agents have been used in the treatment of patients with insulin resistance and PCOS, based on its main pathophysiological substrate which is the hyperinsulinemia. In fact, the metformin is the most used in the literature. However, there are few studies on the use of metformin in adolescents. The evidences of this drugs in this group of patients have showed good therapeutic response with few side effects. The objective of the study is to evaluate the effects of metformin on insulin resistance and levels of melatonin in adolescents with PCOS. It will be performed a prospective, randomized, double-blind and placebo-controlled study with 90 adolescents with PCOS. It will be evaluated clinical and laboratory parameters (TSH, free T4, prolactin, FSH, LH, estradiol, total testosterone, androstenedione, DHEA-s, 17-OH progesterone, SHBG, free androgen index, index of HOMA-IR and QUICKI from fasting glucose and insulin, total cholesterol and fractions, triglycerides, creatinine, AST and ALT and creatinkinase, fibrinogen and PAI-1, and melatonin for 6 months of treatment. |
| Detailed Description | Design: 90 patients will be selected to a prospective, randomized and double-blinded study. They will be assigned to two groups: A) 45 patients, treated with OC (oral contraceptive) and metformin 1500mg/ day. B) 45 patients, treated with OC and placebo. The length of treatment was six months. Inclusion criteria: patients until 19 years-old, at least 2 years after menarche, with Polycystic Ovary Syndrome based on Rotterdan criterion. Exclusion criteria: patients with Diabetes Mellitus, hypertension, hyperprolactinemia, adrenal enzymatic deficiency, Cushing syndrome, thyroidopathy, renal or hepatic disfunction, use of OC or insulin-sensitising drugs in the last 90 days before, pregnancy, androgen tumors, hormonal-sensitive tumors in the past, contra-indication to the medications used in the study. Clinical parameters included are weight and height (for BMI), waist to hip ratio, habits like smoking or drinking, drug addiction, blood pressure measurement, hirsutism and acne. Laboratorial parameters included are TSH, free T4, prolactin, FSH, LH, estradiol, total testosterone, androstenedione, s-DHEA, 17-OH progesterone, SHBG, free androgen index, fasting glucose and insulin, total cholesterol and fractions, triglycerides, creatinin, TGO, TGP, CK, PAI-1, fibrinogen, melatonin. Patients will be evaluated using these parameters in the beginning, 1, 3 and 6 months after use of the drugs. |
| Study Type | Interventional |
| Study Phase | N/A |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment |
| Condition | Polycystic Ovary Syndrome |
| Intervention | Drug: Placebo Capsule (without biologic action) administered three times a day for six months Drug: Metformin Metformin 500mg three times a day for six months |
| Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 90 |
| Estimated Completion Date | December 2013 |
| Estimated Primary Completion Date | October 2013 |
| Eligibility Criteria | Inclusion Criteria: - Patients until 19 years-old, at least 2 years after menarche - Patients with Polycystic Ovary Syndrome based on Rotterdan criteries Exclusion Criteria: - Patients with Diabetes Mellitus, hypertension, hyperprolactinemia, adrenal enzymatic deficiency, Cushing syndrome, thyroidopathy, renal or hepatic disfunction - Use of OC or insulin-sensitising drugs in the last 90 days before - Pregnancy - Androgen tumors, hormonal-sensitive tumors in the past - Contra-indication to the medications used in the study |
| Gender | Female |
| Ages | 11 Years |
| Accepts Healthy Volunteers | Accepts Healthy Volunteers |
| Contacts | Contact: Margareth Iwata 55-11-24786169 megiwata@yahoo.com |
| Location Countries | Brazil |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00988078 |
|---|---|
| Other Study ID Numbers | CEP 2102/08 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | Federal University of São Paulo |
| Study Sponsor | Federal University of São Paulo |
| Collaborators | Not Provided |
| Investigators | Study Director: Jose Maria Soares Junior Federal University os Sao PauloStudy Chair: Alexandre Rossi Federal University os Sao PauloStudy Director: Eduardo Leme Alves da Motta Federal University os Sao PauloPrincipal Investigator: Margareth Chiharu Iwata Federal University of Sao Paulo |
| Verification Date | October 2009 |
Locations[ + expand ][ + ]
| Federal University of Sao Paulo | Sao Paulo, Brazil Contact: Margareth Iwata | megiwata@yahoo.comRecruiting |
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