- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03566797
Secondary Sclerosis Cholangitis Prospective (SSCpro)
Secondary Sclerosing Cholangitis in Critically Ill Patients (SC-CIP): A Prospective Cohort Study
Study Overview
Status
Detailed Description
Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare, quickly progressive, cholestatic liver disease which is observed in patients suffering from a severe illness with the need for long term treatment on an intensive care unit (ICU). Invasive ventilation, polytrauma, hypotension, systemic inflammatory response syndrome, burns, complex operations and severe (co-) morbidities such as obesity have been discussed as risk factors. Patients suffering from SC-CIP do not have any underlying liver disease. Usually, long- term ICU treatment is described as the trigger mechanism for the development of this disease, although also rapid development of SC-CIP after an ICU stay as short as nine days is described in a single case.
The pathogenesis of SC-CIP is not fully understood yet: Ischemic injury of the intrahepatic biliary system, bile cast formation and recurrent biliary infections are discussed as major factors. The disease leads to a progressive destruction of the intra- and extrahepatic biliary tree with the development of strictures resulting in liver fibrosis with in some cases rapid progression to cirrhosis with the need for liver transplantation within months. The gold standard for diagnosis is endoscopic retrograde cholangiopancreaticography (ERCP), although magnetic resonance cholangiopancreatography (MRCP) as non-invasive alternative can lead to the diagnosis in most cases. Prognosis is poor and transplant-free survival has been found to be 40 months in average. Liver transplantation is the only curative treatment, which shows excellent outcome and quality of life comparable to other indication for liver transplantation.
Microbiological analysis of bile from patients with SC-CIP and primary sclerosing cholangitis (PSC) show a significant different microbiological profile in these two cohorts with dominance of drug resistant organisms in the bile of SC-CIP. No data on the gut microbiome in SC-CIP are available so far. Other chronic liver diseases show distinct changes in microbiome composition with potential influence on the inflammation process in these liver diseases (non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, PSC and liver cirrhosis). In general a decrease in diversity, a higher abundance of potentially pathogenic species and a lower abundance of beneficial species has been observed.
Dysbiosis is thought to increase intestinal permeability. Increased gut permeability is most frequently observed in liver cirrhosis but was also found in alcohol-induced injury, NAFLD and hepatitis C-mediated liver injury. With an impaired gut permeability bacteria from the intestinal lumen can be translocated into extraintestinal parts of the body (lymph nodes, blood) and prompt inflammatory responses. Genetic polymorphisms in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene, a known risk factor for bacterial translocation, increases the odds of developing SC-CIP.
It is hypothesized that the gut microbiome composition is altered in SC-CIP and that this is associated with increased gut permeability and markers of inflammation. Reasons for this might lie in gene polymorphisms influencing bacterial translocation or bile acid composition.
The aim of this study is to prospectively assess the incidence of SC-CIP in a cohort of patients at risk for developing SC-CIP (ICU treatment with the need for mechanical ventilation or extracorporeal membrane oxygenation >/= 5 days) and study differences in gut microbiome composition, gut permeability, bacterial translocation, inflammation as well as genetic polymorphisms in patients developing SC-CIP and patients with comparable disease severity who did not develop SC-CIP.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Locations
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Graz, Austria
- Recruiting
- Medical University Graz
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Contact:
- Vanessa Stadlbauer-Köllner, MD
- Phone Number: 82282 0043 316 385
- Email: vanessa.stadlbauer@medunigraz.at
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Participant is willing and able to give informed consent for participation in the study OR "surrogate consent" by the institutional review board.
- Age above 18 years
- Mechanical ventilation or extracorporeal membrane oxygenation >/= 5 days
Exclusion Criteria:
- Primary or secondary sclerosing cholangitis diagnosed before current ICU admission
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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SC-CIP
Patients developing SC-CIP
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noSC-CIP
Patients with similar severity of critical illness not developing SC-CIP
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of SC-CIP in patients at risk
Time Frame: during hospital stay, on average 4 weeks
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risk is defined as need for mechanical ventilation or extracorporeal membrane oxygenation >/= 5 days
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during hospital stay, on average 4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Gut microbiome composition
Time Frame: at inclusion
|
16S rRNA sequencing
|
at inclusion
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Stool zonulin
Time Frame: at inclusion
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gut permeability marker, ELISA
|
at inclusion
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Stool calprotectin
Time Frame: at inclusion
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gut inflammation marker, ELISA
|
at inclusion
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Serum endotoxin
Time Frame: at inclusion
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bacterial translocation marker, cell-based assay
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at inclusion
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Serum lipopolysaccharide binding protein
Time Frame: at inclusion
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bacterial translocation marker, ELISA
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at inclusion
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soluble cluster of differentiation 14 (sCD14)
Time Frame: at inclusion
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bacterial translocation marker, ELISA
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at inclusion
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bile acid transporter polymorphisms
Time Frame: at inclusion
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sequencing of bile acid transporter genes
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at inclusion
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NOD2 polymorphisms
Time Frame: at inclusion
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sequencing of the NOD2 gene
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at inclusion
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- SC_prospective
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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