Trial Outcomes & Findings for Androgen Excess as a Cause for Adipogenic Dysfunction in PCOS Women (NCT NCT01889199)
NCT ID: NCT01889199
Last Updated: 2025-01-10
Results Overview
Lipid content of PCOS subcutaneous (SC) abdominal stem cells during adipocyte maturation in vitro at baseline and after 6 months treatment Lipid staining and immunofluorescence: Newly-formed adipocytes were fixed and stained with Oil-Red-O (Sigma Aldrich, St. Louis, MO) for 20 min at room temperature to visualize lipid droplets. Nuclei were identified by the nuclear staining marker 4',6-diamidino-2-phenoylidole (DAPI) (1:3000 \[Invitrogen, Carlsbad, CA\]). After 4 washes with deionized water, lipid staining was quantified by immunofluorescence. Twenty representative images were taken of fluorescent cells with an EVOS FL Digital Inverted Fluorescence microscope (Westover Scientific Inc, Bothell, WA) and fluorescence units/cell number were quantified using ImageJ software (NIH, Bethesda, MD).
COMPLETED
PHASE2
23 participants
Baseline, 6 months
2025-01-10
Participant Flow
Participant milestones
| Measure |
Sugar Pill
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
5
|
12
|
|
Overall Study
Baseline
|
6
|
5
|
12
|
|
Overall Study
6-month Assessment on Intervention Arms
|
6
|
5
|
0
|
|
Overall Study
COMPLETED
|
6
|
5
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Androgen Excess as a Cause for Adipogenic Dysfunction in PCOS Women
Baseline characteristics by cohort
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
n=12 Participants
Baseline measures assessed on non-PCOS controls
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
23 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, 6 monthsPopulation: Assessed for participants with PCOS
Lipid content of PCOS subcutaneous (SC) abdominal stem cells during adipocyte maturation in vitro at baseline and after 6 months treatment Lipid staining and immunofluorescence: Newly-formed adipocytes were fixed and stained with Oil-Red-O (Sigma Aldrich, St. Louis, MO) for 20 min at room temperature to visualize lipid droplets. Nuclei were identified by the nuclear staining marker 4',6-diamidino-2-phenoylidole (DAPI) (1:3000 \[Invitrogen, Carlsbad, CA\]). After 4 washes with deionized water, lipid staining was quantified by immunofluorescence. Twenty representative images were taken of fluorescent cells with an EVOS FL Digital Inverted Fluorescence microscope (Westover Scientific Inc, Bothell, WA) and fluorescence units/cell number were quantified using ImageJ software (NIH, Bethesda, MD).
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Lipid Content of PCOS Subcutaneous (SC) Abdominal Adipocytes Matured in Vitro.
Baseline
|
2.0 fluorescence units/cell number
Standard Deviation 0.6
|
5.6 fluorescence units/cell number
Standard Deviation 4.1
|
—
|
|
Lipid Content of PCOS Subcutaneous (SC) Abdominal Adipocytes Matured in Vitro.
6 months
|
1.37 fluorescence units/cell number
Standard Deviation 0.7
|
3.8 fluorescence units/cell number
Standard Deviation 3.9
|
—
|
|
Lipid Content of PCOS Subcutaneous (SC) Abdominal Adipocytes Matured in Vitro.
Change
|
-0.6 fluorescence units/cell number
Standard Deviation 0.4
|
-1.8 fluorescence units/cell number
Standard Deviation 0.6
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 monthsPopulation: Control group was assessed at baseline only
Fasting glucose levels at baseline for all participants, and at 6 months for intervention arms
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
n=12 Participants
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Fasting Glucose Levels
Baseline
|
85.6 mg/dL
Standard Deviation 4.6
|
83.9 mg/dL
Standard Deviation 4.8
|
85.8 mg/dL
Standard Deviation 6.1
|
|
Fasting Glucose Levels
6 months
|
85.3 mg/dL
Standard Deviation 4.8
|
88.6 mg/dL
Standard Deviation 5.6
|
—
|
|
Fasting Glucose Levels
Change
|
-0.3 mg/dL
Standard Deviation 3.9
|
4.6 mg/dL
Standard Deviation 1.6
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Assessed only for intervention arms of healthy normal-weight PCOS women by NIH criteria
Number of participants with risk of severe depression as determined by 21 questions on a 4-point Likert scale, scores could range from 0-63, with higher score indicating a worse outcome. Scores above 30 indicate Severe depression, and scores above 40 indicate Extreme Depression.
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Depression as Assessed by Beck Depression Inventory (BDI)
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 months (intervention arms only)Population: Control group was assessed at baseline only
Percent of abdominal (android) fat by Total body dual-energy x-ray absorptiometry (DXA) scan
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
n=12 Participants
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Percent Android Fat Mass
Baseline
|
6.0 percent abdominal (android) fat mass
Standard Deviation 1.4
|
6.1 percent abdominal (android) fat mass
Standard Deviation 1.8
|
5.5 percent abdominal (android) fat mass
Standard Deviation 0.5
|
|
Percent Android Fat Mass
6 months
|
6.4 percent abdominal (android) fat mass
Standard Deviation 1.2
|
5.9 percent abdominal (android) fat mass
Standard Deviation 1.4
|
—
|
|
Percent Android Fat Mass
Change
|
0.4 percent abdominal (android) fat mass
Standard Deviation 0.4
|
-0.3 percent abdominal (android) fat mass
Standard Deviation 0.5
|
—
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Control group was assessed at baseline only
Fasting serum low-density lipoprotein levels at baseline and (for intervention arms only) after 6 months
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
n=12 Participants
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Fasting Serum Lipoprotein Levels
Log triglyceride - Baseline
|
1.9 (log)mg/dL
Standard Deviation 0.3
|
1.7 (log)mg/dL
Standard Deviation 0.1
|
1.7 (log)mg/dL
Standard Deviation 0.1
|
|
Fasting Serum Lipoprotein Levels
Log triglyceride - 6 months
|
1.9 (log)mg/dL
Standard Deviation 0.4
|
1.7 (log)mg/dL
Standard Deviation 0.2
|
—
|
|
Fasting Serum Lipoprotein Levels
Log triglyceride - Change
|
0.0 (log)mg/dL
Standard Deviation 0.1
|
0.0 (log)mg/dL
Standard Deviation 0.1
|
—
|
|
Fasting Serum Lipoprotein Levels
Log non-high-density lipoprotein baseline
|
2.0 (log)mg/dL
Standard Deviation 0.1
|
2.0 (log)mg/dL
Standard Deviation 0.1
|
1.94 (log)mg/dL
Standard Deviation 0.10
|
|
Fasting Serum Lipoprotein Levels
Log non-high-density lipoprotein - 6 months
|
2.0 (log)mg/dL
Standard Deviation 0.1
|
2.0 (log)mg/dL
Standard Deviation 0.1
|
—
|
|
Fasting Serum Lipoprotein Levels
Log non-high-density lipoprotein - change
|
0.0 (log)mg/dL
Standard Deviation 0.0
|
-0.1 (log)mg/dL
Standard Deviation 0.1
|
—
|
|
Fasting Serum Lipoprotein Levels
Log low-density lipoprotein - Baseline
|
1.8 (log)mg/dL
Standard Deviation 0.1
|
2.0 (log)mg/dL
Standard Deviation 0.1
|
1.88 (log)mg/dL
Standard Deviation 0.10
|
|
Fasting Serum Lipoprotein Levels
Log low-density lipoprotein - 6 months
|
1.8 (log)mg/dL
Standard Deviation 0.1
|
1.9 (log)mg/dL
Standard Deviation 0.1
|
—
|
|
Fasting Serum Lipoprotein Levels
Log low-density lipoprotein - Change
|
0.0 (log)mg/dL
Standard Deviation 0.0
|
-0.1 (log)mg/dL
Standard Deviation 0.1
|
—
|
SECONDARY outcome
Timeframe: Baseline, 6 monthsPopulation: Control group was assessed at baseline only
Fasting serum total cholesterol at baseline and (for intervention arms only) after 6 months
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
n=12 Participants
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Fasting Serum Total Cholesterol
Total cholesterol - Baseline
|
153.7 mg/dL
Standard Deviation 29.1
|
184.0 mg/dL
Standard Deviation 27.0
|
153.0 mg/dL
Standard Deviation 21.7
|
|
Fasting Serum Total Cholesterol
Total cholesterol - 6 months
|
155.3 mg/dL
Standard Deviation 31.6
|
168.0 mg/dL
Standard Deviation 14.7
|
—
|
|
Fasting Serum Total Cholesterol
Total cholesterol - Change
|
1.7 mg/dL
Standard Deviation 9.4
|
-16.0 mg/dL
Standard Deviation 24.4
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: Assessed only for intervention arms of healthy normal-weight PCOS women by NIH criteria
This study carefully considers the safety of low-dose flutamide in examining how hyperandrogenism in PCOS affects ovarian function, subcutaneous fat storage and glucose metabolism. The 125 mg oral dose of flutamide has been specifically chosen because it has not been associated with liver enzyme abnormalities (0%, 62.5-125 mg/day), while being as effective as high dose flutamide in improving androgenic symptoms. Furthermore, in the rare event mild elevation of hepatic enzymes occurs with low-dose flutamide despite its dose-dependency, it is easily detected and reversible.
Outcome measures
| Measure |
Sugar Pill
n=6 Participants
Placebo intervention
Placebo: Placebo orally each 28 day cycle for 6 cycles
|
Flutamide
n=5 Participants
Flutamide 125 mg orally daily for six 28-day cycles.
Flutamide: Flutamide 125 mg orally each 28 day cycle for 6 cycles
|
Age- and Body Mass Index-matched Controls
Baseline measures assessed on non-PCOS controls
|
|---|---|---|---|
|
Number of Participants Experiencing Elevated Liver Transaminases (Serum Glutamic Oxaloacetic Transaminase [SGOT]; Serum Glutamic-pyruvic Transaminase [SGPT])
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
Sugar Pill
Flutamide
Age- and Body Mass Index-matched Controls
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Daniel A. Dumesic, MD
University of California, Los Angeles
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place