Endothelial Effects of Basal Insulin: Detemir Versus Glargine - Full Text View

Purpose

Endothelial progenitor cell (EPC) level represents a surrogate marker of cardiovascular risk and an indicator of the ongoing vascular damage. Moreover, EPCs are involved in the pathogenesis of virtually all diabetic complications. Therefore, ways to modulate EPCs are currently considered of utmost importance, especially in high-risk subjects. While many drugs with pleiotropic vasculoprotective effects have shown ability to positively modulate EPCs, there is no data on the effects of specific insulin formulations.

This is a human randomised cross-over comparison trial. The purpose is to compare the effects of two basal insulin analogues (detemir and glargine) added to oral antidiabetic therapy in poorly-controlled type 2 patients with cardiovascular disease on endothelial function and EPC levels.

The aim is to test whether optimized glycemic control with add-on basal insulin analogues improves endothelial damage and regeneration in type 2 diabetes with macroangiopathy and to compare the effects of glargine vs detemir on markers of endothelial damage and regeneration.

EPC level is the most innovative outcome measure of this study and represents the primary endpoint. Endothelial dysfunction/damage, evaluated using soluble markers, will be the secondary outcome. Given the supposed inverse correlation between EPC and endothelial damage, it is expected that EPC increase reflects amelioration in endothelial biology, a result that may have significant clinical implications in this cohort of high-risk patients.

Condition	Intervention	Phase
Type 2 Diabetes Endothelial Dysfunction Cardiovascular Disease	Drug: Glargine Drug: Detemir	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Effects of Optimized Glycemic Control Achieved With add-on Basal Insulin Therapy on Indexes of Endothelial Damage and Regeneration in Type 2 Diabetic Patients With Macroangiopathy. A Randomized Cross-over Trial Comparing Detemir vs Glargine

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Insulin human Insulin glargine Insulin detemir

U.S. FDA Resources

Further study details as provided by University of Padova:

Primary Outcome Measures:

Change in endothelial progenitor cell count [ Time Frame: Basal, 3 months, 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in markers of endothelial damage [ Time Frame: Basal, 3 months, 6 months ] [ Designated as safety issue: No ]
Frequence of hypoglycemias [ Time Frame: during 1st and 2nd arms ] [ Designated as safety issue: Yes ]
The frequency of hypoglycemia will be reported for patients on glargine or detemir during the 1st and 2nd period of treatment.
Change in body weight [ Time Frame: After the 1st and 2nd arms ] [ Designated as safety issue: Yes ]
Change in body weight will be assessed after each arm during treatment with glargine or detemir

Estimated Enrollment:	50
Study Start Date:	May 2008
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Glargine During this arm/phase patients take subcutaneous glargine daily for 3 months.	Drug: Glargine Daily bedtime subcutaneous insulin Glargine in individualized doses. Other Name: Lantus
Experimental: Detemir During this arm/phase, patients take insulin Detemir subcutaneously for 3 months.	Drug: Detemir Daily bedtime subcutaneous insulin Detemir in individualized doses. Other Name: Levemir

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Eligibility

Ages Eligible for Study:	35 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Type 2 diabetes
Macroangiopathy (coronary, or peripheral, or cerebrovascular)
On oral antidiabetic therapy
HbA1c > 7.0%

Exclusion Criteria:

Type 1 diabetes
Acute diabetic decompensation
Use of glitazones
Cancer
Acute disease or infection
Chronic renal failure (serum creatinin > 2.0 mg/dl)
Advanced liver disease (Child B-C)
Immune disease, organ transplantation, immunosuppression
Recent surgery (within 3 months)
Recent cardiovascular events (within 3 months)
Inability to provide informed consent
Pregnancy and lactation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699686

Locations

Italy
Dipartimento di Medicina Clinica e Sperimentale, Divisione di Malattie del Metabolismo
Padova, Italy, 35100

Sponsors and Collaborators

University of Padova

Investigators

Principal Investigator:

Angelo Avogaro, M.D.

University of Padova, Medical School

More Information

Publications:

Fadini GP. An underlying principle for the study of circulating progenitor cells in diabetes and its complications. Diabetologia. 2008 Jul;51(7):1091-4. No abstract available.

Fadini GP, Agostini C, Avogaro A. Endothelial progenitor cells and vascular biology in diabetes mellitus: current knowledge and future perspectives. Curr Diabetes Rev. 2005 Feb;1(1):41-58.

Fadini GP, Baesso I, Agostini C, Cuccato E, Nardelli GB, Lapolla A, Avogaro A. Maternal insulin therapy increases fetal endothelial progenitor cells during diabetic pregnancy. Diabetes Care. 2008 Apr;31(4):808-10. Epub 2007 Dec 27. No abstract available.

Fadini GP, Pucci L, Vanacore R, Baesso I, Penno G, Balbarini A, Di Stefano R, Miccoli R, de Kreutzenberg S, Coracina A, Tiengo A, Agostini C, Del Prato S, Avogaro A. Glucose tolerance is negatively associated with circulating progenitor cell levels. Diabetologia. 2007 Oct;50(10):2156-63. Epub 2007 Jun 20.

Fadini GP, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care. 2007 May;30(5):1305-13. Epub 2007 Feb 2. Review. No abstract available.

Fadini GP, Sartore S, Schiavon M, Albiero M, Baesso I, Cabrelle A, Agostini C, Avogaro A. Diabetes impairs progenitor cell mobilisation after hindlimb ischaemia-reperfusion injury in rats. Diabetologia. 2006 Dec;49(12):3075-84. Epub 2006 Oct 27.

Fadini GP, de Kreutzenberg SV, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A. Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk. Eur Heart J. 2006 Sep;27(18):2247-55. Epub 2006 Aug 15.

Fadini GP, Coracina A, Baesso I, Agostini C, Tiengo A, Avogaro A, de Kreutzenberg SV. Peripheral blood CD34+KDR+ endothelial progenitor cells are determinants of subclinical atherosclerosis in a middle-aged general population. Stroke. 2006 Sep;37(9):2277-82. Epub 2006 Jul 27.

Avogaro A, Fadini GP, Gallo A, Pagnin E, de Kreutzenberg S. Endothelial dysfunction in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2006 Mar;16 Suppl 1:S39-45. Epub 2006 Feb 8. Review.

Fadini GP, Miorin M, Facco M, Bonamico S, Baesso I, Grego F, Menegolo M, de Kreutzenberg SV, Tiengo A, Agostini C, Avogaro A. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol. 2005 May 3;45(9):1449-57.

Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2140-6. Epub 2006 Jul 20.

Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005 Sep 8;353(10):999-1007.

Humpert PM, Neuwirth R, Battista MJ, Voronko O, von Eynatten M, Konrade I, Rudofsky G Jr, Wendt T, Hamann A, Morcos M, Nawroth PP, Bierhaus A. SDF-1 genotype influences insulin-dependent mobilization of adult progenitor cells in type 2 diabetes. Diabetes Care. 2005 Apr;28(4):934-6. No abstract available.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fadini GP, Mancuso P, Bertolini F, de Kreutzenberg S, Avogaro A. Amelioration of glucose control mobilizes circulating pericyte progenitor cells in type 2 diabetic patients with microangiopathy. Exp Diabetes Res. 2012;2012:274363. Epub 2012 Feb 28.

Responsible Party:	Angelo Avogaro, University of Padova, Medical School
ClinicalTrials.gov Identifier:	NCT00699686 History of Changes
Other Study ID Numbers:	LIBRA
Study First Received:	June 17, 2008
Last Updated:	August 16, 2010
Health Authority:	Italy: Institutional Review Board Italy: Ministry of Health

Keywords provided by University of Padova:

Diabetes
Insulin
Endothelium
Cardiovascular disease
Stem cells

Additional relevant MeSH terms:

Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Glargine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013