Effect of Adding Vildagliptin on Beta Cell Function and Cardiovascular Risk Markers in Patients With Moderate Metabolic Control During Metformin Monotherapy

The aim of this pilot-study is to investigate the effect of Vildagliptin in comparison to glimepiride on beta cell function and the cardiovascular risk profile in patients previously treated with Metformin monotherapy.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus Type II
• Intervention / Treatment: Drug: Vildagliptin; Drug: Metformin; Drug: Glimepiride

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55116
    • Recruiting
    • IKFE GmbH
    • Contact: Swantje Anders; Phone Number: +49 6131 327 90 22; Email: s.anders@ikfe-cro.de
    • Contact: Thomas Forst, Prof., MD; Phone Number: +49 6131 576 36 16; Email: thomasf@ikfe.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diabetes mellitus type 2

• HbA1c > 6.5%* ≤ 9.5%

  * NOTE: Patients with cardiovascular preconditions (Coronary Heart Disease or Myocard Infarction) require an HbA1c > 7.0% ≤ 9.5%

• Treatment with Metformin at maximal or maximal tolerated dosage, stable for at least 3 months with indication for treatment with an additional medication as judged by the investigator
• Age 30 - 80 years
• Patient consents that his/her family physician will be informed of trial participation

Exclusion Criteria:

• Pre-treatment with insulin, peroxisome proliferator activated receptor (PPAR) gamma agonists or other oral antidiabetic treatments (except Metformin) within the last three months
• History of type-1-diabetes
• Fasting blood glucose >240mg/dl
• Uncontrolled hypertension (systolic blood pressure >160 and/or diastolic blood pressure >90)
• Anamnestic history of acute infections
• Anamnestic history of epilepsy
• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures
• History of severe or multiple allergies
• Hereditary galactose intolerance, lapp-lactase defect or glucose-galactose mal-absorption
• Treatment with any other investigational drug within 3 months before trial entry
• Pregnant or lactating women
• Sexually active woman of childbearing age not practicing a highly effective method of birth control as defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices, sexual abstinence or vasectomized partner
• Progressive fatal disease
• History of drug or alcohol abuse in the past 2 years
• State after kidney transplantation
• Serum potassium > 5.5 mmol/L
• Acute myocardial infarction, open heart surgery or cerebral event (stroke/transient ischemic attack) within the previous 6 months
• Any elective surgery during study participation
• Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit
• History of pancreatitis
• Anamnestic history of dehydration, diabetic precoma or diabetic ketoacidosis
• Acute or scheduled investigation with iodine containing radiopaque material
• Uncontrolled unstable angina pectoris
• Anamnestic history of pericarditis, myocarditis, endocarditis, hemodynamic relevant aortic stenosis, aortic aneurysm or heart insufficiency NYHA III or IV
• Anamnestic recent pulmonary embolism
• History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT > 3 times the normal reference range), renal (GFR < 60 ml), neurological, psychiatric and/or hematological disease as judged by the investigator
• Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vildagliptin plus Metformin; Metformin (1000 mg BID) + Vildagliptin 50 mg twice daily	Drug: Vildagliptin; Vildagliptin 50 mg twice daily; Drug: Metformin; Metformin 1000 mg BID
Active Comparator: Glimepirid plus Metformin; Metformin (1000 mg BID) + Glimepiride (individual dosage)	Drug: Metformin; Metformin 1000 mg BID; Drug: Glimepiride; Glimepiride at individual dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Postprandial increase in intact proinsulin levels in patient treated with Vildagliptin and Metformin compared to intact proinsulin levels in patients treated with Glimepiride and Metformin (Area under the curve 0-300 min)	One year

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	One year
Change in body weight	One year
Fasting intact proinsulin levels	One year
Max postprandial intact proinsulin levels	One year
Retinal endothelial response to flicker light stimulation	One year
Mean 24h systolic and diastolic blood pressure	One year
Erythrocyte deformability	One year
E-selectin	One year
hsCRP	One year
HbA1c	One year
Fasting blood glucose	One year
Number of hypoglycemic events	One year
Drug related adverse events	One year

Collaborators and Investigators

• Sponsor: ikfe-CRO GmbH
• Collaborators: Novartis Pharmaceuticals; IKFE Institute for Clinical Research and Development
• Investigators: Principal Investigator: Thomas Forst, Prof. Dr., IKFE GmbH

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Anticipated): November 1, 2012

Study Registration Dates

• First Submitted: March 23, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 28, 2012

Study Record Updates

• Last Update Posted (Estimate): March 28, 2012
• Last Update Submitted That Met QC Criteria: March 26, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Glimepiride; Vildagliptin
• Other Study ID Numbers: ikfe-Vilda-001; 2011-004286-32 (EudraCT Number); CLAF237ADE06T (Other Identifier: Novartis Pharma GmbH)