Androgen Excess as a Cause for Adipogenic Dysfunction in PCOS Women

NCT01889199 | Completed Phase 2 Results FDA Drug

• 1 other identifier: UCLA IRB #12-001780
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to collect specimen samples and study medical information from women with Polycystic Ovary Syndrome (PCOS) and women without PCOS. The goal is to learn more about the changes that take place in the body that result in PCOS. We anticipate that 32 women will take part in this study (16 without PCOS and 16 with PCOS). All patients will undergo a physical exam, blood tests, and ultrasound of their ovaries. If they meet the criteria for this study, they will then undergo additional blood tests, removal of a small amount of subcutaneous abdominal fat, measurement of regional body fat (i.e., DXA scan) and a modified frequently-sampled intravenous glucose tolerance test (FSIGTT). The women without PCOS will complete the study at this point. The women with PCOS will be randomized to receive the drug flutamide 125 mg/day or placebo. They will take the drug every day for six 28-day cycles. They will be asked to collect and store a urine sample once a week. They will also be asked to complete a pill diary and menstrual diary. Once a month while they are taking the flutamide/placebo, they will return to the clinic and bring their frozen urine samples. At that time they will undergo a physical exam, toxicity assessment, and blood draw. Quality of Life assessments will be done at the beginning of the study for all participants. Women with PCOS who are taking the flutamide or placebo will be asked to repeat the Quality of Life assessments during the study and at the end of the study. After the six 28-day cycles are completed they will then undergo additional blood tests, removal of a small amount of subcutaneous abdominal fat, measurement of regional body fat (i.e., DXA scan) and a modified frequently-sampled intravenous glucose tolerance test (FSIGTT). Six months following the completion of all study protocol procedures, participants who received flutamide/placebo will be contacted by phone to check on the status of their health. They will be asked if they have experienced any health problems or have become pregnant since they completed the study procedures.

Conditions

Polycystic Ovary Syndrome (PCOS)

Keywords

polycystic ovary syndrome; hirsutism; anovulation; oligomenorrhea; amenorrhea; hyperandrogenism; antiandrogen effect

Outcome Measures

Primary Outcomes (1)

• Lipid Content of PCOS Subcutaneous (SC) Abdominal Adipocytes Matured in Vitro.

  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).

  Baseline, 6 months

Secondary Outcomes (5)

• Fasting Glucose Levels

  Baseline, 6 months

• Depression as Assessed by Beck Depression Inventory (BDI)

  6 months

• Percent Android Fat Mass

  Baseline, 6 months (intervention arms only)

• Fasting Serum Lipoprotein Levels

  6 months

• Fasting Serum Total Cholesterol

  Baseline, 6 months

Other Outcomes (1)

• Number of Participants Experiencing Elevated Liver Transaminases (Serum Glutamic Oxaloacetic Transaminase [SGOT]; Serum Glutamic-pyruvic Transaminase [SGPT])

  6 months

Study Arms (2)

Sugar pill

PLACEBO COMPARATOR

Placebo intervention

Other: Placebo

Flutamide

EXPERIMENTAL

Flutamide 125 mg orally daily for six 28-day cycles.

Drug: Flutamide

Interventions

Flutamide DRUG

Flutamide 125 mg orally each 28 day cycle for 6 cycles

Also known as: Euflex

Flutamide

Placebo OTHER

Placebo orally each 28 day cycle for 6 cycles

Sugar pill

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women between the ages of 18 to 35 years.
• Groups will be: 16 lean controls and 16 age- and BMI-matched PCOS women randomized to flutamide vs. placebo for 6 months.
• i) Lean patients with PCOS: 16 subjects with PCOS (defined by 1990 NIH criteria \[all Aims\]), BMI 18.5-25 kg/m2. This BMI range is defined as normal and has been chosen to examine underlying mechanisms of PCOS-related androgen excess in the genesis of adipogenic and ovarian dysfunction, independent of obesity.
• ii) Lean control women: 16 healthy subjects, BMI 18.5-25 kg/m2. Controls will have regular menstrual cycles, and no evidence of hirsutism, acne, alopecia, polycystic ovaries, and/or endocrine dysfunction. This BMI range has been chosen to match that of the PCOS group.

You may not qualify if:

• The screener will assess the participants response to establish if depression or drug use exclude participation in this study.
• Women taking beta blockers will be excluded.
• Women who have taken birth control pills or had a Mirena IUD or used Plan B contraception during the previous 3 months will be excluded.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Oregon Health and Science University: collaborator

Study Sites (1)

UCaliforniaLA

Los Angeles, California, 90095-1740, United States

Location

Related Publications (1)

• Dumesic DA, Winnett C, Lu G, Grogan TR, Abbott DH, Naik R, Chazenbalk GD. Randomized clinical trial: effect of low-dose flutamide on abdominal adipogenic function in normal-weight women with polycystic ovary syndrome. Fertil Steril. 2023 Jan;119(1):116-126. doi: 10.1016/j.fertnstert.2022.09.324. Epub 2022 Nov 15.

  PMID: 36400597 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Hirsutism; Anovulation; Oligomenorrhea; Amenorrhea; Hyperandrogenism

Interventions

Flutamide

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; Hair Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Virilism; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances; Pathologic Processes; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Daniel A. Dumesic, MD
• Organization: University of California, Los Angeles

DDumesic@mednet.ucla.edu

310-794-5542

Study Officials

• Daniel Dumesic, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division of Reproductive Endocrinology and Infertility

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: June 28, 2013
• Study Start: April 1, 2013
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: January 10, 2025
• Results First Posted: January 10, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)