NCT01367821

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
50

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started May 2011

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2011

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 31, 2011

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 7, 2011

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

October 5, 2012

Status Verified

October 1, 2012

Enrollment Period

1.6 years

First QC Date

May 31, 2011

Last Update Submit

October 4, 2012

Conditions

Obstructive JaundiceDisease as Reason for ERCPImmune DysfunctionImmune Tolerance

Keywords

Obstructive jaundiceERCPImmune dysfunctionEndotoxin toleranceQuorum sensing

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • Change in concentration of systemic quorum sensing signaling molecules

    Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30

Study Arms (2)

Patients with obstructive jaundice

Patients with obstructive jaundice

Healthy volunteers

Healthy volunteers

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients referred to tertiary hepatopancreaticobiliary centre for investigation of obstructive jaundice and Healthy volunteers

You may qualify if:

  • Obstructive jaundice
  • Willing to participate and able to give informed consent
  • Alcohol abstinence during study

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Queen's Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

RECRUITING

Related Publications (8)

  • Blamey SL, Fearon KC, Gilmour WH, Osborne DH, Carter DC. Prediction of risk in biliary surgery. Br J Surg. 1983 Sep;70(9):535-8. doi: 10.1002/bjs.1800700910.

    PMID: 6616158BACKGROUND

  • Han XC, Li JL, Han G. Surgical mortality in patients with malignant obstructive jaundice: a multivariate discriminant analysis. Hepatobiliary Pancreat Dis Int. 2003 Aug;2(3):435-40.

    PMID: 14599955BACKGROUND

  • Povoski SP, Karpeh MS Jr, Conlon KC, Blumgart LH, Brennan MF. Association of preoperative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann Surg. 1999 Aug;230(2):131-42. doi: 10.1097/00000658-199908000-00001.

    PMID: 10450725BACKGROUND

  • Wang Q, Gurusamy KS, Lin H, Xie X, Wang C. Preoperative biliary drainage for obstructive jaundice. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD005444. doi: 10.1002/14651858.CD005444.pub2.

    PMID: 18677779BACKGROUND

  • Diggle SP, Crusz SA, Camara M. Quorum sensing. Curr Biol. 2007 Nov 6;17(21):R907-10. doi: 10.1016/j.cub.2007.08.045. No abstract available.

    PMID: 17983563BACKGROUND

  • Martin CA, Hoven AD, Cook AM. Therapeutic frontiers: preventing and treating infectious diseases by inhibiting bacterial quorum sensing. Eur J Clin Microbiol Infect Dis. 2008 Aug;27(8):635-42. doi: 10.1007/s10096-008-0489-3. Epub 2008 Mar 6.

    PMID: 18322716BACKGROUND

  • Williams P. Bacillus subtilis: a shocking message from a probiotic. Cell Host Microbe. 2007 Jun 14;1(4):248-9. doi: 10.1016/j.chom.2007.05.010.

    PMID: 18005705BACKGROUND

  • Boontham P, Robins A, Chandran P, Pritchard D, Camara M, Williams P, Chuthapisith S, McKechnie A, Rowlands BJ, Eremin O. Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis. Clin Sci (Lond). 2008 Dec;115(11):343-51. doi: 10.1042/CS20080018.

    PMID: 18363571BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma Bile

MeSH Terms

Conditions

Jaundice, ObstructiveImmune System Diseases

Condition Hierarchy (Ancestors)

JaundiceHyperbilirubinemiaPathologic ProcessesPathological Conditions, Signs and SymptomsSkin ManifestationsSigns and Symptoms

Study Officials

  • Abeed H Chowdhury, MBChB MRCS

    University of Nottingham

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Abeed H Chowdhury, MBChB MRCS

CONTACT

441158231144abeed.chowdhury@nottingham.ac.uk

Dileep N Lobo, FRCS FACS

CONTACT

dileep.lobo@nottingham.ac.uk

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 31, 2011

First Posted

June 7, 2011

Study Start

May 1, 2011

Primary Completion

December 1, 2012

Study Completion

December 1, 2012

Last Updated

October 5, 2012

Record last verified: 2012-10

Locations

GB(1)