Effect of Atorvastatin on Vascular Inflammation in Type 2 Diabetes

Sponsor

Korea University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00932048

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Atherosclerosis	Drug: Atorvastatin	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2011

Anticipated Primary Completion Date :

Jan 1, 2012

Anticipated Study Completion Date :

Mar 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

No Intervention: Control

Experimental: Atorvastatin

Drug: Atorvastatin

Atorvastatin 10mg once daily for 12 weeks

Outcome Measures

Primary Outcome Measures

Vascular inflammation analyzed by PET: Define attenuation of plaque inflammation (plaque SUV or TBR) at 12 weeks [12 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)