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

Indiana University

Status and phase: Terminated; Phase 1

Conditions: Polycystic Ovary Syndrome

Treatments: Drug: Salsalate

Study type: Interventional

Funder types: Other

Identifiers

NCT01489319

IU-PCOS-0112

Details and patient eligibility

About

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.

Full 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.

Enrollment: 47 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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47 participants in 6 patient groups

Nl Wt PCOS - Nl Abdominal Adiposity

Experimental group

Description:

10 normal weight women with PCOS who have normal abdominal adiposity established by DEXA

Treatment:

Drug: Salsalate

Drug: Salsalate

Nl Wt PCOS - Increased Abdominal Adiposity

Experimental group

Description:

10 normal weight women with PCOS who have increased abdominal adiposity established by DEXA

Treatment:

Drug: Salsalate

Drug: Salsalate

Obese PCOS

No Intervention group

Description:

10 obese women with PCOS

Nl Wt Controls - Nl Abdominal Adiposity

No Intervention group

Description:

10 normal weight ovulatory women serving as controls who have normal abdominal adiposity established by DEXA

Nl Wt Controls - Increased Abdominal Adiposity

No Intervention group

Description:

10 normal weight ovulatory women serving as controls who have increased abdominal adiposity established by DEXA

Obese Controls

No Intervention group

Description:

10 obese ovulatory women serving as controls