PCOSEarly Phase 1CRM010NCT04597099
Androgen Blockade and Progesterone Augmentation of Gonadotropin Secretion
A Early Phase 1 study testing Micronized progesterone, Flutamide and Estradiol patch in people with PCOS and Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
Trial summary
This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. Read more about this study
- Who is it for?
- Ages 18 to 30 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- PCOS, Polycystic Ovary Syndrome
- What is being tested?
- Micronized progesterone, Flutamide and Estradiol patch
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Oct 2022to 1 Oct 2025
- 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 18 to 30 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Post-pubertal (> 4 years post-menarche) adult woman aged 18-30 years
- PCOS, defined as clinical and/or laboratory evidence of hyperandrogenism (hirsutism and/or elevated serum [calculated] free testosterone concentration) plus ovulatory dysfunction (irregular menses, fewer than 9 per year), but without evidence for other potential causes of hyperandrogenism and/or ovulatory dysfunction
- General good health (excepting overweight, obesity, hyperandrogenism, PCOS, and adequately-treated hypothyroidism)
- Capable of and willing to provide informed consent
- Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period
Who cannot join
- Inability/incapacity to provide informed consent
- Males will be excluded (PCOS is unique to females)
- Age < 18 years or > 30 years (ovarian reserve may decrease beyond age 30)
- Obesity resulting from a well-defined endocrinopathy or genetic syndrome
- Positive pregnancy test or current lactation
- Evidence for non-physiologic or non-PCOS causes of hyperandrogenism and/or anovulation
Show all 24Show fewer
- Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly)
- Total testosterone > 150 ng/dl, which suggests the possibility of virilizing ovarian or adrenal tumor
- DHEA-S elevation > 1.5 times the upper reference range limit. Mild elevations may be seen in PCOS, and will be accepted in these groups
- Early morning 17-hydroxyprogesterone > 200 ng/dl measured in the follicular phase, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase, the 17-hydroxyprogesterone will be repeated during the follicular phase). NOTE: If a 17-hydroxyprogesterone > 200 ng/dl is confirmed on repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl performed by the subject's personal physician will be required for study participation.
- Abnormal thyroid stimulating hormone (TSH): Note that subjects with stable and adequately treated primary hypothyroidism, reflected by normal TSH values, will not be excluded.
- Hyperprolactinemia > 20% higher than the upper limit of normal. Mild prolactin elevations may be seen in women with PCOS, and elevations within 20% higher than the upper limit of normal will be accepted in this group.
- History and/or physical exam findings suggestive of Cushing's syndrome, adrenal insufficiency, or acromegaly
- History and/or physical exam findings suggestive of hypogonadotropic hypogonadism (e.g., symptoms of estrogen deficiency) including functional hypothalamic amenorrhea (which may be suggested by a constellation of symptoms including restrictive eating patterns, excessive exercise, psychological stress, etc.)
- Persistent hematocrit < 37% and hemoglobin < 12 g/dl
- Severe thrombocytopenia (platelets < 50,000 cells/microliter) or leukopenia (total white blood count < 4,000 cells/microliter)
- Previous diagnosis of diabetes, fasting glucose > or = 126 mg/dl, or a hemoglobin A1c > or = 6.5%
- Given that this study involves flutamide use, any liver panel abnormality will be grounds for exclusion
- Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure, asthma requiring intermittent systemic corticosteroids, etc.)
- Decreased renal function evidenced by GFR < 60 ml/min/1.73m2
- A personal history of breast, ovarian, or endometrial cancer
- History of allergy to micronized progesterone, flutamide, or transdermal estradiol
- BMI < 18 or > 40 kg/m2
- Due to the amount of blood being drawn, volunteers with body weight < 110 pounds must be excluded
Trial locations and contacts
1 site in 1 country.
Christopher M McCartney, MD contact
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22901
Melissa Gilrain, BS, 434-243-6911, pcos@virginia.edu
Christopher M McCartney, MD, 434-243-6911, cm2hq@virginia.edu
About this study
Official title: Ability of Androgen-receptor Blockade to Normalize Progesterone-induced Augmentation of Gonadotropin Secretion in PCOS (CRM010)
This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.
Read the detailed description
Women with PCOS appear to exhibit impaired progesterone (P4) augmentation of gonadotropin release (positive feedback), and this is at least partly independent of BMI differences. To test more directly the role of hyperandrogenemia/hyperandrogenism (HA), we will assess if the androgen-receptor blocker flutamide enhances P4 augmentation of gonadotropin release in estradiol (E2)-treated women with PCOS. We will study 10 women with PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study, with subjects undergoing two assessments of P4 positive feedback - once after 4 weeks' pretreatment with flutamide and once after 4-weeks' pretreatment with placebo (in random order). We will assess P4 positive feedback via frequent sampling for 16 hours. Subjects will be pretreated for 3 days (prior to CRU admission) with transdermal E2 (0.2 mg/day), starting no earlier than cycle day 7. Subjects will be admitted to the CRU the evening of day 3 of E2 treatment. Starting at 0200 h, blood will be collected for 16 hours. After 6 h of sampling (0800 h), subjects will receive a single oral dose of P4. A second CRU admission - performed at least 2 months later to permit adequate washout of flutamide (as needed) - will be identical to the first except that placebo pretreatment will be exchanged for flutamide pretreatment or vice versa. We will assess the P4-mediated augmentation of FSH release, with secondary endpoints including the P4-mediated augmentation of LH release. We hypothesize that in E2-pretreated women with PCOS, acute P4 augmentation of FSH release (positive feedback) will be enhanced by androgen-receptor blockade (flutamide).
- Conditions
- PCOS, Polycystic Ovary Syndrome
- Being tested
- Micronized progesterone, Placebo, Flutamide, Estradiol patch
- Keywords
- PCOS, 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.
Micronized progesteroneDrug
Also called progesterone
oral micronized progesterone suspension, 100 mg oral dose at 0800 during each study admission
PlaceboDrug
Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.
FlutamideDrug
Flutamide, 250 mg taken orally twice daily for four weeks before study admission.
Estradiol patchDrug
Also called Vivelle
Two 0.1 mg/day transdermal estradiol patches will be applied 3 days prior to each inpatient admission; on the morning of study admission, these two patches will be removed and immediately replaced with two new 0.1 mg/day patches.
| Study group | Role | What they receive |
|---|---|---|
| Flutamide | Experimental | Prior to the first or second admission (randomly determined), subjects will be pretreated for 4 weeks with Flutamide (250 mg twice daily) Receives: Drug: Micronized progesterone; Drug: Flutamide; Drug: Estradiol patch |
| Placebo | Placebo comparator | Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily). Receives: Drug: Micronized progesterone; Drug: Placebo; Drug: Estradiol patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean FSH concentration with progesterone administration
Change in mean FSH concentrations (post-progesterone FSH concentrations vs. pre-progesterone FSH concentrations)
Measured: After 4 weeks of placebo administration
Change in mean FSH concentration with progesterone administration
Change in mean FSH concentrations (post-progesterone FSH concentrations vs. pre-progesterone FSH concentrations)
Measured: After 4 weeks of flutamide administration
Secondary outcomes (2)
Change in mean LH concentration with progesterone administration
Change in mean LH concentrations (post-progesterone LH concentrations vs. pre-progesterone LH concentrations)
Measured: After 4 weeks of placebo administration
Change in mean LH concentration with progesterone administration
Change in mean LH concentrations (post-progesterone LH concentrations vs. pre-progesterone LH concentrations)
Measured: After 4 weeks of flutamide administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2020
- Study start26 Oct 2022
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Oct 2025 (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.
- 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
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, placebo-controlled, double-blinded, crossover study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Chris McCartney, University of Virginia
- Investigators
- Christopher M McCartney, MD, Principal investigator, Univsersity of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04597099
- Sponsor's protocol ID
- HSR200016
- Other IDs
- R01HD102060
- Acronym
- CRM010
- Status last verified
- Nov 2023
- First submitted
- 11 Oct 2020
- Last updated
- 2 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- 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 2 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ability of Androgen-receptor Blockade to Normalize Progesterone-induced Augmentation of Gonadotropin Secretion in PCOS (CRM010)
- ClinicalTrials.gov ID
- NCT04597099
- Acronym / sponsor ID
- CRM010 / HSR200016
- Conditions
- PCOS, Polycystic Ovary Syndrome
- Keywords
- PCOS, Polycystic Ovary Syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 26 Oct 2022 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 22 Oct 2020 (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.
This study is trying to find out if flutamide (a medication that blocks the effects of testosterone) may help normalize an aspect of pituitary function (specifically, gonadotropin surge generation) in PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study. The investigators hypothesize that in estradiol-pretreated women with PCOS, acute progesterone augmentation of FSH release (positive feedback) will be enhanced by flutamide.
Detailed description
Women with PCOS appear to exhibit impaired progesterone (P4) augmentation of gonadotropin release (positive feedback), and this is at least partly independent of BMI differences. To test more directly the role of hyperandrogenemia/hyperandrogenism (HA), we will assess if the androgen-receptor blocker flutamide enhances P4 augmentation of gonadotropin release in estradiol (E2)-treated women with PCOS. We will study 10 women with PCOS. This is a randomized, placebo-controlled, double-blinded, crossover study, with subjects undergoing two assessments of P4 positive feedback - once after 4 weeks' pretreatment with flutamide and once after 4-weeks' pretreatment with placebo (in random order). We will assess P4 positive feedback via frequent sampling for 16 hours. Subjects will be pretreated for 3 days (prior to CRU admission) with transdermal E2 (0.2 mg/day), starting no earlier than cycle day 7. Subjects will be admitted to the CRU the evening of day 3 of E2 treatment. Starting at 0200 h, blood will be collected for 16 hours. After 6 h of sampling (0800 h), subjects will receive a single oral dose of P4. A second CRU admission - performed at least 2 months later to permit adequate washout of flutamide (as needed) - will be identical to the first except that placebo pretreatment will be exchanged for flutamide pretreatment or vice versa. We will assess the P4-mediated augmentation of FSH release, with secondary endpoints including the P4-mediated augmentation of LH release. We hypothesize that in E2-pretreated women with PCOS, acute P4 augmentation of FSH release (positive feedback) will be enhanced by androgen-receptor blockade (flutamide).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, placebo-controlled, double-blinded, crossover study
| Arm | Type | Receives |
|---|---|---|
| Flutamide | Experimental | Drug: Micronized progesterone, Drug: Flutamide, Drug: Estradiol patchPrior to the first or second admission (randomly determined), subjects will be pretreated for 4 weeks with Flutamide (250 mg twice daily) |
| Placebo | Placebo comparator | Drug: Micronized progesterone, Drug: Placebo, Drug: Estradiol patchPrior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily). |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Post-pubertal (> 4 years post-menarche) adult woman aged 18-30 years
- PCOS, defined as clinical and/or laboratory evidence of hyperandrogenism (hirsutism and/or elevated serum [calculated] free testosterone concentration) plus ovulatory dysfunction (irregular menses, fewer than 9 per year), but without evidence for other potential causes of hyperandrogenism and/or ovulatory dysfunction
- General good health (excepting overweight, obesity, hyperandrogenism, PCOS, and adequately-treated hypothyroidism)
- Capable of and willing to provide informed consent
- Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period
Key exclusion criteria (24 listed)
- Inability/incapacity to provide informed consent
- Males will be excluded (PCOS is unique to females)
- Age < 18 years or > 30 years (ovarian reserve may decrease beyond age 30)
- Obesity resulting from a well-defined endocrinopathy or genetic syndrome
- Positive pregnancy test or current lactation
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 |
|---|---|---|
| Micronized progesteroneAlso: progesteroneoral micronized progesterone suspension, 100 mg oral dose at 0800 during each study admission | Drug | Flutamide, Placebo |
| PlaceboPlacebo contains only inert ingredients and is not expected to exert any direct physiological effects. | Drug | Placebo |
| FlutamideFlutamide, 250 mg taken orally twice daily for four weeks before study admission. | Drug | Flutamide |
| Estradiol patchAlso: VivelleTwo 0.1 mg/day transdermal estradiol patches will be applied 3 days prior to each inpatient admission; on the morning of study admission, these two patches will be removed and immediately replaced with two new 0.1 mg/day patches. | Drug | Flutamide, Placebo |
Primary outcome
Change in mean FSH concentration with progesterone administration
Time frame: After 4 weeks of placebo administration
Change in mean FSH concentrations (post-progesterone FSH concentrations vs. pre-progesterone FSH concentrations)
Change in mean FSH concentration with progesterone administration
Time frame: After 4 weeks of flutamide administration
Change in mean FSH concentrations (post-progesterone FSH concentrations vs. pre-progesterone FSH concentrations)
2 secondary outcomes
Change in mean LH concentration with progesterone administration
Time frame: After 4 weeks of placebo administration
Change in mean LH concentration with progesterone administration
Time frame: After 4 weeks of flutamide administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Christopher M McCartney, MD contact
Christopher M McCartney, MD principal investigator
Univsersity 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 Micronized progesterone, Flutamide and Estradiol patch in people with PCOS and 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 24 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 2 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. Some participants in this study may receive a placebo. 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 Gilrain, BS (4342436911, 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 mean FSH concentration with progesterone administration (time frame: After 4 weeks of placebo administration). The study lists 2 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 2 Nov 2023.