Endothelial Effects of Basal Insulin: Detemir Versus Glargine

NCT00699686 | Completed Phase 4

• 1 other identifier: LIBRA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes; Endothelial Dysfunction; Cardiovascular Disease

Keywords

Diabetes; Insulin; Endothelium; Cardiovascular disease; Stem cells

Outcome Measures

Primary Outcomes (1)

• Change in endothelial progenitor cell count

  Basal, 3 months, 6 months

Secondary Outcomes (3)

• Change in markers of endothelial damage

  Basal, 3 months, 6 months

• Frequence of hypoglycemias

  during 1st and 2nd arms

• Change in body weight

  After the 1st and 2nd arms

Study Arms (2)

Glargine

ACTIVE COMPARATOR

During this arm/phase patients take subcutaneous glargine daily for 3 months.

Drug: Glargine

Detemir

EXPERIMENTAL

During this arm/phase, patients take insulin Detemir subcutaneously for 3 months.

Drug: Detemir

Interventions

Glargine DRUG

Daily bedtime subcutaneous insulin Glargine in individualized doses.

Also known as: Lantus

Glargine

Detemir DRUG

Daily bedtime subcutaneous insulin Detemir in individualized doses.

Also known as: Levemir

Detemir

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

Dipartimento di Medicina Clinica e Sperimentale, Divisione di Malattie del Metabolismo

Padua, 35100, Italy

Location

Related Publications (16)

• Fadini GP. An underlying principle for the study of circulating progenitor cells in diabetes and its complications. Diabetologia. 2008 Jul;51(7):1091-4. doi: 10.1007/s00125-008-1021-0. No abstract available.

  PMID: 18478199 BACKGROUND

• 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. doi: 10.2174/1573399052952640.

  PMID: 18220581 BACKGROUND

• 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. doi: 10.2337/dc07-1996. Epub 2007 Dec 27. No abstract available.

  PMID: 18162496 BACKGROUND

• 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. doi: 10.1007/s00125-007-0732-y. Epub 2007 Jun 20.

  PMID: 17579827 BACKGROUND

• 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. doi: 10.2337/dc06-2305. Epub 2007 Feb 2. No abstract available.

  PMID: 17277037 BACKGROUND

• 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. doi: 10.1007/s00125-006-0401-6. Epub 2006 Oct 27.

  PMID: 17072586 BACKGROUND

• 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. doi: 10.1093/eurheartj/ehl198. Epub 2006 Aug 15.

  PMID: 16912055 BACKGROUND

• 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. doi: 10.1161/01.STR.0000236064.19293.79. Epub 2006 Jul 27.

  PMID: 16873710 BACKGROUND

• 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. doi: 10.1016/j.numecd.2005.10.015. Epub 2006 Feb 8.

  PMID: 16530129 BACKGROUND

• 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. doi: 10.1016/j.jacc.2004.11.067.

  PMID: 15862417 BACKGROUND

• 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. doi: 10.1161/01.ATV.0000237750.44469.88. Epub 2006 Jul 20.

  PMID: 16857948 BACKGROUND

• Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005 Sep 8;353(10):999-1007. doi: 10.1056/NEJMoa043814.

  PMID: 16148285 BACKGROUND

• 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. doi: 10.2337/diacare.28.4.934. No abstract available.

  PMID: 15793201 BACKGROUND

• Fadini GP, Albiero M, Vigili de Kreutzenberg S, Avogaro A. Hypoglycemia affects the changes in endothelial progenitor cell levels during insulin therapy in type 2 diabetic patients. J Endocrinol Invest. 2015 Jul;38(7):733-8. doi: 10.1007/s40618-015-0247-1. Epub 2015 Feb 27.

  PMID: 25722222 DERIVED

• Fadini GP, Iori E, Marescotti MC, Vigili de Kreutzenberg S, Avogaro A. Insulin-induced glucose control improves HDL cholesterol levels but not reverse cholesterol transport in type 2 diabetic patients. Atherosclerosis. 2014 Aug;235(2):415-7. doi: 10.1016/j.atherosclerosis.2014.05.942. Epub 2014 Jun 4.

  PMID: 24933032 DERIVED

• 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. doi: 10.1155/2012/274363. Epub 2012 Feb 28.

  PMID: 22474419 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cardiovascular Diseases; Diabetes Mellitus; Insulin Resistance

Interventions

Insulin Glargine; Insulin Detemir

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Angelo Avogaro, M.D.

  University of Padova, Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 17, 2008
• First Posted: June 18, 2008
• Study Start: May 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: August 17, 2010

Record last verified: 2010-08

Locations

IT (1)