PubertyEarly Phase 1CRM003NCT00929006
Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism
A Early Phase 1 study testing Micronized progesterone suspension in people with Puberty and Hyperandrogenism, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is two-fold. (1) We will determine if in mid- to late pubertal girls without hyperandrogenism (HA), progesterone (P4) acutely reduces waking luteinizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. 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
- Puberty, Hyperandrogenism
- What is being tested?
- Micronized progesterone suspension
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to 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)
- For girls without hyperandrogenism: serum (calculated) free testosterone concentration within the Tanner stage-specific reference range and the absence of hirsutism
- For girls with hyperandrogenism: 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)
Show all 25Show fewer
- 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: Mild prolactin elevations may be seen in 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.)
- 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 such girls.
- 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.
- 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
Charlottesville, Virginia, 22908
Melissa Gilrain, 434-243-6911, pcos@virginia.edu
Christopher McCartney, MD
About this study
Official title: Study to Assess Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism
The purpose of this study is two-fold. (1) We will determine if in mid- to late pubertal girls without hyperandrogenism (HA), progesterone (P4) acutely reduces waking luteinizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. (2) We will determine if in mid- to late pubertal girls with HA, P4 will acutely suppress waking LH frequency to a lesser degree than it does in girls without HA.
Read the detailed description
This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypotheses: (1) In normal mid- to late pubertal girls without hyperandrogenism (HA), progesterone acutely suppresses waking LH pulse frequency more than sleep-associated LH pulse frequency; and (2) compared to normal mid- to late pubertal girls without HA, acute progesterone suppression of waking LH pulse frequency is impaired in mid- to late pubertal girls with HA. Studies will be performed in mid- to late pubertal girls (at least Tanner breast stage 3 but no more than 2 years postmenarcheal). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Immediately before and during the first CRU admission, either oral micronized progesterone (0.8 mg/kg/dose) or placebo (randomized) will be given at 0700, 1500, 2300, and 0700 h. During the 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. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo will exchanged for progesterone or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) Results in pubertal girls without HA were recently published (Kim et al, J Clin Endocrinol Metab 2018;103:1112-1121). Data from girls with HA will be compared to recently-published results in girls without HA. Mean LH pulse frequency while awake will be analyzed via a hierarchical linear mixed model (HLMM). HA status (HA vs. non-HA), sleep status (wake vs. sleep), and treatment (progesterone vs. placebo) will represent fixed-effects, along with all associated interactions. Random effects will be used to account for hierarchical variance-covariance structure of the crossover study design. With regard to hypothesis testing, the association between HA status and wake LH pulse frequency will be evaluated via linear contrasts of HLMM least squares pulse frequency means. The differential impact of exogenous progesterone on wake LH pulse frequency in pubertal girls with and without HA (primary analysis) will be evaluated via the same testing method. Using published and preliminary data, we determined that, if 16 pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.2 pulse/hour differential effect of P4 on wake LH pulse frequency between the HA and the non-HA groups with a two-sided false positive rejection rate of no more than 0.05.
- Conditions
- Puberty, Hyperandrogenism
- Being tested
- Micronized progesterone suspension, Placebo
- Keywords
- hyperandrogenemia, pubertal, polycystic ovary syndrome
- 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 progesterone suspensionDrug
Also called Progesterone
Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone.
PlaceboDrug
Placebo contains only inert ingredients and is not expected to exert any direct physiological effects
| Study group | Role | What they receive |
|---|---|---|
| Micronized progesterone suspension | Experimental | Micronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone. Receives: Drug: Micronized progesterone suspension |
| Placebo | Placebo comparator | Placebo contains only inert ingredients and is not expected to exert any direct physiological effects. Receives: 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 pulse frequency
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 posted26 Jun 2009 (estimated)
- Study startJun 2008
- 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PubertyStudies 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, crossover study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Christine Burt Solorzano, University of Virginia
- Investigators
- Christine M Burt Solorzano, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929006
- Sponsor's protocol ID
- 13717
- Acronym
- CRM003
- Status last verified
- Jul 2025
- First submitted
- 23 Jun 2009
- Last updated
- 5 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data from this study will be deposited in the NICHD Data and Specimen Hub "DASH." We will also provide raw study data (de-identified) as supplementary materials in manuscripts (e.g., see 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 \[PMCID in process\]).
Publications
Kim SH, Lundgren JA, Bhabhra R, Collins JS, Patrie JT, Burt Solorzano CM, Marshall JC, McCartney CR. Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1112-1121. doi: 10.1210/jc.2017-02299.
PubMed 29300925
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 Assess Acute Progesterone Suppression of Wake vs. Sleep Luteinizing Hormone Pulse Frequency in Pubertal Girls With and Without Hyperandrogenism
- ClinicalTrials.gov ID
- NCT00929006
- Acronym / sponsor ID
- CRM003 / 13717
- Conditions
- Puberty, Hyperandrogenism
- Keywords
- hyperandrogenemia, pubertal, polycystic ovary syndrome
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Jun 2008 (actual)
- Primary completion
- 1 Oct 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 26 Jun 2009 (estimated)
- 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 two-fold. (1) We will determine if in mid- to late pubertal girls without hyperandrogenism (HA), progesterone (P4) acutely reduces waking luteinizing hormone (LH) frequency to a greater extent than sleep-associated LH frequency. (2) We will determine if in mid- to late pubertal girls with HA, P4 will acutely suppress waking LH frequency to a lesser degree than it does in girls without HA.
Detailed description
This is a randomized, placebo-controlled, double-blinded crossover study to test the following hypotheses: (1) In normal mid- to late pubertal girls without hyperandrogenism (HA), progesterone acutely suppresses waking LH pulse frequency more than sleep-associated LH pulse frequency; and (2) compared to normal mid- to late pubertal girls without HA, acute progesterone suppression of waking LH pulse frequency is impaired in mid- to late pubertal girls with HA. Studies will be performed in mid- to late pubertal girls (at least Tanner breast stage 3 but no more than 2 years postmenarcheal). Subjects will complete two 18-hour Clinical Research Unit (CRU) admissions in separate menstrual cycles. Immediately before and during the first CRU admission, either oral micronized progesterone (0.8 mg/kg/dose) or placebo (randomized) will be given at 0700, 1500, 2300, and 0700 h. During the 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. A second CRU admission (performed at least 2 months later given blood withdrawal limits) will be identical to the first except that placebo will exchanged for progesterone or vice versa (treatment crossover). The primary endpoint is LH pulse frequency while awake. (LH pulse frequency while asleep is an important secondary endpoint.) Results in pubertal girls without HA were recently published (Kim et al, J Clin Endocrinol Metab 2018;103:1112-1121). Data from girls with HA will be compared to recently-published results in girls without HA. Mean LH pulse frequency while awake will be analyzed via a hierarchical linear mixed model (HLMM). HA status (HA vs. non-HA), sleep status (wake vs. sleep), and treatment (progesterone vs. placebo) will represent fixed-effects, along with all associated interactions. Random effects will be used to account for hierarchical variance-covariance structure of the crossover study design. With regard to hypothesis testing, the association between HA status and wake LH pulse frequency will be evaluated via linear contrasts of HLMM least squares pulse frequency means. The differential impact of exogenous progesterone on wake LH pulse frequency in pubertal girls with and without HA (primary analysis) will be evaluated via the same testing method. Using published and preliminary data, we determined that, if 16 pubertal girls with HA complete both admissions, we should have at least an 80% chance of detecting a 0.2 pulse/hour differential effect of P4 on wake LH pulse frequency between the HA and the non-HA groups 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 |
|---|---|---|
| Micronized progesterone suspension | Experimental | Drug: Micronized progesterone suspensionMicronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo contains only inert ingredients and is not expected to exert any direct physiological effects. |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Mid- to late pubertal adolescent girl (at least Tanner breast stage 3, but no more than 2 years postmenarcheal)
- For girls without hyperandrogenism: serum (calculated) free testosterone concentration within the Tanner stage-specific reference range and the absence of hirsutism
- For girls with hyperandrogenism: 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)
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 progesterone suspensionAlso: ProgesteroneMicronized progesterone 0.8 mg/kg at 0700, 1500, 2300 and 0700 h. Progesterone is a natural hormone. | Drug | Micronized progesterone suspension |
| PlaceboPlacebo contains only inert ingredients and is not expected to exert any direct physiological effects | Drug | Placebo |
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 pulse frequency
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.
- Derived from this study: PubMed 29300925Kim SH, Lundgren JA, Bhabhra R, Collins JS, Patrie JT, Burt Solorzano CM, Marshall JC, McCartney CR. Progesterone-Mediated Inhibition of the GnRH Pulse Generator: Differential Sensitivity as a Function of Sleep Status. J Clin Endocrinol Metab. 2018 Mar 1;103(3):1112-1121. doi: 10.1210/jc.2017-02299.
- Individual participant dataSharing planned: Undecided. Data from this study will be deposited in the NICHD Data and Specimen Hub "DASH." We will also provide raw study data (de-identified) as supplementary materials in manuscripts (e.g., see 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 M Burt Solorzano, 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 Micronized progesterone suspension in people with Puberty and Hyperandrogenism, 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 6 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 (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?
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?
On the ClinicalTrials.gov record for NCT00929006, which also lists 1 linked publication.
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.