I3LTE4: Intensive Insulin Therapy and Production of LTE4 in Patients With Diabetes - Full Text View

Purpose

The primary objective of the study is to assess the effect of a 3-month intensive insulin therapy on urinary leukotriene E4 (LTE4) excretion in patients with diabetes.

Condition	Intervention
Diabetes Mellitus Leucotrienes	Drug: intensive insulin therapy

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Effect of an Intensive Insulin Therapy on the Production of LTE4 in Patients With Diabetes

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines

Drug Information available for: Insulin human

U.S. FDA Resources

Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:

changes in urinary LTE4 excretion and HbA1c after 3-month intensive insulin therapy versus baseline

Secondary Outcome Measures:

urinary 11-dehydroTXB2
hs-CRP
fibrinogen
sICAM-1 plasma levels

Estimated Enrollment:	45
Study Start Date:	May 2006
Study Completion Date:	October 2007

Detailed Description:

Our group has recently reported the results of a preliminary cross-sectional study, which demonstrated that the urinary LTE4 excretion is increased in patients with type 1 diabetes. With regard to recent human genetic studies showing that polymorphisms in the 5-lipoxygenase (5-LO) promoter and FLAP haplotypes is linked to cardiovascular disease susceptibility our data suggested the potential interest of LTE4 as a non-invasive biomarker of cardiovascular risk. In diabetes mellitus, further studies are required to evaluate the 5-LO pathway after improvement of glucose control and concomitantly with established inflammatory cardiovascular biomarkers.

The secondary objectives are:

Before and after 3-month intensive insulin therapy- Relationship between a marker of platelet activation (urinary 11-dehydro-thromboxan B2 :11-dehydroTXB2) and urinary LTE4- Relationship between inflammatory plasma markers of cardiovascular risk (hs-CRP and fibrinogen) and urinary LTE4- Relationship between a plasma marker of endothelial dysfunction (sICAM-1) and urinary LTE4- Changes in LTE4 according to patient subgroups (patients with type 1 and type 2 diabetes mellitus)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

diabetes mellitus (type 1 or type 2)
> 18 year-old
subject has given free, informed written consent
subject entitled to health insurance cover
medical follow-up at the department of Diabetology, Grenoble University Hospital
inappropriate glucose control (HbA1c > 8.5%) requiring an initiation, or revision, of insulin therapy

Exclusion Criteria:

legal incapacity or limited legal competence
pregnant women
heart failure
impaired renal function,defined by a creatinin clearance < 60 ml/mn according to Cockroft formula
asthma
respiratory failure
IV, IM, SC or oral treatment with cortico-steroids for the last 2 months prior to baseline
current smoking > cigarettes / day
any infectious disease for the last 2 months prior to baseline
baseline CRP > 20 mg/l

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00324792

Locations

France
Département d'urologie, néphrologie et endocrinologie-University Hospital of Grenoble
Grenoble, France, 38043

Sponsors and Collaborators

University Hospital, Grenoble

Investigators

Principal Investigator:

Robert Boizel, Dr

CHU Grenoble

More Information

Publications:

Hardy G, Boizel R, Bessard J, Cracowski JL, Bessard G, Halimi S, Stanke-Labesque F. Urinary leukotriene E4 excretion is increased in type 1 diabetic patients: a quantification by liquid chromatography-tandem mass spectrometry. Prostaglandins Other Lipid Mediat. 2005 Dec;78(1-4):291-9. Epub 2005 Nov 2.

Hardy G, Vergnaud S, Lunardi J, Peoc'h M, Bessard G, Stanke-Labesque F. 5-lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats. Prostaglandins Other Lipid Mediat. 2005 Jan;75(1-4):91-103.

Cipollone F, Mezzetti A, Fazia ML, Cuccurullo C, Iezzi A, Ucchino S, Spigonardo F, Bucci M, Cuccurullo F, Prescott SM, Stafforini DM. Association between 5-lipoxygenase expression and plaque instability in humans. Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1665-70. Epub 2005 Jun 2.

Dwyer JH, Allayee H, Dwyer KM, Fan J, Wu H, Mar R, Lusis AJ, Mehrabian M. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med. 2004 Jan 1;350(1):29-37.

Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, Samani NJ, Gudmundsson G, Grant SF, Thorgeirsson G, Sveinbjornsdottir S, Valdimarsson EM, Matthiasson SE, Johannsson H, Gudmundsdottir O, Gurney ME, Sainz J, Thorhallsdottir M, Andresdottir M, Frigge ML, Topol EJ, Kong A, Gudnason V, Hakonarson H, Gulcher JR, Stefansson K. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004 Mar;36(3):233-9. Epub 2004 Feb 8.

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

Boizel R, Bruttmann G, Benhamou PY, Halimi S, Stanke-Labesque F. Regulation of oxidative stress and inflammation by glycaemic control: evidence for reversible activation of the 5-lipoxygenase pathway in type 1, but not in type 2 diabetes. Diabetologia. 2010 Sep;53(9):2068-70. Epub 2010 Jun 10. No abstract available.

ClinicalTrials.gov Identifier:	NCT00324792 History of Changes
Other Study ID Numbers:	DCIC 05 54
Study First Received:	May 10, 2006
Last Updated:	June 11, 2008
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:

Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013