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

Primary Purpose

Polycystic Ovary Syndrome

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Salsalate
Salsalate
Sponsored by
Indiana University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Polycystic Ovary Syndrome focused on measuring inflammation, body composition, hyperandrogenism, insulin resistance

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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)

Sites / Locations

  • Indiana University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

No Intervention

No Intervention

No Intervention

No Intervention

Arm Label

Nl Wt PCOS - Nl Abdominal Adiposity

Nl Wt PCOS - Increased Abdominal Adiposity

Obese PCOS

Nl Wt Controls - Nl Abdominal Adiposity

Nl Wt Controls - Increased Abdominal Adiposity

Obese Controls

Arm Description

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

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

10 obese women with PCOS

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

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

10 obese ovulatory women serving as controls

Outcomes

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.
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.
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.
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.
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.
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
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.

Full Information

First Posted
December 6, 2011
Last Updated
February 8, 2017
Sponsor
Indiana University
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1. Study Identification

Unique Protocol Identification Number
NCT01489319
Brief Title
Evaluation of Oral Lipid Ingestion in Relation to Ovarian Androgen Secretion in Polycystic Ovary Syndrome (PCOS)
Acronym
ELI-ROAS
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

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
The PI left Indiana University. The findings served as preliminary data for a recently awarded NIH R01 grant.
Study Start Date
February 2012 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
inflammation, body composition, hyperandrogenism, insulin resistance

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nl Wt PCOS - Nl Abdominal Adiposity
Arm Type
Experimental
Arm Description
10 normal weight women with PCOS who have normal abdominal adiposity established by DEXA
Arm Title
Nl Wt PCOS - Increased Abdominal Adiposity
Arm Type
Experimental
Arm Description
10 normal weight women with PCOS who have increased abdominal adiposity established by DEXA
Arm Title
Obese PCOS
Arm Type
No Intervention
Arm Description
10 obese women with PCOS
Arm Title
Nl Wt Controls - Nl Abdominal Adiposity
Arm Type
No Intervention
Arm Description
10 normal weight ovulatory women serving as controls who have normal abdominal adiposity established by DEXA
Arm Title
Nl Wt Controls - Increased Abdominal Adiposity
Arm Type
No Intervention
Arm Description
10 normal weight ovulatory women serving as controls who have increased abdominal adiposity established by DEXA
Arm Title
Obese Controls
Arm Type
No Intervention
Arm Description
10 obese ovulatory women serving as controls
Intervention Type
Drug
Intervention Name(s)
Salsalate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Salsalate
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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).
Time Frame
3 years
Secondary Outcome Measure Information:
Title
White blood cell NFkappaB activation following oral lipid ingestion in response to 12 weeks of salsalate or PCE administration.
Description
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.
Time Frame
3 years
Title
Ovarian androgen secretion following HCG administration in response to 12 weeks of salsalate or PCE administration.
Description
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.
Time Frame
3 years
Title
Body composition status measured by DEXA in response to 12 weeks of salsalate or PCE administration.
Description
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.
Time Frame
3 years
Title
Insulin sensitivity derived from an OGTT in response to 12 weeks of salsalate or PCE administration.
Description
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.
Time Frame
3 years
Title
Ovulation rates documented by serum progesterone in response to 12 weeks of salsalate or PCE administration
Description
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.
Time Frame
3 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frank González, M.D.
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32325487
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.
Results Reference
derived
PubMed Identifier
32140727
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.
Results Reference
derived
PubMed Identifier
30590569
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.
Results Reference
derived

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

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