Intestinal Permeability in Patients With Liver Cirrhosis Using Confocal Endoscopy (CEDIP-LCI)

Confocal Endoscopy to Diagnose the Intestinal Permeability in Patients With Compensated and Decompensated Liver Cirrhosis

The CEDIP LCI study is intended to show the difference in intestinal permeability between compensated and decompensated liver cirrhosis by confocal endoscopy.

Study Overview

• Status: Terminated
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Diagnostic test: Fluorescein

Detailed Description

Liver cirrhosis often represents the end of many different liver diseases. A progress of liver cirrhosis with development of bleeding and infection complications represents a significant burden on the health system. It is therefore more important that the molecular basis leading to progress of liver cirrhosis is studied. In the last few years it has been demonstrated in various animal models as well as in human studies that the liver via the portal vein circuit is constantly under the influence of macronutrients, toxins, microbial products and microorganisms from the gastrointestinal tract. Patients with hepatic cirrhosis suffer from increased intestinal permeability so that bacterial components, endotoxins and pathogens enter the portal vein circuit via mesenteric lymph nodes. Bacterial translocations were found in patients with advanced liver cirrhosis and restricted organ function. This translocation causes a local as well as systemic inflammation with an increase in portal hypertension and further deterioration of the hepatic function, as well as a hyperdynamic circulatory situation which in many cases can lead to the death of the patient. These findings on the pathogenesis of portal hypertension and complications of cirrhosis of the liver have already led to the first therapeutic approaches where the occurrence of hepatic encephalopathy could be reduced by a purely intestinal reduction of the bacterial load by the antibiotic rifaxamine.

The intestinal barrier describes a functional and physical unit that ensures regulated intraluminal transport and protects against microorganisms and other pathogenic molecules. In addition to the intestinal epithelium with superposed mucus, intercellular proteins constitute an essential component. These paracellular proteins include tight junctions, anchoring junctions and GAP junctions, which are also responsible for controlled paracellular transport.

The cause of increased intestinal permeability in patients with liver cirrhosis are manifold. In addition to altered microbial colonization and slowed intestinal transit time, structural changes in the intestinal wall and altered expression of the tight junctions.

Due to the increasing insight into the molecular pathogenesis of intestinal permeability including portal hypertension, it is necessary to quantify these parameters more precisely in the clinical routine and to develop possible therapeutic interventions therefrom. An endoscopic procedure is provided by confocal endoscopy, with the aid of which portal hypertension and intestinal permeability can be diagnosed and estimated. With the help of this clinical study, this procedure is to be established.

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55131
    • University Medical Center of the Johannes Gutenber Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with liver cirrhosis

Description

Inclusion Criteria:

• liver cirrhosis
• need of upper endoscopy
• signed consent
• abdominal symptoms with indication for endoscopy

Exclusion Criteria:

• pregnancy
• Lactation
• Hypersensitivity to fluorescein
• Limited coagulation situation (Quick <50%, PTT> 50 sec, thrombocyte count <50000 / μl or disturbed thrombocyte function) despite the substitution of coagulation factors / plasma products
• Limited or non-existent consent
• Restricted or inadequate ability to perform endoscopy and / or confocal imaging: restlessness of the patient, food residues, anatomical variants that make confocal imaging difficult (e.g., strictures)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Liver cirrhosis; Patients with liver cirrhosis are included in this arm. Liver cirrhosis is diagnosed by ultrasound, CT - scan oder by clinical signs.	Diagnostic test: Fluorescein; Measurement of intensity in the gastrointestinal mucosa after intravenous administration of fluorescein by confocal endoscopy; Other Names: Intravenous application of fluorescein
Control group; Patients with abdominal symptoms with the indication for endoscopy without liver cirrhosis and portal Hypertension.	Diagnostic test: Fluorescein; Measurement of intensity in the gastrointestinal mucosa after intravenous administration of fluorescein by confocal endoscopy; Other Names: Intravenous application of fluorescein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of intestinal permeability	Intensity of fluorescein concentration in the gastrointestinal mucosa	August 2020

Collaborators and Investigators

• Sponsor: Johannes Gutenberg University Mainz

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): August 1, 2020

Study Registration Dates

• First Submitted: September 1, 2018
• First Submitted That Met QC Criteria: September 4, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Liver cirrhosis; Portal hypertension; Intestinal permeability; bacterial translocation; confocal endoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: CEDIP_LCI_JGU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No