ObesityCRM002NCT00928759
Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls
An observational study of Obesity and Hyperandrogenemia, run by University of Virginia at 1 site in United States.
Trial summary
The purpose of this study is to learn if obese pre- and early pubertal girls with hyperandrogenemia (HA) are more insulin resistant (i.e., have lower insulin-stimulated glucose disposal) compared to obese peripubertal girls without HA; and that overnight mean luteinizing hormone (LH) concentration is also an… Read more about this study
- Who is it for?
- Ages 8 to 16 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity, Hyperandrogenemia, Polycystic Ovary Syndrome
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Aug 2023
- 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 8 to 16 years
- Women only
- Healthy volunteers accepted
- Child
Study population: Generally healthy peripubertal girls ages 8 - 16 years with a BMI of > or = to 95th percentile will be recruited from the general population of the surrounding area.
Who may be able to join
- Peripubertal (Tanner stage 1 to 5) girl, age 8-16 years
- Obesity (BMI-for-age ≥ 95th percentile)
- Generally healthy (save for exogenous obesity)
- Ability and willingness of subject/parents to provide informed assent/consent
Who cannot join
- Age < 8 or > 16 y
- Greater than 4 y post-menarche
- Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
- Pregnancy or lactation
- Virilization
- Total testosterone > 150 ng/dl, which suggests the possibility of a virilizing neoplasm
Show all 18Show fewer
- DHEAS greater than twice upper limit of age-appropriate normal range
- 17-OHP greater than 250 ng/dl, which suggests the possibility of congenital adrenal hyperplasia (if postmenarcheal, the 17-OHP will be collected during the follicular phase, or > 60 if oligomenorrheic) NOTE: If a 17-OHP > 250 ng/dl is confirmed on repeat testing, an ACTH stimulation test will be offered, with a post-ACTH 17-OHP < 1000 ng/dl being required for study participation
- History of premature adrenarche (i.e., appearance of pubic and/or axillary hair before age 8)
- Fasting glucose > 125 mg/dl or hemoglobin A1c > 7.0%
- Abnormal TSH or prolactin
- Evidence of Cushing's syndrome by history or physical exam (e.g., history of impaired growth, striae)
- Hematocrit < 36% or hemoglobin < 12 g/dl
- Significant and current cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; asthma requiring systemic intermittent corticosteroids; etc.)
- Abnormal liver enzymes, age-specific alkaline phosphatase, or a bilirubin > 1.5 times upper limit of normal
- Abnormal sodium, potassium, bicarbonate concentrations, or elevated creatinine concentration
- Weight less than 34 kg is an exclusion criterion (to ensure safe blood withdrawal)
- Subjects using restricted medication (see restrictions below) are excluded unless the subject's primary care provider approves stopping the medication
Trial locations and contacts
1 site in 1 country.
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
The purpose of this study is to learn if obese pre- and early pubertal girls with hyperandrogenemia (HA) are more insulin resistant (i.e., have lower insulin-stimulated glucose disposal) compared to obese peripubertal girls without HA; and that overnight mean luteinizing hormone (LH) concentration is also an independent predictor of free testosterone concentrations, especially in mid- to late pubertal girls.
Read the detailed description
A number of pathophysiological mechanisms underlie the polycystic ovary syndrome (PCOS). Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA (which can represent a forerunner of adult PCOS) can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA-and the marked variability of androgen levels observed among obese girls-are unknown. We have gathered preliminary data that suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens.
The primary goal of this pilot project is to begin to establish the relationship between insulin resistance (as determined by insulin clamp studies) and free testosterone concentrations in obese peripubertal girls. Secondarily, the aim is to assess the contributions of elevated luteinizing hormone (determined by frequent blood sampling for LH) in obesity-associated HA across puberty.
Subjects will be admitted to the General Clinical Research Center at 1600 h after 4 hours of fasting. We will measure luteinizing hormone every 10 minutes from 1800 h to 0900 h; other hormones (e.g., testosterone) will be assessed as well. Measurements of insulin and glucose will occur before and after a standardized mixed meal (eaten at 1900 h) and while fasting the following morning. A standard hyperinsulinemic euglycemic clamp procedure will be performed from 0900-1100 h.
Characterization of the factors underlying peripubertal HA may permit prediction of which pre- and early pubertal girls will subsequently go on to develop symptoms of PCOS. Data generated by this project will prompt novel future studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.
- Conditions
- Obesity, Hyperandrogenemia, Polycystic Ovary Syndrome
- Keywords
- Obesity, Polycystic Ovary Syndrome
- Medical subject headings
- Obesity, Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| peripubertal obese girls | Peripubertal obese girls, aged 8 - 16 years, who are obese (BMI-for-age percentile greater or equal to 95) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morning free testosterone
Measured: 0700 to 0900 hours
Insulin-stimulated glucose disposal
Measured: 0900 to 1100 hours
Secondary outcomes (3)
Estimated 24-hour mean insulin concentration
Measured: 24 hours
Luteinizing hormone pulse frequency
Measured: 1800 to 0900 hours
Mean luteinizing hormone concentration
Measured: 1800 to 0900 hours
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 startMar 2008
- Primary completionMay 2023 (estimated)
- Study completionAug 2023 (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 ObesityStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 40 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, Chris McCartney, University of Virginia
- Investigators
- Christopher McCartney, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928759
- Sponsor's protocol ID
- 13552
- Other IDs
- P50HD028934
- Acronym
- CRM002
- Status last verified
- May 2022
- First submitted
- 28 Oct 2008
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We do not have current plans to share IPD
Publications
Burt Solorzano CM, Knudsen KL, Anderson AD, Hutchens EG, Collins JS, Patrie JT, Marshall JC, McCartney CR. Insulin Resistance, Hyperinsulinemia, and LH: Relative Roles in Peripubertal Obesity-Associated Hyperandrogenemia. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2571-2582. doi: 10.1210/jc.2018-00131.
PubMed 29897474
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Etiological Factors of Obesity-Associated Hyperandrogenemia in Peripubertal Girls
- ClinicalTrials.gov ID
- NCT00928759
- Acronym / sponsor ID
- CRM002 / 13552
- Conditions
- Obesity, Hyperandrogenemia, Polycystic Ovary Syndrome
- Keywords
- Obesity, Polycystic Ovary Syndrome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 40 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
- Mar 2008
- Primary completion
- May 2023 (estimated)
- Study completion
- Aug 2023 (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 to learn if obese pre- and early pubertal girls with hyperandrogenemia (HA) are more insulin resistant (i.e., have lower insulin-stimulated glucose disposal) compared to obese peripubertal girls without HA; and that overnight mean luteinizing hormone (LH) concentration is also an independent predictor of free testosterone concentrations, especially in mid- to late pubertal girls.
Detailed description
A number of pathophysiological mechanisms underlie the polycystic ovary syndrome (PCOS). Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA (which can represent a forerunner of adult PCOS) can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA-and the marked variability of androgen levels observed among obese girls-are unknown. We have gathered preliminary data that suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens.
The primary goal of this pilot project is to begin to establish the relationship between insulin resistance (as determined by insulin clamp studies) and free testosterone concentrations in obese peripubertal girls. Secondarily, the aim is to assess the contributions of elevated luteinizing hormone (determined by frequent blood sampling for LH) in obesity-associated HA across puberty.
Subjects will be admitted to the General Clinical Research Center at 1600 h after 4 hours of fasting. We will measure luteinizing hormone every 10 minutes from 1800 h to 0900 h; other hormones (e.g., testosterone) will be assessed as well. Measurements of insulin and glucose will occur before and after a standardized mixed meal (eaten at 1900 h) and while fasting the following morning. A standard hyperinsulinemic euglycemic clamp procedure will be performed from 0900-1100 h.
Characterization of the factors underlying peripubertal HA may permit prediction of which pre- and early pubertal girls will subsequently go on to develop symptoms of PCOS. Data generated by this project will prompt novel future studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| peripubertal obese girls | – | –Peripubertal obese girls, aged 8 - 16 years, who are obese (BMI-for-age percentile greater or equal to 95) |
Who may qualify
- Ages
- 8 to 16 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Generally healthy peripubertal girls ages 8 - 16 years with a BMI of > or = to 95th percentile will be recruited from the general population of the surrounding area.
Key inclusion criteria (4 listed)
- Peripubertal (Tanner stage 1 to 5) girl, age 8-16 years
- Obesity (BMI-for-age ≥ 95th percentile)
- Generally healthy (save for exogenous obesity)
- Ability and willingness of subject/parents to provide informed assent/consent
Key exclusion criteria (18 listed)
- Age < 8 or > 16 y
- Greater than 4 y post-menarche
- Obesity associated with a diagnosed (genetic) syndrome (e.g., Prader-Willi syndrome, leptin deficiency), obesity related to medications (e.g., glucocorticoids), etc.
- Pregnancy or lactation
- Virilization
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
Morning free testosterone
Time frame: 0700 to 0900 hours
Insulin-stimulated glucose disposal
Time frame: 0900 to 1100 hours
3 secondary outcomes
Estimated 24-hour mean insulin concentration
Time frame: 24 hours
Luteinizing hormone pulse frequency
Time frame: 1800 to 0900 hours
Mean luteinizing hormone concentration
Time frame: 1800 to 0900 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Derived from this study: PubMed 29897474Burt Solorzano CM, Knudsen KL, Anderson AD, Hutchens EG, Collins JS, Patrie JT, Marshall JC, McCartney CR. Insulin Resistance, Hyperinsulinemia, and LH: Relative Roles in Peripubertal Obesity-Associated Hyperandrogenemia. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2571-2582. doi: 10.1210/jc.2018-00131.
- 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 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?
An observational study of Obesity and Hyperandrogenemia, 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 4 inclusion and 18 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 18 May 2022. 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?
Results are not available in the source record.
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?
Morning free testosterone (time frame: 0700 to 0900 hours). The study lists 2 primary outcomes in all. 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 NCT00928759, 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 18 May 2022.