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| Name | Class |
|---|---|
| Institut National de la Santé Et de la Recherche Médicale, France | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PTP1B dosage | Experimental | PTP1B dosage during sepsis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PTP1B dosage | Biological | PTP1B sampled and dosed during sepsis |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in PTP1B level expression | Change from baseline in PTP1B level expression by biological analysis | Day 5 |
| Number of patients with organ failure | Number of patients with organ failure | Day 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Dose of insulin administered during the sepsis | cumulative dose of insulin administered in the first 5 days of hospitalization | Day 5 |
| Insulin resistance evaluation | Evaluation of insulin resistance by biological analysis |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| steven grangé, MD | Rouen Universitary Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rouen University Hospital | Rouen | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10066179 | Background | 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. | |
| 24578383 |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
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| Day 1 |
| Blood glucose Analysis | Analysis of the variability in Blood glucose | Day 5 |
| Number of death participants at ICU discharge | ICU mortality at day 28 | ICU discharge, day 28 |
| Number of death participants at at the end of the study | Mortality at day 28 | Day 28 |
| Number of death participants at at hospital discharge | Mortality at hospital discharge, average of 10 days after surgical intervention | 10 days (average) |
| Duration of mechanical ventilation | Duration of mechanical ventilation from admission to discharge | Day 28 |
| 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. |
| 24625984 | Background | 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. |
| 18281274 | Background | 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. |
| 19797171 | Background | 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. |
| 23879520 | Result | 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. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |