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

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT00747617
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Drug: recombinant human chorionic gonadotropin	Phase 3

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 The total amount of blood withdrawn will be about 35 teaspoons.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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Theca Cell Function in Women With Polycystic Ovary Syndrome
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: PCOS group Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.	Drug: recombinant human chorionic gonadotropin; Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.; Other Names: Ovidrel
Active Comparator: Control group Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of recombinant human chorionic gonadotropin administered iv on 5 separate occasions.	Drug: recombinant human chorionic gonadotropin; Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of human chorionic gonadotropin administered intravenously on 5 separate occasions.; Other Names: Ovidrel

Outcome Measures

Primary Outcome Measures

1. Serum 17OHP Responses to hCG [24 hrs post dose]

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

Secondary Outcome Measures

1. Serum Testosterone Responses to hCG [-0.5, 0, 24 hrs]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Diego, School of Medicine	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego

Investigators

• Principal Investigator: R, Jeffrey Chang, M.D., UCSD SChool of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Chang RJ. A practical approach to the diagnosis of polycystic ovary syndrome. Am J Obstet Gynecol. 2004 Sep;191(3):713-7. Review.
• Chang RJ. The reproductive phenotype in polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab. 2007 Oct;3(10):688-95. Review.
• 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. Epub 2006 Jun 27.
• 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. Epub 2005 Jan 11.
• 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. Epub 2006 May 23.
• 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.

• Responsible Party: Jeffrey Chang, MD, Principal investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT00747617
• Other Study ID Numbers: 060679
• First Posted: Sep 5, 2008
• Last Update Posted: Nov 21, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Jeffrey Chang, MD, Principal investigator, University of California, San Diego: polycystic ovary syndrome; androgens; ovary; LH
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Syndrome; Chorionic Gonadotropin

Study Results

Participant Flow

Recruitment Details	Subjects recruited from UCSD clinics and coal advertising beginning in 2009 and ending in 2010
Pre-assignment Detail	Subjects involved women with PCOS and normal control women undergoing hCG stimulation

Arm/Group Title	PCOS	Normal
Arm/Group Description	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.
Period Title: Overall Study
STARTED	13	12
COMPLETED	10	11
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	PCOS	Normal	Total
Arm/Group Description	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.	Total of all reporting groups
Overall Participants	13	12	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	12 100%	25 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28.5 (1.1)	30 (1.3)	29 (1.2)
Sex: Female, Male (Count of Participants)
Female	13 100%	12 100%	25 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%	12 100%	25 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

PCOS and Normal groups were analyzed according to peak 17OHP levels at each dose of r-hCG.

Arm/Group Title	PCOS	Normal
Arm/Group Description	Each subject received a dose (1, 10, 25, 100, or 250 micrograms) of iv hCG.	Each subject received a dose (1, 10, 25, 100, or 250 micrograms) of iv hCG.
Measure Participants	10	11
17OHP post 10 micrograms	2.0 (0.3)	1.2 (0.1)
17OHP level post 1 micrograms	1.1 (0.1)	1.0 (0.1)
17OHP level post 25 micrograms	2.7 (0.3)	1.7 (0.2)
17OHP level post 100 micrograms	3.3 (0.6)	2.2 (0.3)
17OHP level post 250 micrograms	4.0 (0.6)	2.1 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PCOS, Normal
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PCOS	Normal
Arm/Group Description	Each subject received a dose (1, 10, 25, 100, or 250 micrograms) of iv hCG.	Each subject received a dose (1, 10, 25, 100, or 250 micrograms) of iv hCG.
Measure Participants	10	11
Mean (Standard Error) [ng/ml]	0.6 (0.1)	0.3 (0.05)

Adverse Events

Time Frame	2 years
Arm/Group Title	PCOS		Normal
Arm/Group Description	Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.		Each subject will receive a dose (1, 10, 25, 100, or 250 micrograms) of hCG administered intravenously on 5 separate occasions.
All Cause Mortality
	PCOS		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Serious Adverse Events
	PCOS		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	PCOS		Normal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.