Statins in Children With Type 1 Diabetes and Hypercholesterolemia

Hypercholesterolemia Clinical Trial

Official title:

Statins in Children With Type 1 Diabetes: Effects on Metabolism, Inflammation and Endothelial Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01236365
• Other study ID #: IRB# 185500
• Status: Completed
• Phase: Phase 3
• Start date: October 2010
• Est. completion date: November 2014

Study information

• Verified date: June 2019
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 2014
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Insulin-Dependent
• Diabetes Mellitus, Type 1
• Hypercholesterolemia

Intervention

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

Locations

Country	Name	City	State
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Nemours Children's Clinic	Orlando	Florida
United States	Nemours Children's Clinic	Pensacola	Florida
United States	Nemours Children's Clinic-Jefferson	Philadelphia	Pennsylvania
United States	Alfred I duPont Hospital	Wilmington	Delaware

Sponsors (4)

Lead Sponsor	Collaborator
Nemours Children's Clinic	Medtronic, Pfizer, Quest Diagnostics

Country where clinical trial is conducted

United States, 

References & Publications (2)

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 chol — View Citation

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 diabete — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Randomization and 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.	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	Randomization and 6 months
Secondary	RAGE	Receptor for Advanced Glycation End Products	Randomization and 6 months
Secondary	Descending Aortic Strain	Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI	Randomization