Functional Improvement of Progenitor Cells and Endothelial Function by Vildagliptin in Diabetes Mellitus (FINNjA-DM). (FINNjA-DM)

SDF-1, an important cytokine for neovascularisation is cleaved by (dipeptidyl peptidase IV) DPPIV.

The aim of this study is to assess the effect of the dipeptidyl peptidase IV inhibitor vildagliptin (Galvus®) on endothelial function as well as number and functional activity of progenitor cells in patients with documented diabetes mellitus.

Study Overview

• Status: Withdrawn
• Conditions: SDF-1 is an Important Cytokine for Neovascularization. Cleavage of SDF-1 is Reduced by DPPIV Inhibitors
• Intervention / Treatment: Drug: Vildagliptin

Detailed Description

The peptidase CD26 (DPPIV/dipeptidyl peptidase IV) removes dipeptides from the amino terminus of proteins and thereby inactivates these cleaved proteins. It was shown, that CD26 cleaves SDF-1 into a non-mitogenic molecule. Inhibition or deletion of CD26 leads to an increased homing of hematopoietic progenitor cells to the bone marrow after transplantation by increasing the invasion capacity of these cells {Campbell et al. 2008; Christopherson et al. 2004}.

The cytokine SDF-1 is released in response to hypoxia, is crucial for progenitor cell homing and recruitment of cells for neovascularisation. Invasion capacity is closely related to the cytokine SDF-1 and the SDF-1 receptor CXCR4 {Ceradini et al. 2004}. The in vivo neovascularisation capacity of progenitor cells is closely correlated to their functional capacity as SDF-1 induced invasion or colony-forming capacity {Heeschen et al. 2004; Britten et al. 2003; Assmus et al. 2007}.

Therefore, the aim of this study is to assess the effect of the dipeptidyl peptidase IV inhibitor vildagliptin on endothelial function as well as number and functional activity of progenitor cells in patients with documented diabetes mellitus.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Germany
  • Frankfurt, Germany, 60590
    • Department of Cardiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with diabetes mellitus type 2 under stable medication
• HbA1c between 7% an 10%
• age between 18 and 80 years
• signed informed consent

Exclusion Criteria:

• Atrial fibrillation (plethysmographic recordings can only obtained in sinus-rhythm)
• CAD with reduced left ventricular ejection fraction (LVEF <45%)
• Pregnancy, chronic or acute infection, fever
• Diabetes mellitus type 1
• Newly diagnosed diabetes, uncontrolled diabetes
• Neoplasm
• Known allergy to study drug
• Severe liver/kidney disease
• HIV, Hepatitis
• Participation at other studies within the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vildagliptin; starting with vildagliptin for 30 days followed by placebo for 30 days	Drug: Vildagliptin; Vildagliptin, 50 mg twice a days, orally for 30 days followed by placebo; Other Names: Galvus (R)
Placebo Comparator: Placebo; starting with placebo for 30 days followed by vildagliptin for 30 days	Drug: Vildagliptin; Vildagliptin, 50 mg twice a days, orally for 30 days followed by placebo; Other Names: Galvus (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endothelial Function	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and Function of Progenitor Cells	30 days

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Investigators: Principal Investigator: Andreas M. Zeiher, MD, Cardiology, University of Frankfurt

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: July 8, 2009
• First Submitted That Met QC Criteria: July 8, 2009
• First Posted (Estimate): July 9, 2009

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: diabetes; endothelial function; CAD; SDF-1
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metaplasia; Diabetes Mellitus; Neovascularization, Pathologic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin
• Other Study ID Numbers: FINNjA-DM