Evaluation of Oral Lipid Ingestion in Relation to Ovarian Androgen Secretion in Polycystic Ovary Syndrome (PCOS) (ELI-ROAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Indiana University
Sponsor:
Information provided by (Responsible Party):
Frank Gonzalez, Indiana University
ClinicalTrials.gov Identifier:
NCT01489319
First received: December 6, 2011
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to determine the relationship between lipid-induced inflammation and ovarian androgen secretion in women with polycystic ovary syndrome (PCOS); and to examine the effect of salsalate and polygonum cuspidatum extract (PCE) containing resveratrol on lipid-induced inflammation, ovarian androgen secretion, body composition and ovulation in a subset of normal weight women with PCOS.


Condition Intervention
Polycystic Ovary Syndrome
Drug: Salsalate

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Evaluation of the Ovarian Dynamic Response and the Inflammatory Response to Oral Lipid Challenge in Relation to Body Composition in Polycystic Ovary Syndrome

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • White blood cell nuclear factor kappa B (NFkappaB) activation in response to oral lipid ingestion and ovarian androgen secretion in response to human chorionic gonadotropin (HCG) stimulation. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome along with insulin sensitivity derived from an oral glucose tolerance test (OGTT) and body composition measured by dual energy absorptiometry (DEXA) will be assessed in all study subjects (PCOS and controls).


Secondary Outcome Measures:
  • White blood cell NFkappaB activation following oral lipid ingestion in response to 12 weeks of salsalate or PCE administration. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed in a subset of normal weight women with PCOS who have either normal (n=4) or increased (n=4) abdominal adiposity.

  • Ovarian androgen secretion following HCG administration in response to 12 weeks of salsalate or PCE administration. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed in a subset of normal weight women with PCOS who have either normal (n=4) or increased (n=4) abdominal adiposity.

  • Body composition status measured by DEXA in response to 12 weeks of salsalate or PCE administration. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed in a subset of normal weight women with PCOS who have either normal (n=4) or increased (n=4) abdominal adiposity.

  • Insulin sensitivity derived from an OGTT in response to 12 weeks of salsalate or PCE administration. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed in a subset of normal weight women with PCOS who have either normal (n=4) or increased (n=4) abdominal adiposity.

  • Ovulation rates documented by serum progesterone in response to 12 weeks of salsalate or PCE administration [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed in a subset of normal weight women with PCOS who have either normal (n=4) or increased (n=4) abdominal adiposity.


Estimated Enrollment: 60
Study Start Date: February 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nl Wt PCOS - Nl Abdominal Adiposity
10 normal weight women with PCOS who have normal abdominal adiposity established by DEXA
Drug: Salsalate
4 out of 10 subjects will receive salsalate 2.0 gm twice a day for 12 weeks; 4 out of 10 subjects will receive PCE 200 mg containing 20% resveratrol twice a day for 12 weeks.
Experimental: Nl Wt PCOS - Increased Abdominal Adiposity
10 normal weight women with PCOS who have increased abdominal adiposity established by DEXA
Drug: Salsalate
4 out of the 10 subjects will receive salsalate 2.0 gm twice a day for 12 weeks; 4 out of 10 subjects will receive PCE 200 mg containing 20% resveratrol twice a day for 12 weeks.
No Intervention: Obese PCOS
10 obese women with PCOS
No Intervention: Nl Wt Controls - Nl Abdominal Adiposity
10 normal weight ovulatory women serving as controls who have normal abdominal adiposity established by DEXA
No Intervention: Nl Wt Controls - Increased Abdominal Adiposity
10 normal weight ovulatory women serving as controls who have increased abdominal adiposity established by DEXA
No Intervention: Obese Controls
10 obese ovulatory women serving as controls

Detailed Description:

The investigator hypothesizes that in women with PCOS, HCG administration will stimulate an exaggerated ovarian androgen response, dairy cream ingestion will stimulate white blood cells to generate an inflammatory response, and that there is a relationship between HCG-stimulated ovarian androgen secretion and the inflammatory response to dairy cream ingestion regardless of body fat status. Thirty (30) women with PCOS (10 normal weight with normal abdominal adiposity, 10 normal weight with increased abdominal adiposity and 10 obese) and 30 ovulatory control women (10 normal weight with normal abdominal adiposity, 10 normal weight with increased abdominal adiposity and 10 obese) will participate over a 3-year period.

The investigator also hypothesizes that both salsalate and PCE administration for 12 weeks will attenuate the ovarian androgen response to HCG administration and the inflammatory response to dairy cream ingestion, reduce abdominal adiposity, increase insulin sensitivity and induce ovulation in normal weight women with PCOS. A subset of 16 women with PCOS of which 8 will receive salsalate (4 normal weight with normal abdominal adiposity and 4 normal weight with increased abdominal adiposity) and 8 will receive PCE (4 normal weight with normal abdominal adiposity and 4 normal weight with increased abdominal adiposity) will participate in this intervention over a 3-year period. This pilot project will help determine the feasibility of conducting a larger double-blind, randomized trial in women with PCOS to further test the latter hypothesis.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

General Inclusion Criteria:

  • Acceptable health based on interview, medical history, physical examination, and lab tests
  • Ability to comply with the requirements of the study
  • Ability and willingness to provide signed, witnessed informed consent

Inclusion Criteria for PCOS:

  • Between the ages of 18-40 years
  • Body mass index between 18 and 25, or between 30 and 40
  • Less than or equal to 8 periods annually
  • An elevated serum androgen level or skin manifestations of androgen excess
  • Normal thyroid function tests and normal prolactin level
  • Exclusion of late-onset adrenal hyperplasia

Inclusion Criteria for Ovulatory Controls:

  • Between the ages of 18-40 years
  • Body mass index between 18 and 25, or between 30 and 40
  • Normal regular monthly periods
  • No clinical evidence of androgen excess
  • No evidence of polycystic ovaries on ultrasound

Exclusion Criteria:

  • Diabetes mellitus
  • Clinically significant pulmonary, cardiac ,renal, hepatic, neurologic, psychiatric, infectious, and malignant disease
  • High blood pressure
  • Current or recent (within 6 weeks prior to study entry) injection of any drugs known or suspected to affect reproductive function including oral contraceptives, metformin, thiazolidinediones, glucocorticoids, GnRH-agonists, or anti-androgens (spironolactone, flutamide, etc)
  • Documented or suspected history of use of recent (within one year) illicit drug abuse or alcoholism
  • Tobacco smoking if salsalate or PCE will be administered
  • Ingestion of any investigational drugs within 4 weeks prior to study onset
  • Pregnancy or lactation (less than or equal to 6 weeks postpartum)
  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: NCT01489319

Contacts
Contact: Tammy J. Garrett, R.N. (317) 948-7064 tgarrett@iupui.edu
Contact: Frank González, M.D. (317) 944-4058 gonzalef@iupui.edu

Locations
United States, Indiana
Indiana University Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Tammy J. Garrett, R.N.    317-948-7064    tgarrett@iupui.edu   
Contact: Frank González, M.D.    (317) 944-4058    gonzalef@iupui.edu   
Principal Investigator: Frank González, M.D.         
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Frank González, M.D. Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Frank Gonzalez, Associate Professor, Director, Division of Reproductive Endocrinology and Infertility, Indiana University
ClinicalTrials.gov Identifier: NCT01489319     History of Changes
Other Study ID Numbers: IU-PCOS-0112
Study First Received: December 6, 2011
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
inflammation
body composition
hyperandrogenism
insulin resistance

Additional relevant MeSH terms:
Polycystic Ovary Syndrome
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Sodium Salicylate
Salicylsalicylic acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 14, 2014