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

Type 2 Diabetes Mellitus Clinical Trial

— VAAST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01604213
• Other study ID #: SHEBA-12-9455-RK-CTIL
• Status: Completed
• Phase: Phase 4
• First received: May 21, 2012
• Last updated: April 17, 2016
• Start date: September 2012
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Inflammation
• Ischemic Heart Disease
• Myocardial Ischemia
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Metformin plus vildagliptin
Oral Metformin 850mg and vildagliptin 50mg, qd initially, up-titrated to BID if clinically necessary
• Metformin only
Oral Metformin 850mg QD, up-titrated to 850mg TID is clinically indicated

Locations

Country	Name	City	State
Israel	Sheba Medical Center, Cardiac Rehabilitation Institute	Tel Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (5)

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. — View Citation

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 Dec;14(12):1061-72. doi: 10.1111/j.1463-1326.2012.01610.x. Epub 2012 May 17. Review. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in serum levels of Interleukin 6 (IL-6)		3 months	No
Secondary	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	3 months	No