Statins in Children With Type 1 Diabetes and Hypercholesterolemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01236365
Recruitment Status : Completed
First Posted : November 8, 2010
Results First Posted : May 21, 2015
Last Update Posted : June 18, 2015
Quest Diagnostics
Information provided by (Responsible Party):
Nelly Mauras, 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Insulin-Dependent Hypercholesterolemia Drug: Atorvastatin Drug: Atorvastatin Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Statins in Children With Type 1 Diabetes: Effects on Metabolism, Inflammation and Endothelial Function
Study Start Date : October 2010
Actual Primary Completion Date : October 2013
Actual Study Completion Date : November 2014

Arm Intervention/treatment
Experimental: Atorvastatin Drug: Atorvastatin
10 or 20 mg daily
Other Name: Lipitor

Placebo Comparator: Placebo Drug: Atorvastatin Placebo
10 or 20 mg daily

Primary Outcome Measures :
  1. 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.

  2. 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 :
  1. 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.

  2. 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.

  3. 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.

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Ages Eligible for Study:   10 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01236365

United States, Delaware
Alfred I duPont Hospital
Wilmington, Delaware, United States
United States, Florida
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Nemours Children's Clinic
Orlando, Florida, United States
Nemours Children's Clinic
Pensacola, Florida, United States, 32504
United States, Pennsylvania
Nemours Children's Clinic-Jefferson
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Nemours Children's Clinic
Quest Diagnostics
Principal Investigator: Nelly Mauras, MD Nemours Children's Clinic 807 Children's Way Jacksonville, Florida 32207

Publications of Results:
Responsible Party: Nelly Mauras, Chief, Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic Identifier: NCT01236365     History of Changes
Other Study ID Numbers: IRB# 185500
First Posted: November 8, 2010    Key Record Dates
Results First Posted: May 21, 2015
Last Update Posted: June 18, 2015
Last Verified: May 2015

Keywords provided by Nelly Mauras, Nemours Children's Clinic:
Type 1 diabetes
C reactive protein
Continuous glucose monitors
Abdominal magnetic resonance imaging
Toll like receptors
Receptors of advanced glycation end products

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Lipid Metabolism Disorders
Atorvastatin Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors