Evaluation of the Ovarian Dynamic Response and the Inflammatory Response to Oral Lipid Challenge in Relation to Body Composition in Polycystic Ovary Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Nl Wt PCOS - Nl Abdominal Adiposity
10 normal weight women with PCOS who have normal abdominal adiposity established by DEXA
干预措施: Salsalate (Drug)
Nl Wt PCOS - Increased Abdominal Adiposity
10 normal weight women with PCOS who have increased abdominal adiposity established by DEXA
干预措施: Salsalate (Drug)
结局指标
主要结局
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.
时间窗: 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).
次要结局
- White blood cell NFkappaB activation following oral lipid ingestion in response to 12 weeks of salsalate or PCE administration.(3 years)
- Ovarian androgen secretion following HCG administration in response to 12 weeks of salsalate or PCE administration.(3 years)
- Body composition status measured by DEXA in response to 12 weeks of salsalate or PCE administration.(3 years)
- Insulin sensitivity derived from an OGTT in response to 12 weeks of salsalate or PCE administration.(3 years)
- Ovulation rates documented by serum progesterone in response to 12 weeks of salsalate or PCE administration(3 years)
研究者
Frank Gonzalez
Associate Professor, Director, Division of Reproductive Endocrinology and Infertility
Indiana University