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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Insulin Glargin; Drug: Human Insulin

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Per M Humpert, Dr.; Phone Number: 8027 +49 6221 56; Email: per.humpert@med.uni-heidelberg.de
• Study Contact Backup: Name: Dimitrios Oikonomou; Phone Number: 37944 +49 6221 56; Email: dimitrios.oikonomou@med.uni-heidelberg.de

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University Clinics Heidelberg, Dept. Medicine1
    • Contact: Dimitrios Oikonomou; Phone Number: 37944 +49 6221 56; Email: dimitrios.oikonomou@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Heidelberg University
• Investigators: Principal Investigator: Per M Humpert, Dr., University of Heidelberg, Dept. Medicine 1, Germany

Publications and helpful links

General Publications

• Oikonomou D, Kopf S, von Bauer R, Djuric Z, Cebola R, Sander A, Englert S, Vittas S, Hidmark A, Morcos M, Korosoglou G, Nawroth PP, Humpert PM. Influence of insulin and glargine on outgrowth and number of circulating endothelial progenitor cells in type 2 diabetes patients: a partially double-blind, randomized, three-arm unicenter study. Cardiovasc Diabetol. 2014 Oct 11;13:137. doi: 10.1186/s12933-014-0137-4.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Anticipated): December 1, 2009
• Study Completion (Anticipated): May 1, 2010

Study Registration Dates

• First Submitted: August 29, 2007
• First Submitted That Met QC Criteria: August 29, 2007
• First Posted (Estimate): August 31, 2007

Study Record Updates

• Last Update Posted (Estimate): February 13, 2009
• Last Update Submitted That Met QC Criteria: February 12, 2009
• Last Verified: February 1, 2009

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; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 2006-006573-24