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

This study has been terminated.
(Lack of recruitment)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00729560
First received: August 5, 2008
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

Polycystic Ovary Syndrome (PCOS) is the major cause of infertility in the United States. Many women with PCOS demonstrate insulin resistance and a compensatory hyperinsulinemia.This is due to both an intrinsic form of insulin resistance unique to PCOS and, in many cases, acquired insulin resistance due to obesity. The importance of this observation lies in the fact that hyperinsulinemia appears to play an important pathogenetic role in the hyperandrogenism and anovulation of both obese and lean women with PCOS.


Condition Intervention
Polycystic Ovary Syndrome
Drug: Flutamide
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Health Services Research
Official Title: Determination if Pharmacologic Blockade of Androgen Action Decreases 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 Polycystic Ovary Syndrome (PCOS)

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • DCI-IPG Measurements in Blood and Urine [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    zero participants analyzed, no assays performed


Enrollment: 8
Study Start Date: July 2008
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Flutamide
Drug: Flutamide
250 mg twice daily for 4 weeks
Placebo Comparator: 2
control to arm 1
Drug: Placebo
Placebo twice daily for 4 weeks

Detailed Description:

Hyperinsulinemia stimulates ovarian production of androgens, especially testosterone, in PCOS. Therefore, it is theoretically possible that testosterone increases urinary clearance of D-chiro-inositol (uCl(DCI) in PCOS, and that this serves as the explanation for the correlation between uClDCI and insulin sensitivity. While we regard this possibility as unlikely, it is important that it be tested. To accomplish this, we will assess obese (Body Mass Index (BMI) >30 kg/m2) women with and without PCOS at baseline, and again after 4 weeks of androgen action blockade with the drug flutamide. Flutamide is an antiandrogen that works by blocking the binding of androgens to the androgen receptor.

We will determine if this pharmacologic blockade i) decreases the renal clearance of DCI, ii) increases the circulating concentration of DCi, and iii) enhances the insulin-stimulated release of the D-chiro-inositol-containing inositolphosphoglycan (DCI-IPG) mediator during an OGTT.

  Eligibility

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

Inclusion Criteria:

(1) Obese (BMI≥30 kg/m2) women with PCOS between 18-40 years of age: i) oligomenorrhea (8 menstrual periods annually), ii) biochemical hyperandrogenemia (elevated total or free testosterone), iii) normal thyroid function tests and serum prolactin, and iv) exclusion of 21α-hydroxylase deficiency by a fasting 17α-hydroxyprogesterone <200 ng/dl.48, (2) acceptable health on the basis of interview, medical history, physical examination, and laboratory tests (complete blood chemistry (CBC), complete metabolic panel (CMP), urinalysis, serum Beta-Human Chorionic Gonadotropin (BhCG)). (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.

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  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00729560

Locations
United States, Virginia
Virginia Commonwealth University General Clinical Research Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Principal Investigator: John E. Nestler, M.D. Virginia Commonwealth University
  More Information

Additional Information:
No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00729560     History of Changes
Other Study ID Numbers: 04487VCUIRB, GCRC0826
Study First Received: August 5, 2008
Results First Received: May 27, 2014
Last Updated: September 5, 2014
Health Authority: United States: Federal Government

Keywords provided by Virginia Commonwealth University:
PCOS

Additional relevant MeSH terms:
Pharmacologic Actions
Polycystic Ovary Syndrome
Syndrome
Adnexal Diseases
Cysts
Disease
Endocrine System Diseases
Genital Diseases, Female
Gonadal Disorders
Neoplasms
Ovarian Cysts
Ovarian Diseases
Pathologic Processes
Flutamide
Inositol phosphate glycan
Androgen Antagonists
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Insulin Antagonists
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014