Overview

This trial is active, not recruiting.

Condition polycystic ovary syndrome
Treatments rosiglitazone, acarbose
Sponsor Jean-Patrice Baillargeon
Collaborator Canadian Institutes of Health Research (CIHR)
Start date August 2006
End date June 2016
Trial size 78 participants
Trial identifier NCT01019356, 06-075

Summary

The investigators hypothesis is that free fatty acids (FFA) accumulation in non fatty tissues would lead to insulin resistance and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism.

The aim is to verify if insulin-related hyperandrogenism can be reversed in women having polycystic ovary syndrome following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose.

For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose basic science
Arm
(Experimental)
Lean and obese PCOS women
rosiglitazone Avandia
4 mg twice daily for 8 weeks orally
(Active Comparator)
Obese PCOS women
acarbose Prandase
100 mg three times daily for 8 weeks orally
(No Intervention)
Obese and lean healthy women evaluated only at baseline

Primary Outcomes

Measure
Androgen hyper-responsiveness to insulin, as determined by the relationship between testosterone and insulin levels (or the ratio of free testosterone to the area under the insulin curve) during an OGTT and 24h urinary clearance of DCI in PCOS women
time frame: 5 years

Secondary Outcomes

Measure
Insulin secretion as well as insulin actions on glucose utilization, hepatic glucose production and free fatty acid supressibility in PCOS women during OGTT and 2 step insulin-glucose clamp
time frame: 5 years
Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp
time frame: 5 years

Eligibility Criteria

Female participants from 18 years up to 40 years old.

Inclusion Criteria: PCOS : - Biochemical hyperandrogenism (free testosterone ≥ 50 pmol/l) - Oligomenorhea (≤ 8 menstrual cycle per year) Health volunteers : - Normal menstrual cycle - Normal levels of free and total testosterone - No family history with PCOS Exclusion Criteria: - Diabetes or glucose intolerance - Current or past use within 3 months of oral contraceptives - Current or past use within 3 months of medications known to affect insulin sensitivity (metformin, PPARy agonists, b-blockers, thiazides, calcium channel blockers, glucocorticoids, etc.) - Pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious or neoplastic disease (other than non-melanoma skin cancer) - Documented or suspected recent (within one year) history of drug abuse or alcoholism - Use of any investigational drug within three months prior to study onset Healthy volunteers : - History of gestational diabetes - Positive family history for first-degree relative with diabetes - Disorders linked to insulin resistance (hypertension, dyslipidemia or acanthosis nigricans)

Additional Information

Official title Role of Insulin Action and Free Fatty Acids in Hyperandrogenism and Role of Metabolism of Inositols in Insulin Resistance of Women With Polycystic Ovary Syndrome
Principal investigator Jean-Patrice Baillargeon, MD, MSc
Description Polycystic ovary syndrome (PCOS) is a very common but complex endocrine disorder affecting 6 to 10% of childbearing age women. To diagnose PCOS, women must display two of these three symptoms: clinical or biochemical hyperandrogenism, oligoamenorrhea, and/or echographycally confirmed polycystic ovary. Many studies have also demonstrated that PCOS women are more insulin resistant than control women when matched for body mass index (BMI). Thus, insulin resistance (IR) and secondary hyperinsulinemia would be important premises in the development of PCOS. In fact, the prevalence of type 2 diabetes (T2D) is tripled in PCOS women. Higher free fatty acid (FFA) concentrations were also observed in the circulation of PCOS women. As FFA accumulates in liver and muscle instead of fat cells, this could be an important cause of IR according to the theory of lipotoxicity. Some indirect evidences are suggesting that FFA accumulation in androgen secreting cells (ovary and adrenal gland) could enhance their androgen production. Based on these findings, our hypothesis is that FFA accumulation in non fatty tissues would lead to IR and hyperandrogenism in PCOS women. Accordingly, Peroxisome Proliferator-Activated Receptor gamma (PPARγ) agonist (rosiglitazone) would be a great therapeutic option for PCOS as their activation induces transcription factors of gene implicated in fatty acids metabolism. The aim is to verify if insulin-related hyperandrogenism can be reversed in PCOS women following an 8-week treatment with rosiglitazone compared to simple insulin reduction with acarbose. For the purpose of this study, 14 lean women (BMI ≤ 25 kg/m2) and 36 obese women (BMI 30-39 kg/m2) with PCOS as well as 14 lean and 14 obese control women will be recruited to determine their insulin sensibility (insulin levels, M-value, metabolic clearance rate of glucose)and FFA metabolism (FFA levels, rythm of apparition and disapearance of FFA) during a 75g oral glucose tolerance test and a 2-step insulin-glucose clamp.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Université de Sherbrooke.