The Effect of Probiotics (VSL) on Portal Hypertension

The investigators will address the hypothesis that portal hypertension is mediated in part by bacterial or endotoxin translocation and the production of inflammatory mediators (tumor necrosis factor-α (TNFα), etc.). The investigators hypothesize that food supplementation with the probiotic product VSL#3 in patients with Child Pugh B/C cirrhosis will have a beneficial effect on in portal pressure (as measured by the HVPG) by reducing inflammatory mediators and improving systemic and splanchnic hemodynamics.

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Key information

Conditions

Portal Hypertension Digestive System Diseases End Stage Liver Disease Fibrosis Hepatic Insufficiency Hypertension, Portal Liver Diseases Liver Failure Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

About this study

We have recently completed an open-label uncontrolled trial of the probiotic VSL#3 in 8 patients with compensated cirrhosis and evidence of portal hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.). The open label design and the inclusion of compensated (Child Pugh A) cirrhotic patients in this initial study were chosen to confirm the safety and tolerance of VSL#3 and the safety of the portal pressure measurements at our center. No changes of physical status occured. There was a non-significant reduction in portal pressure from 19.7 to 18.1 mm Hg after 2 months of VSL#3 supplementation. Furthermore, there was a significant reduction in the serum aldosterone level (p=0.03). IL-8 levels were reduced in 4/6 patients analyzed to date. These results suggest that VSL#3 results in cytokine reduction and an improvement in the effective circulating volume even in these well-compensated cirrhotic patients. The comparison of the rest of the pro-inflammatory mediators and stool microflora is still being analyzed.

The data in our initial study is very promising. As our patients were compensated cirrhotics with normal intestinal permeability and only mild baseline perturbations in hepatic function parameters (INR, bilirubin, albumin) and neurohormonal markers (aldosterone, renin), it is not surprising that a reduction in portal pressure was not identified. Consistent with previous studies however, these local results confirm the safety and tolerance of both VSL#3 as well as portal pressure measurements in cirrhotic patients (20,24,25).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age 18-80
Cirrhosis
Childs-Pugh Class B/C

Exclusion criteria

Bacterial infection
Grade 3-4 hepatic encephalopathy
GI bleeding in the past 2 weeks
Hepatocellular carcinoma beyond the Milan criteria
Transjugular intrahepatic portosystemic shunt (TIPS), surgical shunt
Portal vein thrombosis
Antibiotics in the past 2 weeks
Myocardial infarction, stroke or life-threatening arrhythmia within the last 6 months
Active alcohol or illicit drug use
Failure to consent to the study

Treatment and study plan

Probiotic

Drug

Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.

Other names: VSL#3

Primary outcomes

Reduction in portal pressure

Time frame: 12 months

Sponsors and collaborators

Lead sponsor

University of Alberta

Other

Registry information

Official study title

A Randomized Controlled Trial on the Beneficial Effects of Probiotics on Portal Hemodynamics in Decompensated Cirrhotic Patients

Important dates

Study start: 2009
Primary completion: 2011
Study completion: 2011
First posted: Dec 16, 2009
Registry last updated: Jan 20, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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