Correlation Between PTP1B Expression and Organ Failure During Sepsis

Study Overview
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Brief Summary
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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.

Official Title
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Correlation Between PTP1B Expression and Organ Failure During Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Biological: PTP1B dosage


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTP1B dosage<br>PTP1B dosage during sepsis | Biological: PTP1B dosage<br>* PTP1B sampled and dosed during sepsis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic shock