Polycystic Ovary SyndromeNCT01428193
Effects of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone
A study testing Flutamide, Progesterone and estrace in people with Polycystic Ovary Syndrome and Hyperandrogenism, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to understand the effects of elevated male hormones in adolescent girls and how they effect the development of polycystic ovary syndrome (PCOS). If the investigators understand the effects of elevated male hormones levels in girls, the investigators may be able to better treat girls with… Read more about this study
- Who is it for?
- Ages 13 to 17 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Hyperandrogenism
- What is being tested?
- Flutamide, Progesterone and estrace
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Aug 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 13 to 17 years
- Women only
- No healthy volunteers
- Child
Who may be able to join
- Girls ages 13 to 17
- Tanner IV or V stage of puberty
- Post-menarche
- Hyperandrogenemic (total testosterone > 0.4 ng/mL or free testosterone > 35 pmol/L) with or without hirsutism
- Normal aspartate aminotransferase/alanine aminotransferase (AST/ALT) (AST < 35 U/L, ALT < 55 U/L)
- Hemoglobin > 12 mg/dL or Hematocrit > 36%
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- Normal screening labs (with exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
- Sexually active subjects must agree to abstain or use double barrier contraception during the study
- Subjects must agree not to take any other medications during the course of the study without approval by the study investigators
Who cannot join
- Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
- Elevated AST/ALT (AST > 35 U/L, ALT > 55 U/L)
- Hemoglobin <12 mg/dL or hematocrit < 36%
- Weight < 32 kg
- History of liver disease, peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
- Pregnant or breastfeeding
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- On medications known to affect the reproductive axis within 3 months of the study (including oral contraceptive pills, metformin, and spironolactone)
- On medications known or likely to inhibit or induce CYP1A2 or CYP3A4 (please see "Restrictions on use of other drugs or treatments" section below for common examples of such drugs)
- Are currently participating in another study or have been in one in the last 30 days.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Research in Reproduction, University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: Effect of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenic Adolescent Girls (JCM021)
The purpose of this study is to understand the effects of elevated male hormones in adolescent girls and how they effect the development of polycystic ovary syndrome (PCOS). If the investigators understand the effects of elevated male hormones levels in girls, the investigators may be able to better treat girls with elevated male hormone levels and perhaps even learn how to prevent the development of PCOS. Females with elevated levels of male hormones respond differently to estrace (estradiol) and progesterone than females with normal male hormone levels. The investigators will be giving you estrogen and progesterone to see how you respond after the male hormone has been blocked by a medication called flutamide.
Read the detailed description
Similar to women with PCOS, girls with hyperandrogenemia have an increased frequency of LH pulses when compared to age matched controls. An ongoing study by our group is investigating whether the progesterone insensitivity of the GnRH pulse generator in adult women with PCOS is also seen in adolescent girls with hyperandrogenemia. Analysis of the data to date suggests that the hyperandrogenic adolescent girls have decreased hypothalamic progesterone sensitivity when compared to adolescent controls, with a subgroup (consisting of approximately half of the hyperandrogenic girls) having marked progesterone insensitivity similar to that seen in adult women with PCOS. These data have recently been published.
Given that androgens mediate hypothalamic progesterone insensitivity in adult women with PCOS, we hypothesize that androgens play a similar role in adolescent girls with hyperandrogenemia and that progesterone sensitivity can be restored with the use of the androgen receptor blocker flutamide.
Better understanding the effects of hyperandrogenemia in adolescence and its role in the development of PCOS will hopefully lead to improved prevention and treatment strategies for PCOS. This may prove increasingly important if the current epidemic in childhood obesity results in a growing number of girls with elevated androgen levels.
- Conditions
- Polycystic Ovary Syndrome, Hyperandrogenism
- Being tested
- Flutamide, Progesterone, estrace
- Keywords
- PCOS, hyperandrogenemia
- Medical subject headings
- Polycystic Ovary Syndrome, Hyperandrogenism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlutamideDrug
Subjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day.
ProgesteroneDrug
oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days
estraceDrug
Also called (estradiol)
0.5-1 mg once a day for seven days
| Study group | Role | What they receive |
|---|---|---|
| Flutamide, estrace, progesterone | Experimental | For flutamide, subjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day for approximately 3 weeks.
Subjects will be given oral estrace, 0.5-1 mg once a day for 7 days following the first overnight study admission.
Subjects will be given oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days following the first overnight study admission. Receives: Drug: Flutamide; Drug: Progesterone; Drug: estrace |
What is being measured
The primary outcome is the main question the study is designed to answer.
Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level
The primary outcome variable for the study is the slope of the percent change in LH pulses as a function of day 7 progesterone level.
Measured: 3 weeks after flutamide treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2011 (estimated)
- Study startSep 2006
- Primary completionAug 2017
- Study completionAug 2017
Why it stopped: Haven't enrolled participants since 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
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, John Marshall, University of Virginia
- Investigators
- Christopher R. McCartney, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01428193
- Sponsor's protocol ID
- 12632
- Other IDs
- U54HD028934-18
- Status last verified
- May 2018
- First submitted
- 29 Aug 2011
- Last updated
- 4 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Androgen Blockade on Sensitivity of the GnRH Pulse Generator to Suppression by Estradiol and Progesterone in Hyperandrogenic Adolescent Girls (JCM021)
- ClinicalTrials.gov ID
- NCT01428193
- Acronym / sponsor ID
- 12632
- Conditions
- Polycystic Ovary Syndrome, Hyperandrogenism
- Keywords
- PCOS, hyperandrogenemia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Haven't enrolled participants since 2010
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Sep 2006 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 2 Sep 2011 (estimated)
- Results
- Posted 4 Jun 2018
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 understand the effects of elevated male hormones in adolescent girls and how they effect the development of polycystic ovary syndrome (PCOS). If the investigators understand the effects of elevated male hormones levels in girls, the investigators may be able to better treat girls with elevated male hormone levels and perhaps even learn how to prevent the development of PCOS. Females with elevated levels of male hormones respond differently to estrace (estradiol) and progesterone than females with normal male hormone levels. The investigators will be giving you estrogen and progesterone to see how you respond after the male hormone has been blocked by a medication called flutamide.
Detailed description
Similar to women with PCOS, girls with hyperandrogenemia have an increased frequency of LH pulses when compared to age matched controls. An ongoing study by our group is investigating whether the progesterone insensitivity of the GnRH pulse generator in adult women with PCOS is also seen in adolescent girls with hyperandrogenemia. Analysis of the data to date suggests that the hyperandrogenic adolescent girls have decreased hypothalamic progesterone sensitivity when compared to adolescent controls, with a subgroup (consisting of approximately half of the hyperandrogenic girls) having marked progesterone insensitivity similar to that seen in adult women with PCOS. These data have recently been published.
Given that androgens mediate hypothalamic progesterone insensitivity in adult women with PCOS, we hypothesize that androgens play a similar role in adolescent girls with hyperandrogenemia and that progesterone sensitivity can be restored with the use of the androgen receptor blocker flutamide.
Better understanding the effects of hyperandrogenemia in adolescence and its role in the development of PCOS will hopefully lead to improved prevention and treatment strategies for PCOS. This may prove increasingly important if the current epidemic in childhood obesity results in a growing number of girls with elevated androgen levels.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Flutamide, estrace, progesterone | Experimental | Drug: Flutamide, Drug: Progesterone, Drug: estraceFor flutamide, subjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day for approximately 3 weeks. Subjects will be given oral estrace, 0.5-1 mg once a day for 7 days following the first overnight study admission. Subjects will be given oral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days following the first overnight study admission. |
Who may qualify
- Ages
- 13 to 17 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Girls ages 13 to 17
- Tanner IV or V stage of puberty
- Post-menarche
- Hyperandrogenemic (total testosterone > 0.4 ng/mL or free testosterone > 35 pmol/L) with or without hirsutism
- Normal aspartate aminotransferase/alanine aminotransferase (AST/ALT) (AST < 35 U/L, ALT < 55 U/L)
Key exclusion criteria (9 listed)
- Abnormal screening labs (with the exception of the expected hormonal abnormalities inherent in hyperandrogenemia)
- Elevated AST/ALT (AST > 35 U/L, ALT > 55 U/L)
- Hemoglobin <12 mg/dL or hematocrit < 36%
- Weight < 32 kg
- History of liver disease, peanut allergy, deep venous thrombosis, breast cancer, endometrial cancer, or cervical cancer
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 |
|---|---|---|
| FlutamideSubjects weighing > 50 kg will receive 250 mg orally twice a day, and subjects weighing < 50 kg will receive 125 mg orally twice a day. | Drug | Flutamide, estrace, progesterone |
| Progesteroneoral progesterone suspension (20 mg/ml, 25-100 mg) three times a day at 0700, 1500, and 2300 hr for seven days | Drug | Flutamide, estrace, progesterone |
| estraceAlso: (estradiol)0.5-1 mg once a day for seven days | Drug | Flutamide, estrace, progesterone |
Primary outcome
Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level
Time frame: 3 weeks after flutamide treatment
The primary outcome variable for the study is the slope of the percent change in LH pulses as a function of day 7 progesterone level.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 study testing Flutamide, Progesterone and estrace in people with Polycystic Ovary Syndrome 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 9 inclusion and 9 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: stopped early, as of the sponsor's last update on 4 Jun 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Slope of the Percent Change in Luteinizing Hormone (LH) Pulses as a Function of Day 7 Progesterone Level (time frame: 3 weeks after flutamide treatment). 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 4 Jun 2018.