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

Sponsor

Indiana University (Other)

Overall Status

Terminated

CT.gov ID

NCT01489319

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: Salsalate Drug: Salsalate	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

47 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

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. [3 years]
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. [3 years]
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. [3 years]
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. [3 years]
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. [3 years]
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 [3 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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)