Effect of Atorvastatin on Vascular Inflammation in Type 2 Diabetes

Effect of Atorvastatin on Vascular Inflammation in Type 2 Diabetes: Analysis With 18F-Fluorodeoxyglucose Positron Emission Tomography

Type 2 diabetes mellitus significantly increases the risk for the development of atherosclerosis. Recently, atherosclerosis imaging with 18F-FDG PET (18F-Fluorodeoxyglucose Positron Emission Tomography) is useful for tracking inflammation within plaque and monitoring the response to drug therapy

The purpose of this study is to determine whether FDG-PET is capable of detecting atherosclerotic vascular inflammation and monitoring the early effects of statins in type 2 diabetic patients. The usefulness of FDG-PET in risk stratification is also investigated.

Study Overview

• Status: Withdrawn
• Conditions: Atherosclerosis; Type 2 Diabetes
• Intervention / Treatment: Drug: Atorvastatin

Detailed Description

The early detection of vulnerable plaques is clinically important for risk stratification and also to provide early treatment. Inflammation is important in the both pathogenesis and outcome of atherosclerosis. Plaques containing numerous inflammatory cells, particular macrophages, have a high risk of rupture. Diabetes is a major risk factor for the development of atherosclerosis. Lipid-lowering therapy with statins significantly decreases cardiovascular morbidity and mortality in primary and secondary prevention. Statin exert their benefits through the inhibition of de novo cholesterol synthesis, resulting in significant reductions in plasma low-density lipoprotein cholesterol (LDL-C) levels. It remains controversial whether LDL-C lowering is the only mechanism for the observed beneficial effects. Many LDL-C-independent pleiotropic effects have been postulated. Moreover, Lipid lowering therapy may affect atherosclerosis also through the inhibition of inflammatory marker. These evidences highlight the possibility of statins could be have great impact on plaque inflammation. 18FDG is a glucose analogue that is taken up by cells in proportion to their metabolic activity. Several papers have reported the potential roles of metabolic imaging in the assessment of inflammatory vascular diseases, especially in large vessels. If so, FDG-PET can monitor the direct effect of statins on vascular inflammation. Additionally, monitoring the vascular inflammation by FDG-PET may be useful for determining the risk stratification of atherosclerotic patients. The investigators hypothesize that statins-induced attenuation of vascular inflammation could be monitored clinically by use of FDG-PET approach, and providing information of early efficacy statins therapy caused by stabilization of vulnerable plaque without affecting the lumen size.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 152-050
    • Tae Nyun Kim

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 diabetic patients who are aged 35 to 80 year-old

Exclusion Criteria:

• Insulin use
• Patients who receive any dyslipidaemia under medications (including statins) in recent one year
• Women of child-bearing potential are excluded (i.e. menopausal women or post-hysterectomy women are included in this study) due to radiation exposure in this study
• Active inflammatory diseases
• Vasculitis, symptomatic coronary artery disease, symptomatic cerebrovascular diseases
• Significant concomitant disease such as active infection, malignancy, hepatic or renal dysfunction at the time of enrollment (i.e. T-Bil > 3 mg/dl，ALT > 2.5 times the upper limit of normal range and Creatinine > 2 mg/dl in our hospital)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: Atorvastatin	Drug: Atorvastatin; Atorvastatin 10mg once daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Vascular inflammation analyzed by PET: Define attenuation of plaque inflammation (plaque SUV or TBR) at 12 weeks	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in LDL-cholesterol levels after active treatment	12 weeks
Biomarkers: hs-CRP, adiponectin, MCP-1, PAI-1, TNF-α, IL-6	12 weeks
Change in carotid plaque thickness by ultrasound	12 weeks

Collaborators and Investigators

• Sponsor: Korea University
• Investigators: Principal Investigator: Kyung Mook Choi, MD. PhD, Korea University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): January 1, 2012
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: July 1, 2009
• First Submitted That Met QC Criteria: July 1, 2009
• First Posted (Estimate): July 2, 2009

Study Record Updates

• Last Update Posted (Estimate): September 6, 2013
• Last Update Submitted That Met QC Criteria: September 5, 2013
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; PET; Statins
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: R0709211