Correlation Between PTP1B Expression and Organ Failure During Sepsis

NCT02295514 | Completed DMC

• 1 other identifier: 2014/087/HP
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

Sepsis; Septic shock

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Dose of insulin administered during the sepsis

  Day 5

• Insulin resistance evaluation

  Day 1

• Blood glucose Analysis

  Day 5

• Number of death participants at ICU discharge

  ICU discharge, day 28

• Number of death participants at at the end of the study

  Day 28

Study Arms (1)

PTP1B dosage

EXPERIMENTAL

PTP1B dosage during sepsis

Biological: PTP1B dosage

Interventions

PTP1B dosage BIOLOGICAL

PTP1B sampled and dosed during sepsis

PTP1B dosage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Rouen: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Rouen University Hospital

Rouen, France

Location

Related Publications (6)

• 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.

  PMID: 10066179 BACKGROUND

• 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.

  PMID: 24578383 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.

  PMID: 24625984 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.

  PMID: 18281274 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.

  PMID: 19797171 BACKGROUND

• 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.

  PMID: 23879520 RESULT

MeSH Terms

Conditions

Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• steven grangé, MD

  Rouen Universitary Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: November 20, 2014
• Study Start: January 1, 2015
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 12, 2016

Record last verified: 2016-05

Locations

FR (1)