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

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus; Ischemic Heart Disease
• Interventions: Drug: Metformin plus vildagliptin; Drug: Metformin only

• Registration Number: NCT01604213
• Lead Sponsor: Sheba Medical Center

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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-05-21
• Study First Submitted QC: 2012-05-22
• Study First Posted: 2012-05-23
• Study Start: 2012-09
• Status Verified: 2016-04
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Last Update Submitted: 2016-04-17
• Last Update Posted: 2016-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vildagliptin+metformin	Metformin plus vildagliptin	Oral Vildagliptin+metformin combination
Metformin only	Metformin only	Oral metformin only

Primary Outcome Measures

Name	Time	Method
Reduction in serum levels of Interleukin 6 (IL-6)	3 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Sheba Medical Center, Cardiac Rehabilitation Institute; 🇮🇱 Tel Hashomer, Israel