Clinical trial NCT02295514: Correlation Between PTP1B Expression and Organ Failure During Sepsis
Official title: Correlation Between PTP1B Expression and Organ Failure During Sepsis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Keywords: Sepsis
Septic shock
Lead sponsor: University Hospital, Rouen
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2014-11-20
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: Despite major advances in the treatment and understanding of the pathophysiological mechanisms, mortality of severe sepsis remains high, ranging from 25 to 50%. With a prevalence \> 20% in intensive care units, it is now in a population increasingly aging with many co-morbidities, a real public health problem. Thus, changes in treatment to physiological axes could change the prognosis of these patients. Protein Tyrosine Phosphatase 1B (PTP1B) is involved in the negative regulation of many cellular pathways such as the response to insulin, leptin and certain growth factors and endothelial nitric oxide production. PTP1B appears to be particularly involved in the control of endothelial function and insulin secretion. Under these conditions, encouraging results have been obtained in a model of insulin resistance (obesity, diabetes) and as part of pro-angiogenic therapy by inhibition of PTP1B on models of heart failure. Recent advances have broadened the pathophysiological implications of PTP1B conferring a potential role in the regulation of inflammatory processes. In an experimental model of septic shock (Inserm 1096), the investigators demonstrated a significant improvement in survival and cardiovascular function in genetically deficient mice PTP1B (PTP1B - / -). Finally, PTP1B is involved in the downregulation of the signaling pathway of insulin via a feedback phenomenon. Septic shock induces many changes in carbohydrate metabolism. These changes result in hyperglycemia associated with insulin resistance, an independent risk factor of morbidity and mortality. Taken together, these data suggest that the expression of PTP1B could be useful in septic patients by modulating insulin resistance and thus the prognosis of these patients. This justifies the investigator clinical research project on the relationship between the expression of PTP1B levels, glycemic status and prognosis evaluated by the SOFA score in patients with septic shock with multiple organ failure.


Eligibility criteria: Inclusion Criteria:

* Patients in ICU for septic shock
* Person belonging to a social security system
* Informed patient who signed consent
* Contraceptive method in women of reproductive age

Exclusion Criteria:

* Pregnancy
* Patient not able to take a decision because of an administrative or legal decision
* Patient participating to an other interventional study
* BMI \> 30 kg/m2
* Diabetes with specific treatment

Primary outcomes:
measure: Change from baseline in PTP1B level expression
timeFrame: Day 5
measure: Number of patients with organ failure
timeFrame: Day 5
Secondary outcomes:
measure: Dose of insulin administered during the sepsis
timeFrame: Day 5
measure: Insulin resistance evaluation
timeFrame: Day 1
measure: Blood glucose Analysis
timeFrame: Day 5
measure: Number of death participants at ICU discharge
timeFrame: ICU discharge, day 28
measure: Number of death participants at at the end of the study
timeFrame: Day 28
measure: Number of death participants at at hospital discharge
timeFrame: 10 days (average)
measure: Duration of mechanical ventilation
timeFrame: Day 28
Other outcomes:
Locations:
city: Rouen
country: France
facility: Rouen University Hospital
Study officials:
affiliation: Rouen Universitary Hospital
name: steven grangé, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kennedy BP. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science. 1999 Mar 5;283(5407):1544-8. doi: 10.1126/science.283.5407.1544.
citation: Coquerel D, Neviere R, Delile E, Mulder P, Marechal X, Montaigne D, Renet S, Remy-Jouet I, Gomez E, Henry JP, do Rego JC, Richard V, Tamion F. Gene deletion of protein tyrosine phosphatase 1B protects against sepsis-induced cardiovascular dysfunction and mortality. Arterioscler Thromb Vasc Biol. 2014 May;34(5):1032-44. doi: 10.1161/ATVBAHA.114.303450. Epub 2014 Feb 27.
citation: Traves PG, Pardo V, Pimentel-Santillana M, Gonzalez-Rodriguez A, Mojena M, Rico D, Montenegro Y, Cales C, Martin-Sanz P, Valverde AM, Bosca L. Pivotal role of protein tyrosine phosphatase 1B (PTP1B) in the macrophage response to pro-inflammatory and anti-inflammatory challenge. Cell Death Dis. 2014 Mar 13;5(3):e1125. doi: 10.1038/cddis.2014.90.
citation: Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, Kahn BB. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. J Biol Chem. 2008 May 23;283(21):14230-41. doi: 10.1074/jbc.M800061200. Epub 2008 Feb 14.
citation: Ali MI, Ketsawatsomkron P, Belin de Chantemele EJ, Mintz JD, Muta K, Salet C, Black SM, Tremblay ML, Fulton DJ, Marrero MB, Stepp DW. Deletion of protein tyrosine phosphatase 1b improves peripheral insulin resistance and vascular function in obese, leptin-resistant mice via reduced oxidant tone. Circ Res. 2009 Nov 6;105(10):1013-22. doi: 10.1161/CIRCRESAHA.109.206318. Epub 2009 Sep 24.
citation: Feldhammer M, Uetani N, Miranda-Saavedra D, Tremblay ML. PTP1B: a simple enzyme for a complex world. Crit Rev Biochem Mol Biol. 2013 Sep-Oct;48(5):430-45. doi: 10.3109/10409238.2013.819830. Epub 2013 Jul 23.