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CompletedNCT01019356Updated Jan 20, 2022

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

An interventional study of Rosiglitazone and Acarbose in Polycystic Ovary Syndrome, sponsored by Jean-Patrice Baillargeon. Completed at 1 site in Canada. Open to female participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-01-20.

Sponsored by Jean-Patrice Baillargeon · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
18 Years to 40 Years
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • Polycystic Ovary Syndrome

Keywords

  • PCOS
03

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

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

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)
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
52 participants (actual)

Study arms

  • Experimental
    Rosiglitazone

    Lean and obese PCOS women

    Drug: Rosiglitazone

  • Active comparator
    Acarbose

    Obese PCOS women

    Drug: Acarbose

  • No intervention
    Control

    Obese and lean healthy women evaluated only at baseline

Interventions

  • DrugRosiglitazone

    4 mg twice daily for 8 weeks orally

    Also known as: Avandia

  • DrugAcarbose

    100 mg three times daily for 8 weeks orally

    Also known as: Prandase

05

What researchers measure

Primary outcomes

  1. Androgen hyper-responsiveness to insulin - Ratio

    The calculated ratio of free testosterone to the area under the insulin curve during an OGTT

    Time frame: 8 weeks

Secondary outcomes

  1. Androgen hyper-responsiveness to insulin - Relationship

    Determined by the relationship between testosterone and insulin levels during an OGTT.

    Time frame: 8 weeks

  2. Insulin sensitivity

    Determined by a 2-step insulin-glucose clamp

    Time frame: 8 weeks

  3. Insulin secretion

    Determined by a 2-step insulin-glucose clamp

    Time frame: 8 weeks

  4. Hepatic glucose production

    Determined by a 2-step insulin-glucose clamp

    Time frame: 8 weeks

  5. Plasma DCI-IPG during euglycemic-hyperinsulinemic clamp

    Measured during steady-state

    Time frame: 8 weeks

06

Study locations

1 site
  • Université de Sherbrooke
    Sherbrooke, Quebec J1H 5N4, Canada
07

Registry details

Key details

Study ID
NCT01019356
Lead sponsor
Jean-Patrice Baillargeon
Collaborators
Canadian Institutes of Health Research (CIHR)
Responsible party
Jean-Patrice Baillargeon (MD, Université de Sherbrooke) — Sponsor-investigator
First posted
Nov 25, 2009
Start date
Aug 2006
Primary completion
Jul 2021
Completion
Jul 2021
Last update
Jan 20, 2022

Study contacts

Jean-Patrice Baillargeon, MD, MSc
principal investigator · Université de Sherbrooke

Oversight

Data monitoring committee
No
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