Immune Tolerance Clinical Trial
Official title:
Quorum Sensing Signal Molecules (QSSMs) and Immune Dysfunction in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) for Obstructive Jaundice
Patients with obstructive jaundice (OJ) often require surgical, endoscopic or radiological interventions to facilitate biliary drainage and relieve jaundice. However it is known that patients with OJ have increased surgical risks than non-jaundiced patients undergoing the same procedures. Surgery for severe OJ is associated with a significant post-operative mortality (10-15%) and morbidity (30-65%). The commonest complications are related to sepsis but the pathophysiological mechanisms behind this susceptibility to bacterial infection are not clear. Recent work has shown a pivotal role of bile in the maintenance of enterocyte tight junctions and the expression of tight junction-associated proteins which could account for the translocation of enteric bacteria and bacterial products to mesenteric lymph node complexes, the portal circulation and subsequently the liver. Some of these bacterial products, such as endotoxin and quorum sensing signalling molecules (QSSMs), have immunomodulatory properties which may dampen normal immune responses to infection resulting in life-threatening organ dysfunction. Bacterial endotoxin and quorum sensing signalling molecules (QSSMs) represent good candidates for the mediators of this immune suppression and although there is a compelling case for their involvement in the pathogenesis of sepsis, evidence to support their involvement in the aetiology of infection in OJ is currently lacking.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | December 2012 |
Est. primary completion date | December 2012 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Obstructive jaundice - Willing to participate and able to give informed consent - Alcohol abstinence during study Exclusion Criteria: - Acute Physiology and Chronic Health Evaluation (APACHE) II Score =8 - Severe neutropaenia - Smokers/substance abuse - Diabetes Mellitus - Oral/IV Steroids - On regular antibiotics - Patients with active cholangitis - Patients who have a history liver transplantation or chronic liver disease |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
United Kingdom | Queen's Medical Centre | Nottingham | Nottinghamshire |
Lead Sponsor | Collaborator |
---|---|
University of Nottingham |
United Kingdom,
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in monocyte cytokine responses to endotoxin stimulation | Evaluation of monocyte cytokine responses to endotoxin stimulation at specified time points | Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30 | No |
Secondary | Change in concentration of systemic quorum sensing signaling molecules | Evaluation of the presence of quorum sensing signalling molecules in the systemic circulation at specified time points | Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30 | No |
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