Prospective Influence of Bedtime Insulin Glargine on Mobilization and Function of Endothelial Progenitor Cells

Study Overview
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Brief Summary
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In this trial, it will be studied whether early addition of the long acting insulin analogue Glargine is capable of increasing the number and differentiation of endothelial progenitor cells (EPC) in patients with type 2 diabetes, which can be seen as a marker of vascular regenerative potential and cardiovascular risk. In addition, the effect of Glargine on microvascular function will be studied. This will be done using laser Doppler measurements of the skin; in addition, MRI of the heart will be performed which is capable of quantifying the perfusion reserve of the myocardium and additional functional aspects of ventricular function. A beneficial effect of early addition of bedtime Glargine on EPC and vascular as well as myocardial function in this study might argue for a change in the therapeutic approach in type 2 diabetes and possibly improve the cardiovascular outcome in patients affected.

Official Title
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Prospective Influence of Bedtime Insulin Glargine on Mobilization and Function of Endothelial Progenitor Cells in Patients With Type 2 Diabetes: a Partially Double-Blind, Randomized, Three-Arm Unicenter Study

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Insulin Glargin
* Drug: Human Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Oral antidiabetic therapy Age 35 - 70 6,5%< HbA1c ≤ 9% Ability of subject to understand character and individual consequences of clinical trial Written informed consent must be available before enrollment in the trial For women with childbearing potential, adequate contraception (Pearl Index < 1%, e.g. birth control pill) and negative blood pregnancy test 6,5%< HbA1c ≤ 9% Ability of subject to understand character and individual consequences of clinical trial Written informed consent must be available before enrollment in the trial For women with childbearing potential, adequate contraception (Pearl Index < 1%, e.g. birth control pill) and negative blood pregnancy test Exclusion Criteria: MODY Malignant disease Hematopoietic disorders Impairment of renal function (Serum creatinine > 1,5mg/dl) autoimmune disease treatment with immunosuppressive drugs Psychiatric disease Myocardial ischemia during previous 6 month Acute coronary syndrome pAVK IIb, III, IV (Fontaine-Ratschow) Erythropoietin treatment Glitazone treatment during two weeks before inclusion Insulin treatment during two weeks before inclusion Pregnancy and lactation History of hypersensitivity to the investigational product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational product Participation in other clinical trials and observation period of competing trials, respectively No subject will be allowed to enroll in this trial more than once.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br> | |
| Experimental: 2<br> | Drug: Insulin Glargin<br>* Titration of bedtime insulin glargin aiming at normal morning fasting glucose<br>* Other names: Lantus®, HOE901 (internal code number Sanofi-Aventis);|
| Active Comparator: 3<br> | Drug: Human Insulin<br>* Titration of bedtime human insulin aiming at normal morning fasting glucose<br>* Other names: Insuman Basal®, HR1799(internal code number Sanofi-Aventis);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of number of circulating EPC 4 weeks after start of therapy compared to baseline as detected by FACS analysis |  | 4 weaks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of number of circulating EPC 4 as detected by in vitro outgrowth |  | 4 weeks, 4 months | 
| Skin microvascular function (as measured by laser Doppler perfusion upon heat stimulation) |  | 4 months | 
| Myocardial function and myocardial perfusion reserve as measured by MRI |  | 4 months | 
| Intima-Media-Thickness |  | 4 months | 
| Long-term Glucose control (HbA1c) |  | 4 weeks, 4 months | 
| Short-term Glucose control (fasting glucose) |  | 4 weeks, 4 months | 
| Markers of inflammation and vascular risk in diabetes |  | 4 weeks, 4 months |