Vildagliptin and Endothelium-dependent Vasodilatation

Study Overview
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Brief Summary
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Rationale: Cardiovascular complications in type 2 diabetes are the leading cause of morbidity and mortality associated with the disease. Endothelial dysfunction is regarded as an important factor in these vascular complications. The introduction of glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-IV) inhibitors for the treatment of type 2 diabetes is of special interest because of possible influences on endothelial function. Numerous reports have shown that GLP-1 improves endothelial function. Objective: To determine whether a four week treatment with vildagliptin compared to acarbose improves endothelial dysfunction in patients with type 2 diabetes mellitus.

Official Title
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The Effect of Vildagliptin on Endothelium-dependent Vasodilatation. A Double Blind Cross-over Study in Type 2 Diabetes Mellitus.

Conditions
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Type 2 Diabetes, Endothelial Dysfunction

Intervention / Treatment
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* Drug: vildagliptin + acarbose
* Drug: acarbose + vildagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Age 35-75 years Treatment with metformin monotherapy or metformin combination therapy HbA1c <8.0% Exclusion Criteria: Renal disease defined as creatinine level > 130 umol/l Liver disease defined as aspartate aminotransferase or alanine aminotransferase level of more than three times the upper limit of normal range Current use of acetylsalicylic acid or vitamine K antagonists History of smoking within the past year History of or current abuse of drugs or alcohol History of heartfailure (NYHA class III or IV) Abnormalities on ECG that might interfere with current study protocol Pregnancy or breastfeeding Inability to understand the nature and extent of the trial and procedures required Presence of any medical condition that might interfere with the current study protocol Participation in a drug trial within 60 days prior to the first dose

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vildagliptin treatment first, acarbose treatment second<br> | Drug: vildagliptin + acarbose<br>* 4 week treatment<br>|
| Experimental: acarbose treatment first, vildagliptin treatment second<br> | Drug: acarbose + vildagliptin<br>* 4 week treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forearm vasodilator response to intra-arterial infusion of acetylcholine (endothelium-dependent) following treatment with vildagliptin and following active control with acarbose |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of vildagliptin on inflammatory markers and adipokines |  | 8 weeks | 
| Effect of vildagliptin on fat cell morphology and gene expression |  | 8 weeks | 
| Effect of vildagliptin on ex vivo mononuclear cell responses to various stimuli |  | 8 weeks |