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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Sheba Medical Center
Sponsor:
Information provided by (Responsible Party):
Dr. Robert Klempfner Heart Rehabilitation Institute, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01604213
First received: May 21, 2012
Last updated: July 29, 2013
Last verified: October 2012
  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 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


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (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).

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01604213

Contacts
Contact: Robert V Klempfner, MD 9729 9546281 klempfner@gmail.com
Contact: Robert Klempfner 9729 9546281 klempfner@gmail.com

Locations
Israel
Sheba Medical Center, Cardiac Rehabilitation Institute Recruiting
Tel Hashomer, Israel, 52621
Contact: Robert Klempfner    9729 9546281    klempfner@gmail.com   
Contact: Ilan Goldenberg, Prof.       Ilan.Goldenberg@sheba.health.gov.il   
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Robert Klempfner, MD Sheba Medical Center
  More Information

Publications:

Responsible Party: Dr. Robert Klempfner Heart Rehabilitation Institute, Robert Klempfner MD, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01604213     History of Changes
Other Study ID Numbers: SHEBA-12-9455-RK-CTIL
Study First Received: May 21, 2012
Last Updated: July 29, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Sheba Medical Center:
Type 2 diabetes mellitus
vildagliptin
metformin
atherosclerosis
inflammation
interleukin-6
TNF
atherothrombosis
adiponectin
MMP-9
hs-CRP

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Coronary Artery Disease
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Heart Diseases
Inflammation
Myocardial Ischemia
Thrombosis
Arterial Occlusive Diseases
Cardiovascular Diseases
Embolism and Thrombosis
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pathologic Processes
Vascular Diseases
Metformin
Vildagliptin
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014