Clinical trial NCT01489319: Evaluation of Oral Lipid Ingestion in Relation to Ovarian Androgen Secretion in Polycystic Ovary Syndrome (PCOS)
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Polycystic Ovary Syndrome
Keywords: inflammation
body composition
hyperandrogenism
insulin resistance
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2011-12-09
Enrollment: 47
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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 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)

Primary outcomes:
measure: 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.
timeFrame: 3 years
Secondary outcomes:
measure: White blood cell NFkappaB activation following oral lipid ingestion in response to 12 weeks of salsalate or PCE administration.
timeFrame: 3 years
measure: Ovarian androgen secretion following HCG administration in response to 12 weeks of salsalate or PCE administration.
timeFrame: 3 years
measure: Body composition status measured by DEXA in response to 12 weeks of salsalate or PCE administration.
timeFrame: 3 years
measure: Insulin sensitivity derived from an OGTT in response to 12 weeks of salsalate or PCE administration.
timeFrame: 3 years
measure: Ovulation rates documented by serum progesterone in response to 12 weeks of salsalate or PCE administration
timeFrame: 3 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
Study officials:
affiliation: Indiana University
name: Frank González, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gonzalez F, Considine RV, Abdelhadi OA, Acton AJ. Lipid-induced mononuclear cell cytokine secretion in the development of metabolic aberration and androgen excess in polycystic ovary syndrome. Hum Reprod. 2020 May 1;35(5):1168-1177. doi: 10.1093/humrep/deaa056.
citation: Gonzalez F, Considine RV, Abdelhadi OA, Acton AJ. Inflammation Triggered by Saturated Fat Ingestion Is Linked to Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2020 Jun 1;105(6):e2152-67. doi: 10.1210/clinem/dgaa108.
citation: Gonzalez F, Considine RV, Abdelhadi OA, Acton AJ. Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2019 Mar 1;104(3):934-946. doi: 10.1210/jc.2018-01143.