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Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetics With Coronary Artery Disease (VAAST)

This study has been completed.
Information provided by (Responsible Party):
Dr. Robert Klempfner Heart Rehabilitation Institute, Sheba Medical Center Identifier:
First received: May 21, 2012
Last updated: April 17, 2016
Last verified: April 2016

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 Intervention Phase
Type 2 Diabetes Mellitus
Ischemic Heart Disease
Drug: Metformin plus vildagliptin
Drug: Metformin only
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Vildagliptin/Metformin Combination on Markers of Atherosclerosis, Thrombosis, and Inflammation in Diabetic Patients With Coronary Artery Disease

Resource links provided by NLM:

Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Reduction in serum levels of Interleukin 6 (IL-6) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

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:

    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

Enrollment: 60
Study Start Date: September 2012
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vildagliptin+metformin
Oral Vildagliptin+metformin combination
Drug: Metformin plus vildagliptin
Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary
Other Name: Eucreas
Active Comparator: Metformin only
Oral metformin only
Drug: Metformin only
Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated

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).

Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01604213

Sheba Medical Center, Cardiac Rehabilitation Institute
Tel Hashomer, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
Principal Investigator: Robert Klempfner, MD Sheba Medical Center
  More Information


Responsible Party: Dr. Robert Klempfner Heart Rehabilitation Institute, Robert Klempfner MD, Sheba Medical Center Identifier: NCT01604213     History of Changes
Other Study ID Numbers: SHEBA-12-9455-RK-CTIL 
Study First Received: May 21, 2012
Last Updated: April 17, 2016
Health Authority: Israel: Ministry of Health

Keywords provided by Sheba Medical Center:
Type 2 diabetes mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Embolism and Thrombosis
Hypoglycemic Agents
Physiological Effects of Drugs
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on October 25, 2016