Regulation of Endocrine, Metabolic, Immune and Bioenergetic Responses in Sepsis

NCT00187824 | Unknown

• 1 other identifier: 04/Q0505/2
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis of this study is that bioenergetic failure in human sepsis, related to endocrine, metabolic and mitochondrial dysfunction, is a major determinant of defective host immune responses, increasing disease severity and risk of death. The objectives of this study are to examine the relationship between the severity of illness, and temporal changes in the activity of endocrine, metabolic and bioenergetic pathways, and consequent immune dysfunction in critically ill patients with sepsis and multiple organ failure in the Intensive Care Unit.

Conditions

Sepsis; Critical Illness

Keywords

prospective; observational; hormonal; inflammatory; vioenergetic; immune; sepsis

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1: healthy control patients Patients undergoing elective total hip replacement will be eligible for enrollment in Group 1 after written informed consent has been obtained. Only 1 blood sample and 1 fat and muscle biopsy will be taken intra-operatively
• Group 2: non-septic, critically ill patients Patients requiring intensive care within 48 hours of admission to hospital from home, for a non-septic/non-inflammatory pathology will be eligible for enrollment in the study after informed agreement has been obtained from the closest family member (see Consent below). At enrolment, Group 2 patients must have received mechanical ventilation commencing within 48 hours of admission to intensive care, should be likely to require mechanical ventilation for at least 48 hours, and must not fulfil the 2001 International Sepsis Definition Conference criteria for severe sepsis or septic shock
• Group 3: patients with severe sepsis or septic shock Patients requiring intensive care within 48 hours of admission to hospital from home, and evidence of severe sepsis (organ dysfunction due to infection) or septic shock as defined by the 2001 International Sepsis Definition Conference criteria, will be eligible for enrollment in the study after informed agreement has been obtained from their next-of-kin. Patients with underlying chronic liver disease are excluded from this group, and will be enrolled separately into Group 4.
• Group 4: patients with severe sepsis and underlying chronic liver disease Patients requiring intensive care admission, with underlying Child-Pugh Class A or B, biopsy-proven liver cirrhosis, within 24 h of the onset of severe sepsis (organ dysfunction due to infection) or septic shock as defined by the 2001 International Sepsis Definition Conference criteria), will be eligible for enrollment in the study after informed agreement has been obtained from their next-of-kin

You may not qualify if:

• \- Age \<18 years
• Child-Pugh Class C liver disease
• Chronic dialysis-dependent renal failure
• Hepatitis B or C infection
• Immunosuppression (e.g. haematological malignancy, neutropenia, HIV infection)
• Immunosuppressive drug therapy within past 6 months
• Patient receiving oral or IV steroid therapy for greater than 1 week, within 6 months prior to ICU admission
• Muscle biopsy contraindicated in presence of coagulopathy (INR \>2, platelet count \< 30,000)\*
• Next-of-kin declines agreement / patient declines consent
• Patient receiving thyroid hormone therapy prior to ICU admission
• \*This does not exclude enrolment into the study, particularly in the case of Group 4 patients who frequently develop a coagulopathy as part of their underlying liver dysfunction

Sponsors & Collaborators

• University College London Hospitals: lead

Study Sites (1)

UCL Hospitals NHS Foundation Trust

London, London, NW1, United Kingdom

RECRUITING

Related Publications (1)

• Carre JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, Suliman HB, Piantadosi CA, Mayhew TM, Breen P, Stotz M, Singer M. Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Respir Crit Care Med. 2010 Sep 15;182(6):745-51. doi: 10.1164/rccm.201003-0326OC. Epub 2010 Jun 10.

  PMID: 20538956 DERIVED

MeSH Terms

Conditions

Sepsis; Critical Illness

Condition Hierarchy (Ancestors)

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

Study Officials

• Mervyn Singer, MBBS MD FRCP

  UCL/UCLH

  STUDY DIRECTOR

• Geoff Bellingan, PhD FRCP

  UCL/UCLH

  PRINCIPAL INVESTIGATOR

• Paul Glynne, PhD FRCP

  UCL/UCLH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mervyn Singer, MBBS MD FRCP

CONTACT

+44 207 679 9666; m.singer@ucl.ac.uk

Study Design

• Study Type: observational
• Observational Model: DEFINED POPULATION
• Time Perspective: OTHER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 11, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 2004
• Study Completion: August 1, 2007
• Last Updated: September 16, 2005

Record last verified: 2004-03

Locations

GB (1)