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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Université de Sherbrooke
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Jean-Patrice Baillargeon, Université de Sherbrooke
ClinicalTrials.gov Identifier:
NCT01019356
First received: November 24, 2009
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Polycystic Ovary Syndrome
Drug: Rosiglitazone
Drug: Acarbose

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Université de Sherbrooke:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 78
Study Start Date: August 2006
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rosiglitazone
Lean and obese PCOS women
Drug: Rosiglitazone
4 mg twice daily for 8 weeks orally
Other Name: Avandia
Active Comparator: Acarbose
Obese PCOS women
Drug: Acarbose
100 mg three times daily for 8 weeks orally
Other Name: Prandase
No Intervention: Control
Obese and lean healthy women evaluated only at baseline

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01019356

Contacts
Contact: Jean-Patrice Baillargeon, MD, M.Sc. 819-346-1110 ext 14853 jp.baillargeon@usherbrooke.ca

Locations
Canada, Quebec
Université de Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Jean-Patrice Baillargeon, MD, MSc    819-346-1110 ext 14853    jp.baillargeon@usherbrooke.ca   
Sponsors and Collaborators
Jean-Patrice Baillargeon
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Jean-Patrice Baillargeon, MD, MSc Université de Sherbrooke
  More Information

No publications provided

Responsible Party: Jean-Patrice Baillargeon, MD, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT01019356     History of Changes
Other Study ID Numbers: 06-075
Study First Received: November 24, 2009
Last Updated: April 10, 2014
Health Authority: Canada: Health Canada

Keywords provided by Université de Sherbrooke:
PCOS

Additional relevant MeSH terms:
Adrenogenital Syndrome
Polycystic Ovary Syndrome
Syndrome
Hyperandrogenism
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Disease
Pathologic Processes
46, XX Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Acarbose
Rosiglitazone
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014