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

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:

MedlinePlus related topics: Atherosclerosis Coronary Artery Disease Diabetes Diabetes Type 2 Heart Diseases

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

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 2014
Estimated Primary Completion Date:	December 2013 (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

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:

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. Epub 2011 Oct 17.

Gooßen K, Gräber 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 Apr 20. doi: 10.1111/j.1463-1326.2012.01610.x. [Epub ahead of print]

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.

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. Epub 2009 Aug 28.

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. Epub 2010 Jun 17.

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:	October 4, 2012
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:

Atherosclerosis
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Heart Diseases
Inflammation
Thrombosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders

Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Embolism and Thrombosis
Vildagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013

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