I3LTE4: Intensive Insulin Therapy and Production of LTE4 in Patients With Diabetes

Diabetes Mellitus Clinical Trial

Official title:

Effect of an Intensive Insulin Therapy on the Production of LTE4 in Patients With Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00324792
• Other study ID #: DCIC 05 54
• Status: Completed
• Phase: N/A
• First received: May 10, 2006
• Last updated: June 11, 2008
• Start date: May 2006
• Est. completion date: October 2007

Study information

• Verified date: June 2008
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Diabetes Mellitus
• Leucotrienes

Intervention

Drug:
• intensive insulin therapy

Locations

Country	Name	City	State
France	Département d'urologie, néphrologie et endocrinologie-University Hospital of Grenoble	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	changes in urinary LTE4 excretion and HbA1c after 3-month intensive insulin therapy versus baseline
Secondary	urinary 11-dehydroTXB2
Secondary	hs-CRP
Secondary	fibrinogen
Secondary	sICAM-1 plasma levels