Effects of Fenofibrate on Metabolic and Reproductive Parameters in Polycystic Ovary Syndrome

Effects of Fenofibrate on Metabolic and Reproductive Parameters in Polycystic Ovary Syndrome. A Randomized, Double-Blind, Placebo-Controlled Trial

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.

Study Overview

• Status: Terminated
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Fenofibrate; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • St. Joseph's Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; fenofibrate 200mg/daily for 6 months	Drug: Fenofibrate; fenofibrate 200 mg daily for 6-months
Placebo Comparator: 2; Placebo match for 6 months	Other: Placebo; Placebo match for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hepatic adiposity as assessed using MRI	6-months

Secondary Outcome Measures

Outcome Measure	Time Frame
Body composition using bioelectrical impedance analysis (BIA), anthropometry (skin-fold thickness measurement), and MRI	6-months
Insulin resistance using HOMA-IR	6 months
Biochemical parameters related to insulin resistance (adipocytokines, free fatty acids, 25-hydroxyvitamin D)	6 months
Traditional and non-traditional cardiovascular risk factors (lipids, apolipoproteins, fibrinogen, PAI-1, CRP)	6 months
Reproductive parameters (androgens, hirsutism)	6 months

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Tisha Joy, MD FRCPC, St. Joseph's Health Care, Department of Medicine

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: April 20, 2009
• First Posted (Estimate): April 21, 2009

Study Record Updates

• Last Update Posted (Estimate): April 3, 2015
• Last Update Submitted That Met QC Criteria: April 1, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: polycystic ovary syndrome; diabetes; cardiovascular disease; hormones; hepatic adiposity
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Syndrome; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: R-08-573; 15581 (Other Identifier: UWO Ethics)