Correlation Between PTP1B Expression and Organ Failure During Sepsis

Sepsis Clinical Trial

— SEPP1B  

Official title:

Correlation Between PTP1B Expression and Organ Failure During Sepsis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02295514
• Other study ID #: 2014/087/HP
• Status: Recruiting
• Phase: N/A
• First received: October 23, 2014
• Last updated: September 28, 2015
• Start date: January 2015
• Est. completion date: January 2017

Study information

• Verified date: September 2015
• Source: University Hospital, Rouen
• Contact: steven grangé, MD
• Phone: 0232883023
• Email: steven.grange[@]chu-rouen.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Biological:
• PTP1B dosage
PTP1B sampled and dosed during sepsis

Locations

Country	Name	City	State
France	Rouen University Hospital	Rouen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Rouen	Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (6)

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. — View 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. — View 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. — View 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. Review. — View Citation

Través PG, Pardo V, Pimentel-Santillana M, González-Rodríguez Á, Mojena M, Rico D, Montenegro Y, Calés C, Martín-Sanz P, Valverde AM, Boscá 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:e1125. doi: 10.1038/cddis.2014.90. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in PTP1B level expression	Change from baseline in PTP1B level expression by biological analysis	Day 5	No
Primary	Number of patients with organ failure	Number of patients with organ failure	Day 5	Yes
Secondary	Dose of insulin administered during the sepsis	cumulative dose of insulin administered in the first 5 days of hospitalization	Day 5	No
Secondary	Insulin resistance evaluation	Evaluation of insulin resistance by biological analysis	Day 1	No
Secondary	Blood glucose Analysis	Analysis of the variability in Blood glucose	Day 5	No
Secondary	Number of death participants at ICU discharge	ICU mortality at day 28	ICU discharge, day 28	Yes
Secondary	Number of death participants at at the end of the study	Mortality at day 28	Day 28	Yes
Secondary	Number of death participants at at hospital discharge	Mortality at hospital discharge, average of 10 days after surgical intervention	10 days (average)	Yes
Secondary	Duration of mechanical ventilation	Duration of mechanical ventilation from admission to discharge	Day 28	No