Back to resultsEffects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease (VAAST)
Primary Purpose
Type 2 Diabetes Mellitus, Ischemic Heart Disease
Status
Completed
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Metformin plus vildagliptin
Metformin only
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 diabetes mellitus, vildagliptin, metformin, atherosclerosis, inflammation, interleukin-6, TNF, atherothrombosis, adiponectin, MMP-9, hs-CRP
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 ≥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
Sites / Locations
- Sheba Medical Center, Cardiac Rehabilitation Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Vildagliptin+metformin
Metformin only
Arm Description
Oral Vildagliptin+metformin combination
Oral metformin only
Outcomes
Primary Outcome Measures
Reduction in serum levels of Interleukin 6 (IL-6)
Secondary Outcome Measures
Improvement in other markers of athero-thrombosis and inflammation:
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01604213
Brief Title
Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease
Acronym
VAAST
Official Title
Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetic Patients With Coronary Artery Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sheba Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, Ischemic Heart Disease
Keywords
Type 2 diabetes mellitus, vildagliptin, metformin, atherosclerosis, inflammation, interleukin-6, TNF, atherothrombosis, adiponectin, MMP-9, hs-CRP
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vildagliptin+metformin
Arm Type
Experimental
Arm Description
Oral Vildagliptin+metformin combination
Arm Title
Metformin only
Arm Type
Active Comparator
Arm Description
Oral metformin only
Intervention Type
Drug
Intervention Name(s)
Metformin plus vildagliptin
Other Intervention Name(s)
Eucreas
Intervention Description
Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary
Intervention Type
Drug
Intervention Name(s)
Metformin only
Intervention Description
Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated
Primary Outcome Measure Information:
Title
Reduction in serum levels of Interleukin 6 (IL-6)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Improvement in other markers of athero-thrombosis and inflammation:
Description
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
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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 ≥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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Klempfner, MD
Organizational Affiliation
Sheba Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sheba Medical Center, Cardiac Rehabilitation Institute
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
12. IPD Sharing Statement
Citations:
PubMed Identifier
22007077
Citation
Shah Z, Kampfrath T, Deiuliis JA, Zhong J, Pineda C, Ying Z, Xu X, Lu B, Moffatt-Bruce S, Durairaj R, Sun Q, Mihai G, Maiseyeu A, Rajagopalan S. Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation. 2011 Nov 22;124(21):2338-49. doi: 10.1161/CIRCULATIONAHA.111.041418. Epub 2011 Oct 17.
Results Reference
background
PubMed Identifier
22519906
Citation
Goossen K, Graber S. Longer term safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus: systematic review and meta-analysis. Diabetes Obes Metab. 2012 Dec;14(12):1061-72. doi: 10.1111/j.1463-1326.2012.01610.x. Epub 2012 May 17.
Results Reference
background
PubMed Identifier
20925543
Citation
Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, Woodward M, Ninomiya T, Neal B, MacMahon S, Grobbee DE, Kengne AP, Marre M, Heller S; ADVANCE Collaborative Group. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010 Oct 7;363(15):1410-8. doi: 10.1056/NEJMoa1003795.
Results Reference
background
PubMed Identifier
19766217
Citation
Jenny NS, Brown ER, Detrano R, Folsom AR, Saad MF, Shea S, Szklo M, Herrington DM, Jacobs DR Jr. Associations of inflammatory markers with coronary artery calcification: results from the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2010 Mar;209(1):226-9. doi: 10.1016/j.atherosclerosis.2009.08.037. Epub 2009 Aug 28.
Results Reference
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PubMed Identifier
20560108
Citation
Derosa G, Maffioli P, Ferrari I, Mereu R, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, D'Angelo A, Salvadeo SA. Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients. Horm Metab Res. 2010 Aug;42(9):663-9. doi: 10.1055/s-0030-1255036. Epub 2010 Jun 17.
Results Reference
background
PubMed Identifier
28532406
Citation
Younis A, Eskenazi D, Goldkorn R, Leor J, Naftali-Shani N, Fisman EZ, Tenenbaum A, Goldenberg I, Klempfner R. The addition of vildagliptin to metformin prevents the elevation of interleukin 1ss in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study. Cardiovasc Diabetol. 2017 May 22;16(1):69. doi: 10.1186/s12933-017-0551-5.
Results Reference
derived
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Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease
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