Polycystic Ovary SyndromePhase 1CRM004NCT00930228
Effect of High Testosterone on Sleep-associated Slowing of Follicular Luteinizing Hormone (LH) Frequency in Polycystic Ovary Syndrome
A Phase 1 study testing Flutamide in people with Polycystic Ovary Syndrome, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to determine whether a testosterone receptor blocker (flutamide) will normalize sleep-wake luteinizing hormone pulse frequency relationships in women with polycystic ovary syndrome. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- Flutamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Aug 2024
- Phase
- 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 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects will be 18-35 years old; we use a cutoff age of 35 y because early menopause at this age is very rare.
- No significant health problems (other than PCOS and obesity).
- Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.
- Controls will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.
- PCOS will be defined according to NIH consensus criteria.
- As such, subjects with PCOS will have hyperandrogenism, whether it is clinical (e.g., hirsutism) or biochemical (i.e., elevated plasma T).
- Subjects with PCOS will also have oligo- or amenorrhea (i.e., < 7 periods per year) and no evidence for other endocrinopathies (e.g., hyperprolactinemia, Cushing's syndrome, etc.).
Who cannot join
- Being a study of GnRH pulse regulation in women with and without PCOS, men are excluded.
- Obesity associated with a diagnosed (genetic) syndrome, obesity related to medications (e.g., glucocorticoids), etc.
- Pregnancy or lactation.
- Virilization.
- A total testosterone > 150 ng/dl in women with PCOS (which suggests the possibility of a virilizing neoplasm) (confirmed on repeat).
- Elevated DHEAS (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in PCOS)(confirmed on repeat).
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- Follicular 17-hydroxyprogesterone > 300 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if elevated during the luteal phase and there is a concern about the possibility of congenital adrenal hyperplasia, the 17-hydroxyprogesterone may be collected during the follicular phase, or >60 if oligomenorrheic).
- NOTE: If a 17-hydroxyprogesterone > 300 ng/dl is confirmed on such repeat testing, an ACTH stimulated 17-hydroxyprogesterone < 1000 ng/dl will be required for study participation.
- A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl, or a hemoglobin A1c > 6.5%
- Abnormal TSH (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded; or, for a new diagnosis of hypothyroidism, further study will at the least be delayed pending appropriate treatment) (confirmed on repeat).
- Abnormal prolactin (mild elevations may be seen in PCOS, and elevations < 1.5 times the upper limit of normal will be accepted in this group) (confirmed on repeat).
- Evidence of Cushing's syndrome by history or physical exam.
- Hematocrit < 36% or hemoglobin < 12 g/dl (that is not reversed by iron treatment).
- Significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring intermittent systemic corticosteroids; etc.)
- Liver test abnormalities (confirmed on repeat), with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome.
- Abnormal sodium or potassium (confirmed on repeat); bicarbonate concentration <20 or >30 (confirmed on repeat); or elevated creatinine concentration (confirmed on repeat).
- Due to the amount of blood being drawn in the study, subjects with body weight < 110 lbs will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: Influence of Hyperandrogenemia on the Sleep-associated Slowing of Follicular LH Frequency in Adult Polycystic Ovary Syndrome
The purpose of this study is to determine whether a testosterone receptor blocker (flutamide) will normalize sleep-wake luteinizing hormone pulse frequency relationships in women with polycystic ovary syndrome.
Read the detailed description
During the follicular phase of the normal menstrual cycle, luteinizing hormone (LH) pulse frequency decreases during sleep. These decreases may be important to support follicle stimulating hormone (FSH) synthesis and secretion. Polycystic ovary syndrome (PCOS) is associated with a persistently rapid gonadotropin hormone-releasing hormone (GnRH) pulse frequency, an abnormality that may account for many of the hormonal manifestations of PCOS. Although one prior study suggests that nocturnal LH frequency decreases slightly in PCOS, methodological issues limit interpretation. Our preliminary data suggest that nocturnal LH frequency does not decrease in untreated PCOS, but that nocturnal decreases of LH frequency are restored with androgen receptor blockade (flutamide) in women with PCOS. We have two hypotheses: (1) Prior to flutamide administration, sleep-associated slowing of LH pulse frequency is less pronounced in women with PCOS compared to that of normally-cycling women in the late follicular phase of the menstrual cycle; (2) After 4 weeks of flutamide administration, sleep-associated LH frequency reduction in women with PCOS is similar to that of normally-cycling women in the late follicular phase of the menstrual cycle. Women with PCOS and normally-cycling women will be studied. For each study participant, LH pulse frequency will be determined (from 1500 to 0700 h) after 4 weeks of flutamide and after 4 weeks of placebo. Flutamide and placebo will be given in random order (i.e., cross-over study). Sleep will be formally evaluated. Flutamide will then be given for 4 weeks prior to reassessment of LH pulse frequency. LH pulse frequency will be analyzed by way of hierarchical mixed effect models. We will use statistical analyses to determine: (a) whether the wake vs. sleep difference in LH frequency is the same for PCOS and normal controls prior to flutamide, and (b) whether the mean wake vs. sleep difference in LH frequency is the same for the two groups after flutamide.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Flutamide, Placebo
- Keywords
- Luteinizing hormone, Testosterone
- 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.
FlutamideDrug
Also called Eulexin
Flutamide, 250 mg capsule for oral administration, twice a day for 4 weeks (or menstrual cycle length in normally-cycling controls)
PlaceboDrug
Placebo, for oral administration, twice a day for 4 weeks (or menstrual cycle length in normally-cycling controls)
| Study group | Role | What they receive |
|---|---|---|
| Flutamide | Experimental | Flutamide 250 mg taken by mouth twice a day for 4 weeks. Flutamide is an androgen-receptor blocker. Receives: Drug: Flutamide |
| 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 pulse frequency
Measured: One and two months
Secondary outcomes (4)
Luteinizing hormone pulse amplitude
Measured: One and two months
Mean luteinizing hormone level
Measured: One and two months
Mean follicle stimulating hormone level
Measured: One and two months
Sleep study parameters
Sleep study parameters (sleep stage, overnight ventilatory variables) will be assessed when available
Measured: One and two months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2009 (estimated)
- Study startJan 2009
- Primary completionMay 2024 (estimated)
- Study completionAug 2024 (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
- Phase 1
- Primary purpose
- Other
- 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
- 72 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
- Christopher R McCartney, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00930228
- Sponsor's protocol ID
- 14067
- Acronym
- CRM004
- Status last verified
- Nov 2023
- First submitted
- 24 Jun 2009
- Last updated
- 2 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We do not have current plans to share IPD
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
- Influence of Hyperandrogenemia on the Sleep-associated Slowing of Follicular LH Frequency in Adult Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT00930228
- Acronym / sponsor ID
- CRM004 / 14067
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Luteinizing hormone, Testosterone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- May 2024 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 30 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 to determine whether a testosterone receptor blocker (flutamide) will normalize sleep-wake luteinizing hormone pulse frequency relationships in women with polycystic ovary syndrome.
Detailed description
During the follicular phase of the normal menstrual cycle, luteinizing hormone (LH) pulse frequency decreases during sleep. These decreases may be important to support follicle stimulating hormone (FSH) synthesis and secretion. Polycystic ovary syndrome (PCOS) is associated with a persistently rapid gonadotropin hormone-releasing hormone (GnRH) pulse frequency, an abnormality that may account for many of the hormonal manifestations of PCOS. Although one prior study suggests that nocturnal LH frequency decreases slightly in PCOS, methodological issues limit interpretation. Our preliminary data suggest that nocturnal LH frequency does not decrease in untreated PCOS, but that nocturnal decreases of LH frequency are restored with androgen receptor blockade (flutamide) in women with PCOS. We have two hypotheses: (1) Prior to flutamide administration, sleep-associated slowing of LH pulse frequency is less pronounced in women with PCOS compared to that of normally-cycling women in the late follicular phase of the menstrual cycle; (2) After 4 weeks of flutamide administration, sleep-associated LH frequency reduction in women with PCOS is similar to that of normally-cycling women in the late follicular phase of the menstrual cycle. Women with PCOS and normally-cycling women will be studied. For each study participant, LH pulse frequency will be determined (from 1500 to 0700 h) after 4 weeks of flutamide and after 4 weeks of placebo. Flutamide and placebo will be given in random order (i.e., cross-over study). Sleep will be formally evaluated. Flutamide will then be given for 4 weeks prior to reassessment of LH pulse frequency. LH pulse frequency will be analyzed by way of hierarchical mixed effect models. We will use statistical analyses to determine: (a) whether the wake vs. sleep difference in LH frequency is the same for PCOS and normal controls prior to flutamide, and (b) whether the mean wake vs. sleep difference in LH frequency is the same for the two groups after flutamide.
Study design
- Primary purpose
- Other
- 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 |
|---|---|---|
| Flutamide | Experimental | Drug: FlutamideFlutamide 250 mg taken by mouth twice a day for 4 weeks. Flutamide is an androgen-receptor blocker. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo contains only inert ingredients and is not expected to exert any direct physiological effects. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subjects will be 18-35 years old; we use a cutoff age of 35 y because early menopause at this age is very rare.
- No significant health problems (other than PCOS and obesity).
- Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.
- Controls will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.
- PCOS will be defined according to NIH consensus criteria.
Key exclusion criteria (17 listed)
- Being a study of GnRH pulse regulation in women with and without PCOS, men are excluded.
- Obesity associated with a diagnosed (genetic) syndrome, obesity related to medications (e.g., glucocorticoids), etc.
- Pregnancy or lactation.
- Virilization.
- A total testosterone > 150 ng/dl in women with PCOS (which suggests the possibility of a virilizing neoplasm) (confirmed on repeat).
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 |
|---|---|---|
| FlutamideAlso: EulexinFlutamide, 250 mg capsule for oral administration, twice a day for 4 weeks (or menstrual cycle length in normally-cycling controls) | Drug | Flutamide |
| PlaceboPlacebo, for oral administration, twice a day for 4 weeks (or menstrual cycle length in normally-cycling controls) | Drug | Placebo |
Primary outcome
Luteinizing hormone pulse frequency
Time frame: One and two months
4 secondary outcomes
Luteinizing hormone pulse amplitude
Time frame: One and two months
Mean luteinizing hormone level
Time frame: One and two months
Mean follicle stimulating hormone level
Time frame: One and two months
Sleep study parameters
Time frame: One and two months
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: Undecided. We do not have current plans to share IPD
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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 R 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 Phase 1 study testing Flutamide 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 7 inclusion and 17 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Luteinizing hormone pulse frequency (time frame: One and two months). 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.