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Trial record 81 of 1546 for:    Androgens

Ovarian Morphology and Theca Cell Androgen Production in Women With Polycystic Ovary Syndrome (PCOS)

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ClinicalTrials.gov Identifier: NCT02145247
Recruitment Status : Completed
First Posted : May 22, 2014
Results First Posted : August 12, 2019
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
Jeffrey Chang, MD, University of California, San Diego

Tracking Information
First Submitted Date  ICMJE May 20, 2014
First Posted Date  ICMJE May 22, 2014
Results First Submitted Date  ICMJE March 28, 2019
Results First Posted Date  ICMJE August 12, 2019
Last Update Posted Date August 12, 2019
Actual Study Start Date  ICMJE May 2014
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2019)
Percent Change of 17-OHP Levels From Baseline [ Time Frame: before and 24 hours after adminisration of r-hCG ]
On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms. Blood samples will be obtained before and after r-hCG adminstration
Original Primary Outcome Measures  ICMJE
 (submitted: May 21, 2014)
Hormone changes [ Time Frame: 1 day ]
On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms. Blood samples will be obtained at T = -0.5, 0, and +24 hours
Change History Complete list of historical versions of study NCT02145247 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ovarian Morphology and Theca Cell Androgen Production in Women With Polycystic Ovary Syndrome (PCOS)
Official Title  ICMJE Ovarian Morphology and Theca Cell Androgen Production in Women With Polycystic Ovary Syndrome (PCOS)
Brief Summary Women with PCOS suffer from excess male hormone (androgen) production by the ovary. Androgen is made by cells that surround follicles that contain eggs. As the follicles (and eggs) grow and mature, there are more androgen producing cells. Women with PCOS have more follicles than normal women and therefore more androgen producing cells. While androgen production has been associated with the number of follicles, the relationship to the individual size of follicles in PCOS or normal women. This study intends to determine whether the size and number of ovarian follicles are correlated to androgen production in PCOS and normal women.
Detailed Description

In women with polycystic ovary syndrome (PCOS), the major 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 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 androgen. Stimulatory agents have included GnRH agonist, Lupron, at a dose of 10 microgram per kilogram, or hCG at a dose of 10,000 IU.

The investigators recently showed that hCG administered intravenously in a dose-response fashion revealed gradual increases of 17P and a non-dose dependent increase of serum T and A. The pattern of steroid hormone production revealed the predominant pathway by which androgens are generated in women with PCOS. Extending these studies, the investigators selected the mid-maximal dose of hCG to stimulate ovarian androgens and included morphometric measures of the ovary, such as ovarian follicle number (as determined by ultrasound) and related hormones, such as anti-mullerian hormone and inhibin B, both products of the ovarian follicle. The results showed that increased androgen and 17P responses in PCOS women were associated with increased antral follicle number and greater AMH levels compared to normal women. Inhibin B levels were similar between groups.

Based on responses observed in normal women, the PCOS women were divided into two groups. Those with 17P responses that did not exceed the normal mean plus 2 standard deviations (normal responder PCOS; NR-PCOS) and those that did exceed the normal response (high responder PCOS; HR-PCOS). This separation occurred at a rate of 50%. Notably, serum AMH levels were 2-fold higher in NR-PCOS compared to HR-PCOS. This finding was puzzling as serum AMH levels have been shown to correlate to the number of small follicles present in ovaries suggesting that AMH may be a surrogate for small follicle number. However, both PCOS subgroups had equivalent follicle numbers. The investigators hypothesize that the NR-PCOS have greater number of small follicles compared to HR-PCOS. To address this issue the investigators propose to assess the number of small follicles in NR- and HR-PCOS women and normal controls.

In a secondary consideration the HR-PCOS group was heavier than the NR-PCOS. This implies that the HR-PCOS women may have had greater insulin resistance and hyperinsulinemia that may have contributed to the significantly higher 17P responses to hCG. As a result, the investigators will also perform an oral glucose tolerance test in all subjects.

Power Analysis Results of the investigators' pilot study have shown that approximately 50% of PCOS women will exhibit 17OHP responses to hCG stimulation similar to those of normal women. Consequently, a sample size of 20 subjects in each group has an 80% power to detect a difference in the means of 0.820 ng/ml (the difference between the average 17OHP expression level in high responder PCOS women (HR-PCOS), 2.840 ng/ml, and that of normal responder PCOS (NR-PCOS) women, 2.02 ng/ml), which is a 33% increase. In the proposed study, the investigators believe that HR-PCOS (n=20) will show significantly greater (33% more) 17OHP production in response to hCG stimulation than NR-PCOS (n=20) at a power of 0.8 and a type I error rate of 0.05. The investigators will recruit 25 subjects in each group to allow for subject drop out. A secondary analysis will be performed between women with PCOS and normal controls (n=20).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Polycystic Ovary Syndrome
Intervention  ICMJE Drug: hCG

3. On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms.

4. Blood samples will be obtained at T = -0.5, 0, and +24 hours.

Other Name: Re-combinant human choriogonadotropin
Study Arms  ICMJE
  • Active Comparator: Normal adult women
    1. Images of the both ovaries will be obtained using vaginal ultrasound and the number, size, and spatial arrangement of ovarian follicles will be noted for both ovaries in each subject.
    2. On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms.
    3. Blood samples will be obtained at T = -0.5, 0, and +24 hours.
    4. Blood sample will be used for DNA testing to identify genes that may be associated with androgen production.
    5. One to two weeks after hCG stimulation testing each subject will come to the CTRI for an Oral Glucose Tolerance Test (OGTT). Each subject will ingest 75 gm of a glucose solution and blood samples will be obtained at 0, 15, 30, 60, 120 and 180 minutes after the glucose load.
    Intervention: Drug: hCG
  • Active Comparator: Women with PCOS
    1. Images of the both ovaries will be obtained using vaginal ultrasound and the number, size, and spatial arrangement of ovarian follicles will be noted for both ovaries in each subject.
    2. On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms.
    3. Blood samples will be obtained at T = -0.5, 0, and +24 hours.
    4. Blood sample will be used for DNA testing to identify genes that may be associated with androgen production.
    5. One to two weeks after hCG stimulation testing each subject will come to the CTRI for an Oral Glucose Tolerance Test (OGTT). Each subject will ingest 75 gm of a glucose solution and blood samples will be obtained at 0, 15, 30, 60, 120 and 180 minutes after the glucose load.
    Intervention: Drug: hCG
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 8, 2019)
39
Original Estimated Enrollment  ICMJE
 (submitted: May 21, 2014)
40
Actual Study Completion Date  ICMJE January 2018
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects will be determined to have PCOS based on clinical history of irregular menses and clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on ultrasound
  2. Subjects should not have been on any hormonal therapy or metformin for at least 2 months prior to study start
  3. Subjects will be determined to be normal controls if they have a clinical history of regular periods

Exclusion Criteria:

  1. Women with hemoglobin less than 11 gm/dl at screening evaluation
  2. Women with untreated thyroid abnormalities
  3. Pregnant women or women who are nursing
  4. Women with BMI > 37
  5. Women with known sensitivity to the agents being used
  6. Women with diabetes, or renal, liver, or heart disease
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 37 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02145247
Other Study ID Numbers  ICMJE UCSD-140260
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jeffrey Chang, MD, University of California, San Diego
Study Sponsor  ICMJE University of California, San Diego
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: R. Jeffrey Chang, M.D. University of California, San Diego
PRS Account University of California, San Diego
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP