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

NCT00868140 | Terminated Results DMC

• 2 other identifiers: VCUIRB4480GCRC0824
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 2

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.

Conditions

Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline

• 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.

  6 months

• 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

  baseline

• 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

  6 months

Secondary Outcomes (2)

• Matsuda Index

  Baseline

• Matsuda Index

  6 months

Study Arms (2)

1/Pioglitazone

EXPERIMENTAL

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

Drug: pioglitazone

2/Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

pioglitazone DRUG

pioglitazone 45 mg

1/Pioglitazone

Placebo DRUG

placebo daily

2/Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (2)

Virginia Commonwealth University General Clinical Research Center

Richmond, Virginia, 23298, United States

Location

Hospital de Clinical Caracas

Caracas, 1071, Venezuela

Location

Related Publications (1)

• 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.

  PMID: 27028341 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. John Nestler
• Organization: Virginia Commonwealth University

john.nestler@vcuhealth.org

(804) 828-3389

Study Officials

• John E. Nestler, M.D.

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2009
• First Posted: March 24, 2009
• Study Start: February 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 10, 2016
• Results First Posted: June 10, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

VE (1); US (1)