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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DK120612-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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Girls with obesity and polycystic ovarian syndrome will receive either glucagon like peptide-1 receptor agonist therapy or a dietary intervention for 12 weeks to decrease the metabolic syndrome, in particular to lower hepatic fat and improve insulin sensitivity.
In obese girls with polycystic ovarian syndrome, testosterone and obesity combine to create unique pathology to increase metabolic disease including fatty liver and insulin resistance, which may be mediated by altered glucagon like peptide-1 activity. The investigators will treat girls with obesity and polycystic ovarian syndrome for 4 months with a glucagon like peptide-1 receptor agonist compared to dietary intervention to primarily lower hepatic fat and secondarily improve whole body and adipose insulin sensitivity. Mechanisms of hepatic metabolism, including rates of de novo lipogenesis and relative mitochondrial flux will also be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diet Intervention | Active Comparator | Weight loss with dietary intervention |
|
| GLP-1 Intervention | Experimental | Participants will take a daily oral tablet of semaglutide for 4 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide 3mg and 7mg [Rybelsus] | Drug | Once daily oral tablet of semaglutide for 4 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hepatic Fat Fraction | Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. A negative value means a decrease in liver fat, and a positive value means an increase in liver fat. | Baseline and 12 weeks |
| Change in Weight | Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Rate of De Novo Lipogenesis (DNL) | Change from baseline of the rate of overnight de novo lipogenesis (DNL) will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction. A negative value means a decrease in newly synthesized lipids after the 12 week intervention, and a positive value means an increase in newly synthesized lipids after the 12 week intervention. A lower value is better. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percentage of Indirect Glycerol Carbon Contributions to Newly Synthesized Triglycerides and Glucose | This outcome evaluates mitochondrial function and excess tricarboxylic acid (TCA) cycle substrate cycling by measuring indirect carbon contributions to newly synthesized triglycerides and glucose using stable isotope-labeled glycerol. Participants receive orally administered [U-13C3]glycerol mixed in water, and plasma glucose and lipids are analyzed by 13C NMR spectroscopy. Indirect glycerol carbon contribution reflects the fraction of glycerol carbons that first enter the TCA cycle before incorporation into triglycerides and glucose. A decrease in the percentage of indirect contributions is beneficial, indicating decreased oxidative stress resulting from excess TCA cycling. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Melanie Cree-Green, MD, PhD | Children's Hospital Colorado | 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. |
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There were 5 participants who screen failed, and 4 participants who withdrew due to not tolerating the study medication.
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| ID | Title | Description |
|---|---|---|
| FG000 | Diet Intervention | Weight loss with dietary intervention Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm |
| FG001 | GLP-1 Intervention | Participants will take a daily oral tablet of semaglutide for 4 months. Semaglutide 3mg and 7mg [Rybelsus]: Once daily oral tablet of semaglutide for 4 months |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
12-21 year old participabnts with polycystic ovary syndrome
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| ID | Title | Description |
|---|---|---|
| BG000 | Diet Intervention | Weight loss with dietary intervention Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm |
| BG001 | GLP-1 Intervention | Participants will take a daily oral tablet of semaglutide for 4 months. Semaglutide 3mg and 7mg [Rybelsus]: Once daily oral tablet of semaglutide for 4 months |
| 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 | Change in Hepatic Fat Fraction | Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. A negative value means a decrease in liver fat, and a positive value means an increase in liver fat. | Posted | Mean | Standard Deviation | Change in percentage of liver fat | Baseline and 12 weeks |
|
Measured up to 4 months from enrollment
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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 | Diet Intervention | Weight loss with dietary intervention Weight loss diet: Prescribed weight loss diet to match weight loss in Drug arm |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Melanie Cree, MD, PhD | University of Colorado Anschutz Medical Campus | 720-777-5743 | melanie.cree@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 | Nov 4, 2022 | Apr 11, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D063766 | Pediatric Obesity |
| D065626 | Non-alcoholic Fatty Liver Disease |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
| D004038 | Diet, Reducing |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 |
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| Weight loss diet | Other | Prescribed weight loss diet to match weight loss in Drug arm |
|
| Baseline and 12 weeks |
| Change in Whole Body Insulin Sensitivity | Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model. | Baseline and 12 weeks |
| Change in Adipose Insulin Sensitivity | Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids, and the nadir of free fatty acids during the oral glucose tolerance test. Percent suppression of FFAs during the OGTT was calculated as fasting FFA minus the minimal FFA value divided by fasting FFA. This was calculated for baseline and after 12-weeks of intervention. The change was calculated by subtracting the final-baseline values. A higher absolute value means there was an improvement in adipose insulin sensitivity after 12-weeks of treatment. | Baseline and 12 weeks |
| Baseline and 12 weeks |
| Change in Free Androgen Index | The Free Androgen Index (FAI) is a test for hyperandrogenism in women, using testosterone and sex hormone binding globulin (SHBG) as markers. The calculation is FAI = Total Testosterone (nmol/ L)) x 100 / Sex Hormone-Binding Globulin (SHBG) (nmol/ L). Typical values for the FAI in women are 7-10, and FAI is usually elevated in women with PCOS. The change in FAI will be calculated after 12 weeks of diet or semaglutide intervention. A negative value means an improvement as there was a decrease in androgen levels after 12 weeks of treatment. | Baseline and 12 weeks |
| BG002 | 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 |
|
|
|
| Primary | Change in Weight | Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported. | Posted | Mean | Standard Deviation | Change in weight (KG) | Baseline and 12 weeks |
|
|
|
| Secondary | Change in Rate of De Novo Lipogenesis (DNL) | Change from baseline of the rate of overnight de novo lipogenesis (DNL) will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction. A negative value means a decrease in newly synthesized lipids after the 12 week intervention, and a positive value means an increase in newly synthesized lipids after the 12 week intervention. A lower value is better. | Posted | Mean | Standard Deviation | mg/dL | Baseline and 12 weeks |
|
|
|
| Secondary | Change in Whole Body Insulin Sensitivity | Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model. | Posted | Mean | Standard Deviation | dl/kg/min per microU/ml | Baseline and 12 weeks |
|
|
|
| Secondary | Change in Adipose Insulin Sensitivity | Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids, and the nadir of free fatty acids during the oral glucose tolerance test. Percent suppression of FFAs during the OGTT was calculated as fasting FFA minus the minimal FFA value divided by fasting FFA. This was calculated for baseline and after 12-weeks of intervention. The change was calculated by subtracting the final-baseline values. A higher absolute value means there was an improvement in adipose insulin sensitivity after 12-weeks of treatment. | Posted | Mean | Standard Deviation | percentage of change | Baseline and 12 weeks |
|
|
|
| Other Pre-specified | Change in Percentage of Indirect Glycerol Carbon Contributions to Newly Synthesized Triglycerides and Glucose | This outcome evaluates mitochondrial function and excess tricarboxylic acid (TCA) cycle substrate cycling by measuring indirect carbon contributions to newly synthesized triglycerides and glucose using stable isotope-labeled glycerol. Participants receive orally administered [U-13C3]glycerol mixed in water, and plasma glucose and lipids are analyzed by 13C NMR spectroscopy. Indirect glycerol carbon contribution reflects the fraction of glycerol carbons that first enter the TCA cycle before incorporation into triglycerides and glucose. A decrease in the percentage of indirect contributions is beneficial, indicating decreased oxidative stress resulting from excess TCA cycling. | Posted | Mean | Standard Deviation | percentage of indirect glycerol carbon c | Baseline and 12 weeks |
|
|
|
| Other Pre-specified | Change in Free Androgen Index | The Free Androgen Index (FAI) is a test for hyperandrogenism in women, using testosterone and sex hormone binding globulin (SHBG) as markers. The calculation is FAI = Total Testosterone (nmol/ L)) x 100 / Sex Hormone-Binding Globulin (SHBG) (nmol/ L). Typical values for the FAI in women are 7-10, and FAI is usually elevated in women with PCOS. The change in FAI will be calculated after 12 weeks of diet or semaglutide intervention. A negative value means an improvement as there was a decrease in androgen levels after 12 weeks of treatment. | Posted | Mean | Standard Deviation | unitless | Baseline and 12 weeks |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 0 |
| 17 |
| EG001 | GLP-1 Intervention | Participants will take a daily oral tablet of semaglutide for 4 months. Semaglutide 3mg and 7mg [Rybelsus]: Once daily oral tablet of semaglutide for 4 months | 0 | 38 | 0 | 38 | 0 | 38 |
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| D009750 |
| Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |