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

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00729560
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 8
• Location: 1
• Arms: 2
• Duration (Months): 43
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Flutamide; Drug: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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)
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. DCI-IPG Measurements in Blood and Urine [2 years]

   zero participants analyzed, no assays performed

Eligibility Criteria

Criteria

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

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

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University General Clinical Research Center	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: John E. Nestler, M.D., Virginia Commonwealth University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT00729560
• Other Study ID Numbers: 04487VCUIRB; GCRC0826
• First Posted: Aug 7, 2008
• Last Update Posted: Sep 8, 2014
• Last Verified: Sep 1, 2014

• Keywords provided by Virginia Commonwealth University: PCOS
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Syndrome; Flutamide

Study Results

Participant Flow

Arm/Group Title	Flutamide and Placebo Control Subjects
Arm/Group Description	Number of participants randomized to each Arm/Group is unknown, study was terminated before unblinding and no key exists.
Period Title: Overall Study
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Flutamide Treated and Placebo Control
Arm/Group Description	Flutamide treated: 250 mg twice daily for 4 weeks or Placebo control: twice daily for 4 weeks. Study was terminated due to insufficient enrollment. Randomization is unknown as study was terminated prior to unblinding and no key can be found. Consequently, we are unable to differentiate between treated and control subjects.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	8 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	8 100%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	DCI-IPG Measurements in Blood and Urine
Description	zero participants analyzed, no assays performed
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Flutamide and Placebo Control Subjects
Arm/Group Description	Number of participants randomized to each Arm/Group is unknown, study was terminated before unblinding and no key exists.
Measure Participants	0

Adverse Events

Arm/Group Title	Flutamide Treated and Placebo Control Subjects
Arm/Group Description	Flutamide: 250 mg twice daily for 4 weeks or Placebo: twice daily for 4 weeks
All Cause Mortality
	Flutamide Treated and Placebo Control Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Flutamide Treated and Placebo Control Subjects
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Flutamide Treated and Placebo Control Subjects
	Affected / at Risk (%)	# Events
Total	0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.