Polycystic Ovary SyndromeEarly Phase 1SHK001NCT03905603
Relative Contributions of Predictors of Hyperandrogenism in Older vs. Young Women With PCOS
A Early Phase 1 study testing ACTH and rhCG in people with Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
Trial summary
The objective of the study is to determine the relative contributions of four established predictors of hyperandrogenism (luteinizing hormone [LH] secretion, ovarian response to recombinant human chorionic gonadotropin [r-hCG] administration, adrenal response to adrenocorticotropic hormone [ACTH] administration, and… Read more about this study
- Who is it for?
- Ages 20 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- ACTH and rhCG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2019to 1 May 2026
- Phase
- Early Phase 1
- 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 20 to 49 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women with PCOS aged 20-30 years and 40-49 years. Subject is considered to have PCOS if she has current or verifiable history of: a) clinical and/or biochemical evidence of hyperandrogenism plus b) oligomenorrhea (average menstrual cycle length >45 days or fewer than 9 menses/year) or irregular menstruation (substantially inconsistent menstrual cycle length). Note: For subjects aged 40-49 years, they will be allowed to participate if they have fewer than 10 menses/year (average menstrual cycle length >35 days) as long as they have a compelling past history of oligomenorrhea or irregular menstruation.
- Screening safety labs within normal reference ranges although mild abnormalities that are common in obesity and/or hyperandrogenism will not be grounds for exclusion (see exclusion criteria).
- Subjects must be willing and able to provide written informed consent.
- Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of the study
- Willingness and ability to comply with scheduled visits and study procedures
Who cannot join
- Postmenopausal status (i.e., absence of periods for previous year plus elevated follicle stimulating hormone [FSH] level)
- Biochemical evidence for perimenopause as defined by an anti-Mullerian hormone <0.5 ng/mL. As an alternative, cycle day 3 FSH > 9 IU/L (with concomitant estradiol level >80 pg/mL), if this testing is available, will serve as evidence of perimenopause status. NOTE: If FSH >9 IU/L on screening (but it is not cycle day 3), FSH and estradiol will be repeated on cycle day 3.
- History of hysterectomy and/or bilateral oophorectomy
- BMI ≥ 40 kg/m2
- Inability to comprehend what will be done during the study or why it will be done.
- Being a study of older women with PCOS, children and men will be excluded.
Show all 32Show fewer
- Pregnancy or lactation within the past 6 months. Subjects with a positive pregnancy test will be informed of the result by the screening physician.
- Prisoners.
- History of (or clinical evidence for) Cushing's syndrome or adrenal insufficiency.
- History of congenital adrenal hyperplasia or 17-hydroxyprogesterone (17-OHP) >200 ng/dL, which suggest the possibility of congenital adrenal hyperplasia. 17-OHP will be collected during follicular phase. NOTE: if a 17-OHP >200 ng/dL and is confirmed on repeat testing, an ACTH-stimulated 17-OHP <1000 ng/dL will be required for study participation.
- Total testosterone >150 ng/dL, which suggests the possibility of virilizing neoplasm.
- DHEA-S greater than 1.5 times the upper limit of normal range (mild elevations may be seen in PCOS, so elevations < 1.5 times the upper limit of normal will be accepted in these groups).
- Virilization
- Diagnosis of diabetes mellitus (DM), fasting glucose ≥ 126 mg/dL, or a hemoglobin A1c of ≥ 6.5%.
- Abnormal thyroid stimulating hormone (TSH). Subjects with stable and adequately-treated hypothyroidism, reflected by normal TSH values, will not be excluded.
- Moderate to severe hyperprolactinemia. Mild prolactin elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in this group.
- Persistent liver abnormalities, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Mild transaminase elevations may be seen in women with obesity, so elevations <1.5 times the upper limit of normal will be accepted in this group.
- Hemoglobin level is less than 11 g/dL.
- Persistent hematocrit <36% and hemoglobin <12 g/dL.
- Subjects who remain anemic after two sequential months of ferrous gluconate (325 mg twice daily) will be excluded from study participation.
- Abnormal sodium, potassium, or bicarbonate concentrations or elevated creatinine concentration.
- Significant history of pulmonary dysfunction (e.g., asthma or COPD requiring intermittent systemic corticosteroid, pulmonary hypertension, etc.).
- History of known or suspected congestive heart failure.
- History of known or suspected ischemic heart disease or cerebrovascular disease.
- History of moderate to severe hypertriglyceridemia (triglyceride level > 500 mg/dL). Subjects with stable and adequately treated hypertriglyceridemia reflected by normal triglyceride values will not be excluded.
- History of breast, ovarian, or endometrial cancer.
- The cut off threshold for estimated dominant ovarian cyst size on the day of r-hCG injection will be 18 mm. Since the ultrasound will be assessed 3-4 days prior to r-hCG administration, we will estimate the size of the dominant follicle (at the time of r-hCG administration) using the typical rate of ovarian follicle growth of 1.4 mm per day. If the dominant follicle size exceeds the cut off threshold, the subject will be asked to repeat the transvaginal ultrasound: if menses begin within 3 weeks of the prior ultrasound, the ultrasound would be repeated during the new menstrual cycle. If menses do not occur within 3 weeks of the prior ultrasound, the ultrasound will then be scheduled at the subject's earliest convenience.
- Ovarian enlargement, defined by ovarian volume greater than 15 mm on transvaginal ultrasound. If the ovarian volume exceeds the cut off threshold, the participant will be given an option to repeat the transvaginal ultrasound in 2-3 months.
- History of venous thromboembolism (e.g. deep venous thrombosis (DVT), pulmonary embolism (PE)).
- History of blood clotting disorders (e.g., protein C, protein S, positive antiphospholipid antibodies).
- First-degree relative history of blood clotting disorder, unless the same disorder has been formally excluded for the study subject. Note: any abnormal labs may be repeated to exclude a lab error.
- No medications known to affect the reproductive system can be taken in the 2 months prior to screening and 3 months prior to the study. Such medications include oral contraceptive pills, metformin, progestins, glucocorticoids, anti-psychotics and/or mood stabilizers that are known to cause hormone abnormalities.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22901
Melissa Gilrain, BS, 434-243-6911, pcos@virginia.edu
Chris McCartney, MD, 434-243-6911, cm2hq@virginia.edu
About this study
The objective of the study is to determine the relative contributions of four established predictors of hyperandrogenism (luteinizing hormone [LH] secretion, ovarian response to recombinant human chorionic gonadotropin [r-hCG] administration, adrenal response to adrenocorticotropic hormone [ACTH] administration, and hyperinsulinemia) in older vs. young women with Polycystic Ovary Syndrome (PCOS) in a cross-sectional, physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS.
Read the detailed description
PCOS is a highly prevalent reproductive disorder characterized by hyperandrogenism (HA) and oligo/anovulation. PCOS is also associated with metabolic syndrome, obesity and insulin resistance. In young women with PCOS, several factors contribute to HA: a) excess LH secretion, b) abnormal ovarian steroidogenesis, c) abnormal adrenal steroidogenesis, and d) hyperinsulinemia/ insulin resistance. Of interest, HA (and menstrual function) improves with age in PCOS. However, the relative contributions of the aforementioned HA-related factors in young adult vs. late reproductive-aged women with PCOS are not known. Identifying the most important predictor(s) of HA in older women with PCOS will be critically important for devising the most relevant therapeutic strategies for older women with PCOS. The investigators propose to determine the relative contributions of four established predictors of HA (LH secretion, ovarian response to r-hCG administration, adrenal response to ACTH administration, and hyperinsulinemia) in older vs. young women with PCOS in a physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS. In addition, the investigators hypothesize that, in older vs. young women with PCOS: a) ovarian response to r-hCG will be a weaker independent predictor of free T; b) mean LH will be a stronger independent predictor of free T; and c) the predictive ability of adrenal response to ACTH will be similar. This will be a cross-sectional physiological study. Ordinary Least Square (OLS) regression will be utilized to determine the relative contributions of 4 established predictors of HA in older vs. young women with PCOS. Statistical plans include intra-age group hypothesis testing, inter-age group hypothesis testing, and a ranking of the importance of predictors in each age group.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- ACTH, rhCG
- Keywords
- Polycystic Ovary Syndrome
- 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.
ACTHDrug
Also called Cosyntropin
ACTH (Cosyntropin) 250 mcg will be given once during the study.
rhCGDrug
Also called Ovidrel
rhCG (Ovidrel) 250 mcg will be given once during the study.
| Study group | Role | What they receive |
|---|---|---|
| ACTH (Cosyntropin), rhCG (Ovidrel) | Experimental | ACTH (Cosyntropin) administered 250 mcg IV; rhCG (Ovidrel) administered 250 mcg IV Receives: Drug: ACTH; Drug: rhCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in calculated free testosterone concentrations
pg/mL
Measured: baseline, 30 mininutes and 1 hour after adrenocorticotropic hormone (ACTH), 24 hours after recombinant human chorionic gonadotropin (rhCG).
Mean luteinizing hormone (LH) concentrations
IU/L
Measured: overnight frequent blood sampling (every 10 mininutes for 12 hours)
Change in ovarian 17-hydroxyprogesterone to r-hCG
ng/mL
Measured: baseline, and 24 hours after receiving rhCG
Change in adrenal 17-hydroxyprogesterone to ACTH
ng/mL
Measured: baseline, 30 minutes, and 60 minutes after ACTH
Mean insulin level during oral glucose tolerance test
uIU/mL
Measured: during 2 hours of oral glucose tolerance test
Secondary outcomes (6)
Matsuda index
It is an index calculated by using glucose and insulin levels
Measured: during 2 hours of glucose tolerance test
LH pulse frequency
pulses/hour
Measured: overnight frequent blood sampling (every 10 minutes for 12 hours)
Change in dehydroepiandrosterone (DHEA) to r-hCG
ng/mL
Measured: baseline, and 24 hours after r-hCG
Change in DHEA to ACTH
ng/mL
Measured: baseline, 30 minutes and 1 hour after ACTH
Change in androstenedione to r-hCG
ng/mL
Measured: baseline, and 24 hours after r-hCG
Change in androstenedione to ACTH
ng/mL
Measured: baseline, 30 minutes and 1 hour after ACTH
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study start8 Oct 2019
- Primary completion1 Apr 2026 (estimated)
- Study completion1 May 2026 (estimated)
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 VirginiaThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a cross-sectional physiological observational study.
- Masking
- None (open label)
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chris McCartney, University of Virginia
- Investigators
- Chris McCartney, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03905603
- Sponsor's protocol ID
- 21723
- Acronym
- SHK001
- Status last verified
- Nov 2023
- First submitted
- 2 Apr 2019
- Last updated
- 3 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Contributions of Predictors of Hyperandrogenism in Older vs. Young Women With PCOS
- ClinicalTrials.gov ID
- NCT03905603
- Acronym / sponsor ID
- SHK001 / 21723
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Polycystic Ovary Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 8 Oct 2019 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 May 2026 (estimated)
- First posted
- 5 Apr 2019 (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.
The objective of the study is to determine the relative contributions of four established predictors of hyperandrogenism (luteinizing hormone [LH] secretion, ovarian response to recombinant human chorionic gonadotropin [r-hCG] administration, adrenal response to adrenocorticotropic hormone [ACTH] administration, and hyperinsulinemia) in older vs. young women with Polycystic Ovary Syndrome (PCOS) in a cross-sectional, physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS.
Detailed description
PCOS is a highly prevalent reproductive disorder characterized by hyperandrogenism (HA) and oligo/anovulation. PCOS is also associated with metabolic syndrome, obesity and insulin resistance. In young women with PCOS, several factors contribute to HA: a) excess LH secretion, b) abnormal ovarian steroidogenesis, c) abnormal adrenal steroidogenesis, and d) hyperinsulinemia/ insulin resistance. Of interest, HA (and menstrual function) improves with age in PCOS. However, the relative contributions of the aforementioned HA-related factors in young adult vs. late reproductive-aged women with PCOS are not known. Identifying the most important predictor(s) of HA in older women with PCOS will be critically important for devising the most relevant therapeutic strategies for older women with PCOS. The investigators propose to determine the relative contributions of four established predictors of HA (LH secretion, ovarian response to r-hCG administration, adrenal response to ACTH administration, and hyperinsulinemia) in older vs. young women with PCOS in a physiological study. The investigators hypothesize that hyperinsulinemia is a stronger independent predictor of free testosterone (T) in older reproductive aged (vs. young) women with PCOS. In addition, the investigators hypothesize that, in older vs. young women with PCOS: a) ovarian response to r-hCG will be a weaker independent predictor of free T; b) mean LH will be a stronger independent predictor of free T; and c) the predictive ability of adrenal response to ACTH will be similar. This will be a cross-sectional physiological study. Ordinary Least Square (OLS) regression will be utilized to determine the relative contributions of 4 established predictors of HA in older vs. young women with PCOS. Statistical plans include intra-age group hypothesis testing, inter-age group hypothesis testing, and a ranking of the importance of predictors in each age group.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a cross-sectional physiological observational study.
| Arm | Type | Receives |
|---|---|---|
| ACTH (Cosyntropin), rhCG (Ovidrel) | Experimental | Drug: ACTH, Drug: rhCGACTH (Cosyntropin) administered 250 mcg IV; rhCG (Ovidrel) administered 250 mcg IV |
Who may qualify
- Ages
- 20 to 49 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Women with PCOS aged 20-30 years and 40-49 years. Subject is considered to have PCOS if she has current or verifiable history of: a) clinical and/or biochemical evidence of hyperandrogenism plus b) oligomenorrhea (average menstrual cycle length >45 days or fewer than 9 menses/year) or irregular menstruation (substantially inconsistent menstrual cycle length). Note: For subjects aged 40-49 years, they will be allowed to participate if they have fewer than 10 menses/year (average menstrual cycle length >35 days) as long as they have a compelling past history of oligomenorrhea or irregular menstruation.
- Screening safety labs within normal reference ranges although mild abnormalities that are common in obesity and/or hyperandrogenism will not be grounds for exclusion (see exclusion criteria).
- Subjects must be willing and able to provide written informed consent.
- Willingness to strictly avoid pregnancy (using non-hormonal methods) during the time of the study
- Willingness and ability to comply with scheduled visits and study procedures
Key exclusion criteria (32 listed)
- Postmenopausal status (i.e., absence of periods for previous year plus elevated follicle stimulating hormone [FSH] level)
- Biochemical evidence for perimenopause as defined by an anti-Mullerian hormone <0.5 ng/mL. As an alternative, cycle day 3 FSH > 9 IU/L (with concomitant estradiol level >80 pg/mL), if this testing is available, will serve as evidence of perimenopause status. NOTE: If FSH >9 IU/L on screening (but it is not cycle day 3), FSH and estradiol will be repeated on cycle day 3.
- History of hysterectomy and/or bilateral oophorectomy
- BMI ≥ 40 kg/m2
- Inability to comprehend what will be done during the study or why it will be done.
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 |
|---|---|---|
| ACTHAlso: CosyntropinACTH (Cosyntropin) 250 mcg will be given once during the study. | Drug | ACTH (Cosyntropin), rhCG (Ovidrel) |
| rhCGAlso: OvidrelrhCG (Ovidrel) 250 mcg will be given once during the study. | Drug | ACTH (Cosyntropin), rhCG (Ovidrel) |
Primary outcome
Change in calculated free testosterone concentrations
Time frame: baseline, 30 mininutes and 1 hour after adrenocorticotropic hormone (ACTH), 24 hours after recombinant human chorionic gonadotropin (rhCG).
pg/mL
Mean luteinizing hormone (LH) concentrations
Time frame: overnight frequent blood sampling (every 10 mininutes for 12 hours)
IU/L
Change in ovarian 17-hydroxyprogesterone to r-hCG
Time frame: baseline, and 24 hours after receiving rhCG
ng/mL
Change in adrenal 17-hydroxyprogesterone to ACTH
Time frame: baseline, 30 minutes, and 60 minutes after ACTH
ng/mL
Mean insulin level during oral glucose tolerance test
Time frame: during 2 hours of oral glucose tolerance test
uIU/mL
6 secondary outcomes
Matsuda index
Time frame: during 2 hours of glucose tolerance test
LH pulse frequency
Time frame: overnight frequent blood sampling (every 10 minutes for 12 hours)
Change in dehydroepiandrosterone (DHEA) to r-hCG
Time frame: baseline, and 24 hours after r-hCG
Change in DHEA to ACTH
Time frame: baseline, 30 minutes and 1 hour after ACTH
Change in androstenedione to r-hCG
Time frame: baseline, and 24 hours after r-hCG
Change in androstenedione to ACTH
Time frame: baseline, 30 minutes and 1 hour after ACTH
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2023.
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.
Chris McCartney, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ACTH and rhCG in people with Polycystic Ovary Syndrome, run by University of Virginia 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 5 inclusion and 32 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 3 Nov 2023. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Melissa G Gilrain, BS (434-243-6911, pcos@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in calculated free testosterone concentrations (time frame: baseline, 30 mininutes and 1 hour after adrenocorticotropic hormone (ACTH), 24 hours after recombinant human chorionic gonadotropin (rhCG).). The study lists 5 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 3 Nov 2023.