Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Secondary Sclerosing Cholangitis in Critically Ill Patients (SSC-CIP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02545309
Recruitment Status : Recruiting
First Posted : September 9, 2015
Last Update Posted : February 6, 2020
Information provided by (Responsible Party):
Medical University of Graz

Brief Summary:
SSC-CIP is increasing in patients after critical illness. Pathogenesis is still largely unclear. The investigators hypothesize that genetic variants of biliary transporter genes are frequent in patients with SSC-CIP. In approximately 140 patients and controls the rate of genetic variants in biliary transporter genes, gut permeability and gut microbiome as well as bone health will be studied.

Condition or disease
Secondary Sclerosing Cholangitis

Detailed Description:

SSC is a process of fibroobliteration of intra- and extrahepatic bile ducts due to the fact that the bile ducts receive their blood supply exclusively through the hepatic artery and therefore are more prone to ischemia than other parts of the liver. Several factors, such as intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis can lead to SSC. A relatively new entity is SSC occurring after critical illness (SSC-CIP). So far 97 cases have been reported in literature. All these patients recovered from critical illness, where they received ventilation with positive end-expiratory pressure and vasopressors. A rapid increase in cholestasis and irregular strictures of the intrahepatic bile ducts were observed within weeks after the onset of the critical illness. On endoscopic retrograde cholangiography typically biliary casts can be found. Patients with SSC-CIP furthermore have a distinct microbial profile in bile with frequent detection of difficult to treat organisms. To date, only liver transplantation (in selected patients) provides a curative treatment. Prognosis of SSC-CIP is poor with a mortality rate of 36% after 18 months and the need for liver transplantation in 23%.

To date not much is known about potential risk factors for the development of SSC-CIP. Since not all patients receiving high pressure ventilation and vasopressors develop SSC-CIP, it can be hypothesized that other, patient-specific, factors may play a role in the development of SSC-CIP. Since it is a disease of bile ducts, genetic variants in biliary transporters might play a role. Genetic variants of bile acid transporters, such as BSEP (Bile salt export pump) or MDR3 (multidrug resistance protein 3) have been described as inducers and modifiers of liver disease, such as intrahepatic cholestasis of pregnancy, drug induced cholestasis or treatment success of hepatitis C.

Another potentially important but underreported problem in SSC-CIP is impaired bone health. It is well known, that chronic liver disease, often results in metabolic bone disease: reduced bone mineral density is found in up to 60% and atraumatic fractures in 20% of patients. Specifically chronic cholestatic liver disease is associated with increased fracture risk. This can result in spontaneous or low-impact fractures in such patients, adversely affecting quality of life and survival.

However, no data on bone mineral density and bone mineral metabolism in SSC-CIP are available yet.

The investigators therefore aim to analyse a panel of potentially relevant genes in bile acid transport and bile composition in patients with SSC-CIP to identify potential genetic variants associated with the development of SSC-CIP. Serum markers of bone mineral metabolism and osteodensitometry data will be obtained too. Furthermore, since the microbial profile in bile of SSC-CIP patients shows a predominance of difficult to treat pathogens, changes in gut microbiome composition and/or gut permeability with consecutive translocation of bacterial products into the circulation might be of relevance. From a clinical point of view mortality in SSC-CIP is often related to multi-organ failure. Since infections play an important role in the development of multi-organ failure, the investigators also hypothesize, that SSC-CIP leads to an impairment of innate immune responses.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 140 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Secondary Sclerosing Cholangitis in Critically Ill Patients (SSC-CIP): A Pilot Study on the Possible Genetic Basis of the Disease
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Patients with secondary sclerosing cholangitis in critically ill patients
Patients with similar degree of critical illness who do not develop secondary sclerosing cholangitis in critically ill patients

Primary Outcome Measures :
  1. bile acid transporter genes [ Time Frame: Day 1 ]
    Rate of genetic variants in biliary transporter genes

Secondary Outcome Measures :
  1. gut permeability [ Time Frame: Day 1 ]
    degree of increase in gut permeability

  2. bile acids [ Time Frame: Day 1 ]
    changes in bile acid composition

  3. bone health [ Time Frame: Day 1 ]
    Lumbar spine Z-Scores

Biospecimen Retention:   Samples With DNA
Serum Stool Urine DNA

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with no liver disease in the past, who develop secondary sclerosing cholangitis during/after a critical illness

Inclusion Criteria:

  • informed consent
  • Age above 18 years
  • secondary sclerosing cholangitis in critically ill patients

Exclusion Criteria:

  • mechanical cholestasis
  • primary sclerosing cholangitis
  • primary biliary cirrhosis
  • Immune globulin G4 associated cholangitis
  • toxic cholestasis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02545309

Layout table for location contacts
Contact: Vanessa Stadlbauer, MD 0043 316 385 ext 82282

Layout table for location information
Department of Internal Medicine, Medical University of Graz Recruiting
Graz, Austria, 8010
Contact: Vanessa Stadlbauer, MD    0043316385 ext 82282   
Sponsors and Collaborators
Medical University of Graz
Layout table for investigator information
Principal Investigator: Vanessa Stadlbauer, MD Medical University of Graz

Layout table for additonal information
Responsible Party: Medical University of Graz Identifier: NCT02545309    
Other Study ID Numbers: 26-569 ex 13/14
First Posted: September 9, 2015    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Cholangitis, Sclerosing
Neoplastic Processes
Pathologic Processes
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases