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The Investigators will measure if hepatic metabolism is upregulated in obese girls with PCOS and hepatic steatosis (HS), compared to PCOS without HS and obese controls without HS.
This will be a cross-sectional study with 4 groups of youth. A 6 hour OSTT (Oral Sugar Tolerance Test) with an oral U-C13 glycerol tracer will be paired with nuclear magnetic resonance spectroscopy (NMR) isotopomer analysis of serum samples to describe flux through the hepatic pentose phosphate pathway, TCA cycle and FAS pathways in girls with PCOS receiving lifestyle only, metformin or oral contraceptive treatment, and obese girls with regular menses receiving lifestyle therapy. Hepatic steatosis will be measured with MRI.
Please note that 3 study groups: PCOS on metformin, PCOS on oral contraceptive treatment, and obese girls with regular menses were not funded in the study, so no participants were enrolled in these 3 arms of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Untreated PCOS | PCOS per NIH criteria. Obese Lifestyle treatment only. |
| |
| Metformin PCOS-(Study arm not funded) | PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months. |
| |
| Oral Contraceptive PCOS-(Study arm not funded) | PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months. |
| |
| Obese Control group-(Study arm not funded) | Obese Regular menses at least 18 months post-menarche Females only |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| oral glucose tolerance test | Diagnostic Test | 6 hours OGTT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hepatic Fat Fraction | Amount of fat in the liver measured by MRI and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. | Measured up to 4 months from enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Hepatic Metabolism Ratios | Percent indirect glucose at 360 minutes following an oral sugar tolerance test (OGTT) with an isotope labeled oral glycerol tracer. | Measured up to 4 months from enrollment |
| Whole Body Insulin Sensitivity |
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Inclusion Criteria:
Female
Ages 12-21
Sedentary- less than 2.5 hours of moderate (jogging, swimming etc) exercise a week.
BMI equal or greater than the 90th percentile for age and gender
For PCOS groups:
For PCOS groups:
For non-PCOS groups:
Exclusion Criteria:
Use of medications known to affect insulin sensitivity:
Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
Severe illness requiring hospitalization within 60 days
Diabetes, defined as Hemoglobin A1C > 6.4%
BMI percentile less than the 90th percentile for age and sex.
Weight >325 lbs or <84 lbs.
Anemia, defined as Hemoglobin < 10 mg/dL
Diagnosed major psychiatric or developmental disorder limiting informed consent
Implanted metal devices that are not compatible with MRI
Use of blood pressure medications
Known liver disease other than NAFLD or AST or ALT >150 mg/mL
-
Females only
Girls age 12-21. Obese >90th percentile for BMI for age.
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| Name | Affiliation | Role |
|---|---|---|
| Melanie Cree-Green, MD, PhD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anshutz Medical Campus/Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42014131 | Derived | Boster JM, Cree MG, Kelsey MM, Nadeau KJ, Chaidez A, Pan Z, Sundaram SS. Relative Skeletal Muscle Mass Is Associated With Hepatic Steatosis in Adolescents With Overweight and Obesity. Pediatr Obes. 2026 Apr;21(4):e70108. doi: 10.1111/ijpo.70108. | |
| 31301251 | Derived | Carreau AM, Pyle L, Garcia-Reyes Y, Rahat H, Vigers T, Jensen T, Scherzinger A, Nadeau KJ, Cree-Green M. Clinical prediction score of nonalcoholic fatty liver disease in adolescent girls with polycystic ovary syndrome (PCOS-HS index). Clin Endocrinol (Oxf). 2019 Oct;91(4):544-552. doi: 10.1111/cen.14062. Epub 2019 Aug 16. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Untreated PCOS | PCOS per NIH criteria. Obese Lifestyle treatment only. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| FG001 | Metformin PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| FG002 | Oral Contraceptive PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| FG003 | Obese Control Group-(Study Arm Not Funded) | Obese Regular menses at least 18 months post-menarche Females only oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Only participants enrolled in the untreated PCOS group. No participants were enrolled in the other arms of the study due to funding.
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| ID | Title | Description |
|---|---|---|
| BG000 | Untreated PCOS | PCOS per NIH criteria. Obese Lifestyle treatment only. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| BG001 | Metformin PCOS-(Study Arm Not Funded) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hepatic Fat Fraction | Amount of fat in the liver measured by MRI and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. | Adolescent females with dx of PCOS | Posted | Mean | Standard Deviation | Percent | Measured up to 4 months from enrollment |
|
9 days. Participants wore a couple of watches at home for 7 days and the metabolic study was 2 days long.
Adverse events only reported for the untreated PCOS group, since no participants were enrolled in the other groups.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Untreated PCOS | PCOS per NIH criteria. Obese Lifestyle treatment only. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
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Due to the Covid-19 outbreak, and lack of funding we were unable to enroll the participants in the metformin arm, oral contraceptive arm, and the obese control group. Only enrolled participants in untreated PCOS group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Melanie Cree-Green, PI | University of Colorado | 720-777-5743 | melanie.green@childrenscolorado.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 17, 2017 | May 4, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| D009765 | Obesity |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| ID | Term |
|---|---|
| D005951 | Glucose Tolerance Test |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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DNA for hepatic steatosis related genes
| MRI of liver | Diagnostic Test | MRI of the liver and use of DIXON method |
|
Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.
| Measured up to 4 months from enrollment |
| Sleep Duration | Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data. | Measured up to 4 months from enrollment |
| Sleep Quality | Apnea Hypopnea Index (AHI) will be measured using WatchPAT. The higher the AHI, indicates more severe sleep apnea. The AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep. Normal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour | Measured up to 4 months from enrollment |
| Hepatic Phosphate Concentrations | 31 phosphorus spectroscopy will be utilized to measure hepatic Phosphodiesterase (PDE)/Total phosphate concentration. This is measured in the MRI using a phosphorus coil. | Measured up to 4 months from enrollment |
PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.
oral glucose tolerance test: 6 hours OGTT
MRI of liver: MRI of the liver and use of DIXON method
| BG002 | Oral Contraceptive PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| BG003 | Obese Control Group-(Study Arm Not Funded) | Obese Regular menses at least 18 months post-menarche Females only oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Oral Contraceptive PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
| OG003 | Obese Control Group-(Study Arm Not Funded) | Obese Regular menses at least 18 months post-menarche Females only oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method |
|
|
| Secondary | Hepatic Metabolism Ratios | Percent indirect glucose at 360 minutes following an oral sugar tolerance test (OGTT) with an isotope labeled oral glycerol tracer. | Adolescent females with diagnosis of PCOS | Posted | Mean | Standard Deviation | percentage of indirect glucose | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Whole Body Insulin Sensitivity | Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model. | Adolescent females with dx of PCOS | Posted | Mean | Standard Deviation | dL/kg/min per uU/mL | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Sleep Duration | Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data. | Adolescent females with dx of PCOS | Posted | Mean | Standard Deviation | Minutes | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Sleep Quality | Apnea Hypopnea Index (AHI) will be measured using WatchPAT. The higher the AHI, indicates more severe sleep apnea. The AHI is the number of times you have apnea or hypopnea during one night, divided by the hours of sleep. Normal sleep: An AHI of fewer than five events, on average, per hour Mild sleep apnea: An AHI of five to 14 events per hour Moderate sleep apnea: An AHI of 15 to 29 events per hour Severe sleep apnea: An AHI of 30 or more events per hour | Adolescent females with dx of PCOS | Posted | Mean | Standard Deviation | Apnea Hypoxia Index | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Hepatic Phosphate Concentrations | 31 phosphorus spectroscopy will be utilized to measure hepatic Phosphodiesterase (PDE)/Total phosphate concentration. This is measured in the MRI using a phosphorus coil. | Untreated PCOS, All participants whom the scan worked for. Did not work in those with a large waist circumference | Posted | Mean | Standard Deviation | percentage of PDE/total phosphate | Measured up to 4 months from enrollment |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 0 |
| 17 |
| EG001 | Metformin PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method | 0 | 0 | 0 | 0 | 0 | 0 |
| EG002 | Oral Contraceptive PCOS-(Study Arm Not Funded) | PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months. oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method | 0 | 0 | 0 | 0 | 0 | 0 |
| EG003 | Obese Control Group-(Study Arm Not Funded) | Obese Regular menses at least 18 months post-menarche Females only oral glucose tolerance test: 6 hours OGTT MRI of liver: MRI of the liver and use of DIXON method | 0 | 0 | 0 | 0 | 0 | 0 |
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| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D003933 | Diagnosis |
| D003940 | Diagnostic Techniques, Endocrine |
| D008919 | Investigative Techniques |