Clinical trial NCT01236365: Statins in Children With Type 1 Diabetes and Hypercholesterolemia
Official title: Statins in Children With Type 1 Diabetes: Effects on Metabolism, Inflammation and Endothelial Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Insulin-Dependent
Hypercholesterolemia
Keywords: 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
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Medtronic
name: Quest Diagnostics-Nichols Insitute
First posted: 2010-11-08
Enrollment: 42
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: LDL-C Levels Assessed at Randomization and 6 Months
timeFrame: Randomization and 6 months
measure: Hs-CRP Levels Assessed at Randomization and 6 Months
timeFrame: Randomization and 6 months
Secondary outcomes:
measure: MAGE
timeFrame: Randomization and 6 months
measure: RAGE
timeFrame: Randomization and 6 months
measure: Descending Aortic Strain
timeFrame: Randomization
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Alfred I duPont Hospital
state: Delaware
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Philadelphia
country: United States
facility: Nemours Children's Clinic-Jefferson
state: Pennsylvania
Study officials:
affiliation: Nemours Children's Clinic 807 Children's Way Jacksonville, Florida 32207
name: Nelly Mauras, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 cholesterol (LDL-C) and type 1 diabetes. Pediatr Diabetes. 2015 Mar;16(2):79-89. doi: 10.1111/pedi.12245. Epub 2014 Nov 22.
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 diabetes mellitus. Pediatr Diabetes. 2015 Mar;16(2):90-7. doi: 10.1111/pedi.12241. Epub 2014 Dec 18.