Role of Insulin Action and Free Fatty Acids in Hyperandrogenism of Women With Polycystic Ovary Syndrome

Polycystic Ovary Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01019356
• Other study ID #: 06-075
• Status: Completed
• Phase: N/A
• Start date: August 2006
• Est. completion date: July 2021

Study information

• Verified date: January 2022
• Source: Université de Sherbrooke
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 2021
• Est. primary completion date: July 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hyperandrogenism
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Rosiglitazone
4 mg twice daily for 8 weeks orally
• Acarbose
100 mg three times daily for 8 weeks orally

Locations

Country	Name	City	State
Canada	Université de Sherbrooke	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Jean-Patrice Baillargeon	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Androgen hyper-responsiveness to insulin - Ratio	The calculated ratio of free testosterone to the area under the insulin curve during an OGTT	8 weeks
Secondary	Androgen hyper-responsiveness to insulin - Relationship	Determined by the relationship between testosterone and insulin levels during an OGTT.	8 weeks
Secondary	Insulin sensitivity	Determined by a 2-step insulin-glucose clamp	8 weeks
Secondary	Insulin secretion	Determined by a 2-step insulin-glucose clamp	8 weeks
Secondary	Hepatic glucose production	Determined by a 2-step insulin-glucose clamp	8 weeks
Secondary	Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp	Measured during steady-state	8 weeks