CAVD Clinical Trial
Official title:
An Open-label, Randomized Study of Inhibitory Effect of Evogliptin, the Dipeptidyl Peptidase-4 Inhibitor, on the Progression of Aortic Valve Calcification in Patients With Type 2 Diabetes Mellitus and Mild-to-moderate Aortic Stenosis
The purpose of this study is to assess an inhibitory effect of Evogliptin on the progression of mild-to-moderate aortic stenosis in patients with T2DM and calcific aortic stenosis.
Despite a lot of clinician's efforts to develop an effective medical treatment of calcific
aortic valve disease (CAVD) for decades, there is no scientifically-proved medical treatment
yet. Since the pathological features of CAVD are characterized by inflammatory cell
infiltration and lipid deposition, as in atherosclerosis, statin drugs that are proved to be
effective in the treatment of cardiovascular disease, have been used in the most recent
randomized clinical trials; however, different types of medications showed negative results
and thus, CAVD represents an unmet clinical need.
Researchers of Asan Medical Center have proved that dipeptidyl-peptidase-4 (DPP-4)-IGF
(insulin-like growth factor)-1 axis is important for pathologic osteoblast transformation of
valvular interstitial cell (VIC), and reported that the administration of DPP-4 inhibitor
prevents the calcification effectively in the actual animal model of CAVD. Under a normal
condition, IGF-1 suppresses the pathologic transformation of VIC; however, when endothelial
cells are damaged due to aging or various pathological conditions, DPP-4 expression is
increased in valvular tissue. Since DPP-4 acts as an enzyme that degrades IGF-1, it reduces
normal IGF-1 activity and increases transformation of VIC to osteoblast, causing pathological
calcification and worsening CAVD.
After comparing six different DPP-4 inhibitors, researchers of Asan Medical Center discovered
that evogliptin has higher cardiac tissue distribution compared to other DPP-4 inhibitors. In
addition, the DPP-4 inhibitors with high cardiac tissue distribution have shown decreased
incidence rate of severe CAVD in the retrospective study. Based on these findings, this study
will examine the effect of evogliptin on progression of CAVD.
The study is a randomized, open-label trial of evogliptin in subjects with T2DM and
moderate-to-severe CAVD. Subjects who have agreed to participate in the study and signed the
ICF will undergo a screening period and those who meet the eligibility criteria will be
randomized in a 1:1 ratio to evogliptin or non-evogliptin group. The subjects will take the
drug for 96 weeks and will be closely monitored for efficacy. The effectiveness of evogliptin
on inhibition of CAVD progression will be evaluated by comparing the change in aortic valve
calcium volume in the evogliptin group against that of the non-evogliptin group.
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