Mitochondrial Function of Immune Cells in Sepsis (MitoSepsis)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01600989
First received: May 11, 2012
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

Introduction: Evidence suggests that sepsis and septic shock severely impair mitochondria and that the resulting mitochondrial dysfunction is related to the severity and outcome of the resulting organ dysfunction. In sepsis mitochondrial abnormalities - biochemical and ultrastructural - have been recognized in multiple organs, including liver, kidney, skeletal and heart muscle tissue and blood cells. Circulating immune cells play an important role in the pathophysiology of sepsis. Stimulation of the immune system alters the energy requirements of immune cells; down-regulation of immune-cell activity has been associated with prolonged sepsis and unfavourable outcome. The aim of the project is to comprehensively investigate changes in mitochondrial function of immune cells in patients with severe sepsis and septic shock. The following main hypotheses will be evaluated:

  • Severe sepsis and septic shock leads to increased energy requirements of immune cells and to an increase in mitochondrial enzyme activities and energy production.
  • Changes of mitochondrial function in human immune cells are associated with alterations in clinical and laboratory markers of severity of sepsis.
  • Prolonged sepsis and unfavourable outcome is associated with down regulation of mitochondrial function.

Methods: A total of 30 adult patients admitted to the intensive care unit (ICU) due to severe sepsis or septic shock will be included in the study; 30 healthy volunteers serve as controls. Patients with any type of chronic infectious, inflammatory or autoimmune diseases, after transplantations or receiving immunosuppressive agents are excluded.

Collected baseline characteristics include patient demographics, diagnosis and severity of illness scores at the time of admission. Daily collected follow up data include clinical and laboratory parameters of organ dysfunction, use of vasopressors/inotropes, use of antibiotics, use of steroids and results of microbiological cultures/stains.

Negative identification and isolation of monocytes, B cells and CD4 T cells will be performed daily from ICU admission to discharge using an antibody-antigen mediated immunomagnetic cell isolation procedure that depletes all blood cells except the specific target cells. Mitochondrial function of immune cells will be assessed by measurement of mitochondrial complex activity for complexes I to IV by a standard titration protocol. Additionally, the levels of pro- and anti-inflammatory cytokines (Interleukin (IL)-1, IL-6, IL-10, TNF-α) will be assessed throughout the stay in the ICU. For comparison mitochondrial function of of monocytes, B cells and CD4 T cells and cytokine levels will be measured in a group of 10 healthy volunteers.

Analysis plan: Changes in mitochondrial function of immune cells over time compared to a healthy control group and during the course of severe sepsis and septic shock is the main outcome parameter of this study. Assessed predictors are determined by the severity of the underlying septic condition and include clinical and laboratory evidence for dysfunction of vital organ systems and changes in levels of inflammatory and anti-inflammatory cytokines.


Condition Intervention
Shock, Septic
Other: blood sampling

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mitochondrial Function of Immune Cells in Severe Sepsis and Septic Shock - a Prospective Observational Cohort Study

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Mitochondrial function of immune cells [ Time Frame: At the time of ICU admission ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in mitochondrial function of immune cells [ Time Frame: 24 hours after ICU admission ] [ Designated as safety issue: No ]
  • Change from baseline in mitochondrial function of immune cells [ Time Frame: 48 hours after ICU admission ] [ Designated as safety issue: No ]
  • Change from baseline in mitochondrial function of immune cells [ Time Frame: At time of resoltion of sepsis, expected to be after 5 days ] [ Designated as safety issue: No ]
  • Levels of cytokines (of IL-1, IL-6, IL-10 and TNFa) [ Time Frame: At ICU admission, 24h and 48h after admission, & at time of resolution of sepsis (expected to be after 5 days) ] [ Designated as safety issue: No ]
  • ICU mortality [ Time Frame: At time of dismissal from ICU, expected to be after 7 days ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum, isolated B-cells, T-cells, Monocytes


Enrollment: 60
Study Start Date: May 2012
Study Completion Date: November 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Patients with severe sepsis / septic shock
30 Adult patients (age > 18years), with severe sepsis or septic shock as defined by the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference guidelines at the time of admission to ICU.
Other: blood sampling
Blood samples will be taken at ICU admission, and 24h and 48h after admission, and at time of resolution of sepsis
Healthy volunteers
Healthy volunteers
Other: blood sampling
Blood samples will be taken twice at a 7 day interval

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

30 patients with severe sepsis or septic shock at ICU admission

Criteria

Inclusion Criteria:

  • Adult patients (age > 18years)
  • Severe sepsis or septic shock as defined by the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference guidelines at the time of admission to ICU.

Exclusion Criteria

  • Patients with any type of chronic infectious, inflammatory or autoimmune diseases
  • Patients after hematopoietic or solid organ transplantation
  • Patients receiving long term treatment with steroids or other immunosuppressive agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01600989

Locations
Switzerland
Department of Intensive Care Medicine, Bern University Hospital (Inselspital) and University of Bern
Bern, Switzerland, 3010
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
Study Chair: Tobias Merz Department of Intensive Care Medicine, Bern University Hospital (Inselspital) and University of Bern
  More Information

No publications provided

Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01600989     History of Changes
Other Study ID Numbers: 015/10
Study First Received: May 11, 2012
Last Updated: April 24, 2014
Health Authority: Switzerland: Ethikkommission

Keywords provided by University Hospital Inselspital, Berne:
shock septic
monocytes
lymphocytes
mitochondria
interleukins
Tumor Necrosis Factor-alpha
Hypoxia-Inducible Factor 1, alpha Subunit

Additional relevant MeSH terms:
Shock
Shock, Septic
Pathologic Processes
Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation

ClinicalTrials.gov processed this record on October 19, 2014