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| ID | Type | Description | Link |
|---|---|---|---|
| R01DK073411 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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The purpose of this study is to investigate the metabolic effects of anti-androgens and oral contraceptive pills (OCPs), compared with placebo, in the treatment of women with PCOS. We hypothesized that controlling elevated androgen levels with either anti-androgens or OCPs would produce improvement in metabolic markers in PCOS women and would reduce their long term metabolic risk.
Polycystic ovary syndrome (PCOS) is one of the most common conditions of young women, and it is frequently associated with insulin resistance or metabolic syndrome (MBS). In addition, affected women have significantly elevated mean low-density lipoprotein (LDL) levels and an increased prevalence of at risk LDL levels, independent of obesity. We are directly testing the role of androgens in the metabolic abnormalities in PCOS by examining the impact of direct androgen receptor blockade by anti-androgen medications and indirect suppression of androgen production through suppression of leutinizing hormone (LH) with oral contraceptive pills (OCPs), compared with placebo, on visceral adiposity, circulating LDL levels, insulin secretion and sensitivity as measured by frequently-sampled IV glucose tolerance tests (FSIGT) and oral glucose tolerance tests (OGTT), resting energy expenditure, and maximal aerobic capacity measurement.
Note: Originally there were 2 additional study arm, Metformin only and Metformin + Flutamide. These study arms were ultimately eliminated and were not included in analysis of baseline characteristics or endpoints.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | oral contraceptive (35 mg ethinyl estradiol) |
|
| 2 | Experimental | Flutamide 250 mg twice daily |
|
| 3 | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| flutamide | Drug | 250 mg twice daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level) | 6 months |
| Change in High-density Lipoprotein (HDL) Levels During Study Period | Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL) | 6 months |
| Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT) | 6 months |
| Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage) | 6 months |
| Change in Disposition Index | Change in disposition index (DI, insulin secretion corrected for insulin secretion) as measured by frequently-sampled IV glucose tolerance test (DI at study endpoint - baseline DI) | 6 months |
| Change in Resting Energy Expenditure (REE) Over the Study Period | Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE) | 6 months |
| Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrea Dunaif, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern Memorial Hospital | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9709934 | Background | Diamanti-Kandarakis E, Mitrakou A, Raptis S, Tolis G, Duleba AJ. The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1998 Aug;83(8):2699-705. doi: 10.1210/jcem.83.8.5041. | |
| 16868063 | Background | Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab. 2006 Oct;91(10):3970-80. doi: 10.1210/jc.2005-2250. Epub 2006 Jul 25. |
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97 total subjects enrolled. Prior to randomization, 16 subjects were excluded or dropped out, leaving 81 active subjects. Early in the study, 2 of the 5 study arms were discontinued: participants receiving Metformin only (8 subjects) and those receiving Metformin + Flutamide (6 subjects) - leaving 67 subjects whose data were analyzed
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| ID | Title | Description |
|---|---|---|
| FG000 | Oral Contraceptive - 1 | Oral contraceptive (containing 35mcg of ethinyl estradiol and 3mg of drospirenone) Oral contraceptive: one active pill per day for three weeks and then 1 sugar pill per day for one week |
| FG001 | Flutamide - 2 | Flutamide Flutamide: 250 mg twice daily |
| FG002 | Placebo - 3 | Placebo only |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Oral Contraceptive - 1 | Oral contraceptive (containing 35mcg of ethinyl estradiol and 3mg of drospirenone) |
| BG001 | Flutamide - 2 | Flutamide Flutamide: 250 mg twice daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Low-density Lipoprotein (LDL) Levels Over the Study Period | Change in low-density lipoprotein (LDL) levels over the study period (LDL level at study endpoint - baseline LDL level) | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
6 months - adverse event data collected over the study period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oral Contraceptive - 1 | Oral contraceptive (containing 35mcg of ethinyl estradiol and 3mg of drospirenone) Oral contraceptive: one active pill per day for three weeks and then 1 sugar pill per day for one week |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abnormal LFTs | Hepatobiliary disorders |
Please note there were 2 additional arms at the start of the study: Metformin alone (n=8) and Metformin+Flutamide (n=6), which were discontinued. These arms are therefore not included in these results data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Laura Torchen | Northwestern University | 312-227-6492 | ltorchen@luriechildrens.org |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D024821 | Metabolic Syndrome |
| D050177 | Overweight |
| D007246 | Infertility |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| D005485 | Flutamide |
| D004997 | Ethinyl Estradiol |
| C035144 | drospirenone |
| C534342 | drospirenone and ethinyl estradiol combination |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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| ethinyl estradiol 35 mcg and drospirenone 3 mg |
| Drug |
one active pill per day for three weeks and then 1 sugar pill per day for one week |
|
|
| placebo | Other |
|
|
Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max) |
| 6 months |
| 14725687 | Background | Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004 Feb;60(2):241-9. doi: 10.1111/j.1365-2265.2004.01973.x. |
| 17785364 | Background | Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007 Nov;92(11):4191-8. doi: 10.1210/jc.2007-0761. Epub 2007 Sep 4. |
| BG002 | Placebo - 3 | Placebo |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Body mass index (kg/m^2) | Mean | Standard Deviation | kg/m^2 |
|
Placebo
|
|
| Primary | Change in High-density Lipoprotein (HDL) Levels During Study Period | Change in high-density lipoprotein (HDL) levels during study period (HDL level at study endpoint - baseline HDL) | Posted | Mean | Standard Deviation | mg/dL | 6 months |
|
|
|
| Primary | Change in Visceral Adipose Tissue (VAT) Volume as Measured by MRI | Change in visceral adipose tissue (VAT) volume as measured by MRI (VAT at study endpoint - baseline VAT) | Posted | Mean | Standard Deviation | L | 6 months |
|
|
|
| Primary | Change in Fat Percentage as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan Over the Study Period | Change in fat percentage as measured by DEXA scan over the study period (Fat percentage at study endpoint - baseline fat percentage) | Posted | Mean | Standard Deviation | percentage of body mass | 6 months |
|
|
|
| Primary | Change in Disposition Index | Change in disposition index (DI, insulin secretion corrected for insulin secretion) as measured by frequently-sampled IV glucose tolerance test (DI at study endpoint - baseline DI) | Posted | Mean | Standard Deviation | min^-1 | 6 months |
|
|
|
| Primary | Change in Resting Energy Expenditure (REE) Over the Study Period | Change in resting energy expenditure (REE) over the study period (REE at study endpoint - baseline REE) | Posted | Mean | Standard Deviation | Kcal/day | 6 months |
|
|
|
| Primary | Change in Maximal Aerobic Exercise Capacity (VO2 Max) Over the Study Period | Change in maximal aerobic exercise capacity (VO2 max) over the study period (VO2 max at study endpoint - baseline VO2 max) | Posted | Mean | Standard Deviation | L/min | 6 months |
|
|
|
| 0 |
| 21 |
| 1 |
| 21 |
| EG001 | Flutamide - 2 | Flutamide Flutamide: 250 mg twice daily | 0 | 24 | 4 | 24 |
| EG002 | Placebo - 3 | Placebo only | 0 | 22 | 0 | 22 |
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| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000588 |
| Amines |
| D009651 | Norpregnatrienes |
| D009650 | Norpregnanes |
| D009654 | Norsteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D042782 | Estrogenic Steroids, Alkylated |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002241 | Carbohydrates |