Clinical trial NCT00884819: Effects of Fenofibrate on Metabolic and Reproductive Parameters in Polycystic Ovary Syndrome
Official title: Effects of Fenofibrate on Metabolic and Reproductive Parameters in Polycystic Ovary Syndrome. A Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Keywords: polycystic ovary syndrome
hepatic adiposity
diabetes
hormones
cardiovascular disease
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2009-04-21
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective randomized, double-blind placebo-controlled trial of 6 months' duration evaluating the effect of fenofibrate (200 mg/day) in females with polycystic ovary syndrome and mild hypertriglyceridemia. The investigators primary objective will be to determine whether fenofibrate will reduce hepatic adiposity as measured using MRI, and our secondary outcomes will be to delineate the impact of fenofibrate on biochemical or clinical parameters for insulin resistance, cardiovascular disease, and reproductive status.


Eligibility criteria: Inclusion Criteria:

* premenopausal women ≥ 18 years
* diagnosis of PCOS based on the recent 2006 Androgen Excess Society criteria (modified from Rotterdam 2003)
* waist circumference \>88 cm
* fasting TG 2.0 - 5.0 mmol/L
* stable on any type of oral contraceptive for a minimum of 3-months

Exclusion Criteria:

* known contraindications for MRI
* pregnancy, lactation, desire to become pregnant
* participation in another clinical trial
* fasting TF level ≥ 5.0 mmol/L
* AST or ALT \> 2.5 times upper limit of normal (ULN)
* creatinine kinase (CK) \> 6x ULN
* creatinine \> 115 μmol/L
* fasting glucose ≥ 7.0 mmol/L and/or 2h glucose post oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L or personal history of DM2
* personal history of renal disease, liver disease (except NAFLD), or heart disease
* body mass index (BMI) \< 18 or \> 40 kg/m²
* increased alcohol use (\>9 standard drinks per week \[standard drink = 12oz beer, 5oz wine, or 1.5oz spirits\]) or drug use
* use of other hormonal contraception, growth hormone, glucocorticoids, anti-diabetic/anti-dyslipidemia medications, or anabolic steroids.

Primary outcomes:
measure: Hepatic adiposity as assessed using MRI
timeFrame: 6-months
Secondary outcomes:
measure: Body composition using bioelectrical impedance analysis (BIA), anthropometry (skin-fold thickness measurement), and MRI
timeFrame: 6-months
measure: Insulin resistance using HOMA-IR
timeFrame: 6 months
measure: Biochemical parameters related to insulin resistance (adipocytokines, free fatty acids, 25-hydroxyvitamin D)
timeFrame: 6 months
measure: Traditional and non-traditional cardiovascular risk factors (lipids, apolipoproteins, fibrinogen, PAI-1, CRP)
timeFrame: 6 months
measure: Reproductive parameters (androgens, hirsutism)
timeFrame: 6 months
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: St. Joseph's Health Care, Department of Medicine
name: Tisha Joy, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Toda K, Okada T, Miyaura C, Saibara T. Fenofibrate, a ligand for PPARalpha, inhibits aromatase cytochrome P450 expression in the ovary of mouse. J Lipid Res. 2003 Feb;44(2):265-70. doi: 10.1194/jlr.M200327-JLR200. Epub 2002 Nov 4.
citation: Wysocki J, Belowski D, Kalina M, Kochanski L, Okopien B, Kalina Z. Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther. 2004 Apr;42(4):212-7. doi: 10.5414/cpp42212.
citation: Lee HJ, Choi SS, Park MK, An YJ, Seo SY, Kim MC, Hong SH, Hwang TH, Kang DY, Garber AJ, Kim DK. Fenofibrate lowers abdominal and skeletal adiposity and improves insulin sensitivity in OLETF rats. Biochem Biophys Res Commun. 2002 Aug 16;296(2):293-9. doi: 10.1016/s0006-291x(02)00822-7.
citation: Idzior-Walus B, Sieradzki J, Rostworowski W, Zdzienicka A, Kawalec E, Wojcik J, Zarnecki A, Blane G. Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X. Eur J Clin Invest. 2000 Oct;30(10):871-8. doi: 10.1046/j.1365-2362.2000.00734.x.
citation: Yong QW, Thavintharan S, Cheng A, Chew LS. The effect of fenofibrate on insulin sensitivity and plasma lipid profile in non-diabetic males with low high density lipoprotein/dyslipidaemic syndrome. Ann Acad Med Singap. 1999 Nov;28(6):778-82.