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

• Sponsor: University of California, San Diego (Other)
• Overall Status: Completed
• CT.gov ID: NCT01154192
• Collaborator: University of Virginia (Other)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 37
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU. The investigators propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

Condition or Disease	Intervention/Treatment	Phase
PCOS	Drug: Dexamethasone; Drug: recombinant human chorionic gonadotropin (r-hCG)	Phase 3

Detailed Description

In women with polycystic ovary syndrome (PCOS), the cardinal physiological abnormality is excessive ovarian androgen production marked by increased serum testosterone (T) and androstenedione (A) levels. Studies to determine the alteration in ovarian steroidogenesis that lead to abnormal production of ovarian androgens have revealed increased CYP17 gene expression with accentuated 17-hydroxylase activity leading to exaggerated 17-hydroxyprogesterone (17P) responses to luteinizing hormone (LH) stimulation. In contrast, T and A responses did not distinguish between PCOS and normal women, although these androgens were clearly greater in the former compared to the latter group. As a result, 17P responsiveness has been employed to determine the functional capacity of the ovary to produce androgens. The stimulatory agents that have been used included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU.We propose to conduct a study that will determine the pattern of androgen responsiveness to 25ucg of hCG after 24 hours in adolescents with PCOS, those with oligomenorrhea, and in normal controls. This will allow for a comparison of these adolescents' ovarian functional capacity to produce androgens.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Theca Cell Function in Adolescents With Polycystic Ovary Syndrome (PCOS)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PCOS group Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Drug: Dexamethasone; Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: recombinant human chorionic gonadotropin (r-hCG) ; Drug: recombinant human chorionic gonadotropin (r-hCG); Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: Ovidrel
Experimental: Normal group Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.	Drug: Dexamethasone; Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: recombinant human chorionic gonadotropin (r-hCG) ; Drug: recombinant human chorionic gonadotropin (r-hCG); Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: Ovidrel
Experimental: Oligomenorrhea group Intervention: Each subject in the Oligomenorrhea group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.	Drug: Dexamethasone; Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: recombinant human chorionic gonadotropin (r-hCG) ; Drug: recombinant human chorionic gonadotropin (r-hCG); Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.; Other Names: Ovidrel

Outcome Measures

Primary Outcome Measures

1. 17OHP Levels After hCG [24 hours]

   Assess serum levels of 17OHP after stimulation with recombinant hCG

Secondary Outcome Measures

1. Testosterone [24 hours]

   Assess seruim levels of testosterone after stimulation with recombinant hCG

2. Androstenedione [24 hours]

   Assess serum levels of androstenedione after stimaultion with recombinant hCG

3. DHEA [24 hours]

   Assess serum levels of DHEA after stimulation with recombinant hCG

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 18 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:

• Pregnancy

• On oral contraceptives

• On insulin lowering drugs

• On anti-androgens (i.e., spironolactone, flutamide, finasteride, etc)

• On medications that will influence androgen metabolism or clearance

• On medications that will inhibit the cytochrome P450 enzyme system (Cimetidine, ketoconazole, etc)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD School of Medicine	La Jolla	California	United States	92093

Sponsors and Collaborators

• University of California, San Diego
• University of Virginia

Investigators

• Principal Investigator: R. Jeffery Chang, M.D., UCSD School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey Chang, MD, Principal Investigator, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01154192
• Other Study ID Numbers: 081696
• First Posted: Jun 30, 2010
• Last Update Posted: Apr 30, 2019
• Last Verified: Apr 1, 2019

• 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: PCOS; oligomenorrhea; irregular menses; hyperandrogenemia; elevated testosterone; adolescents; androgens; ovary; LH
• Additional relevant MeSH terms: Polycystic Ovary Syndrome; Dexamethasone; Chorionic Gonadotropin

Study Results

Participant Flow

Arm/Group Title	PCOS Group	Normal Group	There Were Only 2 Groups: PCOS and Normal Subjects
Arm/Group Description	Intervention: Each subject in the PCOS group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements. Dexamethasone: Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones. recombinant human chorionic gonadotropin (r-hCG): Each subject in each group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin (r-hCG). Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements. Dexamethasone
Period Title: Overall Study
STARTED	14	10	0
COMPLETED	14	10	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	PCOS Group	Normal Group	Oligomenorrhea Group	Total
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.	Total of all reporting groups
Overall Participants	14	10	0	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.9 (1.0)	15.4 (1.2)	15.3 (1.0)
Sex: Female, Male (Count of Participants)
Female	14 100%	10 100%	24 Infinity
Male	0 0%	0 0%	0 NaN
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	17OHP Levels After hCG
Description	Assess serum levels of 17OHP after stimulation with recombinant hCG
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Oligmenorhea group not included in study

Arm/Group Title	PCOS Group	Normal Group	Oligomenorrhea Group
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.
Measure Participants	14	10	0
Mean (Standard Error) [ng/ml]	3.2 (0.5)	1.3 (0.3)

2. Secondary Outcome

Title	Testosterone
Description	Assess seruim levels of testosterone after stimulation with recombinant hCG
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Oligpmenrreha group not included in study

Arm/Group Title	PCOS Group	Normal Group	Oligomenorrhea Group
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements. .
Measure Participants	14	10	0
Mean (Standard Error) [ng/ml]	1.6 (0.2)	1.0 (0.2)

3. Secondary Outcome

Title	Androstenedione
Description	Assess serum levels of androstenedione after stimaultion with recombinant hCG
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Oligomenorreha group not inlcuded in study

Arm/Group Title	PCOS Group	Normal Group	Oligomenorrhea Group
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.
Measure Participants	14	10	0
Mean (Standard Error) [ng/ml]	2.1 (0.2)	0.9 (0.2)

4. Secondary Outcome

Title	DHEA
Description	Assess serum levels of DHEA after stimulation with recombinant hCG
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Oligomenrrhea group not included in study

Arm/Group Title	PCOS Group	Normal Group	Oligomenorrhea Group
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.	Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.
Measure Participants	14	10	0
Mean (Standard Error) [ng/ml]	1.6 (0.2)	1.0 (0.2)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	The number of participants at risk for Other Adverse Events, All-Cause Mortality, and Serious Adverse Events should be 24
Arm/Group Title	PCOS Group		Normal Group		Oligomenorrhea Group
Arm/Group Description	Intervention: Each subject in the PCOS group will receive 1 mg of oral dexamethasone in the evening and return in the morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will also have blood drawn at times -0.5, 0, 0.5, and 24 hours after the injection of r-hCG for measurement of steroid hormones.		Intervention: Each subject in the Normal group will receive dexamethasone 1 mg orally in the evening and return the next morning for an injection of 25ug of IV recombinant human chorionic gonadotropin. Subjects will the have blood drawn at -0.5, 0, 0.5, and 24 hours after hCG injection for steroid hormone measurements.		Not included in the study
All Cause Mortality
	PCOS Group		Normal Group		Oligomenorrhea Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/10 (0%)		0/0 (NaN)
Serious Adverse Events
	PCOS Group		Normal Group		Oligomenorrhea Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/10 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	PCOS Group		Normal Group		Oligomenorrhea Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/10 (0%)		0/0 (NaN)

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.