|- candidate number||1896|
|- NTR Number||NTR550|
|- Date ISRCTN created||14-feb-2006|
|- date ISRCTN requested||3-feb-2006|
|- Date Registered NTR||15-dec-2005|
|- Secondary IDs||N/A |
|- Public Title||Vascular function in polycystic ovary patients after treatment with metformin: itís role in polycystic-ovary-syndrome-associated insulin resistance.|
|- Scientific Title||Vascular function in polycystic ovary patients after treatment with metformin: itís role in polycystic-ovary-syndrome-associated insulin resistance.|
|- hypothesis||The specific aim in the current study is to evaluate if the use of the insulin lowering agent metformin in polycystic ovary syndrome (PCOS) has effect on micro- and macro circulation. |
|- Healt Condition(s) or Problem(s) studied||Polycystic ovary syndrome (PCOS)|
|- Inclusion criteria||1. PCOS as judged in early routine patient work-up by 3 out of the following 4 criteria:|
a. Oligo (mean length of the menstrual cycle > 35 days) - or amenorrhoea (based on history of oligomenorrhoea);
b. Evidence of hyperandrogenism, whether clinical (hirsutism, acne, or male pattern balding) or biochemical (elevated serum androgen level [total testosterone > 2 nmol/l, and / or androstedione > 9], determined in a period while the patient was not using any medication with potential endocrine influence);
c. Elevated serum LH level (≥ 6.5 IU/l), determined at least 2 weeks after the beginning of a menstrual period and 3 weeks before the subsequent menstrual period in the presence of a normal FSH level (< 10 IU/l, determined in a period while the patient was not using any medication with potential endocrine influence);
d. A polycystic ovary morphology (defined by the presence of eight or more subcapsular follicular cysts ≤ 10mm and increased ovarian stroma) by ultrasound performed at our department.
2. Age: 18- 40 years;
3. One phase combined oral anticonceptives with 30 ethinylestradiol (preferred are microgynon 30, stediril Ď30í, Yasmin and Diane) for at least 3 months but no other medication to avoid hormonal cyclicity and for contraceptive purposes;
4. Informed consent.
|- Exclusion criteria||1. Cardiovascular disease (hypertension (>160/90 mmHg), stroke, coronary artery disease, peripheral vascular disease, heart failure);|
2. Diabetes mellitus (according to ADA criteria);
3. Hypothyroidism, hyperprolactinemia, Cushingís syndrome nonclassical congenital adrenal hyperplasia;
4. Smoking for the last three months;
5. Alcohol use > 4U/day;
7. Diseases that influence reproductive hormone status;
8. Kidney and liver dysfunction or congestive heart failure (which can cause lactic acidosis when taking metformin).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2006|
|- planned closingdate||1-okt-2007|
|- Target number of participants||40|
Patients will be randomised to receive metformin or placebo, two times a day 1000 mg for 6 months.
The measurements will take place at baseline and after metformin therapy. The micro- and macro circulation will be measured.
|- Primary outcome||Vascular function after metformin therapy compared to vascular function at baseline (micro and macrovascular measurements).|
|- Secondary outcome||N/A|
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES|| I.J.G. Ketel|
|- CONTACT for SCIENTIFIC QUERIES||Dr. C.B. Lambalk|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|Merck, CardioMetabolic Care, Lyon - France|
|- Brief summary||Polycystic ovary syndrome (PCOS) is a common endocrine- metabolic disease that occurs in up to 5% of reproductive- age women. PCOS is considered not only a reproductive endocrinopathy but also a metabolic disorder. As such, women with PCOS would be expected to exhibit an increased risk of type 2 diabetes, hypertension and cardiovascular disease.
Recent studies suggest that impaired vascular function contributes to an increase in cardiovascular disaeses in women with PCOS. Since insulin resistance might play a major role in vascular function of women with PCOS, efforts have focused on improving insulin sensitivity through diet modification, weight reduction and, most recently, insulin- lowering agents. Metformin have been shown to improve insulin sensitivity, hyperandrogenism and improves at least some features of metabolic syndrome, such as hyperlipidemia, hypertension and central obesity. Considering its beneficial effect in PCOS measured, we will administrate metformin to determine whether it could improve vascular function by decreasing insulin resistance. In a randomised double blind study we will evaluate the effect of 6 months of metformin 1000 mg two times a day or placebo in PCOS patients. Before and after treatment we will measure micro and macro circulation. To obtain this information we will study 40 PCOS patients. The study will take place at the Department of Reproductive medicine and the department of Internal Medicine of the VU Medical Center. The duration of this study will be about 2 year.|
|- Main changes (audit trail)|
|- RECORD||15-dec-2005 - 5-jan-2010|