Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| UL1TR001082 | U.S. NIH Grant/Contract | View source | |
| K23DK107871 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
Not provided
Not provided
Not provided
Not provided
Women with polycystic ovarian syndrome (PCOS) have increased rates of hepatic steatosis compared to weight similar women with regular menses. It is unclear if this is related to high testosterone or insulin resistance. The investigators will assess hepatic glucose release, rates of lipolysis and hepatic de novo lipogenesis in the fasted and postprandial state to determine if alterations in the processes contribute to hepatic steatosis. Participants will be overweight, sedentary girls with or without PCOS. Those with PCOS will either be medication naive, or must be taking metformin or combined oral contraceptives (COCPs) for a period of at least 6 months prior to study procedures.
Hepatic glucose release will be assessed with a stable isotope glycerol tracer, lipolysis with a glycerol tracer, and hepatic de novo lipogenesis with an acetate tracer. Data will be collected fasting and after a glucose challenge. The degree of hepatic steatosis and abdominal fat partitioning will be assessed with Magnetic Resonance Imaging (MRI), and total body composition with Dual-energy X-ray absorptiometry (DEXA).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PCOS, medication naive + Byetta | Experimental | PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. |
|
| Control | No Intervention | Up to 25 girls without PCOS | |
| PCOS medication naive | No Intervention | Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. | |
| PCOS on COCPs | No Intervention | Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. | |
| PCOS on metformin | No Intervention | Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Byetta 5Mcg Pen Injection | Drug | 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola |
|
| Measure | Description | Time Frame |
|---|---|---|
| Hepatic Glucose Release | Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia | Measured up to 4 months from enrollment |
| Measure | Description | Time Frame |
|---|---|---|
| Hepatic Phosphate Concentrations | Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy. The ratio of the following will be reported over total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 using SAMM II software. This software uses participant weight, glucose and insulin concentrations at various time points during the oral glucose tolerance test to calculate the participant insulin sensitivity. The higher the Si value means more insulin sensitivity. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Melanie Cree Green, MD, PhD | Department of Endocrinology | 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. |
Not provided
Not provided
Data will only be shared with IRB approved personnel.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Control | Up to 25 girls without PCOS. No participants received an intervention in this specific study. |
| FG001 | PCOS Medication Naive | Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. No participants received an intervention in this specific study. |
| FG002 | PCOS, Medication Naive + Byetta | PCOS, medication naive; These 10 participants received 2 doses of Byetta during their metabolic visit prior to the oral glucose tolerance testing. These participants recieved Byetta 5Mcg Pen Injection: 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola |
| FG003 | PCOS on COCPs | Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. No participants received an intervention in this specific study. |
| FG004 | PCOS on Metformin | Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures No participants received an intervention in this specific study. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Control | Up to 25 girls without PCOS |
| BG001 | PCOS Medication Naive | Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 Glucose Release | Hepatic glucose release will be measured by the rate of appearance of a glucose tracer. Glucose rate of appearance reflects the amount of glucose being release by primarily the liver during fasting. A higher glucose rate of appearance is often seen with dysglycemia | Not all participants had complete data to analyze the glucose RA. | Posted | Mean | Standard Deviation | mg/kg/min | Measured up to 4 months from enrollment |
|
Measured up to 4 months from enrollment
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Control | Up to 25 girls without PCOS | 0 |
Not provided
Not provided
Due to the Covid-19 outbreak, we were unable to enroll the last 4 participants in the PCOS on metformin arm, so the results may not reach statistical significance. We had delays in getting tracer results due to the mass spec machine being down, and once raw data was obtained, we needed to work with a mathematician to calculate the rates of appearance of the tracer results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Melanie Cree-Green, PI | University of Colorado Anschutz Medical Campus | 720-777-5743 | melanie.green@childrenscolorado.org |
Not provided
| 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 | Nov 26, 2018 | Apr 11, 2024 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D011085 | Polycystic Ovary Syndrome |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077270 | Exenatide |
| C058388 | penclomedine |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014688 | Venoms |
| D045424 | Complex Mixtures |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Measured up to 4 months from enrollment |
| Rates of Lipolysis | Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. Glycerol rate of appearance reflects the amount of glycerol being released into the blood stream as a results of lipolysis. Higher rates of lipolysis are thought to be associated with insulin resistance. | Measured up to 4 months from enrollment |
| 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 |
| Hepatic de Novo Lipogenesis | Hepatic de novo lipogenesis will be measured by with an acetate tracer by mass spectroscopy. De novo lipogenesis can contribute to non-alcoholic fatty liver disease, so having a lower value is better. | Measured up to 4 months from enrollment |
| Measured up to 4 months from enrollment |
| Sleep Quality | Apnea Hypopnea Index (AHI) will be measured using WatchPAT. In children and adolescents the scale that will be used is AHI>5 is considered mild sleep apnea. 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 |
| 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 |
| 30888398 | Derived | Simon SL, McWhirter L, Diniz Behn C, Bubar KM, Kaar JL, Pyle L, Rahat H, Garcia-Reyes Y, Carreau AM, Wright KP, Nadeau KJ, Cree-Green M. Morning Circadian Misalignment Is Associated With Insulin Resistance in Girls With Obesity and Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3525-3534. doi: 10.1210/jc.2018-02385. |
| Screen Failure |
|
| Nurse not able to place IV so unable to complete visit |
|
| BG002 | PCOS, Medication Naive + Byetta | PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola |
| BG003 | PCOS on COCPs | Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. |
| BG004 | PCOS on Metformin | Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | PCOS, Medication Naive + Byetta | PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola |
| OG003 | PCOS on COCPs | Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. |
| OG004 | PCOS on Metformin | Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures |
|
|
| Secondary | Hepatic Phosphate Concentrations | Hepatic phosphate relative concentrations will be measured with 31 phosphorus magnetic resonance spectroscopy. The ratio of the following will be reported over total phosphate concentration: Phosphodiesterase (PDE), phosphomonoester (PME), Adenosine triphosphate (ATP), Inorganic Phosphate (Pi),Nicotinamide adenine dinucleotide phosphate (NADPH), Uridine diphosphate glucose (UDPG) | The phosphorus coil for the liver was purchased towards the end of the study, so not all participants had the 31p measured. | Posted | Mean | Standard Deviation | ratio over total phosphate | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Rates of Lipolysis | Rate of lipolysis will be measured by the rate of appearance of a glycerol tracer. Glycerol rate of appearance reflects the amount of glycerol being released into the blood stream as a results of lipolysis. Higher rates of lipolysis are thought to be associated with insulin resistance. | Not all participants had complete data to analyze the glycerol RA. | Posted | Mean | Standard Deviation | mg/kg/min | Measured up to 4 months from enrollment |
|
|
|
| Secondary | 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. | Unable to analyze 2 participants in the PCOS medication naive group. One screen failed and the second who withdrew from the study. | Posted | Mean | Standard Deviation | percent fat | Measured up to 4 months from enrollment |
|
|
|
| Secondary | Hepatic de Novo Lipogenesis | Hepatic de novo lipogenesis will be measured by with an acetate tracer by mass spectroscopy. De novo lipogenesis can contribute to non-alcoholic fatty liver disease, so having a lower value is better. | Not everyone in the study received the acetate tracer. We had a problem with the analysis of the acetate tracer on 3 participants: 1 from the control group and 2 from the metformin group, so we did not obtain data for those 3 participants. | Posted | Mean | Standard Deviation | mg/dL | Measured up to 4 months from enrollment |
|
|
|
| Other Pre-specified | 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 using SAMM II software. This software uses participant weight, glucose and insulin concentrations at various time points during the oral glucose tolerance test to calculate the participant insulin sensitivity. The higher the Si value means more insulin sensitivity. | We were unable to calculate Si for some of the participants, because we were missing some lab values that are required for the formula. | Posted | Mean | Standard Deviation | dL/kg/min/μU/mL | Measured up to 4 months from enrollment |
|
|
|
| Other Pre-specified | Sleep Quality | Apnea Hypopnea Index (AHI) will be measured using WatchPAT. In children and adolescents the scale that will be used is AHI>5 is considered mild sleep apnea. 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 | The WatchPAT device was purchased towards the end of the study, so this was only used on a few participants for which results are reported here. | Posted | Mean | Standard Deviation | Apnea Hypopnea Index | Measured up to 4 months from enrollment |
|
|
|
| Other Pre-specified | Sleep Duration | Sleep duration will be assessed using home actigraphy using the Philips Actigraph wrist-worn watch, and collects 7 days of data. | Watch failed to record data on: 3 participants in the control group, 2 in the PCOS medication naive group, and 1 in the Byetta group. Two participants withdrew from the PCOS medication naive group. | Posted | Mean | Standard Deviation | minutes | Measured up to 4 months from enrollment |
|
|
|
| 24 |
| 0 |
| 24 |
| 0 |
| 24 |
| EG001 | PCOS Medication Naive | Up to 45 girls with PCOS with no exposure to hormone therapy or metformin in the preceding 6 months. | 0 | 42 | 0 | 42 | 0 | 42 |
| EG002 | PCOS, Medication Naive + Byetta | PCOS, medication naive; 10 girls with PCOS will receive 2 doses of Byetta. Byetta 5Mcg Pen Injection: 10 participants will receive 2 doses of Byetta, one at 7 PM the night prior to metabolic study and the second 30 min before ingestion of glucola | 0 | 10 | 0 | 10 | 0 | 10 |
| EG003 | PCOS on COCPs | Up to 10 girls with PCOS and 6 months of therapy with combined oral contraceptives (COCPs) prior to study procedures. | 0 | 10 | 0 | 10 | 0 | 10 |
| EG004 | PCOS on Metformin | Up to 10 girls with PCOS and 6 months of therapy with metformin prior to study procedures | 0 | 6 | 0 | 6 | 0 | 6 |
Not provided
Not provided
| D009369 |
| Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | 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 |
| D014118 |
| Toxins, Biological |
| D001685 | Biological Factors |
| PME/TP |
|
| ATP/TP |
|
| Pi/TP |
|
| NADPH/TP |
|
| UDPG/TP |
|