NCT01236365

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
42

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Oct 2010

Typical duration for phase_3

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2010

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

November 2, 2010

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 8, 2010

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2014

Completed
7 months until next milestone

Results Posted

Study results publicly available

May 21, 2015

Completed
Last Updated

June 25, 2019

Status Verified

June 1, 2019

Enrollment Period

3 years

First QC Date

November 2, 2010

Results QC Date

December 29, 2014

Last Update Submit

June 4, 2019

Conditions

Keywords

Type 1 diabetesChildrenStatinsHypercholesterolemiaLipoproteinsC reactive proteinContinuous glucose monitorsAdolescenceAbdominal magnetic resonance imagingToll like receptorsReceptors of advanced glycation end productsNutrition

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (3)

  • MAGE

    Randomization and 6 months

  • RAGE

    Randomization and 6 months

  • Descending Aortic Strain

    Randomization

Study Arms (2)

Atorvastatin

EXPERIMENTAL
Drug: Atorvastatin

Placebo

PLACEBO COMPARATOR
Drug: Atorvastatin Placebo

Interventions

10 or 20 mg daily

Also known as: Lipitor
Atorvastatin

10 or 20 mg daily

Placebo

Eligibility Criteria

Age10 Years - 20 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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
  • 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
  • +1 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Alfred I duPont Hospital

Wilmington, Delaware, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic

Orlando, Florida, United States

Location

Nemours Children's Clinic

Pensacola, Florida, 32504, United States

Location

Nemours Children's Clinic-Jefferson

Philadelphia, Pennsylvania, 19107, United States

Location

Related 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 cholesterol (LDL-C) and type 1 diabetes. Pediatr Diabetes. 2015 Mar;16(2):79-89. doi: 10.1111/pedi.12245. Epub 2014 Nov 22.

  • 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.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Hypercholesterolemia

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesHyperlipidemiasDyslipidemiasLipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

PyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeptanoic AcidsFatty AcidsLipids

Results Point of Contact

Title
Nelly Mauras, MD
Organization
Nemours Children's Clinic

Study Officials

  • Nelly Mauras, MD

    Nemours Children's Clinic 807 Children's Way Jacksonville, Florida 32207

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief, Division of Endocrinology, Diabetes & Metabolism

Study Record Dates

First Submitted

November 2, 2010

First Posted

November 8, 2010

Study Start

October 1, 2010

Primary Completion

October 1, 2013

Study Completion

November 1, 2014

Last Updated

June 25, 2019

Results First Posted

May 21, 2015

Record last verified: 2019-06

Locations