Obstructive JaundiceNCT01367821
Immune Function in Patients With Obstructive Jaundice
An observational study of Obstructive Jaundice and Disease as Reason for ERCP, run by University of Nottingham at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Obstructive Jaundice, Disease as Reason for ERCP, Immune Dysfunction
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2011to Dec 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients referred to tertiary hepatopancreaticobiliary centre for investigation of obstructive jaundice and Healthy volunteers
Who may be able to join
- Obstructive jaundice
- Willing to participate and able to give informed consent
- Alcohol abstinence during study
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Dileep N Lobo, FRCS FACS contact
United Kingdom1 site, 1 recruiting
- Recruiting
Queen's Medical Centre
Nottingham, Nottinghamshire, NG7 2UH
Abeed H Chowdhury, MBChB MRCS, 441158231144, abeed.chowdhury@nottingham.ac.uk
Abeed H Chowdhury, MBChB MRCS
About this study
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.
Read the detailed description
Obstructive jaundice (OJ) is a condition where a blockage of flow of bile from the liver leads to the accumulation of bile products in the blood resulting in yellowing and itching of the skin. Common causes of OJ include gallstones and also tumours of the pancreas or bile duct. Relieving this type of jaundice and treating the underlying cause can include endoscopic or surgical procedures. It is known however, that patients with OJ have increased surgical risks than non-jaundiced patients who undergo the same operations. Studies have shown that surgery for severe OJ is associated with a postoperative mortality in the region of 10-15% and morbidity rates of 30-65%. Complications related to bacterial infection are common and patients developing severe infections may require treatment with broad spectrum antibiotics with care in intensive or high dependency units.
Although antibiotics have proved invaluable in treating postoperative infections they carry the potential for adverse effects. Antibiotics can suppress normal gut bacteria and allow disease causing bacteria to proliferate, such as Clostridium difficile. This usually manifests as mild-to-moderate diarrhoea but can occasionally cause life-threatening bowel inflammation. The widespread use of antibiotics is also central to the development of bacterial strains with antibiotic resistance. This clinical problem also has economic, political and environmental implications for the National Health Service. Adherence to measures of infection control, education and antibiotic policy can minimise antibiotic resistance; however the limits surrounding such approaches have led to a demand for novel or alternative strategies.
It has recently been discovered that bacteria are able to communicate by producing specialised molecules known as quorum sensing signalling molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. At specific colony sizes the concentration of QSSMs reaches a critical threshold leading to the activation of genes that cause an infection. Disruption of quorum sensing has been shown to reduce the severity of infection in animal studies and this has led to the development of inhibitors of quorum sensing as a possible strategy in antibacterial therapy.
Previous work conducted at the University of Nottingham has demonstrated that QSSMs also influence the number and function of a specific type of immune cell known as 'antigen presenting cells'. These cells are pivotal in allowing the immune system to recognise components of bacteria as foreign and thereby mount the appropriate response. It was found that large numbers of these types of cells underwent programmed cell death (cell suicide) in the presence of QSSMs compared to when QSSMs were absent. This mirrors the situation in blood sampled from patients with severe infections where there is a greater proportion of cell deaths among antigen presenting cells than other types of immune cell.
It is likely that the susceptibility to infectious complications in patients with obstructive jaundice is due to the interplay of various factors. The absence of intestinal bile has implications for the integrity of the bowel wall as a barrier, changes in gut microflora flora and translocation of both bacteria and their products. In addition, it is clear that a form of immune dysfunction occurs, which dampens the normal response following exposure to bacterial products. This immune dysfunction may avert powerful inflammatory cascades resulting in life-threatening multi organ dysfunction but at the expense of conditions that favour bacterial survival. QSSMs represent good candidates for the mediators of this immune dysfunction and although there is a compelling case for their involvement in the pathogenesis of sepsis, definitive evidence to support their role in infective processes in OJ is currently lacking.
- Keywords
- Obstructive jaundice, ERCP, Immune dysfunction, Endotoxin tolerance, Quorum sensing
- Medical subject headings
- Jaundice, Obstructive, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with obstructive jaundice | Patients with obstructive jaundice | |
| Healthy volunteers | Healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in monocyte cytokine responses to endotoxin stimulation
Evaluation of monocyte cytokine responses to endotoxin stimulation at specified time points
Measured: Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30
Secondary outcomes (1)
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
Measured: Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startMay 2011
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Obstructive JaundiceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Abeed H Chowdhury, MBChB MRCS, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367821
- Sponsor's protocol ID
- 10040
- Other IDs
- 10/H0408/53
- Status last verified
- Oct 2012
- First submitted
- 31 May 2011
- Last updated
- 5 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 6616158Han 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.
PubMed 14599955Povoski 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.
PubMed 10450725Wang 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.
PubMed 18677779Diggle 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.
PubMed 17983563Martin 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.
PubMed 18322716Williams 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.
PubMed 18005705Boontham 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.
PubMed 18363571
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quorum Sensing Signal Molecules (QSSMs) and Immune Dysfunction in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) for Obstructive Jaundice
- ClinicalTrials.gov ID
- NCT01367821
- Acronym / sponsor ID
- 10040
- Keywords
- Obstructive jaundice, ERCP, Immune dysfunction, Endotoxin tolerance, Quorum sensing
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Obstructive jaundice (OJ) is a condition where a blockage of flow of bile from the liver leads to the accumulation of bile products in the blood resulting in yellowing and itching of the skin. Common causes of OJ include gallstones and also tumours of the pancreas or bile duct. Relieving this type of jaundice and treating the underlying cause can include endoscopic or surgical procedures. It is known however, that patients with OJ have increased surgical risks than non-jaundiced patients who undergo the same operations. Studies have shown that surgery for severe OJ is associated with a postoperative mortality in the region of 10-15% and morbidity rates of 30-65%. Complications related to bacterial infection are common and patients developing severe infections may require treatment with broad spectrum antibiotics with care in intensive or high dependency units.
Although antibiotics have proved invaluable in treating postoperative infections they carry the potential for adverse effects. Antibiotics can suppress normal gut bacteria and allow disease causing bacteria to proliferate, such as Clostridium difficile. This usually manifests as mild-to-moderate diarrhoea but can occasionally cause life-threatening bowel inflammation. The widespread use of antibiotics is also central to the development of bacterial strains with antibiotic resistance. This clinical problem also has economic, political and environmental implications for the National Health Service. Adherence to measures of infection control, education and antibiotic policy can minimise antibiotic resistance; however the limits surrounding such approaches have led to a demand for novel or alternative strategies.
It has recently been discovered that bacteria are able to communicate by producing specialised molecules known as quorum sensing signalling molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. At specific colony sizes the concentration of QSSMs reaches a critical threshold leading to the activation of genes that cause an infection. Disruption of quorum sensing has been shown to reduce the severity of infection in animal studies and this has led to the development of inhibitors of quorum sensing as a possible strategy in antibacterial therapy.
Previous work conducted at the University of Nottingham has demonstrated that QSSMs also influence the number and function of a specific type of immune cell known as 'antigen presenting cells'. These cells are pivotal in allowing the immune system to recognise components of bacteria as foreign and thereby mount the appropriate response. It was found that large numbers of these types of cells underwent programmed cell death (cell suicide) in the presence of QSSMs compared to when QSSMs were absent. This mirrors the situation in blood sampled from patients with severe infections where there is a greater proportion of cell deaths among antigen presenting cells than other types of immune cell.
It is likely that the susceptibility to infectious complications in patients with obstructive jaundice is due to the interplay of various factors. The absence of intestinal bile has implications for the integrity of the bowel wall as a barrier, changes in gut microflora flora and translocation of both bacteria and their products. In addition, it is clear that a form of immune dysfunction occurs, which dampens the normal response following exposure to bacterial products. This immune dysfunction may avert powerful inflammatory cascades resulting in life-threatening multi organ dysfunction but at the expense of conditions that favour bacterial survival. QSSMs represent good candidates for the mediators of this immune dysfunction and although there is a compelling case for their involvement in the pathogenesis of sepsis, definitive evidence to support their role in infective processes in OJ is currently lacking.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with obstructive jaundice | – | –Patients with obstructive jaundice |
| Healthy volunteers | – | –Healthy volunteers |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients referred to tertiary hepatopancreaticobiliary centre for investigation of obstructive jaundice and Healthy volunteers
Key inclusion criteria (3 listed)
- Obstructive jaundice
- Willing to participate and able to give informed consent
- Alcohol abstinence during study
Key exclusion criteria (8 listed)
- Acute Physiology and Chronic Health Evaluation (APACHE) II Score ≥8
- Severe neutropaenia
- Smokers/substance abuse
- Diabetes Mellitus
- Oral/IV Steroids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in monocyte cytokine responses to endotoxin stimulation
Time frame: Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30
Evaluation of monocyte cytokine responses to endotoxin stimulation at specified time points
1 secondary outcome
Change in concentration of systemic quorum sensing signaling molecules
Time frame: Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2012.
- Background: PubMed 6616158Blamey 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.
- Background: PubMed 14599955Han 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.
- Background: PubMed 10450725Povoski 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.
- Background: PubMed 18677779Wang 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.
- Background: PubMed 17983563Diggle 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.
- Background: PubMed 18322716Martin 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.
- Background: PubMed 18005705Williams 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.
- Background: PubMed 18363571Boontham 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.
Related trials for Obstructive Jaundice
Not yet recruiting
Supraglottic Oxygenation Via Oral Transtracheal Catheter for Reducing the Incidence of Hypoxemia During ERCP Under Sedation
Choledocholithiasis With Cholecystitis With Obstruction, Obstructive Jaundice
Not yet recruiting
Suprapapillary Versus Transpapillary Plastic Stents for Unresectable Malignant Hilar Biliary Obstruction
Biliary Tract Neoplasms, Biliary Drainage
Not yet recruiting
Impact of Intraoperative PTCD Catheter Retention Versus Removal on Postoperative Short-term Outcomes After Pancreaticoduodenectomy in Obstructive Jaundice
Obstructive Jaundice, Pancreatic Head Cancer
Not yet recruiting
Determinants of Technical Success and Safety in Therapeutic ERCP for Obstructive Jaundice
Obstructive Jaundice, ERCP
Active, not recruiting
A RCT of Low MBO Drainage Strategies
Jaundice, Obstructive, Cholangiopancreatography, Endoscopic Retrograde
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dileep N Lobo, FRCS FACS contact
Abeed H Chowdhury, MBChB MRCS principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obstructive Jaundice and Disease as Reason for ERCP, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Abeed H Chowdhury, MBChB MRCS (441158231144, abeed.chowdhury@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in monocyte cytokine responses to endotoxin stimulation (time frame: Baseline (pre ERCP) and post ERCP days 1, 7, 14 and 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01367821, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2012.