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

Primary Purpose

Polycystic Ovary Syndrome

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
pioglitazone
Placebo
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Polycystic Ovary Syndrome

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Virginia Commonwealth University General Clinical Research Center
  • Hospital de Clinical Caracas

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1/Pioglitazone

2/Placebo

Arm Description

Pioglitazone in pill form at 45mg twice per day for 6 months

Placebo control to arm 1 in pill form identical to treatment form also twice per day for 6 months

Outcomes

Primary Outcome Measures

AUC DCI-IPG (%/Min)
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT before 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.
AUC DCI-IPG (%/Min)
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
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)
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

Matsuda Index
Whole body insulin sensitivity as determined by the Matsuda Index as calculated using the following formula: 10,000 divided by the square root of (FPI* FPG) * (xGPC* xIPC) Where FPI is fasting plasma insulin expressed as uU/ml, FPG is fasting plasma glucose expressed as mg/dL, xGPC is mean plasma glucose concentration after the load and xIPC is the mean insulin concentration after the load. Values calculated on samples taken at 0, 30, 60, 90 and 120 minutes of a 2 hour OGTT. Values typically range from 0 to 12 units with higher scores indicating better insulin sensitivity. A value of 2.5 or less is indicative of insulin resistance.
Matsuda Index
Whole body insulin sensitivity as determined by the Matsuda Index

Full Information

First Posted
March 22, 2009
Last Updated
May 2, 2016
Sponsor
Virginia Commonwealth University
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1. Study Identification

Unique Protocol Identification Number
NCT00868140
Brief Title
Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)
Acronym
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

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
Lack of recruitment
Study Start Date
February 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1/Pioglitazone
Arm Type
Experimental
Arm Description
Pioglitazone in pill form at 45mg twice per day for 6 months
Arm Title
2/Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo control to arm 1 in pill form identical to treatment form also twice per day for 6 months
Intervention Type
Drug
Intervention Name(s)
pioglitazone
Intervention Description
pioglitazone 45 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo daily
Primary Outcome Measure Information:
Title
AUC DCI-IPG (%/Min)
Description
Change in the Area Under the Curve DCI-IPG measurements in blood samples taken at 15 minute intervals during the 2 hour OGTT before 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.
Time Frame
Baseline
Title
AUC DCI-IPG (%/Min)
Description
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.
Time Frame
6 months
Title
Fasting Serum Insulin
Description
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
Time Frame
baseline
Title
Fasting Serum Insulin (uIU/ml)
Description
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
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Matsuda Index
Description
Whole body insulin sensitivity as determined by the Matsuda Index as calculated using the following formula: 10,000 divided by the square root of (FPI* FPG) * (xGPC* xIPC) Where FPI is fasting plasma insulin expressed as uU/ml, FPG is fasting plasma glucose expressed as mg/dL, xGPC is mean plasma glucose concentration after the load and xIPC is the mean insulin concentration after the load. Values calculated on samples taken at 0, 30, 60, 90 and 120 minutes of a 2 hour OGTT. Values typically range from 0 to 12 units with higher scores indicating better insulin sensitivity. A value of 2.5 or less is indicative of insulin resistance.
Time Frame
Baseline
Title
Matsuda Index
Description
Whole body insulin sensitivity as determined by the Matsuda Index
Time Frame
6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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, 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). Signed, witnessed informed consent. Ability to comply with study requirements. Exclusion Criteria: 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). Current use of oral contraceptives. Documented or suspected recent (within one year) history of drug abuse or alcoholism. Ingestion of any investigational drug within two months prior to study onset.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John E. Nestler, M.D.
Organizational Affiliation
Virginia Commonwealth University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Commonwealth University General Clinical Research Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Hospital de Clinical Caracas
City
Caracas
ZIP/Postal Code
1071
Country
Venezuela

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
individual data kept confidential, secured and not shared beyond authorized study staff
Citations:
PubMed Identifier
27028341
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.
Results Reference
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Effects of Pioglitazone on Insulin and Glucose Metabolism in Women With Polycystic Ovary Syndrome (PCOS)

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