PCOSNCT03489668
Androgen Responses to hCG and Ovarian Morphology in PCOS
A study testing MetFORMIN 500 Mg Oral Tablet in people with PCOS, run by Poznan University of Medical Sciences at 1 site in Poland.
Trial summary
Rationale and Hypothesis We have previously reported that theca cells (TC) responses to hCG in women with PCOS represent a spectrum where some exhibit exaggerated increases of 17OHP while in others 17OHP responses resemble those of normal women (Maas KH et al, JCEM, 2015). 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
- PCOS
- What is being tested?
- MetFORMIN 500 Mg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 sitePoland
- Study dates
- 20 Jan 2018to 31 Mar 2020
- Phase
- Interventional
- 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
- <8 spontaneous menses per year • hyperandrogenism clinically (Ferriman-Gallway score≥8 or total testosterone>0.5ng/ml).
Who cannot join
- CAH, hyperprolactinemia, thyroid disorder, Cushings syndrome, hypothalamic anovulation
Trial locations and contacts
1 site in 1 country.
Antoni Duleba, Prof contact
Poland1 site, 1 recruiting
- Recruiting
Division of Infertility and Reproductive Endocrinology, Department of Gynecology and Obsterics
Poznan
Beata Banaszewska, MD PhD, bbeata48@gmail.com
Mateusz Trzciński, MD, mtrzcinski13@gmail.com
About this study
Official title: The Relationship Between Theca Cell Responses to hCG and Ovarian Morphology in Women With PCOS Compared to Normal Women
Rationale and Hypothesis We have previously reported that theca cells (TC) responses to hCG in women with PCOS represent a spectrum where some exhibit exaggerated increases of 17OHP while in others 17OHP responses resemble those of normal women (Maas KH et al, JCEM, 2015). The basis for this differential responsiveness is not clear. Earlier studies reported that 17OHP responses to gonadotropin stimulation were heterogeneous among PCOS women, which was attributed to the degree of hyperinsulinemia (Pasquali R et al, JCEM, 2007). However, assessment of the ovary was omitted in the analysis. In preliminary studies, we have found that in women with PCOS, insulin sensitivity was strongly correlated with insulin sensitivity index as assessed by the method of Matsuda and DeFronzo (Diabetes Care, 1999). However, the study lacked sufficient numbers. Further analysis of insulin sensitivity with respect to hCG stimulated theca cell responses is warranted.
We have also examined 17OHP responses to hCG in relationship to antral follicle count and anti-Müllerian hormone (AMH) in PCOS and normal women. In PCOS women, as expected, serum AMH correlated with antral follicle count. However, TC responses in PCOS were inversely related to AMH (Maas KH et al, JCEM, 2015). These novel observations suggested that in PCOS AMH production may reflect redistribution of the follicle population. In human ovaries maximal immunodetection of AMH is observed in small (< 4 mm) antral follicles followed by a rapid and progressive decline until an absence of the protein by 8 mm (Weenen C et al, Mol Hum Reprod, 2004). This consideration raises the issue of whether normal AMH levels represent more advanced follicle growth in some PCOS women compared with that of others with elevated AMH levels. An increased stage of follicle development would be accompanied by increased TC hyperplasia and may account for greater 17OHP responses to hCG stimulation. A comparison of TC responses to hCG with ovarian morphology has not be done in women with PCOS.
Based on these findings, we hypothesize that in PCOS, heterogeneous TC responses to hCG reflect differences in morphometric development of the follicle population. In addition, the positive correlation between insulin sensitivity and TC responses to hCG suggest an effect of hyperinsulinemia. We propose to investigate the relationship between theca cell responses to hCG, follicle morphology, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.
Read the detailed description
50-100 PCOS and 50-100 normal women matched for age (<37 yr) and BMI (<35) will be studied. PCOS and normal women in the mid-follicular phase (day 5-7) of the menstrual cycle will receive an iv injection of hCG as previously described (see Experimental Design). Basal and stimulated blood samples will be assessed for 17OHP, androgens, gonadotropins and AMH. Detailed 3-D ultrasound imaging will be done prior to hCG stimulation (see Experimental Design). Ovarian morphology will include volume, antral follicle number, and the size of each follicle visualized.
Screening 100 women with PCOS and 100 normal women will be studied.
PCOS will be defined according to NIH criteria:
- <8 spontaneous menses per year
- hyperandrogenism clinically (Ferriman-Gallway score≥8 or total testosterone>0.5ng/ml).
- Absence of CAH, hyperprolactinemia, thyroid disorder, Cushings syndrome, hypothalamic anovulation.
Subjects will have a screening visit to establish eligibility and to sign the informed consent. They will have a history and physical examination performed which will include a urine pregnancy test, a transvaginal ultrasound, thyroid studies, a fasting chemistry panel, and a hemoglobin.
Experimental Design Phase 1 (Pretreatment)
- In all subjects images of the both ovaries will be obtained using 3D technology and the number, size, and spatial arrangement of ovarian follicles will be noted for both ovaries in each subject.
- Normal subjects will be studied during the mid-follicular phase of the cycle (Days 5-9) while PCOS women will be anovulatory and will not have a cycle day parameter.
- On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms.
- Blood samples will be obtained at 1 hour before (T = -1), immediately prior (T = 0), and 24 hours after (T = +24) iv hCG injection.
- Sera will be assayed at all time points for steroid and peptide hormones including 17OHP, androstenedione, testosterone, estradiol, progesterone, LH, FSH, and AMH.
- All subjects will undergo an oral glucose tolerance test. Each will be placed on a 300-gram carbohydrate diet for three days before the study. On the day of testing each subject will ingest 75 gm of a glucose solution and blood samples for glucose and insulin will be obtained at 0, 15, 30, 60, 120 and 180 minutes after the glucose load.
Phase 2 (Posttreatment)
- Each PCOS subject will be administered metformin, 1500 mg/day for 3 months. All subjects will be encouraged to maintain same dietary and exercise activity throughout the course of study.
- After 3 months of treatment, all tests as described in Phase 1 will be repeated.
- Conditions
- PCOS
- Being tested
- MetFORMIN 500 Mg Oral Tablet
- Keywords
- PCOS, Androgen, 3D ultrasound
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetFORMIN 500 Mg Oral TabletDrug
metformin administration 1500mg per day
| Study group | Role | What they receive |
|---|---|---|
| PCOS | Active comparator | Metformin administration 1500mg/day Receives: Drug: MetFORMIN 500 Mg Oral Tablet |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
17-OHP responses to hCG in PCOS and normal women
Demonstrating a relationship between theca cell responses to hCG, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.
Measured: 2 years
Secondary outcomes (1)
Ovarian morphology in PCOS and normal women
Demonstrating a relationship between theca cell responses to hCG and follicle morphology, before and following treatment with an insulin lowering drug, metformin.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2018
- Study start20 Jan 2018
- Primary completion31 Jan 2020 (estimated)
- Study completion31 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PCOSStudies of the same condition, open and under way.
- 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
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Poznan University of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, San Diego
- Responsible party
- Principal investigator, Beata Banaszewska, Poznan University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03489668
- Sponsor's protocol ID
- PoznanUMS6
- Status last verified
- Aug 2018
- First submitted
- 29 Mar 2018
- Last updated
- 9 Aug 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Theca Cell Responses to hCG and Ovarian Morphology in Women With PCOS Compared to Normal Women
- ClinicalTrials.gov ID
- NCT03489668
- Acronym / sponsor ID
- PoznanUMS6
- Conditions
- PCOS
- Keywords
- PCOS, Androgen, 3D ultrasound
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Poznan University of Medical SciencesUniversity, hospital or other
- Collaborators
- University of California, San Diego
- Study start
- 20 Jan 2018 (actual)
- Primary completion
- 31 Jan 2020 (estimated)
- Study completion
- 31 Mar 2020 (estimated)
- First posted
- 5 Apr 2018 (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.
Rationale and Hypothesis We have previously reported that theca cells (TC) responses to hCG in women with PCOS represent a spectrum where some exhibit exaggerated increases of 17OHP while in others 17OHP responses resemble those of normal women (Maas KH et al, JCEM, 2015). The basis for this differential responsiveness is not clear. Earlier studies reported that 17OHP responses to gonadotropin stimulation were heterogeneous among PCOS women, which was attributed to the degree of hyperinsulinemia (Pasquali R et al, JCEM, 2007). However, assessment of the ovary was omitted in the analysis. In preliminary studies, we have found that in women with PCOS, insulin sensitivity was strongly correlated with insulin sensitivity index as assessed by the method of Matsuda and DeFronzo (Diabetes Care, 1999). However, the study lacked sufficient numbers. Further analysis of insulin sensitivity with respect to hCG stimulated theca cell responses is warranted.
We have also examined 17OHP responses to hCG in relationship to antral follicle count and anti-Müllerian hormone (AMH) in PCOS and normal women. In PCOS women, as expected, serum AMH correlated with antral follicle count. However, TC responses in PCOS were inversely related to AMH (Maas KH et al, JCEM, 2015). These novel observations suggested that in PCOS AMH production may reflect redistribution of the follicle population. In human ovaries maximal immunodetection of AMH is observed in small (< 4 mm) antral follicles followed by a rapid and progressive decline until an absence of the protein by 8 mm (Weenen C et al, Mol Hum Reprod, 2004). This consideration raises the issue of whether normal AMH levels represent more advanced follicle growth in some PCOS women compared with that of others with elevated AMH levels. An increased stage of follicle development would be accompanied by increased TC hyperplasia and may account for greater 17OHP responses to hCG stimulation. A comparison of TC responses to hCG with ovarian morphology has not be done in women with PCOS.
Based on these findings, we hypothesize that in PCOS, heterogeneous TC responses to hCG reflect differences in morphometric development of the follicle population. In addition, the positive correlation between insulin sensitivity and TC responses to hCG suggest an effect of hyperinsulinemia. We propose to investigate the relationship between theca cell responses to hCG, follicle morphology, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.
Detailed description
50-100 PCOS and 50-100 normal women matched for age (<37 yr) and BMI (<35) will be studied. PCOS and normal women in the mid-follicular phase (day 5-7) of the menstrual cycle will receive an iv injection of hCG as previously described (see Experimental Design). Basal and stimulated blood samples will be assessed for 17OHP, androgens, gonadotropins and AMH. Detailed 3-D ultrasound imaging will be done prior to hCG stimulation (see Experimental Design). Ovarian morphology will include volume, antral follicle number, and the size of each follicle visualized.
Screening 100 women with PCOS and 100 normal women will be studied.
PCOS will be defined according to NIH criteria:
- <8 spontaneous menses per year
- hyperandrogenism clinically (Ferriman-Gallway score≥8 or total testosterone>0.5ng/ml).
- Absence of CAH, hyperprolactinemia, thyroid disorder, Cushings syndrome, hypothalamic anovulation.
Subjects will have a screening visit to establish eligibility and to sign the informed consent. They will have a history and physical examination performed which will include a urine pregnancy test, a transvaginal ultrasound, thyroid studies, a fasting chemistry panel, and a hemoglobin.
Experimental Design Phase 1 (Pretreatment)
- In all subjects images of the both ovaries will be obtained using 3D technology and the number, size, and spatial arrangement of ovarian follicles will be noted for both ovaries in each subject.
- Normal subjects will be studied during the mid-follicular phase of the cycle (Days 5-9) while PCOS women will be anovulatory and will not have a cycle day parameter.
- On study day one, recombinant-hCG (r-hCG) will be administered intravenously at a dose of 25 micrograms.
- Blood samples will be obtained at 1 hour before (T = -1), immediately prior (T = 0), and 24 hours after (T = +24) iv hCG injection.
- Sera will be assayed at all time points for steroid and peptide hormones including 17OHP, androstenedione, testosterone, estradiol, progesterone, LH, FSH, and AMH.
- All subjects will undergo an oral glucose tolerance test. Each will be placed on a 300-gram carbohydrate diet for three days before the study. On the day of testing each subject will ingest 75 gm of a glucose solution and blood samples for glucose and insulin will be obtained at 0, 15, 30, 60, 120 and 180 minutes after the glucose load.
Phase 2 (Posttreatment)
- Each PCOS subject will be administered metformin, 1500 mg/day for 3 months. All subjects will be encouraged to maintain same dietary and exercise activity throughout the course of study.
- After 3 months of treatment, all tests as described in Phase 1 will be repeated.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PCOS | Active comparator | Drug: MetFORMIN 500 Mg Oral TabletMetformin administration 1500mg/day |
| Control | No intervention | – |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- <8 spontaneous menses per year • hyperandrogenism clinically (Ferriman-Gallway score≥8 or total testosterone>0.5ng/ml).
Key exclusion criteria (1 listed)
- CAH, hyperprolactinemia, thyroid disorder, Cushings syndrome, hypothalamic anovulation
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 |
|---|---|---|
| MetFORMIN 500 Mg Oral Tabletmetformin administration 1500mg per day | Drug | PCOS |
Primary outcome
17-OHP responses to hCG in PCOS and normal women
Time frame: 2 years
Demonstrating a relationship between theca cell responses to hCG, and insulin sensitivity before and following treatment with an insulin lowering drug, metformin.
1 secondary outcome
Ovarian morphology in PCOS and normal women
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Individual participant dataSharing planned: Undecided
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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.
Antoni Duleba, Prof contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MetFORMIN 500 Mg Oral Tablet in people with PCOS, run by Poznan University of Medical Sciences at 1 site in Poland.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 9 Aug 2018. 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 Poland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Beata E Banaszewska, MD PhD (+48501303173, bbeata48@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
17-OHP responses to hCG in PCOS and normal women (time frame: 2 years). 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 9 Aug 2018.