Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease
Overview[ - collapse ][ - ]
| Purpose | 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. |
|---|---|
| Condition | Type 2 Diabetes Mellitus Ischemic Heart Disease |
| Intervention | Drug: Metformin plus vildagliptin Drug: Metformin only |
| Phase | Phase 4 |
| Sponsor | Sheba Medical Center |
| Responsible Party | Sheba Medical Center |
| ClinicalTrials.gov Identifier | NCT01604213 |
| First Received | May 21, 2012 |
| Last Updated | July 29, 2013 |
| Last verified | October 2012 |
Tracking Information[ + expand ][ + ]
| First Received Date | May 21, 2012 |
|---|---|
| Last Updated Date | July 29, 2013 |
| Start Date | September 2012 |
| Estimated Primary Completion Date | February 2015 |
| Current Primary Outcome Measures | Reduction in serum levels of Interleukin 6 (IL-6) [Time Frame: 3 months] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Improvement in other markers of athero-thrombosis and inflammation: [Time Frame: 3 months] [Designated as safety issue: No]I. Improvement in other markers of athero-thrombosis and inflammation: High sensitivity C-reactive protein (hs-CRP), Platelet reactivity Adiponectin levels IL-1 beta Matrix metallo-peptidase 9 (MMP-9) Additional exploratory markers including: IL-1 alpha ,, IL-17, TNF-alpha, MCP-1 |
Descriptive Information[ + expand ][ + ]
| Brief Title | Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease |
|---|---|
| Official Title | Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetic Patients With Coronary Artery Disease |
| 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). |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment |
| Condition |
|
| Intervention | Drug: Metformin plus vildagliptin Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary Other Names: EucreasDrug: Metformin only Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 60 |
| Estimated Completion Date | February 2015 |
| Estimated Primary Completion Date | December 2014 |
| Eligibility Criteria | 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 ≥7.0% - 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 |
| Gender | Both |
| Ages | 21 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Robert V Klempfner, MD 9729 9546281 klempfner@gmail.com |
| Location Countries | Israel |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01604213 |
|---|---|
| Other Study ID Numbers | SHEBA-12-9455-RK-CTIL |
| Has Data Monitoring Committee | No |
| Information Provided By | Sheba Medical Center |
| Study Sponsor | Sheba Medical Center |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Robert Klempfner, MD Sheba Medical Center |
| Verification Date | October 2012 |
Locations[ + expand ][ + ]
| Sheba Medical Center, Cardiac Rehabilitation Institute | Tel Hashomer, Israel, 52621 Contact: Robert Klempfner | 9729 9546281 | klempfner@gmail.comRecruiting |
|---|