Polycystic Ovary SyndromeNCT02145247
Ovarian Morphology and Theca Cell Androgen Production in Women With Polycystic Ovary Syndrome (PCOS)
A study testing hCG in people with Polycystic Ovary Syndrome, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 37 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- hCG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Jan 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 37 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Subjects should not have been on any hormonal therapy or metformin for at least 2 months prior to study start
- Subjects will be determined to be normal controls if they have a clinical history of regular periods
Who cannot join
- Women with hemoglobin less than 11 gm/dl at screening evaluation
- Women with untreated thyroid abnormalities
- Pregnant women or women who are nursing
- Women with BMI > 37
- Women with known sensitivity to the agents being used
- Women with diabetes, or renal, liver, or heart disease
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92037
About this study
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.
Read the 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).
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- hCG
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hCGDrug
Also called Re-combinant human choriogonadotropin
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Normal adult women | Active comparator | 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. Receives: Drug: hCG |
| Women with PCOS | Active comparator | 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. Receives: Drug: hCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change of 17-OHP Levels From Baseline
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
Measured: before and 24 hours after adminisration of r-hCG
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2014 (estimated)
- Study startMay 2014
- Primary completionFeb 2017
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Chang, MD, University of California, San Diego
- Investigators
- R. Jeffrey Chang, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02145247
- Sponsor's protocol ID
- UCSD-140260
- Status last verified
- Aug 2019
- First submitted
- 20 May 2014
- Last updated
- 12 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 21270326Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Mar;91(3):941-5. doi: 10.1210/jc.2005-2076. Epub 2005 Dec 20.
PubMed 16368745Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, Duhamel A, Catteau-Jonard S. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod. 2011 Nov;26(11):3123-9. doi: 10.1093/humrep/der297. Epub 2011 Sep 16.
PubMed 21926054Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC. Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab. 2004 Jan;89(1):318-23. doi: 10.1210/jc.2003-030932.
PubMed 14715867
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Morphology and Theca Cell Androgen Production in Women With Polycystic Ovary Syndrome (PCOS)
- ClinicalTrials.gov ID
- NCT02145247
- Acronym / sponsor ID
- UCSD-140260
- Conditions
- Polycystic Ovary Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- May 2014 (actual)
- Primary completion
- Feb 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 22 May 2014 (estimated)
- Results
- Posted 12 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal adult women | Active comparator | Drug: hCG1. 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. |
| Women with PCOS | Active comparator | Drug: hCG1. 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. |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
- Subjects should not have been on any hormonal therapy or metformin for at least 2 months prior to study start
- Subjects will be determined to be normal controls if they have a clinical history of regular periods
Key exclusion criteria (6 listed)
- Women with hemoglobin less than 11 gm/dl at screening evaluation
- Women with untreated thyroid abnormalities
- Pregnant women or women who are nursing
- Women with BMI > 37
- Women with known sensitivity to the agents being used
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hCGAlso: Re-combinant human choriogonadotropin3. 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. | Drug | Normal adult women, Women with PCOS |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21270326Rosencrantz 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.
- Background: PubMed 16368745Pigny P, Jonard S, Robert Y, Dewailly D. Serum anti-Mullerian hormone as a surrogate for antral follicle count for definition of the polycystic ovary syndrome. J Clin Endocrinol Metab. 2006 Mar;91(3):941-5. doi: 10.1210/jc.2005-2076. Epub 2005 Dec 20.
- Background: PubMed 21926054Dewailly D, Gronier H, Poncelet E, Robin G, Leroy M, Pigny P, Duhamel A, Catteau-Jonard S. Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries. Hum Reprod. 2011 Nov;26(11):3123-9. doi: 10.1093/humrep/der297. Epub 2011 Sep 16.
- Background: PubMed 14715867Laven JS, Mulders AG, Visser JA, Themmen AP, De Jong FH, Fauser BC. Anti-Mullerian hormone serum concentrations in normoovulatory and anovulatory women of reproductive age. J Clin Endocrinol Metab. 2004 Jan;89(1):318-23. doi: 10.1210/jc.2003-030932.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R. Jeffrey Chang, M.D. principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hCG in people with Polycystic Ovary Syndrome, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change of 17-OHP Levels From Baseline (time frame: before and 24 hours after adminisration of r-hCG). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02145247, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2019.