Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Thrasher Research Fund | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
In Protocol #2, we will select 30 obese pubertal and 30 obese prepubertal subjects with an abnormal cytokine profile (i.e. fibrinogen and/or hsCRP concentration greater than or equal to 2 Standard Deviations (SD) above the mean established in our lab for lean controls in Protocol #1). They will be randomly assigned to either lifestyle intervention (diet/exercise) or diet/exercise plus metformin for 6 months. After the 6 month evaluation the subjects will cross over the treatment arms, i.e., those that were doing diet/exercise intervention only will add metformin, those that were doing the diet/exercise plus metformin will discontinue the metformin and continue with diet/exercise changes only. Intrahepatic fat contents will be measured as well.
The investigators hypothesize that obese children in these age groups will have increased cardiovascular risk related to their obese state before reaching the currently defined criteria of metabolic syndrome.
The investigators hypothesize that these cardiovascular risks can be reduced with lifestyle and drug interventions.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diet/Exercise only, then Diet/Exercise plus Metformin | Experimental | Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). |
|
| Diet/Exercise plus Metformin, then Diet/Exercise only | Active Comparator | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Metformin, 250mg by mouth twice a day with meals will be started and if tolerated increased to 500mg twice a day in 3 days in those less than 12 years old and titrated further to 1000mg twice a day if tolerated. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months | Value at 6 months minus value at baseline. HsCRP is an acute phase protein which is a sensitive marker for systemic inflammation. HsCRP concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA), with an hsCRP lower sensitivity of 0.156 mg/L. | Baseline and 6 months |
| Change From Baseline in Fibrinogen at 6 Months | Value at 6 months minus value at baseline. Fibrinogen is a hepatic-derived factor directly involved in clotting and in the viscosity characteristics of blood flow. It binds to platelets and contributes to their aggregation, promotes fibrin formation and is also an acute phase reactant that is increased in inflammatory states. Fibrinogen concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA). | Baseline and 6 months |
| Change From Baseline in Interleukin 6 (IL-6) at 6 Months | Value at 6 months minus value at baseline. IL-6 is a pro-inflammatory cytokine thought to produce a state of low-grade inflammation in obese individuals. IL-6 stimulates hepatic production of C-reactive protein (CRP), an acute phase protein which is a sensitive marker for systemic inflammation. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Minneapolis, MN, USA). | Baseline and 6 months |
| Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at 6 Months | Value at 6 months minus value at baseline. PAI-1 is the primary physiological inhibitor of fibrinolysis and proteolysis. High PAI-1 levels have been linked to thrombosis and fibrosis, insulin resistance and obesity. PAI-1 was measured by ELISA (American Diagnostica, Stamford, CT, USA). | Baseline and 6 months |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Nelly Mauras, MD | Nemours Children's Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nemours Children's Clinic | Jacksonville | Florida | 32207 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20061420 | Result | Mauras N, Delgiorno C, Kollman C, Bird K, Morgan M, Sweeten S, Balagopal P, Damaso L. Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children. J Clin Endocrinol Metab. 2010 Mar;95(3):1060-8. doi: 10.1210/jc.2009-1887. Epub 2010 Jan 8. | |
| 22015710 |
Not provided
Not provided
375 participants recruited; 177 obese participants screened, 111 excluded (62 did not meet inclusion criteria and 4 refused participation).
Participants recruited from pediatric endocrinology clinics, in Jacksonville, USA between November 2003 and April 2008.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Diet/Exercise Only, Then Diet/Exercise Plus Metformin | Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). |
| FG001 | Diet/Exercise Plus Metformin, Then Diet/Exercise Only |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention -Baseline to 6Months |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Dietary modification with caloric restriction | Behavioral | The life style intervention changes will include a hypocaloric diet representing at least a 500 kcal/day reduction based on their dietary histories and Resting Energy Expenditure (REE) determined by the initial calorimetry. |
|
| Establishment of exercise protocol | Behavioral | Participants will attend the Fitness Center 3 times per week and supervised by an exercise technician or exercise specialist. Exercise will be individually prescribed for each participant based on their functional abilities. Exercise will consist of 5-10 minutes for warm up and stretching, followed by 15-30 minutes of cardiovascular exercise (i.e. treadmill, bicycle ergometer, rower, nustep, etc), 10-20 minutes of strength training (supervised using weight stack equipment), and 5-10 minutes of cool down and stretching. As children typically do not need an exercise prescription based on heart rate, we will familiarize them with perceived exertion scales and monitor that they are exercising in the moderate to hard range of perception of effort. Participants will be started at 15 minutes of cardiovascular exercise and 10 minutes of strength training exercise, progressing by 2-3 minutes every week until 30 and 20 minutes is achieved for each respectively. |
|
| Rynders C, Weltman A, Delgiorno C, Balagopal P, Damaso L, Killen K, Mauras N. Lifestyle intervention improves fitness independent of metformin in obese adolescents. Med Sci Sports Exerc. 2012 May;44(5):786-92. doi: 10.1249/MSS.0b013e31823cef5e. |
| 22570948 | Result | Mauras N, DelGiorno C, Hossain J, Bird K, Killen K, Merinbaum D, Weltman A, Damaso L, Balagopal P. Metformin use in children with obesity and normal glucose tolerance--effects on cardiovascular markers and intrahepatic fat. J Pediatr Endocrinol Metab. 2012;25(1-2):33-40. doi: 10.1515/jpem-2011-0450. |
| 22819275 | Derived | Benson M, Hossain J, Caulfield MP, Damaso L, Gidding S, Mauras N. Lipoprotein subfractions by ion mobility in lean and obese children. J Pediatr. 2012 Dec;161(6):997-1003. doi: 10.1016/j.jpeds.2012.05.060. Epub 2012 Jul 20. |
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Second Intervention -6Months to 12Months |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Diet/Exercise Only, Then Diet/Exercise Plus Metformin | Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). |
| BG001 | Diet/Exercise Plus Metformin, Then Diet/Exercise Only | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). |
| BG002 | Total | Total of all reporting groups |
| 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 | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | 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 | Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) at 6 Months | Value at 6 months minus value at baseline. HsCRP is an acute phase protein which is a sensitive marker for systemic inflammation. HsCRP concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA), with an hsCRP lower sensitivity of 0.156 mg/L. | 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group did not have an hsCRP level available for analysis. | Posted | Median | Inter-Quartile Range | mg/dL | Baseline and 6 months |
|
|
| ||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Fibrinogen at 6 Months | Value at 6 months minus value at baseline. Fibrinogen is a hepatic-derived factor directly involved in clotting and in the viscosity characteristics of blood flow. It binds to platelets and contributes to their aggregation, promotes fibrin formation and is also an acute phase reactant that is increased in inflammatory states. Fibrinogen concentrations were measured in our laboratory by immuno-nephelometry (Siemens Healthcare Diagnostics, Deerfield IL, USA). | 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group did not have a Fibrinogen level available for analysis. | Posted | Median | Inter-Quartile Range | mg/dL | Baseline and 6 months |
| ||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Interleukin 6 (IL-6) at 6 Months | Value at 6 months minus value at baseline. IL-6 is a pro-inflammatory cytokine thought to produce a state of low-grade inflammation in obese individuals. IL-6 stimulates hepatic production of C-reactive protein (CRP), an acute phase protein which is a sensitive marker for systemic inflammation. IL-6 was measured by enzyme-linked immunosorbent assay (ELISA; R&D Systems, Minneapolis, MN, USA). | Posted | Median | Inter-Quartile Range | pg/mL | Baseline and 6 months |
| |||||||||||||||||||||||||||||||||||||
| Primary | Change From Baseline in Plasminogen Activator Inhibitor-1 (PAI-1) at 6 Months | Value at 6 months minus value at baseline. PAI-1 is the primary physiological inhibitor of fibrinolysis and proteolysis. High PAI-1 levels have been linked to thrombosis and fibrosis, insulin resistance and obesity. PAI-1 was measured by ELISA (American Diagnostica, Stamford, CT, USA). | 1 Subject in the "Diet/Exercise plus Metformin, then Diet/Exercise (Pubertal)" Group and 1 Subject in the "Diet/Exercise, then Diet/Exercise plus Metformin (Pubertal)" Group did not have a PAI-1 level available for analysis. | Posted | Median | Inter-Quartile Range | ng/ML | Baseline and 6 months |
|
Not provided
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 | Diet/Exercise Only, Then Diet/Exercise Plus Metformin | Diet/Exercise only in first intervention period and Diet/Exercise plus Metformin in second intervention period (no washout period). | 0 | 31 | 0 | 31 | ||
| EG001 | Diet/Exercise Plus Metformin, Then Diet/Exercise Only | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). | 0 | 35 | 0 | 35 |
Not provided
Not provided
Protocol #2 attrition was high, such that, we could not derive conclusions beyond the 6 month time period. Therefore, conclusions were based on participants after completing the first intervention without crossover to the second intervention.
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nelly Mauras, Chief, Division of Endocrinology | Nemours Children's Clinic | 904-697-3674 | nmauras@nemours.org |
| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| 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 |
Not provided
Not provided
| ID | Term |
|---|---|
| D008687 | Metformin |
| D004035 | Diet Therapy |
| D031204 | Caloric Restriction |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D002149 | Energy Intake |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
Not provided
Not provided
| Lost to Follow-up |
|
| >=65 years |
|
| Male |
|
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants. |
| OG003 | Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants. |
|
|
| OG003 | Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants. |
|
|
Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants. |
| OG003 | Diet/Exercise Plus Metformin, Then Diet/Exercise (Pubertal) | Diet/Exercise plus Metformin in first intervention period and Diet/Exercise only in second intervention period (no washout period). Results displayed for prepubertal versus pubertal participants. |
|
|