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| ID | Type | Description | Link |
|---|---|---|---|
| Protocol 914 | Other Identifier | Children's Hospital Colorado | |
| 1-11-JF-23 | Other Grant/Funding Number | American Diabetes Association | |
| 5K12HD057022 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| American Diabetes Association | OTHER |
| National Institutes of Health (NIH) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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The Health Influences of Puberty (HIP) Study is designed to explore the relationships between puberty and the onset of type 2 diabetes in adolescents. The results of this study will help us better understand how to prevent type 2 diabetes in these youth. Children go through many changes during puberty, including important hormonal and behavioral alterations. Among these changes, it has long been known that, during puberty, insulin does not work as well as it does before and after puberty. This is called physiologic insulin resistance. In healthy children, this does not cause diabetes or affect blood sugar in any way because the body is able to compensate by making more insulin. Indeed, this is thought to be an important part of the adolescent growth spurt. However, in some children with increased risk for developing type 2 diabetes due to obesity and genetics, the worsening insulin resistance of puberty cannot be compensated for and these youth get diabetes early. The investigators believe this is because type 2 diabetes is rarely, if ever, seen before puberty begins, and the peak of diabetes onset in adolescents occurs at the time of the worst insulin resistance. This specific research project has two goals: 1. To examine effects of obesity on how well the body's insulin works during puberty, and 2. To see if treatment of obese children during this critical period of puberty with a medication that improves insulin resistance (metformin) will help prevent early onset type 2 diabetes.
Specific Aims:
Pediatric insulin resistance and related disorders, such as type 2 diabetes mellitus (T2DM), are increasing in prevalence, and portend significant end-organ and cardiovascular morbidity and mortality. Thus, measures aimed at understanding its causes and preventing its onset are critical. The physiologic decrease in insulin sensitivity in all adolescents during puberty is well-established. It is also known that obese adolescents start out less insulin sensitive at the onset of puberty than lean adolescents, and that their insulin sensitivity worsens as puberty progresses. While there are both longitudinal and cross-sectional data confirming the natural recovery of pre-pubertal insulin sensitivity in normal weight adolescents after puberty is completed, it is unknown whether obese adolescents recover their pre-pubertal insulin sensitivity. Failure to regain pre-pubertal insulin sensitivity at the end of puberty, and failure of compensatory insulin secretion, may accelerate progression from obesity to insulin resistance to T2DM in at-risk youth and contribute to long-term cardiovascular risk.
In addition, obesity and insulin resistance are associated with earlier onset of puberty and premature adrenarche in females. Insulin resistance also contributes to the gonadal dysfunction of polycystic ovarian disease in fully pubertal females and is associated with hypogonadism in older adult males. Little is known about effects of obesity and insulin resistance on gonadal function in young males. However, persistent metabolic changes at the end of puberty may contribute to gonadal dysfunction in obese youth. Currently, there are few longitudinal studies in either sex that evaluate the interactions among obesity, insulin resistance and gonadal function during puberty.
The investigators' long-term goal is to better understand the metabolic changes that occur during puberty, their underlying mechanisms, and their potential contribution to adult disease. The overall aim is to evaluate the effects of obesity on the evolution of insulin sensitivity and gonadal function during puberty. In addition, because improvement in insulin action during puberty may slow β-cell deterioration, the investigators will evaluate whether compensatory insulin secretion is also affected in obese adolescents and whether treatment with metformin improves β-cell response.
HYPOTHESES:
To test these hypotheses, we propose to address the following Specific Aims:
SPECIFIC AIM 1 (Observational Arm):
To compare longitudinal changes in insulin sensitivity and secretion and their correlates in obese and normal weight adolescents during puberty.
SPECIFIC AIM 2 (Treatment Arm):
To compare longitudinal changes in insulin sensitivity and secretion and their correlates in obese adolescents treated with metformin or placebo during puberty.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese metformin arm | Experimental | Double-blinded placebo-controlled trial of metformin during puberty, treatment arm Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 2-3) until puberty completion (Tanner 5), approximately 3 years |
|
| Obese placebo arm | Placebo Comparator | Double-blinded placebo-controlled trial of metformin during puberty, placebo arm Dosage form: Placebo stamped to match 1000 mg metformin tablets Placebo comparator: Stamped placebo pill matching metformin dose Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 2-3) until puberty completion (Tanner 5), approximately 3 years |
|
| Obese - NT | No Intervention | Comparator group for the observational comparison of metabolic changes in youth with normal weight and obesity as they progress through puberty. Duration: From early puberty (Tanner 2-3) until puberty completion (Tanner 5), approximately 3 years | |
| Normal weight | No Intervention | Comparator group for the observational comparison of metabolic changes in youth with normal weight and obesity as they progress through puberty. Duration: From early puberty (Tanner 2-3) until puberty completion (Tanner 5), approximately 3 years |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | After randomization, the study drug (metformin or placebo) is gradually titrated to full dose of 1000 mg BID (or to maximum tolerated, at least 500 mg BID) over a period of 4 weeks to minimize adverse gastrointestinal effects. Participants are seen every three months to measure compliance and dispense new study drug. Every 6 months, they also have a physical examination in order to determine puberty staging. Study measurements (IVGTT, bloodwork, DXA) are performed at Tanner 4 puberty and Tanner 5 (puberty completion), at which time the study drug is stopped. Study measurements will be performed again 6 months after study drug is completed to assess if effects are persistent after study drug is stopped. During the treatment period, all participants receive standard lifestyle counseling. |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Sensitivity | As measured by in intravenous glucose tolerance test (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist. | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin Secretion (Acute Insulin Response to Glucose, AIRg) | As measured by IVGTT as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Please see primary outcome for more detail about timing of measurement. | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Megan Kelsey, MD, MS | University of Colorado Denver/Children's Hospital Colorado | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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. | |
| 41771666 | Derived | Cohen CC, Moore JM, Bothwell S, Pyle L, Lopez-Paniagua D, Ware MA, Whooten R, Zeitler PS, Nadeau KJ, Kelsey MM. Adipose Depot Changes and Associated Metabolic Risk in the Longitudinal Health Influences of Puberty Study. Pediatr Obes. 2026 Mar;21(3):e70083. doi: 10.1111/ijpo.70083. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Weight | Normal Weight by BMI. No treatment. |
| FG001 | Obese - NT | Obese by BMI. These participants were not prescribed any intervention (Non-treated). |
| FG002 | Obese - Placebo | Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
| FG003 | Obese - Metformin | Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Both the Obese - NT participants and Obese - Placebo participants were included in the "observational arm" of the study. Thus, this arm was a comparison between youth with normal weight and untreated and youth with obesity who were either a) untreated or b) treated with placebo
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Weight | Normal Weight by BMI. No treatment. |
| BG001 | Obese - NT | Obese by BMI. Participants were not taking metformin or placebo |
| 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 | Insulin Sensitivity | As measured by in intravenous glucose tolerance test (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist. | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | x10-4/min-1/mIU/mL | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
|
Adverse event data were collected at each med visit approximately every 6 months
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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 | Obese - Metformin | Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years Metformin: After randomization, the study drug (metformin or placebo) is gradually titrated to full dose of 1000 mg BID (or to maximum tolerated, at least 500 mg BID) over a period of 4 weeks to minimize adverse gastrointestinal effects. Participants are seen every three months to measure compliance and dispense new study drug. Every 6 months, they also have a physical examination in order to determine puberty staging. Study measurements (IVGTT, bloodwork, DXA) are performed at Tanner 4 puberty and Tanner 5 (puberty completion), at which time the study drug is stopped. Study measurements will be performed again 6 months after study drug is completed to assess if effects are persistent after study drug is stopped. During the treatment period, all participants receive standard lifestyle counseling. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bloating | Gastrointestinal disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Megan Kelsey | University of Colorado School of Medicine | 720-777-0991 | megan.kelsey@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 | Mar 25, 2016 | Mar 24, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D006058 | Gonadal Disorders |
| D003924 | Diabetes Mellitus, Type 2 |
| D007006 | Hypogonadism |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Children's Hospital Colorado |
| OTHER |
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|
|
| Placebo | Drug | Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
|
| Disposition Index | Please see primary outcome for more detail about timing of measurement. Disposition index is measured via (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. It reflects the product of outcome measures 1 and 2 (Si x AIRg). | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
| Low Density Lipoprotein | Please see primary outcome for more detail about timing of measurement. | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
| Insulin-like Growth Factor 1 | IGF-1 measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Total Testosterone | Testosterone measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Estradiol | Estradiol measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Sex Hormone Binding Globulin | SHBG measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Dehydroepiandrosterone Sulfate | DHEA-S measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| High Sensitivity C-reactive Protein | hsCRP measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Aspartate Aminotransferase (AST) | AST measured in serum at each time point | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Alanine Transaminase (ALT) | ALT measured in serum at each time point | Baseline (Tanner 2-3), Tanner 4, Tanner 5 |
| Change in Urinary Luteinizing Hormone | LH measured in an overnight urine sample at time points below | Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline) |
| Change in Urinary Follicle-stimulating Hormone | FSH measured in overnight urine sample at time points below | Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline |
| Change in Urinary Estradiol Metabolites | estradiol metabolite (E1c) measured in an overnight urine sample at each time point | Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline |
| Hemoglobin A1c | HbA1c measured by HPLC at time points below | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Leptin | Leptin measured in serum at time points below | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Percent Body Fat | % body fat measured by DXA at time points below | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Visceral Adipose | Percent Visceral Fat, Measured in a subset (10 per group) by single slice MRI | Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| Liver Adipose | Liver fat percent. Measured in a subset (10 per group) by fast MRI technique | Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
| High Density Lipoprotein | Please see primary outcome for more detail about timing of measurement. | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
| 33728428 | Derived | Kelsey MM, Hilkin A, Pyle L, Severn C, Utzschneider K, Van Pelt RE, Zeitler PS, Nadeau KJ. Two-Year Treatment With Metformin During Puberty Does Not Preserve beta-Cell Function in Youth With Obesity. J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2622-e2632. doi: 10.1210/clinem/dgab170. |
| 31996919 | Derived | Kelsey MM, Pyle L, Hilkin A, Severn CD, Utzschneider K, Van Pelt RE, Nadeau KJ, Zeitler PS. The Impact of Obesity On Insulin Sensitivity and Secretion During Pubertal Progression: A Longitudinal Study. J Clin Endocrinol Metab. 2020 May 1;105(5):e2061-8. doi: 10.1210/clinem/dgaa043. |
| BG002 | Obese - Placebo | Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
| BG003 | Obese - Metformin | Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Obese - NT | Obese by BMI. These participants were not assigned an intervention (non-treated). |
| OG002 | Obese - Placebo | Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
| OG003 | Obese - Metformin | Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years |
|
|
| Secondary | Insulin Secretion (Acute Insulin Response to Glucose, AIRg) | As measured by IVGTT as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. Please see primary outcome for more detail about timing of measurement. | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | µIU/mL | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
|
|
|
| Secondary | Disposition Index | Please see primary outcome for more detail about timing of measurement. Disposition index is measured via (IVGTT) as calculated by Bergman's minimal model. Higher numbers indicate a better outcome. It reflects the product of outcome measures 1 and 2 (Si x AIRg). | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | x10-4/min-1 | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
|
|
|
| Secondary | Low Density Lipoprotein | Please see primary outcome for more detail about timing of measurement. | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | mg/dl | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
|
|
|
| Secondary | Insulin-like Growth Factor 1 | IGF-1 measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | ng/ml | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Total Testosterone | Testosterone measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | ng/dl | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Estradiol | Estradiol measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Sex Hormone Binding Globulin | SHBG measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | nmol/l | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Dehydroepiandrosterone Sulfate | DHEA-S measured in serum at each time point | Posted | Mean | Standard Deviation | mcg/dl | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | High Sensitivity C-reactive Protein | hsCRP measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Aspartate Aminotransferase (AST) | AST measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | international units per liter | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Alanine Transaminase (ALT) | ALT measured in serum at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | international units per liter | Baseline (Tanner 2-3), Tanner 4, Tanner 5 |
|
|
|
| Secondary | Change in Urinary Luteinizing Hormone | LH measured in an overnight urine sample at time points below | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | international units per liter | Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline) |
|
|
|
| Secondary | Change in Urinary Follicle-stimulating Hormone | FSH measured in overnight urine sample at time points below | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | international units per milliliter (IU/m | Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline |
|
|
|
| Secondary | Change in Urinary Estradiol Metabolites | estradiol metabolite (E1c) measured in an overnight urine sample at each time point | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | ng/mgCr | Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline |
|
|
|
| Secondary | Hemoglobin A1c | HbA1c measured by HPLC at time points below | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | mmol/mol | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Leptin | Leptin measured in serum at time points below | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | ng/mL | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Percent Body Fat | % body fat measured by DXA at time points below | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | percentage of body fat | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Visceral Adipose | Percent Visceral Fat, Measured in a subset (10 per group) by single slice MRI | Data was not collected for some participants at all visits. | Posted | Mean | Standard Deviation | Percent | Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | Liver Adipose | Liver fat percent. Measured in a subset (10 per group) by fast MRI technique | Data was not collected for some participants at all visits. | Posted | Mean | Standard Deviation | percentage of liver mass | Baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline |
|
|
|
| Secondary | High Density Lipoprotein | Please see primary outcome for more detail about timing of measurement. | 24 participants analyzed in the Obese NT Placebo group are also analyzed in the Obese Placebo group. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 11 |
| 20 |
| EG001 | Obese - Placebo | Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years | 0 | 24 | 0 | 24 | 14 | 24 |
| EG002 | Normal Weight (No Treatment) | Normal Weight by BMI. No treatment. | 0 | 47 | 0 | 47 | 0 | 47 |
| EG003 | Obese (No Treatment) | Obese by BMI. These participants were not prescribed any intervention (Non-treated). | 0 | 13 | 0 | 13 | 0 | 13 |
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D003920 | Diabetes Mellitus |
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|
|
| Tanner 5 |
|
|
|
| Tanner 5 |
|
|
| Tanner 4 |
|
| Tanner 5 |
|
| Post-Puberty |
|