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

Sponsored by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00868140

Purpose

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 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 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,

Condition	Intervention
Polycystic Ovary Syndrome	Drug: pioglitazone Drug: Placebo

MedlinePlus related topics: Obesity

Drug Information available for: Insulin Pioglitazone Pioglitazone hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Health Services Research, Randomized, Single Blind (Subject), Placebo Control, Parallel Assignment
Official Title:	Determination if Indirectly Reducing Circulating Insulin by Improving Insulin Sensitivity With Pioglitazone, Decreases Renal Clearance of DCI, Increases the Circulating Concentration of DCI, and Enhances Insulin-Stimulated Release of the DCI-IPG Mediator in Obese Women With PCOS

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

DCI-IPG and DCI measurements in blood and urine [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Measurement of sex steroids [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	66
Study Start Date:	February 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Pioglitazone	Drug: pioglitazone pioglitazone 45 mg
2: Placebo Comparator control to arm 1	Drug: Placebo placebo daily

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 obese23 and lean24 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.25 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

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Obese (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 (CBC, SMA20, urinalysis, negative pregnancy test).
Signed, witnessed informed consent.
Ability to comply with study requirements.

Exclusion Criteria:

Diabetes mellitus by fasting glucose or 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868140

Contacts

Contact: Terre Y. Williams

804 828-2663

tywillia@vcu.edu

Locations

United States, Virginia
Virginia Commonwealth University General Clinical Research Center	Recruiting
Richmond, Virginia, United States, 23298
Contact: Terre Y. Williams 804-828-2663 tywillia@vcu.edu
Contact: Manar T. Nazmy 804 827-0171 mtnazmy@vcu.edu
Principal Investigator: John E. Nestler, M.D.
Venezuela
Hospital de Clinical Caracas	Recruiting
Caracas, Venezuela, 1071
Contact: Daniela Jakubowicz, M.D. 305 308 42 06 daniela.jak@gmail.com
Principal Investigator: Daniela Jakubowicz, M.D.

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

More Information

No publications provided

Responsible Party:	Virginia Commonwealth University ( John E. Nestler, M.D. )
Study ID Numbers:	VCUIRB4480, GCRC0824
Study First Received:	March 22, 2009
Last Updated:	March 23, 2009
ClinicalTrials.gov Identifier:	NCT00868140 History of Changes
Health Authority:	United States: Federal Government

Study placed in the following topic categories:

Obesity
Pioglitazone
Gonadal Disorders
Endocrine System Diseases
Ovarian Diseases
Cysts
Polycystic Ovarian Syndrome

Insulin
Genital Diseases, Female
Hypoglycemic Agents
Polycystic Ovary Syndrome
Endocrinopathy
Ovarian Cysts

Additional relevant MeSH terms:

Disease
Pioglitazone
Gonadal Disorders
Physiological Effects of Drugs
Endocrine System Diseases
Ovarian Diseases
Cysts
Pharmacologic Actions

Adnexal Diseases
Genital Diseases, Female
Neoplasms
Hypoglycemic Agents
Pathologic Processes
Syndrome
Polycystic Ovary Syndrome
Ovarian Cysts

ClinicalTrials.gov processed this record on May 07, 2009