Clinical trial NCT00868140: Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)
Official title: Determination if Indirectly Reducing Circulating Insulin by Improving Insulin Sensitivity With Pioglitazone Reduces Renal Clearance of D-chiro-inositol (DCI) Increases the Circulating Concentration of DCI and Enhances Insulin-stimulated Release of the D-chiro-inositol-containing Inositolphosphoglycan (DCI-IPG) Mediator in Obese Women With PCOS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2009-03-24
Enrollment: 51
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

Eligibility criteria: 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.

Primary outcomes:
measure: AUC DCI-IPG (%/Min)
timeFrame: Baseline
measure: AUC DCI-IPG (%/Min)
timeFrame: 6 months
measure: Fasting Serum Insulin
timeFrame: baseline
measure: Fasting Serum Insulin (uIU/ml)
timeFrame: 6 months
Secondary outcomes:
measure: Matsuda Index
timeFrame: Baseline
measure: Matsuda Index
timeFrame: 6 months
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University General Clinical Research Center
state: Virginia
city: Caracas
country: Venezuela
facility: Hospital de Clinical Caracas
Study officials:
affiliation: Virginia Commonwealth University
name: John E. Nestler, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gupta A, Jakubowicz D, Nestler JE. Pioglitazone Therapy Increases Insulin-Stimulated Release of d-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome. Metab Syndr Relat Disord. 2016 Oct;14(8):391-396. doi: 10.1089/met.2016.0009. Epub 2016 Mar 30.