Diabetes Mellitus, Atherosclerosis Clinical Trial
Official title:
The Impact of Rosiglitazone on Regression of Atherosclerosis: A Serial 18F-Fluorodeoxyglucose Positron Emission Tomography Study
Cardiovascular events are the leading cause of death in developed countries worldwide, including Taiwan. The disruption of atherosclerotic plaques and the subsequent formation of thrombi are currently recognized as the major cause of morbidity and mortality of cardiovascular diseases. Therefore, early detection of vulnerable plaques is clinically important for risk stratification and also to provide early treatment. Several imaging approaches have been adapted to detect vulnerable plaques, however, most of them are based on morphologic characteristics of atheroma. We hypothesize that PPARγ-induced plaque regression could be monitored clinically by use of 18FDG PET/CT approach, which could assess the inflammatory activity, and can be detected noninvasively earlier than previously reported.
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. The discovery of the peroxisome proliferator-activated
receptor γ (PPARγ) gene led to the hope of favorably influencing the insulin resistance
syndrome. The administration of PPARγ agonists have been shown to reduce insulin resistance,
to reduce the expression of leptin, to lower plasma free fatty acid level and to lower blood
pressure. Moreover, beyond the glucose effect, PPARγ agonists may theoretically affect
atherosclerosis also through the inhibition of inflammatory cytokines secreted from the
macrophage, such as IL-6, IL-1β, TNF-α, etc. These evidences highlight the possibility of
PPARγ agonists could be have great impact on plaque regression.
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. However, PET has
limited spatial resolution. Recently, a combined PET/CT is emerged as a promising modality
which could provide both anatomical and functional information. We hypothesize that PPARγ
agonists-induced plaque regression could be monitored clinically by use of 18FDG PET/CT
approach, and providing information of early efficacy PPARγ treatment caused by
stabilization of vulnerable plaque without affecting the lumen size.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment