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

NCT ID: NCT00324792

Last Updated: 2008-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-05-31

Study Completion Date

2007-10-31

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Diabetes Mellitus Leucotrienes

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Interventions

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intensive insulin therapy

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Grenoble

OTHER

Sponsor Role lead

Principal Investigators

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Robert Boizel, Dr

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Locations

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

Grenoble, , France

Site Status

Countries

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France

References

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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. doi: 10.1016/j.prostaglandins.2005.10.001. Epub 2005 Nov 2.

Reference Type BACKGROUND
PMID: 16303623 (View on PubMed)

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. doi: 10.1016/j.prostaglandins.2004.10.002.

Reference Type BACKGROUND
PMID: 15789618 (View on PubMed)

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. doi: 10.1161/01.ATV.0000172632.96987.2d. Epub 2005 Jun 2.

Reference Type BACKGROUND
PMID: 15933245 (View on PubMed)

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. doi: 10.1056/NEJMoa025079.

Reference Type BACKGROUND
PMID: 14702425 (View on PubMed)

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. doi: 10.1038/ng1311. Epub 2004 Feb 8.

Reference Type BACKGROUND
PMID: 14770184 (View on PubMed)

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. doi: 10.1007/s00125-010-1822-9. Epub 2010 Jun 10. No abstract available.

Reference Type DERIVED
PMID: 20535444 (View on PubMed)

Other Identifiers

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DCIC 05 54

Identifier Type: -

Identifier Source: org_study_id