Statins in Children With Type 1 Diabetes and Hypercholesterolemia

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Medtronic
Quest Diagnostics
Information provided by (Responsible Party):
Nelly Mauras, Nemours Children's Clinic
ClinicalTrials.gov Identifier:
NCT01236365
First received: November 2, 2010
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Diabetes Mellitus, Insulin-Dependent
Hypercholesterolemia
Drug: Atorvastatin
Drug: Atorvastatin Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Statins in Children With Type 1 Diabetes: Effects on Metabolism, Inflammation and Endothelial Function

Resource links provided by NLM:


Further study details as provided by Nemours Children's Clinic:

Primary Outcome Measures:
  • To investigate if the use of statins in children with type 1 DM is safe, improves measures of LDL-C and decreases the concentration of inflammatory markers. [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    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 LCL-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.


Secondary Outcome Measures:
  • To characterize the relationship between glycemic variability- measured by the mean amplitude of glycemic excursion with continuous glucose monitoring. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Investigate gene expression and concentration of key molecules that participate in the inflammatory process and arterial plaque formation. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Measure subclinical atherosclerosis and vascular stiffness with the use of abdominal aortic MRI. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 89
Study Start Date: October 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin Drug: Atorvastatin
10 or 20 mg daily
Other Name: Lipitor
Placebo Comparator: Placebo Drug: Atorvastatin Placebo
10 or 20 mg daily

  Eligibility

Ages Eligible for Study:   10 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01236365

Locations
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
Pfizer
Medtronic
Quest Diagnostics
Investigators
Principal Investigator: Nelly Mauras, MD Nemours Children's Clinic 807 Children's Way Jacksonville, Florida 32207
  More Information

No publications provided

Responsible Party: Nelly Mauras, Chief, Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic
ClinicalTrials.gov Identifier: NCT01236365     History of Changes
Other Study ID Numbers: IRB# 185500
Study First Received: November 2, 2010
Last Updated: December 19, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Nemours Children's Clinic:
Type 1 diabetes
Children
Statins
Hypercholesterolemia
Lipoproteins
C reactive protein
Continuous glucose monitors
Adolescence
Abdominal magnetic resonance imaging
Toll like receptors
Receptors of advanced glycation end products
Nutrition

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

ClinicalTrials.gov processed this record on September 14, 2014