Statins in Children With Type 1 Diabetes and Hypercholesterolemia

Phase 3

Completed

Conditions: Diabetes Mellitus, Insulin-Dependent
Hypercholesterolemia

Interventions: Drug: Atorvastatin
Drug: Atorvastatin Placebo

Registration Number: NCT01236365

Lead Sponsor: Nemours Children's Clinic

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

Inclusion Criteria

Project 1

T1DM diagnosed clinically for > 1 year
any HbA1C
on stable insulin therapy
Ages: 10 - 20 years
both genders
BMI < 85th percentile
Fasting LDL-C>100mg/dl
Normal thyroid function

Inclusion Criteria:Projects 2 and 3

T1DM diagnosed clinically for > 3 year
HbA1C > 8%
on stable insulin therapy
Ages: 12- 20 years
both genders
BMI < 85th percentile
Fasting LDL-C>100mg/dl
Normal thyroid function

Exclusion Criteria

Projects 1,2 and 3

Severe dyslipidemia (LDL-C >160, TG > 400 mg/dl)
Smoking
Pregnancy
Current use of anti-inflammatory or immunomodulatory drugs, lipid lowering, antidiabetic drugs
Patients with hypertension and/or microalbuminuria will be allowed using balanced randomization and standardized treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin	-
Placebo	Atorvastatin Placebo	-

Primary Outcome Measures

Name	Time	Method
LDL-C Levels Assessed at Randomization and 6 Months	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	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

Name	Time	Method
RAGE	Randomization and 6 months	Receptor for Advanced Glycation End Products
MAGE	Randomization and 6 months	Mean amplitude of glycemic excursion (MAGE) with continuous glucose monitoring (CGM - IPro®, Medtronic Minimed) worn blindly for 6d to assess glucose variability
Descending Aortic Strain	Randomization	Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI

Trial Locations

Locations (3): Nemours Children's Clinic
🇺🇸
Pensacola, Florida, United States
Alfred I duPont Hospital
🇺🇸
Wilmington, Delaware, United States
Nemours Children's Clinic-Jefferson
🇺🇸
Philadelphia, Pennsylvania, United States