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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
| Medtronic | INDUSTRY |
| Quest Diagnostics-Nichols Insitute | INDUSTRY |
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Children with type1 diabetes (T1DM) have increased risk for cardiovascular disease (CVD) due to chronic increase in the blood sugars and inflammation. If there is also increased in cholesterol, it creates a highly abnormal environment not fully corrected by improved control of the blood sugars. CVD remains the principal risk of mortality in T1DM, and its prevention and treatment, compelling in children. This grant proposal encompasses 3 separate, yet interrelated projects addressing different aspects of CVD risk in children with T1DM. Project #1: a randomized controlled trial on the safety and efficacy of a class of drugs called "statins", which lower bad cholesterol in the body, in children with diabetes and elevated bad cholesterol. We will measure changes in concentration of blood inflammatory markers and for the 1st time, correlate levels of these markers with changes in blood sugar as measured by continuous glucose sensors, instruments that measure the blood sugar continuously through a small needle under the skin. Project #2: is a laboratory study to investigate the genetics and concentration of key molecules that participate in the inflammatory cascade and atheromatous plaque formation that causes CVD. Expression levels in children with T1DM will be compared with those in healthy controls for the 1st time. Project #3: examines the use of abdominal aortic MRI to measure damage to the arteries in children with T1DM and healthy age-matched controls. The results of these studies will likely provide important new data on the use of statins in children with diabetes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | 10 or 20 mg daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| LDL-C Levels Assessed at Randomization and 6 Months | To assess if the use of statins in children with type 1 DM is safe, improves measures of LDL-C. Subjects will have a physical exam, laboratories, nutritional counseling and moderate aerobic exercise recommended. Diabetes management will be intensified. At 3 months fasting lipoprotein fractions (ion mobility)re-drawn and if LDL-C >100mg/dl patients will be randomized to treatment with statins or placebo for 6 months, randomization stratified by BP and microalbuminuria, duration of diabetes and HgA1C. At 1 month safety labs will be repeated and blood withdrawn again at 3 and 6 months from baseline. | Randomization and 6 months |
| Hs-CRP Levels Assessed at Randomization and 6 Months | To assess if the use of statins in children with type 1 DM decreases the concentration of inflammatory markers. | Randomization and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| MAGE | Mean amplitude of glycemic excursion (MAGE) with continuous glucose monitoring (CGM - IPro®, Medtronic Minimed) worn blindly for 6d to assess glucose variability | Randomization and 6 months |
| RAGE |
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Inclusion Criteria:Project 1
Inclusion Criteria:Projects 2 and 3
Exclusion Criteria:Projects 1,2 and 3
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| Name | Affiliation | Role |
|---|---|---|
| Nelly Mauras, MD | Nemours Children's Clinic 807 Children's Way Jacksonville, Florida 32207 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alfred I duPont Hospital | Wilmington | Delaware | United States | |||
| Nemours Children's Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25418907 | Result | Canas JA, Ross JL, Taboada MV, Sikes KM, Damaso LC, Hossain J, Caulfield MP, Gidding SS, Mauras N. A randomized, double blind, placebo-controlled pilot trial of the safety and efficacy of atorvastatin in children with elevated low-density lipoprotein cholesterol (LDL-C) and type 1 diabetes. Pediatr Diabetes. 2015 Mar;16(2):79-89. doi: 10.1111/pedi.12245. Epub 2014 Nov 22. | |
| 25524487 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Atorvastatin | Atorvastatin: 10 or 20 mg daily |
| FG001 | Placebo | Placebo: 10 or 20 mg daily |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Atorvastatin | Atorvastatin: 10 or 20 mg daily |
| BG001 | Placebo | Atorvastatin Placebo: 10 or 20 mg daily |
| 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 | LDL-C Levels Assessed at Randomization and 6 Months | To assess if the use of statins in children with type 1 DM is safe, improves measures of LDL-C. Subjects will have a physical exam, laboratories, nutritional counseling and moderate aerobic exercise recommended. Diabetes management will be intensified. At 3 months fasting lipoprotein fractions (ion mobility)re-drawn and if LDL-C >100mg/dl patients will be randomized to treatment with statins or placebo for 6 months, randomization stratified by BP and microalbuminuria, duration of diabetes and HgA1C. At 1 month safety labs will be repeated and blood withdrawn again at 3 and 6 months from baseline. | Project #1. Adjusted for age, gender and ISS (Insulin sensitivity score) | Posted | Mean | Standard Error | mg/dL | Randomization and 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 | Atorvastatin | Atorvastatin: 10 or 20 mg daily |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fall | Musculoskeletal and connective tissue disorders | Systematic Assessment | Fell from horse and sustained a concussion and fractured finger |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cut/Laceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nelly Mauras, MD | Nemours Children's Clinic | 904-697-3674 | nmauras@nemours.org |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Atorvastatin Placebo | Drug | 10 or 20 mg daily |
|
Receptor for Advanced Glycation End Products
| Randomization and 6 months |
| Descending Aortic Strain | Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI | Randomization |
| Jacksonville |
| Florida |
| 32207 |
| United States |
| Nemours Children's Clinic | Orlando | Florida | United States |
| Nemours Children's Clinic | Pensacola | Florida | 32504 | United States |
| Nemours Children's Clinic-Jefferson | Philadelphia | Pennsylvania | 19107 | United States |
| Result |
| McCulloch MA, Mauras N, Canas JA, Hossain J, Sikes KM, Damaso LC, Redheuil A, Ross JL, Gidding SS. Magnetic resonance imaging measures of decreased aortic strain and distensibility are proportionate to insulin resistance in adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2015 Mar;16(2):90-7. doi: 10.1111/pedi.12241. Epub 2014 Dec 18. |
| Dropped at Randomization due to high LFT |
|
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Region of Enrollment | Number | participants |
|
| Atorvastatin LDL-C at 6 Months |
| OG002 | Placebo LDL-C at Randomization |
| OG003 | Placebo LDL-C at 6 Months |
|
|
|
| Primary | Hs-CRP Levels Assessed at Randomization and 6 Months | To assess if the use of statins in children with type 1 DM decreases the concentration of inflammatory markers. | Project #1 | Posted | Median | Inter-Quartile Range | mg/dL | Randomization and 6 months |
|
|
|
|
| Secondary | MAGE | Mean amplitude of glycemic excursion (MAGE) with continuous glucose monitoring (CGM - IPro®, Medtronic Minimed) worn blindly for 6d to assess glucose variability | Project #1. 4 Atorvastatin and 8 Placebo Subjects did not complete their CGM at 6months. | Posted | Mean | Standard Error | mg/dL | Randomization and 6 months |
|
|
|
| Secondary | RAGE | Receptor for Advanced Glycation End Products | Project #2. Study Subjects were given the option to participate in the Project #2 genetic substudy; 9 Atorvastatin and 12 Placebo Subjects participated in Project #2. 1 Atorvastatin and 1 Placebo Subject did not complete the 6 month genetic test. | Posted | Mean | Standard Error | pg/mL | Randomization and 6 months |
|
|
|
| Secondary | Descending Aortic Strain | Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI | Project #3. Study Subjects were given the option to participate in the Project #3 MRI substudy; 11 Atorvastatin and 8 Placebo Subjects participated in Project #3. | Posted | Mean | Standard Deviation | percent area change | Randomization |
|
|
|
|
| 1 |
| 21 |
| 11 |
| 21 |
| EG001 | Placebo | Atorvastatin Placebo: 10 or 20 mg daily | 0 | 21 | 7 | 21 |
|
| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Costochondritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Stomach Discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Acid Reflux | Gastrointestinal disorders | Systematic Assessment |
|
| Ovarian Cyst | Reproductive system and breast disorders | Systematic Assessment |
|
| Hematuria with Flank Pain | Renal and urinary disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Lower Extremity Cramping | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hand Fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Sinus Symptoms | Ear and labyrinth disorders | Systematic Assessment |
|
| Throat Infection | Infections and infestations | Systematic Assessment |
|
| Abnormal Chemistry Labs | Hepatobiliary disorders | Systematic Assessment |
|
| Elevated CK Blood Level | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Hypoglycemic Seizure | Nervous system disorders | Systematic Assessment |
|
| Fatigue | Social circumstances | Systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |