Rosiglitazone and Metformin: Outcomes Trial in Nondiabetic Patients With Stable Coronary Syndromes (Romance) Pilot Study
Status:
Terminated
Trial end date:
2008-01-01
Target enrollment:
Participant gender:
Summary
Nearly half of all Americans will die from cardiovascular disease caused by the build up of
atherosclerotic plaque within coronary arteries. Most deaths in these patients arise from the
development of acute coronary syndromes (ACS) such as myocardial infarction, unstable angina,
or sudden death. ACS is characterized by coronary plaque erosion or rupture, which is
triggered by endothelial changes, including inflammation, and thrombosis. Diabetes, with
insulin resistance as a major component, has been shown to engender adverse metabolic events
within the endothelial cell [1], including impaired endothelial function, augmented
vasoconstriction, increased inflammation and thrombosis. Activation of the transcription
factors nuclear factor KB (NF-KB) and activator protein 1 (AP-1) induces inflammatory gene
expression, with liberation of leukocyte-attracting chemokines, increased production of
inflammatory cytokines, and augmented expression of cellular adhesion molecules. These
metabolic processes may therefore play a significant role in the development of ACS.The
hypothesis is that rosiglitazone and metformin, or the combination of both may provide
positive anti-atherogenic effect, even among patients without diabetes. This pilot study
proposes to evaluate the effect of placebo vs. combined rosiglitazone/metformin (Avandamet®)
on surrogate blood markers of atherosclerosis activity among non-diabetic and pre-diabetic
patients with known stable coronary syndromes. This will provide further evidence justifying
a large definitive outcomes-based clinical trial.