Statins in Children With Type 1 Diabetes and Hypercholesterolemia
This study has been completed.
First Posted: November 8, 2010
Last Update Posted: June 18, 2015
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Information provided by (Responsible Party):
Nelly Mauras, Nemours Children's Clinic
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.
Diabetes Mellitus, Insulin-Dependent
Drug: Atorvastatin Placebo
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||Statins in Children With Type 1 Diabetes: Effects on Metabolism, Inflammation and Endothelial Function
Primary Outcome Measures:
- LDL-C Levels Assessed at Randomization and 6 Months [ Time Frame: 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.
- Hs-CRP Levels Assessed at Randomization and 6 Months [ Time Frame: Randomization and 6 months ]
To assess if the use of statins in children with type 1 DM decreases the concentration of inflammatory markers.
Secondary Outcome Measures:
- Relationship Between Glycemic Variability- Measured by the Mean Amplitude of Glycemic Excursion With Continuous Glucose Monitoring. [ Time Frame: Randomization and 6 months ]
At randomization, 3 and 6 months a CGM (IPro®, Medtronic Minimed) will be worn blindly for 6d to assess glucose variability to correlate mean amplitude of glycemic excursions (MAGE) with changes in Lp particles and hsCRP.
- Gene Expression and Concentration of Key Molecules That Participate in the Inflammatory Process and Arterial Plaque Formation. [ Time Frame: 6 months ]
We will restrict participation in protocol #2 to those with T1DM for >3 years and a HbA1C >8% using a stratified balanced randomization. Blood will be withdrawn for a special genetic test. Age-matched, non-diabetic healthy controls will be recruited for comparison.
- Subclinical Atherosclerosis and Vascular Stiffness With the Use of Abdominal Aortic MRI. [ Time Frame: 6 months ]
T1DM patients will have an MRI scan of the abdominal aorta using an image acquisition protocol to measure subclinical atherosclerosis and arterial stiffness. Subjects will be rescanned at the conclusion of the 6 month trial. A group of healthy, non diabetic age-matched controls will be scanned as well.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||October 2013 (Final data collection date for primary outcome measure)
10 or 20 mg daily
Other Name: Lipitor
Placebo Comparator: Placebo
Drug: Atorvastatin Placebo
10 or 20 mg daily