Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)

Not Applicable

Terminated

• Conditions: Polycystic Ovary Syndrome
• Interventions: Drug: pioglitazone; Drug: Placebo

• Registration Number: NCT00868140
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

Our hypothesis is that hyperinsulinemia increases the renal clearance of D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS) and that this leads to a reduction in circulating insulin-stimulated D-chiro-inositol-containing inositol phosphoglycan (DCI-IPG) release. To assess the effects of a chronic reduction in circulating insulin on DCI metabolism, we propose to reduce circulating insulin in obese women with PCOS by improving insulin sensitivity with the drug pioglitazone. Pioglitazone is a thiazolidinedione that improves peripheral insulin sensitivity, presumably by activation of the peroxisome proliferator-activated receptor gamma (PPARγ) receptor. Administration of pioglitazone to women with PCOS has been shown to improve insulin sensitivity, reduce insulin secretion, and decrease both fasting and post-prandial serum insulin concentrations.

Detailed Description

This protocol focuses on the hypothesis that a deficiency in a putative inositolphosphoglycan (IPG) mediator of insulin action, namely a D-chiro-inositol-containing IPG (DCI-IPG), contributes to the insulin resistance of some women with PCOS. Our interest in this area stems directly from our previous studies, which demonstrated that administration of the precursor, D-chiro-inositol (DCI), to both obese and lean women with PCOS improved glucose intolerance while reducing circulating insulin, and simultaneously improved ovulatory function and decreased serum androgens. These findings were recently confirmed in a large-scale study by an independent group. The findings of these three studies suggested that administration of DCI improved insulin sensitivity in PCOS, which then resulted in an improved hormonal and metabolic milieu.

Study Timeline

• Study Start: 2009-02
• Study First Submitted: 2009-03-22
• Study First Submitted QC: 2009-03-23
• Study First Posted: 2009-03-24
• Primary Completion: 2011-06
• Study Completion: 2011-08
• Disposition First Submitted: 2014-08-01
• Disposition First Submitted QC: 2014-08-01
• Disposition First Posted: 2014-08-06
• Results First Submitted: 2016-02-19
• Status Verified: 2016-05
• Results First Submitted QC: 2016-05-02
• Last Update Submitted: 2016-05-02
• Results First Posted: 2016-06-10
• Last Update Posted: 2016-06-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 51

Inclusion Criteria

1. Obese (Body Mass Index or BMI greater than or equal to 30 kg/m2) women with PCOS between 18-40 years of age:

   • oligomenorrhea (less than 8 menstrual periods annually)
   • biochemical hyperandrogenemia (elevated total or free testosterone)
   • normal thyroid function tests and serum prolactin; AND
   • exclusion of 21a-hydroxylase deficiency by a fasting 17a-hydroxyprogesterone less than 200 ng/dl.51,

2. acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (Complete Blood Chemistry or CBC, Comprehensive Metabolic Panel denoted SMA20, urinalysis, negative pregnancy test).

3. Signed, witnessed informed consent.

4. Ability to comply with study requirements.

Exclusion Criteria

1. Diabetes mellitus by fasting glucose or oral glucose tolerance test (OGTT), or clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, neoplastic and malignant disease (other than non-melanoma skin cancer).
2. Current use of oral contraceptives.
3. Documented or suspected recent (within one year) history of drug abuse or alcoholism.
4. Ingestion of any investigational drug within two months prior to study onset.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1/Pioglitazone	pioglitazone	Pioglitazone in pill form at 45mg twice per day for 6 months
2/Placebo	Placebo	Placebo control to arm 1 in pill form identical to treatment form also twice per day for 6 months

Primary Outcome Measures

Name	Time	Method
AUC DCI-IPG (%/Min)	6 months	Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT following 6 months of treatment with pioglitazone or placebo. Values reported as a percentage of bioactivity measured at time 0. Negative values indicate a decrease relative to the time 0 measurement.
Fasting Serum Insulin	baseline	Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT before treatment with either pioglitazone or placebo
Fasting Serum Insulin (uIU/ml)	6 months	Fasting serum insulin (uIU.min/ml) measured at 0, 60 and 120 minutes of a 2 hour OGTT following 6 months treatment with either pioglitazone or placebo

Secondary Outcome Measures

Name	Time	Method
Matsuda Index	6 months	Whole body insulin sensitivity as determined by the Matsuda Index

Trial Locations

Locations (2)

Hospital de Clinical Caracas; 🇻🇪 Caracas, Venezuela

Virginia Commonwealth University General Clinical Research Center; 🇺🇸 Richmond, Virginia, United States