Intestinal Permeability in Patients With Liver Cirrhosis Using Confocal Endoscopy

Terminated

• Conditions: Cirrhosis, Liver
• Interventions: Diagnostic Test: Fluorescein

• Registration Number: NCT03658551
• Lead Sponsor: Johannes Gutenberg University Mainz

Brief Summary

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

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 Timeline

• Study Start: 2017-08-01
• Study First Submitted: 2018-09-01
• Study First Submitted QC: 2018-09-04
• Study First Posted: 2018-09-05
• Primary Completion: 2020-08-01
• Study Completion: 2020-08-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-28
• Last Update Posted: 2022-04-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 15

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control group	Fluorescein	Patients with abdominal symptoms with the indication for endoscopy without liver cirrhosis and portal Hypertension.
Liver cirrhosis	Fluorescein	Patients with liver cirrhosis are included in this arm. Liver cirrhosis is diagnosed by ultrasound, CT - scan oder by clinical signs.

Primary Outcome Measures

Name	Time	Method
Amount of intestinal permeability	August 2020	Intensity of fluorescein concentration in the gastrointestinal mucosa

Trial Locations

Locations (1)

University Medical Center of the Johannes Gutenber Univeristy; 🇩🇪 Mainz, Germany