Ischemic Heart Disease, Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, vildagliptin, metformin, atherosclerosis, inflammation, interleukin-6, TNF, atherothrombosis, adiponectin, MMP-9, hs-CRP
Brief summary
The purpose of this study is to demonstrate that combined vildagliptin-metformin therapy is associated with clinically significant reductions in biological markers of inflammation, pro-thrombogenicity, and atherosclerosis as compared to metformin mono-therapy in a population of diabetic patients with coronary artery disease who undergo cardiac rehabilitation. The pre-specified established biological markers of inflammation, pro-thrombogenicity, and atherosclerosis will include: interleukin-6 (IL-6 - primary biological marker), hs-CRP, platelet reactivity testing, MMP-9, Interleukin 1 beta (IL-1 beta) and adiponectin levels.
Detailed description
The study is designed as a single-center, randomized, non-blinded, clinical trial to provide evidence on the effects of vildagliptin on key biomarkers of atherothrombosis and inflammation. We plan to prospectively enroll 60 patients with proven coronary artery disease and randomize them in a 2:1 ratio to either vildagliptin-metformin therapy (n=40) or metformin therapy (n=20).
Interventions
DRUGMetformin plus vildagliptin
Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary
DRUGMetformin only
Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated
Sponsors
Sheba Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes Mellitus on oral mono-therapy or diet only treatment * Stable documented ischemic Heart disease (\>30 days post AMI, CABG or PCI) * Sub-optimal Hb A1c as defined ≥6.5% * Age \> 21 * Life expectancy \>1 year
Exclusion criteria
* Significant renal impairment (creatinine ≥1.4 mg\\dL females or ≥1.5 mg\\dL males) * Planned coronary intervention or planed surgical intervention (PCI or CABG) * Planned surgical intervention * Recent (\<30 day) acute coronary syndrome (ACS) * Hypersensitivity to either of the study drug components * History of lactic acidosis * Type I diabetes * Current Hb A1c \>9% * Current Insulin treatment * Active treatment with GLP-1 or DPP4i medication * Hepatic impairment or ALT\\AST elevations beyond X2 upper normal limit or known hepatic failure * Inability to comply with study protocol * Active malignancy other than basal cell carcinoma (BCC) * Clinically advanced congestive heart failure - NYHA III-IV * Severe left ventricular dysfunction (LVEF\<30%) with NYHA II or any NYHA class with documented recent heart failure decompensation (\<3 months) * Severe stable cardiac angina CCS III - IV or Unstable angina * Chronic inflammation (i.e. IBD, Lupus, inflammatory arthritis, rheumatoid arthritis) or chronic infection (i.e. chronic diabetic foot infection) * Pregnancy, lactation or child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction in serum levels of Interleukin 6 (IL-6) | 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in other markers of athero-thrombosis and inflammation: | 3 months | I. Improvement in other markers of athero-thrombosis and inflammation: 1. High sensitivity C-reactive protein (hs-CRP), 2. Platelet reactivity 3. Adiponectin levels 4. IL-1 beta 5. Matrix metallo-peptidase 9 (MMP-9) 6. Additional exploratory markers including: IL-1 alpha ,, IL-17, TNF-alpha, MCP-1 |
Countries
Israel
Outcome results
None listed