HyperandrogenismEarly Phase 1CRM008NCT03068910
Hyperandrogenemia and Altered Day-night LH Pulse Patterns
A Early Phase 1 study testing Micronized progesterone and Spironolactone in people with Hyperandrogenism and Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism, androgen-receptor blockade (spironolactone) improves the ability of progesterone to acutely reduce waking luteinizing hormone pulse frequency (primary endpoint). Read more about this study
- Who is it for?
- Ages 10 to 17 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hyperandrogenism, Polycystic Ovary Syndrome, Puberty
- What is being tested?
- Micronized progesterone and Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2016to 1 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 10 to 17 years
- Women only
- Healthy volunteers accepted
- Child
Who may be able to join
- Mid- to late pubertal adolescent girl (at least Tanner breast stage 3, but no more than 2 years postmenarcheal)
- Hyperandrogenism, defined as a serum (calculated) free testosterone concentration greater than the Tanner stage-specific reference range and/or unequivocal evidence for hirsutism
- General good health (excepting overweight, obesity, hyperandrogenism, and adequately-treated hypothyroidism)
- Capable of and willing to provide informed assent (adolescents under age 16 years) and/or consent (adolescents over age 16 years; custodial parents or guardians of all adolescent volunteers)
- 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 (hyperandrogenism is unique to females)
- 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
- Evidence of virilization (e.g., rapidly progressive hirsutism, deepening of the voice, clitoromegaly)
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- 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 adolescent HA and 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 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 adolescents and women with HA/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 < 36% 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%
- Persistent liver panel abnormalities, with two exceptions. Mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome. Also, mild transaminase elevations may be seen in obesity/HA/PCOS; therefore, elevations < 1.5 times the upper limit of normal will be accepted in this group.
- 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 any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous cell skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years
- History of allergy to micronized progesterone or spironolactone
- Body mass index (BMI)-for-age percentile < 5% (underweight)
- Due to the amount of blood being drawn, adolescent volunteers with body weight < 25 kg will be excluded.
- Restrictions on use of other drugs or treatments: No medications known to affect the reproductive system, glucose metabolism, lipid metabolism, or blood pressure can be taken in the 2 months prior to the screening visit and in the 3 months prior to the start of the study medications. Such medications include oral contraceptive pills, progestins, metformin, systemic glucocorticoids, some antipsychotic medications, and sympathomimetics/stimulants (e.g., methylphenidate).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Virginia Clinical Research Unit
Charlottesville, Virginia, 22908
Melissa Gilrain, BS, 434-243-6911, mg7zb@uvahealth.org
Christine Burt Solorzano, M.D., 434-243-6911, cmb6w@virginia.edu
About this study
Official title: Study to Evaluate if Androgen-receptor Blockade (Spironolactone) Improves Progesterone-suppression of Wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism
The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism, androgen-receptor blockade (spironolactone) improves the ability of progesterone to acutely reduce waking luteinizing hormone pulse frequency (primary endpoint).
Read the detailed description
This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypothesis: In mid- to late pubertal girls with hyperandrogenism (HA), acute progesterone suppression of waking LH pulse frequency is greater after 2 weeks of spironolactone pretreatment compared to after 2 weeks of placebo pretreatment. We will only study mid- to late pubertal girls with HA (i.e., girls who would be candidates for therapeutic spironolactone use). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Subjects will be randomized to be pretreated for 2 weeks with either oral spironolactone (50 mg twice daily) or placebo prior to the first CRU admission. Immediately before and during each CRU admission, oral micronized progesterone (0.8 mg/kg/dose) will be given at 0700, 1500, 2300, and 0700 h. During each CRU admission, blood will be obtained every 10 minutes through an indwelling iv catheter from 1800 to 1200 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. Formal polysomnography will be performed during CRU admissions. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo pretreatment will exchanged for spironolactone pretreatment or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) The wake LH pulse frequency data from the spironolactone and placebo admissions will be analyzed via a hierarchical linear mixed model (HLMM). The admission (spironolactone vs. placebo) will represent the fixed effect factor of the HLMM. Random effects will be utilized to account for the hierarchical variance-covariance structure of the two-period cross-over design. Wake LH pulse frequency in response to exogenous progesterone will be compared between the spironolactone admission and the placebo admission via a linear contrast of the HLMM least squares LH pulse frequency means. A similar analysis will be performed for sleep-related LH pulse frequency. Using published and preliminary data, we determined that, if 16 mid- to late pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.35 pulse/hour mean within-subject difference in wake LH pulse frequency between the spironolactone and placebo admissions with a two-sided false positive rejection rate of no more than 0.05.
- Conditions
- Hyperandrogenism, Polycystic Ovary Syndrome, Puberty
- Being tested
- Micronized progesterone, Spironolactone, Placebo
- Keywords
- Hyperandrogenism, Polycystic ovary syndrome, Puberty
- Medical subject headings
- Hyperandrogenism, Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Micronized progesteroneDrug
Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.
SpironolactoneDrug
Spironolactone is an androgen-receptor blocker commonly used (off-label) for hyperandrogenism. The spironolactone dose will be 50 mg taken orally twice daily (for two weeks before admission to the Clinical Research Unit).
PlaceboDrug
Placebo contains only inert ingredients and is not expected to exert any direct physiological effects.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Prior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with spironolactone (50 mg twice daily). Receives: Drug: Micronized progesterone; Drug: Placebo |
| 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: Spironolactone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Luteinizing hormone (LH) pulse frequency
LH pulse frequency while awake vs. while asleep
Measured: During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start21 Jul 2016
- Primary completion1 Oct 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperandrogenismStudies 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, placebo-controlled, crossover study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 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, Christine Burt Solorzano, University of Virginia
- Investigators
- Christine Burt Solorzano, M.D., Principal investigator, University of Virginia Center for Research in Reproduction
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068910
- Sponsor's protocol ID
- 18489
- Other IDs
- P50HD028934
- Acronym
- CRM008
- Status last verified
- Jul 2025
- First submitted
- 23 Feb 2017
- Last updated
- 5 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We plan to share IPD. Data from this study will be deposited in the NICHD Data and Specimen Hub "DASH." We also plan to provide raw study data (de-identified) as supplementary materials in the resulting manuscript as was done for Kim SH, et al. Progesterone-mediated inhibition of the GnRH pulse generator: differential sensitivity as a function of sleep status. J Clin Endocrinol Metab 2018; 103: 1112-1121 \[PMCID in process\].
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study to Evaluate if Androgen-receptor Blockade (Spironolactone) Improves Progesterone-suppression of Wake Luteinizing Hormone Pulse Frequency in Pubertal Girls With Hyperandrogenism
- ClinicalTrials.gov ID
- NCT03068910
- Acronym / sponsor ID
- CRM008 / 18489
- Conditions
- Hyperandrogenism, Polycystic Ovary Syndrome, Puberty
- Keywords
- Hyperandrogenism, Polycystic ovary syndrome, Puberty
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 32 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
- 21 Jul 2016 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 3 Mar 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.
The purpose of this study is to determine if, in mid- to late pubertal girls with hyperandrogenism, androgen-receptor blockade (spironolactone) improves the ability of progesterone to acutely reduce waking luteinizing hormone pulse frequency (primary endpoint).
Detailed description
This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypothesis: In mid- to late pubertal girls with hyperandrogenism (HA), acute progesterone suppression of waking LH pulse frequency is greater after 2 weeks of spironolactone pretreatment compared to after 2 weeks of placebo pretreatment. We will only study mid- to late pubertal girls with HA (i.e., girls who would be candidates for therapeutic spironolactone use). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Subjects will be randomized to be pretreated for 2 weeks with either oral spironolactone (50 mg twice daily) or placebo prior to the first CRU admission. Immediately before and during each CRU admission, oral micronized progesterone (0.8 mg/kg/dose) will be given at 0700, 1500, 2300, and 0700 h. During each CRU admission, blood will be obtained every 10 minutes through an indwelling iv catheter from 1800 to 1200 h. This will allow full characterization of pulsatile LH secretion in addition to other hormone measurements. Formal polysomnography will be performed during CRU admissions. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo pretreatment will exchanged for spironolactone pretreatment or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) The wake LH pulse frequency data from the spironolactone and placebo admissions will be analyzed via a hierarchical linear mixed model (HLMM). The admission (spironolactone vs. placebo) will represent the fixed effect factor of the HLMM. Random effects will be utilized to account for the hierarchical variance-covariance structure of the two-period cross-over design. Wake LH pulse frequency in response to exogenous progesterone will be compared between the spironolactone admission and the placebo admission via a linear contrast of the HLMM least squares LH pulse frequency means. A similar analysis will be performed for sleep-related LH pulse frequency. Using published and preliminary data, we determined that, if 16 mid- to late pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.35 pulse/hour mean within-subject difference in wake LH pulse frequency between the spironolactone and placebo admissions with a two-sided false positive rejection rate of no more than 0.05.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, placebo-controlled, crossover study
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: Micronized progesterone, Drug: PlaceboPrior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with spironolactone (50 mg twice daily). |
| Placebo | Placebo comparator | Drug: Spironolactone, Drug: PlaceboPrior to the first or the second admission (randomly determined), participants will be pretreated for 2 weeks with placebo (twice daily). |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Mid- to late pubertal adolescent girl (at least Tanner breast stage 3, but no more than 2 years postmenarcheal)
- Hyperandrogenism, defined as a serum (calculated) free testosterone concentration greater than the Tanner stage-specific reference range and/or unequivocal evidence for hirsutism
- General good health (excepting overweight, obesity, hyperandrogenism, and adequately-treated hypothyroidism)
- Capable of and willing to provide informed assent (adolescents under age 16 years) and/or consent (adolescents over age 16 years; custodial parents or guardians of all adolescent volunteers)
- Willing to strictly avoid pregnancy with use of reliable non-hormonal methods during the study period
Key exclusion criteria (25 listed)
- Inability/incapacity to provide informed consent
- Males will be excluded (hyperandrogenism is unique to females)
- 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
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 progesteroneMicronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone. | Drug | Spironolactone |
| SpironolactoneSpironolactone is an androgen-receptor blocker commonly used (off-label) for hyperandrogenism. The spironolactone dose will be 50 mg taken orally twice daily (for two weeks before admission to the Clinical Research Unit). | Drug | Placebo |
| PlaceboPlacebo contains only inert ingredients and is not expected to exert any direct physiological effects. | Drug | Placebo, Spironolactone |
Primary outcome
Luteinizing hormone (LH) pulse frequency
Time frame: During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first)
LH pulse frequency while awake vs. while asleep
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2025.
- Individual participant dataSharing planned: Undecided. We plan to share IPD. Data from this study will be deposited in the NICHD Data and Specimen Hub "DASH." We also plan to provide raw study data (de-identified) as supplementary materials in the resulting manuscript as was done for Kim SH, et al. Progesterone-mediated inhibition of the GnRH pulse generator: differential sensitivity as a function of sleep status. J Clin Endocrinol Metab 2018; 103: 1112-1121 [PMCID in process].
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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.
Christine Burt Solorzano, M.D. principal investigator
University of Virginia Center for Research in Reproduction
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 and Spironolactone in people with Hyperandrogenism 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 25 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: looking for participants now, as of the sponsor's last update on 5 Aug 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melissa Gilrain, MS (434-243-6911, mg7zb@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Luteinizing hormone (LH) pulse frequency (time frame: During first CRU admission and during the second CRU admission (which occurs at least 2 months after the first)). 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 5 Aug 2025.