Trial record 18 of 22 for:    Open Studies | "Amenorrhea"

Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of California, Los Angeles
Sponsor:
Collaborators:
University of Wisconsin, Madison
Oregon Health and Science University
Information provided by (Responsible Party):
Daniel A. Dumesic, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01889199
First received: June 20, 2013
Last updated: December 28, 2013
Last verified: December 2013
  Purpose

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 59 women will take part in this study (15 without PCOS and 44 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., MRI, DXA scan), a modified frequently-sampled intravenous glucose tolerance test (FSIGTT), and determination of ovarian function (via a follicle stimulating hormone [FSH] test). The women without PCOS will be 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.

Six months following the completion of 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.

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., MRI, DXA scan), a modified frequently-sampled intravenous glucose tolerance test (FSIGTT), and determination of ovarian function (via a FSH test).


Condition Intervention Phase
Polycystic Ovary Syndrome (PCOS)
Drug: Flutamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Androgen Excess as a Mechanism for Adipogenic Dysfunction in PCOS Women

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will improve impaired glucose tolerance by glucose tolerance testing and normalize the size of enlarged subcutaneous (SC) fat cells by fat biopsy. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Women with PCOS exhibit impaired glucose tolerance that correlates with enlarged subcutaneous (SC) abdominal adipocytes. Since a common denominator to these abnormalities is hyperandrogenism, we hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will improve glucose tolerance by glucose tolerance testing and reduce subcutaneous (SC) abdominal adipocyte size, as determined by SC abdominal fat biopsy.

  • Six-month flutamide (antiandrogen) administration to lean women with polycystic ovary syndrome (PCOS) will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Women with PCOS exhibit oligo-ovulation, in part due to hyperandrogenism. We hypothesize that 6-month flutamide (antiandrogen) administration to lean PCOS women will establish ovulatory menstrual cycles, as determined by menstrual diaries and weekly urinary progesterone (metabolite) determinations.


Secondary Outcome Measures:
  • Quality of Life Questionnaires [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Liver transaminases (serum glutamic oxaloacetic transaminase [SGOT]; serum glutamic-pyruvic transaminase [SGPT]) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 59
Study Start Date: April 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar pill
Placebo intervention
Experimental: Flutamide
Flutamide 125 mg orally daily for six 28-day cycles.
Drug: Flutamide
Flutamide or Placebo 125 mg orally each 28 day cycle for 6 cycles
Other Name: Euflex

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Non-Hispanic Caucasian women between the ages of 18 to 35 years.

Groups will be: 12 lean controls (Aim 1); 36 age- and BMI-matched PCOS women randomized to flutamide vs. placebo for 6 months (Aims 1 and 2).

i) Lean patients with PCOS: 36 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: 12 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.

Up to 44 lean PCOS patients and 15 lean controls will be recruited, for a total of 59 study participants over a 5-year interval, accounting for a 20% rate of patient drop-out or insufficient adipose procurement.

Exclusion Criteria:

  • Exclusion criteria for study participation are: present or past history (<5 years) of smoking, cancer, alcohol abuse, drug addiction, severe depression, or post traumatic stress; diabetes; uncontrolled hypertension (≥ 165/100); clinically significant hepatic or renal disease, or other major medical illness; recent (within 3 months) use of androgens, anabolic steroids or hormonal agents (including birth control pills or insulin sensitizers). These exclusion criteria are chosen to avoid effects from medical conditions, environmental factors or exogenous agents. Women taking the drug warfarin, CYP active medications, or herbs will be excluded.

Since this study involves MRI testing, women with pacemakers, metal implants, or claustrophobia will be excluded.

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01889199

Contacts
Contact: Daniel A Dumesic, MD (310) 794-5542 DDumesic@mednet.ucla.edu
Contact: Andrea Rapkin, MD (310) 825-6301 ARapkin@mednet.ucla.edu

Locations
United States, California
UCaliforniaLA Recruiting
Los Angeles, California, United States, 90095-1740
Contact: Daniel A Dumesic, MD    310-794-5542    DDumesic@mednet.ucla.edu   
Contact: Rapkin Andrea, MD    (310) 825-6301    ARapkin@mednet.ucla.edu   
Sponsors and Collaborators
University of California, Los Angeles
University of Wisconsin, Madison
Oregon Health and Science University
  More Information

No publications provided

Responsible Party: Daniel A. Dumesic, MD, Professor and Division Chief, Division of Reproductive Endocrinology and Infertility, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01889199     History of Changes
Other Study ID Numbers: UCLA IRB #12-001780
Study First Received: June 20, 2013
Last Updated: December 28, 2013
Health Authority: United States: Institutional Review Board
UCLA Office of the Human Research Protection Program, United States:

Keywords provided by University of California, Los Angeles:
polycystic ovary syndrome
hirsutism
anovulation
oligomenorrhea
amenorrhea
hyperandrogenism
antiandrogen effect

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

ClinicalTrials.gov processed this record on August 01, 2014