Adrenal HyperplasiaNCT01313455
Adrenal Hyperplasia Among Young People With PCOS
An observational study of Adrenal Hyperplasia and Polycystic Ovarian Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Background: Polycystic ovarian syndrome (PCOS) is a group of disorders related to problems with the secretion of certain hormones, which can lead to reproductive and other issues in women. Frequent complications of PCOS include irregular menstruation, development of ovarian cysts, and insulin resistance. Read more about this study
- Who is it for?
- Ages 16 to 29 years, women only
- Conditions the study is for
- Adrenal Hyperplasia, Polycystic Ovarian Syndrome, Oligomenorrhea
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Mar 2011to 24 Oct 2017
- Phase
- Observational
- 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 16 to 29 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Women 16-24 years old with PCOS defined as biochemical hyperandrogenism with associated findings of either menstrual irregularity and /or polycystic ovaries on ultrasound; hyperandrogenism defined as elevation of any of the following androgens: free testosterone, total testosterone, DHEAS, DHEA, 17 0H progesterone, androstenedione, 17OH pregnenolone; a polycystic ovary on ultrasound should either have 12 follicles measuring 2-9 mm in diameter, or have an increased ovarian volume of 10 CC or greater; menstrual irregularity defined as: Amenorrhea refers to absence of bleeding for at least three usual cycle lengths; oligomenorrhea refers to bleeding that occurs at an interval greater than 35 days.
- We would like patients to have oligomenorrhea for at least six usual cycle lengths. Patients have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study
- Women 18-25 years old with normal menstrual function; they have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study.
Who cannot join
- Patients who have hyperandrogenism due to 21 hydroxylase deficiency non- classic adrenal hyperplasia androgen secreting neoplasms
- Women with known or suspected androgenic/anabolic drug use
- Women with severe insulin resistance-acanthosis nigricans syndrome; Fasting insulin levels are obtained to rule out syndromes of severe insulin resistance and hyperandrogenism; if insulin is above 80 mU/mL in the fasting state, and/or >300 mU/mL following a 2- or 3-hour oral glucose tolerance test (obtained elsewhere), patients are not eligible.
- Women with thyroid dysfunction, hyperprolactinemia, (defined as prolactin level greater than or equal to 3 times the upper reference limit), less than 2 years post menarche, and patients on medications that alter steroidogenesis such as oral contraceptive pills, for less than a month prior to the date of inclusion in the study. (see above: patients have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study)
- Women with prior history of pregnancy.
- Young women with hyperandrogenemia, hirsutism or known adrenal tumors or other endocrine diseases, patients on multiple medications, known insulin resistance, or any other chronic or acute illness are not eligible as controls for this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Adrenal Hyperplasia Among Young Patients With Polycystic Ovarian Syndrome
Background:
- Polycystic ovarian syndrome (PCOS) is a group of disorders related to problems with the secretion of certain hormones, which can lead to reproductive and other issues in women. Frequent complications of PCOS include irregular menstruation, development of ovarian cysts, and insulin resistance. The adrenal glands, which sit on top of the kidney, are involved in the production of certain hormones and the regulation of steroid levels in the blood, and may be affected in women with PCOS. Researchers are interested in studying possible connections between the adrenal glands and PCOS in young women who have been diagnosed with PCOS and healthy volunteers with normal menstrual function.
Read more
Objectives:
- To investigate possible connections between adrenal gland steroid hormone secretion and polycystic ovarian syndrome.
Eligibility:
- Women between 16 and 29 years of age who have been diagnosed with PCOS, or who are healthy volunteers with normal menstrual function.
- Participants must be willing to discontinue the use of oral contraceptives or any other medications that alter steroid hormone production for at least 1 month before the start of the study.
Design:
- Participants will be screened with a physical examination, medical history, and blood and urine tests. All participants will also have a pelvic (ovarian) ultrasound.
- All participants will be admitted to the hospital for a 1-week testing period, which will involve the following tests:
- Regular blood draws for two 2-hour periods (late evening and early morning) to measure hormone levels
- Fasting blood draws with a dose of corticotropin to test the body's adrenal function
- Hormone level measurement following regular doses of dexamethasone (a drug that controls the function of the adrenal gland)
- Daily urine collection for 6 days.
- Other studies, such as imaging studies of the adrenal glands, may be conducted as required by the study researchers.
Read the detailed description
Polycystic ovarian syndrome (PCOS) is a heterogeneous group of disorders presenting with hyperandrogenism in adolescents and young women. The etiology of this condition remains unknown, despite its many identified links to insulin resistance, hypertension and metabolic syndrome, as well as its potential connection to the various forms of congenital adrenal hyperplasia (CAH).
The adrenal glands are the only source in the body of adrenocortical steroids. In normal physiology, the pituitary hormone ACTH regulates the secretion of glucocorticoids, while the secretion of mineralocorticoids is controlled by the renin-angiotensin system. In addition to these two steroids, the adrenal gland secretes lesser amounts of intermediate metabolites of these steroids, as well as the sex-steroids DHEA, DHEAS, androstenedione, testosterone, estrogen, and estrone. Dysregulated secretion of any of these hormones can be caused by the development of hyperplasia of the adrenocortical tissue, which may be mild and lead to specific clinical syndromes depending on the identity of the secreted hormones. Bilateral adrenocortical hyperplasia (BAH) is now an increasingly diagnosed cause of adrenal dysfunction.
We propose that there is a subgroup of patients with PCOS who actually have non-CAH primary forms of BAH. To investigate this possibility, we propose to study the hypothalamic-pituitary-adrenal axis (HPAA) over the next 2 years in 120 young girls and women (ages 16 to 25 years) that we will compare to 30 age- and race-matched normal females. Patients will be recruited primarily (although not exclusively) from a busy New York City clinic run by the Pediatric Endocrine Division at the Infants and Children's Hospital of Brooklyn at Maimonides and SUNY Downstate. All patients will undergo standard testing of the HPAA including oral low- and high-dose dexamethasone (DEX)-suppression testing (Liddle s test). Paradoxical rise of cortisol and/or other steroid metabolites in response to DEX is considered a sensitive test for the diagnosis of BAH. Patients with such responses will be molecularly investigated for the known causes of BAH (GNAS, PRKAR1A, PDE11A, PDE8B and other mutations).
The first goal of this study is to identify any possible contributions of the BAH phenotypes and genotypes to the pathophysiology of PCOS, a yet unknown factor in the etiology of this multifaceted disorder. The second goal is to perform a comparative analysis of the expression of large sets of genes in cells of these patients using gene arrays and other genetic analyses. This study will generate important information about the molecular pathways that are affected in this subgroup of patients with PCOS. Thirdly, this study will also allow for the collection of DNA from affected and non-affected relatives of the patients to perform genetic studies and identify causative genetic defects. Finally, the study is expected to lead to new diagnostic and therapeutic methods for at least certain forms of PCOS.
- Conditions
- Adrenal Hyperplasia, Polycystic Ovarian Syndrome, Oligomenorrhea, Obesity, Hyperandrogenism
- Keywords
- Oligomenorrhea, Adrenal Hyperplasia, Obesity, Hyperandrogenism, Polycystic Ovarian Syndrome, PCOS, Polycystic Ovary, Healthy Volunteer, HV
- Medical subject headings
- Adrenal Hyperplasia, Congenital, Polycystic Ovary Syndrome, Oligomenorrhea, Obesity, Hyperandrogenism
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2011 (estimated)
- Study start10 Mar 2011
- Study completion24 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Adrenal HyperplasiaStudies 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
- Observational
- Time perspective
- Prospective
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Maya B Lodish, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313455
- Sponsor's protocol ID
- 110119
- Other IDs
- 11-CH-0119
- Status last verified
- 24 Oct 2017
- First submitted
- 10 Mar 2011
- Last updated
- 31 May 2019
- Results posted
- No
Publications
Rosenfield RL. What every physician should know about polycystic ovary syndrome. Dermatol Ther. 2008 Sep-Oct;21(5):354-61. doi: 10.1111/j.1529-8019.2008.00217.x.
PubMed 18844713Karch S, Manzambi ZA, Salaun JJ. Field trials with Vectolex (Bacillus sphaericus) and Vectobac (Bacillus thuringiensis (H-14)) against Anopheles gambiae and Culex quinquefasciatus breeding in Zaire. J Am Mosq Control Assoc. 1991 Jun;7(2):176-9.
PubMed 1895075Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009 Apr;23(2):181-92. doi: 10.1016/j.beem.2008.10.014.
PubMed 19500762Gourgari E, Lodish M, Keil M, Sinaii N, Turkbey E, Lyssikatos C, Nesterova M, de la Luz Sierra M, Xekouki P, Khurana D, Ten S, Dobs A, Stratakis CA. Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2016 Sep;101(9):3353-60. doi: 10.1210/jc.2015-4019. Epub 2016 Jun 23.
PubMed 27336356
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adrenal Hyperplasia Among Young Patients With Polycystic Ovarian Syndrome
- ClinicalTrials.gov ID
- NCT01313455
- Acronym / sponsor ID
- 110119
- Conditions
- Adrenal Hyperplasia, Polycystic Ovarian Syndrome, Oligomenorrhea, Obesity, Hyperandrogenism
- Keywords
- Oligomenorrhea, Adrenal Hyperplasia, Obesity, Hyperandrogenism, Polycystic Ovarian Syndrome, PCOS, Polycystic Ovary, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 10 Mar 2011
- Study completion
- 24 Oct 2017
- First posted
- 11 Mar 2011 (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.
Background:
- Polycystic ovarian syndrome (PCOS) is a group of disorders related to problems with the secretion of certain hormones, which can lead to reproductive and other issues in women. Frequent complications of PCOS include irregular menstruation, development of ovarian cysts, and insulin resistance. The adrenal glands, which sit on top of the kidney, are involved in the production of certain hormones and the regulation of steroid levels in the blood, and may be affected in women with PCOS. Researchers are interested in studying possible connections between the adrenal glands and PCOS in young women who have been diagnosed with PCOS and healthy volunteers with normal menstrual function.
Objectives:
- To investigate possible connections between adrenal gland steroid hormone secretion and polycystic ovarian syndrome.
Eligibility:
- Women between 16 and 29 years of age who have been diagnosed with PCOS, or who are healthy volunteers with normal menstrual function.
- Participants must be willing to discontinue the use of oral contraceptives or any other medications that alter steroid hormone production for at least 1 month before the start of the study.
Design:
- Participants will be screened with a physical examination, medical history, and blood and urine tests. All participants will also have a pelvic (ovarian) ultrasound.
- All participants will be admitted to the hospital for a 1-week testing period, which will involve the following tests:
- Regular blood draws for two 2-hour periods (late evening and early morning) to measure hormone levels
- Fasting blood draws with a dose of corticotropin to test the body's adrenal function
- Hormone level measurement following regular doses of dexamethasone (a drug that controls the function of the adrenal gland)
- Daily urine collection for 6 days.
- Other studies, such as imaging studies of the adrenal glands, may be conducted as required by the study researchers.
Detailed description
Polycystic ovarian syndrome (PCOS) is a heterogeneous group of disorders presenting with hyperandrogenism in adolescents and young women. The etiology of this condition remains unknown, despite its many identified links to insulin resistance, hypertension and metabolic syndrome, as well as its potential connection to the various forms of congenital adrenal hyperplasia (CAH).
The adrenal glands are the only source in the body of adrenocortical steroids. In normal physiology, the pituitary hormone ACTH regulates the secretion of glucocorticoids, while the secretion of mineralocorticoids is controlled by the renin-angiotensin system. In addition to these two steroids, the adrenal gland secretes lesser amounts of intermediate metabolites of these steroids, as well as the sex-steroids DHEA, DHEAS, androstenedione, testosterone, estrogen, and estrone. Dysregulated secretion of any of these hormones can be caused by the development of hyperplasia of the adrenocortical tissue, which may be mild and lead to specific clinical syndromes depending on the identity of the secreted hormones. Bilateral adrenocortical hyperplasia (BAH) is now an increasingly diagnosed cause of adrenal dysfunction.
We propose that there is a subgroup of patients with PCOS who actually have non-CAH primary forms of BAH. To investigate this possibility, we propose to study the hypothalamic-pituitary-adrenal axis (HPAA) over the next 2 years in 120 young girls and women (ages 16 to 25 years) that we will compare to 30 age- and race-matched normal females. Patients will be recruited primarily (although not exclusively) from a busy New York City clinic run by the Pediatric Endocrine Division at the Infants and Children's Hospital of Brooklyn at Maimonides and SUNY Downstate. All patients will undergo standard testing of the HPAA including oral low- and high-dose dexamethasone (DEX)-suppression testing (Liddle s test). Paradoxical rise of cortisol and/or other steroid metabolites in response to DEX is considered a sensitive test for the diagnosis of BAH. Patients with such responses will be molecularly investigated for the known causes of BAH (GNAS, PRKAR1A, PDE11A, PDE8B and other mutations).
The first goal of this study is to identify any possible contributions of the BAH phenotypes and genotypes to the pathophysiology of PCOS, a yet unknown factor in the etiology of this multifaceted disorder. The second goal is to perform a comparative analysis of the expression of large sets of genes in cells of these patients using gene arrays and other genetic analyses. This study will generate important information about the molecular pathways that are affected in this subgroup of patients with PCOS. Thirdly, this study will also allow for the collection of DNA from affected and non-affected relatives of the patients to perform genetic studies and identify causative genetic defects. Finally, the study is expected to lead to new diagnostic and therapeutic methods for at least certain forms of PCOS.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 16 to 29 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Women 16-24 years old with PCOS defined as biochemical hyperandrogenism with associated findings of either menstrual irregularity and /or polycystic ovaries on ultrasound; hyperandrogenism defined as elevation of any of the following androgens: free testosterone, total testosterone, DHEAS, DHEA, 17 0H progesterone, androstenedione, 17OH pregnenolone; a polycystic ovary on ultrasound should either have 12 follicles measuring 2-9 mm in diameter, or have an increased ovarian volume of 10 CC or greater; menstrual irregularity defined as: Amenorrhea refers to absence of bleeding for at least three usual cycle lengths; oligomenorrhea refers to bleeding that occurs at an interval greater than 35 days.
- We would like patients to have oligomenorrhea for at least six usual cycle lengths. Patients have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study
- Women 18-25 years old with normal menstrual function; they have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study.
Key exclusion criteria (6 listed)
- Patients who have hyperandrogenism due to 21 hydroxylase deficiency non- classic adrenal hyperplasia androgen secreting neoplasms
- Women with known or suspected androgenic/anabolic drug use
- Women with severe insulin resistance-acanthosis nigricans syndrome; Fasting insulin levels are obtained to rule out syndromes of severe insulin resistance and hyperandrogenism; if insulin is above 80 mU/mL in the fasting state, and/or >300 mU/mL following a 2- or 3-hour oral glucose tolerance test (obtained elsewhere), patients are not eligible.
- Women with thyroid dysfunction, hyperprolactinemia, (defined as prolactin level greater than or equal to 3 times the upper reference limit), less than 2 years post menarche, and patients on medications that alter steroidogenesis such as oral contraceptive pills, for less than a month prior to the date of inclusion in the study. (see above: patients have to be off oral contraceptive pills or any other medications that alter steroidogenesis for at least one month prior to participating in the study)
- Women with prior history of pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2019.
- Background: PubMed 18844713Rosenfield RL. What every physician should know about polycystic ovary syndrome. Dermatol Ther. 2008 Sep-Oct;21(5):354-61. doi: 10.1111/j.1529-8019.2008.00217.x.
- Background: PubMed 1895075Karch S, Manzambi ZA, Salaun JJ. Field trials with Vectolex (Bacillus sphaericus) and Vectobac (Bacillus thuringiensis (H-14)) against Anopheles gambiae and Culex quinquefasciatus breeding in Zaire. J Am Mosq Control Assoc. 1991 Jun;7(2):176-9.
- Background: PubMed 19500762Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009 Apr;23(2):181-92. doi: 10.1016/j.beem.2008.10.014.
- Derived from this study: PubMed 27336356Gourgari E, Lodish M, Keil M, Sinaii N, Turkbey E, Lyssikatos C, Nesterova M, de la Luz Sierra M, Xekouki P, Khurana D, Ten S, Dobs A, Stratakis CA. Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2016 Sep;101(9):3353-60. doi: 10.1210/jc.2015-4019. Epub 2016 Jun 23.
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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.
Maya B Lodish, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adrenal Hyperplasia and Polycystic Ovarian Syndrome, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 3 inclusion and 6 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: finished, as of the sponsor's last update on 31 May 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01313455, which also lists 4 linked publications.
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 31 May 2019.