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Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS)

Primary Purpose

Polycystic Ovary Syndrome

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
recombinant human chorionic gonadotropin
Sponsored by
University of California, San Diego
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Polycystic Ovary Syndrome focused on measuring polycystic ovary syndrome, androgens, ovary, LH

Eligibility Criteria

18 Years - 35 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Normal CBC (Hemoglobin must be at least 11mg/dl)
  • Normal renal and liver function tests
  • Normal vital signs including normal blood pressure

Exclusion Criteria:

  • No oral contraceptives
  • No insulin lowering drugs
  • No anti-androgens (i.e., spironolactone, flutamide, finasteride, etc)
  • No medications that will influence androgen metabolism or clearance
  • No medications that will inhibit the cytochrome P450 enzyme system (cimetidine, ketoconozole, etc)
  • No use of clomiphene citrate within 3 months prior to study

Sites / Locations

  • University of California, San Diego, School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

PCOS group

Control group

Arm Description

Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.

Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.

Outcomes

Primary Outcome Measures

Serum 17OHP Responses to hCG
Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects

Secondary Outcome Measures

Serum Testosterone Responses to hCG
Mean serum testosterone levels before and after hCG injection. Serum testosterone levels before (-0.5 and 0 hrs) were averaged to achieve a single value

Full Information

First Posted
September 4, 2008
Last Updated
October 25, 2018
Sponsor
University of California, San Diego
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1. Study Identification

Unique Protocol Identification Number
NCT00747617
Brief Title
Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS)
Official Title
Theca Cell Function in Women With Polycystic Ovary Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
September 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The mechanism for increased androgen production in women with polycystic ovary syndrome (PCOS) is not well understood. Excess androgen production by the ovary is stimulated by increased pituitary luteinizing hormone (LH) secretion in this disorder. The investigators hypothesize that in PCOS women ovarian theca cells, which are responsible for androgen synthesis, are more sensitive to LH stimulation compared to that of theca cells from normal women. To test this hypothesis, the investigators propose to conduct a dose-response study in which androgen responses to multiple doses of human chorionic gonadotgropin (hCG), an LH surrogate, will be assessed in PCOS and normal women.
Detailed Description
Each subject (normal and PCOS women) will be admitted to the UCSD General Clinical Research Center (GCRC) for study on 5 occasions. All subjects will receive an intravenous injection of hCG dose of 1, 10, 25, 100, and 250 micrograms, each of which will be given on one of 5 different days each separated by at least two weeks at 8 AM. Blood samples will be obtained at t -0.5, 0, and 24 hours after injection. All visits to the GCRC will be done as out patients. The total amount of blood withdrawn will be about 35 teaspoons. For normal control subjects this will be over a period of about 4-6 months and for PCOS subjects this will be over a period of about 6-10 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
polycystic ovary syndrome, androgens, ovary, LH

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PCOS group
Arm Type
Active Comparator
Arm Description
Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.
Intervention Type
Drug
Intervention Name(s)
recombinant human chorionic gonadotropin
Other Intervention Name(s)
Ovidrel
Intervention Description
Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.
Primary Outcome Measure Information:
Title
Serum 17OHP Responses to hCG
Description
Assess serum 17OHP levels following each dose of hCG adminstration in PCOS and normal subjects
Time Frame
24 hrs post dose
Secondary Outcome Measure Information:
Title
Serum Testosterone Responses to hCG
Description
Mean serum testosterone levels before and after hCG injection. Serum testosterone levels before (-0.5 and 0 hrs) were averaged to achieve a single value
Time Frame
-0.5, 0, 24 hrs

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Normal CBC (Hemoglobin must be at least 11mg/dl) Normal renal and liver function tests Normal vital signs including normal blood pressure Exclusion Criteria: No oral contraceptives No insulin lowering drugs No anti-androgens (i.e., spironolactone, flutamide, finasteride, etc) No medications that will influence androgen metabolism or clearance No medications that will inhibit the cytochrome P450 enzyme system (cimetidine, ketoconozole, etc) No use of clomiphene citrate within 3 months prior to study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R, Jeffrey Chang, M.D.
Organizational Affiliation
UCSD SChool of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego, School of Medicine
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17893687
Citation
Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95. doi: 10.1038/ncpendmet0637.
Results Reference
background
PubMed Identifier
18285408
Citation
Wachs DS, Coffler MS, Malcom PJ, Shimasaki S, Chang RJ. Increased androgen response to follicle-stimulating hormone administration in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 May;93(5):1827-33. doi: 10.1210/jc.2007-2664. Epub 2008 Feb 19.
Results Reference
background
PubMed Identifier
16720653
Citation
Wachs DS, Coffler MS, Malcom PJ, Chang RJ. Comparison of follicle-stimulating-hormone-stimulated dimeric inhibin and estradiol responses as indicators of granulosa cell function in polycystic ovary syndrome and normal women. J Clin Endocrinol Metab. 2006 Aug;91(8):2920-5. doi: 10.1210/jc.2006-0442. Epub 2006 May 23.
Results Reference
background
PubMed Identifier
16804036
Citation
Mehta RV, Malcom PJ, Chang RJ. The effect of androgen blockade on granulosa cell estradiol production after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Sep;91(9):3503-6. doi: 10.1210/jc.2006-0752. Epub 2006 Jun 27.
Results Reference
background
PubMed Identifier
15644405
Citation
Mehta RV, Patel KS, Coffler MS, Dahan MH, Yoo RY, Archer JS, Malcom PJ, Chang RJ. Luteinizing hormone secretion is not influenced by insulin infusion in women with polycystic ovary syndrome despite improved insulin sensitivity during pioglitazone treatment. J Clin Endocrinol Metab. 2005 Apr;90(4):2136-41. doi: 10.1210/jc.2004-1040. Epub 2005 Jan 11.
Results Reference
background
PubMed Identifier
15467530
Citation
Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004 Sep;191(3):713-7. doi: 10.1016/j.ajog.2004.04.045.
Results Reference
background
PubMed Identifier
27473350
Citation
Maas KH, Chuan S, Harrison E, Cook-Andersen H, Duleba AJ, Chang RJ. Androgen responses to adrenocorticotropic hormone infusion among individual women with polycystic ovary syndrome. Fertil Steril. 2016 Oct;106(5):1252-1257. doi: 10.1016/j.fertnstert.2016.06.039. Epub 2016 Jul 26.
Results Reference
derived
PubMed Identifier
25313914
Citation
Maas KH, Chuan SS, Cook-Andersen H, Su HI, Duleba A, Chang RJ. Relationship between 17-hydroxyprogesterone responses to human chorionic gonadotropin and markers of ovarian follicle morphology in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015 Jan;100(1):293-300. doi: 10.1210/jc.2014-2956.
Results Reference
derived
PubMed Identifier
25303490
Citation
Cook-Andersen H, Chuan SS, Maas K, Rosencrantz MA, Su HI, Lawson M, Mason HD, Chang RJ. Lack of Serum anti-Mullerian hormone responses after recombinant human chorionic gonadotropin stimulation in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2015 Jan;100(1):251-7. doi: 10.1210/jc.2014-2948.
Results Reference
derived
PubMed Identifier
24188875
Citation
Shayya RF, Rosencrantz MA, Chuan SS, Cook-Andersen H, Roudebush WE, Irene Su H, Shimasaki S, Chang RJ. Decreased inhibin B responses following recombinant human chorionic gonadotropin administration in normal women and women with polycystic ovary syndrome. Fertil Steril. 2014 Jan;101(1):275-9. doi: 10.1016/j.fertnstert.2013.09.037. Epub 2013 Nov 1.
Results Reference
derived
PubMed Identifier
21270326
Citation
Rosencrantz MA, Coffler MS, Haggan A, Duke KB, Donohue MC, Shayya RF, Su HI, Chang RJ. Clinical evidence for predominance of delta-5 steroid production in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011 Apr;96(4):1106-13. doi: 10.1210/jc.2010-2200. Epub 2011 Jan 26.
Results Reference
derived

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Theca Cell Function in Women With Polycystic Ovary Syndrome (PCOS)

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