Polycystic Ovary SyndromePhase 4NCT03252223
Ovarian Response to Recombinant Follicle Stimulating Hormone in Women With PCOS
A Phase 4 study testing Recombinant Follicle Stimulating Hormone in people with Polycystic Ovary Syndrome and Healthy, run by University of California, San Diego at 1 site in United States.
Trial summary
Women with PCOS suffer from anovulation and, as a result, infertility. Efforts to clinically induce ovulation in these women using follicle stimulating hormone (FSH) administered subcutaneously seemingly requires prolonged administration compared to that of ovulatory women without PCOS. 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, Healthy, Anovulation
- What is being tested?
- Recombinant Follicle Stimulating Hormone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2017to 30 Jun 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 determined to have PCOS based on clinical history of irregular menses and clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on ultrasound OR
- Subjects determined to 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
- Women with any hormonal therapy or metformin for at least 2 months prior to study start.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92037
About this study
Official title: Ovarian Function in Women With Polycystic Ovary Syndrome
Women with PCOS suffer from anovulation and, as a result, infertility. Efforts to clinically induce ovulation in these women using follicle stimulating hormone (FSH) administered subcutaneously seemingly requires prolonged administration compared to that of ovulatory women without PCOS. The apparent differing ovarian responsiveness to FSH between PCOS and normal women has not been carefully studied. We propose to address this issue by performing a dose-response study and examine ovarian follicle (estrogen, E2) responses to FSH administered subcutaneously in women with PCOS compared to responses observed in normal women.
Read the detailed description
In women with polycystic ovary syndrome (PCOS) androgen excess is fundamental to the clinical and physiological alterations of this disorder. In particular, androgen overproduction induces distinctive PCO morphology and appears to influence follicle function. Studies conducted in animals and nonhuman primates have demonstrated that androgens increase follicle number and in small antral follicles enhance granulosa cell (GC) responsiveness to gonadotropin stimulation. However, androgens also have been shown to clearly inhibit GC aromatase activity, and in PCOS follicular fluid, androgen content is abnormally increased. Efforts to reconcile these differences are nonexistent. Moreover, appropriate clinical studies to examine the effects of androgen on follicle health in women are lacking. Excessive androgen exposure in women due to functional tumors or high-dose testosterone treatment in F-M transsexuals has been associated with PCO morphology. Use of androgen therapy to promote follicle growth prior to ovarian hyperstimulation in women undergoing in vitro fertilization has not provided consistent results. However, in these studies GC responses to FSH were not carefully assessed, study populations were exclusively women with previously poor ovarian responses to FSH, and women with PCOS were not included. In fact, there are essentially no clinical studies that have addressed in detail the impact of androgen on follicle function in normal or PCOS women. We hypothesize that androgen facilitates GC responses to FSH in normal women and androgen excess further amplifies follicle growth and function in women with PCOS. We propose to study the effect of increased ovarian androgen on follicle function by increasing intraovarian androgen accumulation using aromatase inhibition followed by FSH stimulation. The experiments in this project are designed to provide insight into whether androgen excess facilitates or interferes with follicle function and ovulation in women with PCOS.
- Conditions
- Polycystic Ovary Syndrome, Healthy, Anovulation, Hyperandrogenism
- Being tested
- Recombinant Follicle Stimulating Hormone
- Keywords
- polycystic ovary syndrome, anovulation, hyperandrogenism
- Medical subject headings
- Polycystic Ovary Syndrome, Anovulation, Hyperandrogenism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Follicle Stimulating HormoneDrug
A modified dose-response study will be done using recombinant FSH (r-FSH), injected sc for 3 days at any one dose. r-FSH will be administered at weight-adjusted doses equivalent to 37.5, 75, and 150 IU based on an average weight of 70 kg, which approximates the weight of the average woman in the United States according to the Centers for Disease Control. Therefore, the actual dose of r-FSH will be 0.53 IU/kg for the 37.5 dose group. Accordingly, r-FSH will be repeated at doses of 1.1 IU/kg and 2.2 IU/kg that are equivalent to 75 and 150 IU for a 70 kg subject. Each FSH stimulation test will be assigned randomly and be separated by an interval of 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Women with normal menses | Active comparator | Not described Receives: Drug: Recombinant Follicle Stimulating Hormone |
| Women with Polycystic Ovary Syndrome | Active comparator | Not described Receives: Drug: Recombinant Follicle Stimulating Hormone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in granulosa cell function in 24 hours intervals following FSH administration
Granulosa function will be assessed using estradiol and inhibin levels
Measured: Serum levels will be assessed daily during each 3 day FSH stimulation test and for five days following the initial FSH administration
Change in follicle count in following FSH administration
Number of ovarian follicles will be assessed by pelvic ultrasound
Measured: With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
Change in follicular size in following FSH administration
Size of ovarian follicles will be assessed by pelvic ultrasound
Measured: With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2017
- Study start2 Oct 2017
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Jeffrey Chang, MD, University of California, San Diego
- Investigators
- R. Jeffrey Chang, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03252223
- Sponsor's protocol ID
- 170684
- Other IDs
- P50HD012303, K12HD001259
- Status last verified
- Sep 2021
- First submitted
- 8 Aug 2017
- Last updated
- 8 Sep 2021
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ovarian Function in Women With Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT03252223
- Acronym / sponsor ID
- 170684
- Conditions
- Polycystic Ovary Syndrome, Healthy, Anovulation, Hyperandrogenism
- Keywords
- polycystic ovary syndrome, anovulation, hyperandrogenism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 2 Oct 2017 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 17 Aug 2017 (actual)
- Results
- Not posted in the source record
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 anovulation and, as a result, infertility. Efforts to clinically induce ovulation in these women using follicle stimulating hormone (FSH) administered subcutaneously seemingly requires prolonged administration compared to that of ovulatory women without PCOS. The apparent differing ovarian responsiveness to FSH between PCOS and normal women has not been carefully studied. We propose to address this issue by performing a dose-response study and examine ovarian follicle (estrogen, E2) responses to FSH administered subcutaneously in women with PCOS compared to responses observed in normal women.
Detailed description
In women with polycystic ovary syndrome (PCOS) androgen excess is fundamental to the clinical and physiological alterations of this disorder. In particular, androgen overproduction induces distinctive PCO morphology and appears to influence follicle function. Studies conducted in animals and nonhuman primates have demonstrated that androgens increase follicle number and in small antral follicles enhance granulosa cell (GC) responsiveness to gonadotropin stimulation. However, androgens also have been shown to clearly inhibit GC aromatase activity, and in PCOS follicular fluid, androgen content is abnormally increased. Efforts to reconcile these differences are nonexistent. Moreover, appropriate clinical studies to examine the effects of androgen on follicle health in women are lacking. Excessive androgen exposure in women due to functional tumors or high-dose testosterone treatment in F-M transsexuals has been associated with PCO morphology. Use of androgen therapy to promote follicle growth prior to ovarian hyperstimulation in women undergoing in vitro fertilization has not provided consistent results. However, in these studies GC responses to FSH were not carefully assessed, study populations were exclusively women with previously poor ovarian responses to FSH, and women with PCOS were not included. In fact, there are essentially no clinical studies that have addressed in detail the impact of androgen on follicle function in normal or PCOS women. We hypothesize that androgen facilitates GC responses to FSH in normal women and androgen excess further amplifies follicle growth and function in women with PCOS. We propose to study the effect of increased ovarian androgen on follicle function by increasing intraovarian androgen accumulation using aromatase inhibition followed by FSH stimulation. The experiments in this project are designed to provide insight into whether androgen excess facilitates or interferes with follicle function and ovulation in women with PCOS.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women with normal menses | Active comparator | Drug: Recombinant Follicle Stimulating Hormone |
| Women with Polycystic Ovary Syndrome | Active comparator | Drug: Recombinant Follicle Stimulating Hormone |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Subjects determined to have PCOS based on clinical history of irregular menses and clinical or laboratory evidence of hyperandrogenism and polycystic ovaries on ultrasound OR
- Subjects determined to have a clinical history of regular periods.
Key exclusion criteria (7 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 |
|---|---|---|
| Recombinant Follicle Stimulating HormoneA modified dose-response study will be done using recombinant FSH (r-FSH), injected sc for 3 days at any one dose. r-FSH will be administered at weight-adjusted doses equivalent to 37.5, 75, and 150 IU based on an average weight of 70 kg, which approximates the weight of the average woman in the United States according to the Centers for Disease Control. Therefore, the actual dose of r-FSH will be 0.53 IU/kg for the 37.5 dose group. Accordingly, r-FSH will be repeated at doses of 1.1 IU/kg and 2.2 IU/kg that are equivalent to 75 and 150 IU for a 70 kg subject. Each FSH stimulation test will be assigned randomly and be separated by an interval of 8 weeks. | Drug | Women with Polycystic Ovary Syndrome, Women with normal menses |
Primary outcome
Change in granulosa cell function in 24 hours intervals following FSH administration
Time frame: Serum levels will be assessed daily during each 3 day FSH stimulation test and for five days following the initial FSH administration
Granulosa function will be assessed using estradiol and inhibin levels
Change in follicle count in following FSH administration
Time frame: With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
Number of ovarian follicles will be assessed by pelvic ultrasound
Change in follicular size in following FSH administration
Time frame: With each dose tested, a pelvic ultrasound will be done before and 3 days after commencing FSH
Size of ovarian follicles will be assessed by pelvic ultrasound
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2021.
- Individual participant dataSharing planned: No
Related trials for Polycystic Ovary Syndrome
Recruiting
Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
Polycystic Ovary Syndrome (PCOS)
Recruiting
The Effects of the Mediterranean Diet and Synbiotics in Polycystic Ovary Syndrome
PCOS (Polycystic Ovary Syndrome)
Recruiting
Brown Adipose Tissue Modulation in Polycystic Ovary Syndrome Using Infrared Thermography
Polycystic Ovary Syndrome (PCOS)
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, MD 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 Phase 4 study testing Recombinant Follicle Stimulating Hormone in people with Polycystic Ovary Syndrome and Healthy, 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 2 inclusion and 7 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 8 Sep 2021. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in granulosa cell function in 24 hours intervals following FSH administration (time frame: Serum levels will be assessed daily during each 3 day FSH stimulation test and for five days following the initial FSH administration). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2021.